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1.
Odontology ; 112(4): 1113-1122, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38528238

RESUMEN

Chronic apical periodontitis (CAP) is characterized by inflammation and destruction of the apical periodontium that is of pulpal origin, appearing as an apical radiolucent area, and does not produce clinical symptoms. Little is known about whether the PD-1/PD-L1 ratio is associated with the balance between RANKL and OPG in CAP. The relationship between PD-1/PD-L1 and RANKL/OPG in CAP is investigated in this study. A CAP rat model was established using Sprague-Dawley rats. The pulp chambers were exposed to the oral cavity to allow bacterial contamination. The apical tissues of the bilateral mandibular first molars were analyzed for histological morphology using hematoxylin and eosin (H&E) staining. Immunohistochemistry and qRT-PCR were used to determine the expression of PD-1, PD-L1, OPG, and RANKL mRNA and proteins in periapical tissues and mandibular samples, respectively. The radiological images indicated a poorly defined low-density shadow and alveolar bone resorption after periodontitis induction. Histological analysis revealed an infiltration of inflammatory cells and alveolar bone resorption in the periapical tissues. Mandibular mRNA and periapical protein expression of PD-1, PD-L1, and RANKL was upregulated 7-28 days after periodontitis induction, while the expression of OPG was downregulated. No significant relationship was observed between PD-1/PD-L1 and RANKL/OPG at either mRNA or protein levels in CAP. There is an increased expression of PD-1, PD-L1, and RANKL and a decreased expression of OPG, indicating progression of CAP.


Asunto(s)
Antígeno B7-H1 , Modelos Animales de Enfermedad , Osteoprotegerina , Periodontitis Periapical , Ligando RANK , Ratas Sprague-Dawley , Animales , Periodontitis Periapical/metabolismo , Periodontitis Periapical/patología , Ratas , Ligando RANK/metabolismo , Osteoprotegerina/metabolismo , Antígeno B7-H1/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Inmunohistoquímica , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa
2.
Hepatology ; 75(1): 182-195, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34396571

RESUMEN

BACKGROUND AND AIM: HBV DNA can be reduced using antiviral drugs in patients with chronic hepatitis B (CHB); however, the rate of HBeAg seroconversion remains low. A clinical trial was conducted to assess the efficacy and safety of a de novo designed liposome-based nanoparticle lipopeptide vaccine, εPA-44, for CHB. APPROACH AND RESULTS: A two-stage phase 2 trial, which included a 76-week, randomized, double-blind, placebo-controlled trial (stage 1) and a 68-week open-label extension (stage 2), was conducted in 15 centers across China (Clinicaltrials.gov No. NCT00869778). In stage 1, 360 human leukocyte antigen A2 (HLA-A2)-positive and HBeAg-positive patients were randomly and equally distributed to receive six subcutaneous injections of 600 µg or 900 µg εPA-44 or placebo at week 0, 4, 8, 12, 20, and 28. In stage 2, 183 patients received extended 900 µg εPA-44, and 26 patients were observed for relapse without further treatment. The primary endpoint was the percentage of patients with HBeAg seroconversion at week 76. At week 76, patients receiving 900 µg εPA-44 achieved significantly higher HBeAg seroconversion rate (38.8%) versus placebo (20.2%) (95% CI, 6.9-29.6%; p = 0.002). With a combined endpoint of HBeAg seroconversion, alanine aminotransferase normalization and HBV DNA < 2,000 IU/mL, both 900 µg (18.1%) and 600 µg (14.3%), resulted in significantly higher rate versus placebo (5.0%) (p = 0.002 and p = 0.02, respectively) at week 76. In stage 2, none (0 of 20) of 900 µg εPA-44-treated patients experienced serologic relapse. The safety profile of εPA-44 was comparable to that of placebo. CONCLUSIONS: Among HLA-A2-positive patients with progressive CHB, a finite duration of 900 µg εPA-44 monotherapy resulted in significantly higher HBeAg seroconversion rate than placebo and sustained off-treatment effect. A phase 3 trial is ongoing (ChiCTR2100043708).


Asunto(s)
Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Hepatitis B Crónica/terapia , Vacunas contra Hepatitis Viral/administración & dosificación , Adolescente , Adulto , Método Doble Ciego , Femenino , Antígenos e de la Hepatitis B/inmunología , Hepatitis B Crónica/sangre , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/virología , Humanos , Inyecciones Subcutáneas , Liposomas , Masculino , Sistema de Administración de Fármacos con Nanopartículas , Seroconversión , Respuesta Virológica Sostenida , Vacunas de Subunidad/administración & dosificación , Vacunas de Subunidad/efectos adversos , Vacunas de Subunidad/química , Vacunas contra Hepatitis Viral/efectos adversos , Vacunas contra Hepatitis Viral/química , Adulto Joven
3.
Odontology ; 111(1): 154-164, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36057921

RESUMEN

This study was to investigate whether the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) and T-helper 17 (Th17)/regulatory T (Treg) balance are associated with chronic apical periodontitis (CAP) relived by 0.1% nano-silver. CAP rat models were established by opening the first molars of the right and left mandible and exposing the pulp cavity to the oral cavity. CAP model was verified by cone-beam computed tomography, X-ray digital radiovisiography, and hematoxylin-eosin (H and E) staining. The rats were randomly divided into the sham, Ca(OH)2, and 0.1% nano-silver groups (n = 12 in each group) 2 weeks after surgery. The pathological changes in the apical area were detected by H and E staining. PD-1, PD-L1, RORγT, IL-17, and Foxp3 in periapical tissues were detected by qRT-PCR and immunohistochemistry. Th17/Treg and PD-1/PD-L1 were analyzed by flow cytometry. After 7, 14, and 21 days of 0.1% nano-silver treatment, inflammatory cells in the apical region were slightly reduced and inflammatory infiltration was relieved compared with the sham group. RORγT, IL-17, PD-1, and PD-L1 decreased and Foxp3 increased after 7, 14, and 21 days of 0.1% nano-silver treatment compared with the sham group (p < 0.05); however, there were no significant differences with Ca(OH)2 group (p > 0.05). Flow cytometry revealed that 0.1% nano-silver solution decreased Th17/Treg and PD-1/PD-L1 ratio. 0.1% Nano-silver significantly reduced the inflammation of CAP in rats. PD-1/PD-L1 was included in Th17/Treg balance restored by 0.1% nano-silver.


Asunto(s)
Periodontitis Periapical , Periodontitis , Animales , Ratas , Antígeno B7-H1/metabolismo , Factores de Transcripción Forkhead/metabolismo , Interleucina-17/metabolismo , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo , Receptor de Muerte Celular Programada 1 , Linfocitos T Reguladores/metabolismo
4.
Int J Mol Sci ; 24(9)2023 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-37175817

RESUMEN

Secondary cell wall (SCW) thickening has a significant effect on the growth and development of plants, as well as in the resistance to various biotic and abiotic stresses. Lignin accounts for the strength of SCW. It is synthesized through the phenylpropanoid pathway that also leads to flavonoid synthesis. The coupling strategies for lignin and flavonoid syntheses are diverse in plants. How their syntheses are balanced by transcriptional regulation in fleshy fruits is still unclear. The diploid strawberry (Fragaria vesca) is a model for fleshy fruits research due to its small genome and wide scope of genetic transformation. SCW thickening is regulated by a multilevel transcriptional regulatory network wherein vascular-related NAC domains (VNDs) act as key regulators. In this study, we systematically characterized VNDs in Fragaria vesca and explored their functions. The overexpression of FvVND4c in diploid strawberry fruits resulted in SCW thickening and fruit color changes accompanied with the accumulation of lignin and flavonoids. Genes related to these phenotypes were also induced upon FvVND4c overexpression. Among the induced genes, we found FvMYB46 to be a direct downstream regulator of FvVND4c. The overexpression of FvMYB46 resulted in similar phenotypes as FvVND4c, except for the color change. Transcriptomic analyses suggest that both FvVND4c and FvMYB46 act on phenylpropanoid and flavonoid biosynthesis pathways, and induce lignin synthesis for SCW. These results suggest that FvVND4c and FvMYB46 cooperatively regulate SCW thickening and flavonoid accumulation in Fragaria vesca.


Asunto(s)
Fragaria , Fragaria/metabolismo , Flavonoides/farmacología , Expresión Génica Ectópica , Lignina/metabolismo , Frutas/metabolismo , Pared Celular/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/metabolismo
5.
Exp Cell Res ; 381(1): 39-49, 2019 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-31071315

RESUMEN

Stromal-derived factor-1α (SDF-1α) is a chemokine signaling molecule that binds to the transmembrane receptor CXC chemokine receptor-4 (CXCR4) and carries out important functions in development tissue homeostasis. SDF-1α signaling via CXCR4 regulates the recruitment of stem and precursor cells to support tissue-specific repair or regeneration. In this study, we examined the contribution of SDF-1α signaling to the odontogenic differentiation of stem cells from the apical papilla (SCAP) induced by bone morphogenic protein 2 (BMP-2). CXCR4 expression was detected in cultured SCAP and SDF-1α promoted the migration of SCAP in Transwell assays. Blocking SDF-1α signaling by treatment with siRNA significantly affected BMP-2-induced mineralized nodule formation and alkaline phosphatase (ALP) activity. Moreover, blocking SDF-1α signaling inhibited the BMP-2-induced early expression of runt-related factor-2 (Runx-2) and strongly suppressed the induction of dentin matrix protein 1 (DMP-1) and dentin sialophosphoprotein (DSPP) expression by BMP-2. Furthermore, the interaction between SDF-1α and BMP-2 signaling was mediated via intracellular Smads and Erk activation. In conclusion, our results demonstrated that SDF-1α can significantly promote the migration of SCAP. Moreover, we revealed corequirement of the SDF-1α/CXCR4 signaling pathways in the BMP-2-induced odontogenic differentiation of SCAP, and these findings may be applied in new strategies for dental pulp regeneration.


Asunto(s)
Proteína Morfogenética Ósea 2/metabolismo , Quimiocina CXCL12/metabolismo , Papila Dental/citología , Odontogénesis , Transducción de Señal , Células Madre/fisiología , Adolescente , Movimiento Celular , Separación Celular , Niño , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Humanos , Sistema de Señalización de MAP Quinasas , Masculino , Fosfoproteínas/metabolismo , ARN Interferente Pequeño , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Proteínas Smad/metabolismo , Células Madre/metabolismo
6.
Small ; 13(4)2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27008568

RESUMEN

Surface wettability plays a key role in addressing issues ranging from basic life activities to our daily life, and thus being able to control it is an attractive goal. Learning from nature, both of its structure and function, brings us much inspiration in designing smart polymers to tackle this major challenge. Life functions particularly depend on biomolecular recognition-induced interfacial properties from the aqueous phase onto either "soft" cell and tissue or "hard" inorganic bone and tooth surfaces. The driving force is noncovalent weak interactions rather than strong covalent combinations. An overview is provided of the weak interactions that perform vital actions in mediating biological processes, which serve as a basis for elaborating multi-component polymers with special wettabilities. The role of smart polymers from molecular recognitions to macroscopic properties are highlighted. The rationale is that highly selective weak interactions are capable of creating a dynamic synergetic communication in the building components of polymers. Biomolecules could selectively induce conformational transitions of polymer chains, and then drive a switching of physicochemical properties, e.g., roughness, stiffness and compositions, which are an integrated embodiment of macroscopic surface wettabilities.


Asunto(s)
Polímeros/química , Animales , Materiales Biomiméticos/química , Humanos , Dióxido de Silicio/química , Humectabilidad
7.
Plant Biotechnol J ; 15(6): 718-728, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27879048

RESUMEN

A novel approach is developed for coordinated expression of multiple proteins from a single transgene in plants. An Ssp DnaE mini-intein variant engineered for hyper-N-terminal autocleavage is covalently linked to the foot-and-mouth disease virus 2A (F2A) peptide with unique ribosome skipping property, via a peptide linker, to create an 'IntF2A' self-excising fusion protein domain. This IntF2A domain acts, in cis, to direct highly effective release of its flanking proteins of interest (POIs) from a 'polyprotein' precursor in plants. This is successfully demonstrated in stably transformed cultured tobacco cells as well as in different organs of transgenic tobacco plants. Highly efficient polyprotein processing mediated by the IntF2A domain was also demonstrated in lettuce and Nicotiana benthamiana based on transient expression. Protein constituents released from the polyprotein precursor displayed proper function and accumulated at similar levels inside the cells. Importantly, no C-terminal F2A extension remains on the released POIs. We demonstrated co-expression of as many as three proteins in plants without compromising expression levels when compared with those using single-protein vectors. Accurate differential cellular targeting of released POIs is also achieved. In addition, we succeeded in expressing a fully assembled and functional chimeric anti-His Tag antibody in N. benthamiana leaves. The IntF2A-based polyprotein transgene system overcomes key impediments of existing strategies for multiprotein co-expression in plants, which is particularly important for gene/trait stacking.


Asunto(s)
Inteínas/fisiología , Plantas Modificadas Genéticamente/metabolismo , Proteínas Virales/metabolismo , Virus de la Fiebre Aftosa/genética , Inteínas/genética , Péptidos/genética , Plantas Modificadas Genéticamente/genética , Procesamiento Proteico-Postraduccional/genética , Proteínas Virales/genética
8.
PLoS One ; 19(3): e0298271, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38502664

RESUMEN

Multiple Sclerosis (MS) is an immune-related disease and the relationship between MS and cancer has raised attention. Previous studies of the relationship between MS and cancer have reached conflicting conclusions. In this study, the two-sample MR method is used to investigate whether MS has a causal correlation with cancers and offer scientific evidence for cancer prevention. Single nucleotide polymorphisms (SNPs) related to MS were obtained from the genome-wide association study (GWAS) based on International Multiple Sclerosis Genetics Consortium (IMSGC) and SNPs related to 15 types of cancers were obtained from the GWASs based on UK Biobank. Inverse variance weighted (IVW) method was mainly used to assess causal effects. Sensitivity analyses were conducted with Cochran's Q-test, MR Egger intercept, leave-one-out test, and MR Steiger method. IVW analysis showed that MS was only associated with a marginal increased risk of cervical cancer (OR 1.0004, 95% CI 1.0002-1.0007, p = 0.0003). Sensitivity analyses showed that the results of MR analysis were robust and found no heterogeneity, no pleiotropy, and no reverse causation. In conclusion, this study finds no causal relationship between MS and 15 types of cancers except cervical cancer.


Asunto(s)
Esclerosis Múltiple , Neoplasias del Cuello Uterino , Femenino , Humanos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/genética , Nonoxinol
9.
Environ Pollut ; 317: 120818, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-36481467

RESUMEN

The widespread coexistence of hydrophilic organic compounds and microplastics (MPs) in the environment has greatly increased their associated environmental problems. To evaluate the potential carrier effect of oxygen-containing MPs on coexisting pollutants, adsorption behaviors of four hydrophilic organic compounds (benzoic acid, sulfamethoxazole, sulfamerazine and ciprofloxacin) on MPs (pristine and weathered polyamide (PA)) were studied in the aquatic environment. The results showed that the surface morphology, size, oxygen content, molecular structure, surface charge and crystallinity of PA were changed after weathering, and the weathering degree of PA treated with heat-activated potassium persulfate was the highest. The main adsorption mechanisms included hydrogen bonding, hydrophobic interaction, charge-assisted hydrogen bonding, and electrostatic interaction. Hydrogen bonding and hydrophobic interaction contributed to the adsorption, while electrostatic interaction weakened the adsorption under the specific pH conditions. The formation of charge-assisted hydrogen bonding (CAHB) was also verified through pH influence experiments, and this force can overcome the electrostatic repulsion. The high adsorption of KPA (PA weathered by K2S2O8) under alkaline conditions was well explained by the formation of homonuclear CAHB due to the increase of oxygen-containing functional groups compared to the other three PA. Additionally, weathering did not always enhance the adsorption of hydrophilic organic compounds on PA, which was related to the changes in surface charge, crystallinity and hydrophilicity of PA. Overall, the physical and chemical properties (e.g., specific surface area, oxygen content, molecular structure) of PA after weathering and its trend of adsorption were different from other oxygen-free MPs in this study. This work can provide basic data for environmental risk of MPs and contribute to clarify and understand the processes of oxygenated MPs in the aquatic environment.


Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Microplásticos/química , Plásticos/química , Nylons , Adsorción , Contaminantes Químicos del Agua/análisis , Compuestos Orgánicos , Interacciones Hidrofóbicas e Hidrofílicas
10.
Acta Biomater ; 160: 73-86, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36804823

RESUMEN

The irrational use of natural compounds in the treatment of diseases can lead to serious side effects, especially hepatoxicity, and its toxic effects are usually cumulative and imperceptible. Therefore, an accurate sensing platform is urgently needed to monitor the hepatotoxicity of natural compounds. Here, we deposited a thermo-responsive alginate-RGD/Pluronic hydrogel to construct an in vitro three-dimensional(3D) hepar-platform, and a thorough validation was adopted to evaluate the bioprinted hepatic constructs. The engineered hepar-platform was then employed to access its biological response toward Emodin (EM) and Triptolide (TP), two typical hepatotoxic natural compounds. Subsequently, we integrated it with a robust fluorescent sensor based on hybridization chain reaction amplification strategy (HCR) to monitor the early hepatotoxic biomarker - glutathione-S-transferase-alpha (GST-α) secreted by this 3D constructs. Our study was the first attempt to construct an accurate hepar-on-a-sensor platform that could effectively detect GST-α for monitoring the hepatoxic effects of natural compounds. The limit of detection of the platform was 0.3 ng ml-1 and the accuracy of this platform was verified by enzyme linked immunosorbent assay. Furthermore, the variation of GST-α induced by EM and TP was consistent with hepatotoxicity studies, thus providing an important application value for evaluating the hepatotoxicity of natural compounds. STATEMENT OF SIGNIFICANCE: 1. We deposited a thermo-responsive alginate-RGD/Pluronic hydrogel to construct an in vitro three-dimensional(3D) hepar-platform, and elucidated the essential reasons why hybrid bioinks more suitable for 3D extrusion from biomaterials itself. Also, a thorough validation associated with a series of important proteins and genes involved in liver cell metabolism was adopted to evaluate the bioprinted hepatic constructs accurately 2. Glutathione-S-transferase-alpha is a soluble trace biomarker for acute hepatotoxic injury, the hepatotoxic effects of natural compounds on the secretion of GST-α has not been reported to date. We integrated our 3D hepar-platform with recognition molecules-aptamers and HCR amplification strategy to monitor the variation of GST-α, aiming at developing a robust and stable fluorescent biosensing platform to monitor the hepatoxicity of natural compounds.


Asunto(s)
Bioimpresión , Enfermedad Hepática Inducida por Sustancias y Drogas , Humanos , Poloxámero , Hidrogeles , Biomarcadores , Colorantes , Alginatos , Glutatión , Oligopéptidos , Impresión Tridimensional , Andamios del Tejido , Ingeniería de Tejidos
11.
J Biotechnol ; 358: 1-8, 2022 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-35995093

RESUMEN

Simultaneous coexpression of multiple proteins is essential for biotechnology and synthetic biology. Currently, the most popular polyprotein coexpression system utilizes the foot-and-mouth disease virus (FMDV) 2A peptide that mediates translational ribosome-skipping events. However, due to unfavorable consumer acceptance of transgenic products containing animal-virus sequences, novel non-viral 2A-like peptides from purple sea urchin (Strongylcentrotus purpuratus) and California sea slug (Aplysia californica) were investigated for polyprotein coexpression in this study. We demonstrated that these non-viral 2A sequences functioned similarly to their viral counterpart in polyprotein processing, in both plant and mammalian cells, and were successfully used to express a functional recombinant antibody. The new non-viral 2A-like sequences offer an alternative tool for engineering multigenic traits or production of protein complexes as biomedicine via coexpression of protein subunits.


Asunto(s)
Virus de la Fiebre Aftosa , Proteínas Virales , Animales , Virus de la Fiebre Aftosa/genética , Virus de la Fiebre Aftosa/metabolismo , Mamíferos , Péptidos/metabolismo , Poliproteínas/metabolismo , Subunidades de Proteína/metabolismo , Proteínas Virales/metabolismo
12.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 28(3): 517-20, 542, 2011 Jun.
Artículo en Zh | MEDLINE | ID: mdl-21774214

RESUMEN

Star-shaped polymer of epoxidized soybean oil (ESO) and lactide is a new material. Its degradation function has an importance to its applications. There are many factors affecting its degradation. This paper is mainly aimed at investigation in which the surface morphology, pH, molecular weight and weight loss rate, branching ESO-lactide star polymers the degree of change were studied. It was found through the experiments that, the changing rates of the branching ESO-lactide star polymers were slower than the degree of PDLLA change compared to the surface morphology, pH, molecular weight and weight loss rate. This has a guiding significance to the further application of ESO-lactide.


Asunto(s)
Poliésteres/química , Polímeros/química , Aceite de Soja/química
13.
ACS Nano ; 15(3): 4518-4533, 2021 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-33619957

RESUMEN

Herein, a functional class of microenvironment-associated nanomaterials is reported for improving the second near-infrared (NIR-II) imaging and photothermal therapeutic effect on intracranial tumors via a spontaneous membrane-adsorption approach. Specific peptides, photothermal agents, and biological alkylating agents were designed to endow the nanogels with high targeting specificity, photothermal properties, and pharmacological effects. Importantly, the frozen scanning electron microscopy technology (cryo-SEM) was utilized to observe the self-association of nanomaterials on tumor cells. Interestingly, the spontaneous membrane-adsorption behavior of nanomaterials was captured through direct imaging evidence. Histological analysis showed that the cross-linking adhesion in intracranial tumor and monodispersity in normal tissues of the nanogels not only enhanced the retention time but also ensured excellent biocompatibility. Impressively, in vivo data confirmed that the microenvironment-associated nanogels could significantly enhance brain tumor clearance rate within a short treatment timeframe (only two weeks). In short, utilizing the spontaneous membrane-adsorption strategy can significantly improve NIR-II diagnosis and phototherapy in brain diseases while avoiding high-risk complications.


Asunto(s)
Neoplasias Encefálicas , Nanopartículas , Adsorción , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/terapia , Humanos , Nanogeles , Fototerapia , Microambiente Tumoral
14.
Biomaterials ; 269: 120629, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33387938

RESUMEN

Metastatic cancer is a persistent clinical enigma, which requires combination of several treatment modules. Here, we developed an all-in-one nanomedicine strategy to systemically co-deliver photosensitive, chemotherapeutic, and immunomodulating agents for effective immunochemo-photothermal therapy (PTT) to inhibit both primary tumor and distal metastatic tumor. Two types of polydopamine (dp)-coated nanoparticles (NPs) (N/PGEM/dp-5 and N/PGEM/dp-16) co-loaded with gemcitabine (GEM) and NLG919, a potent indoleamine-2, 3-dioxygenase (IDO) inhibitor, were prepared. N/PGEM/dp-16 NPs with a thicker dp coating layer showed higher photothermal conversion ability, more favorable biodistribution profile and better tumor inhibition effect compared to N/PGEM/dp-5 NPs with a thinner coating layer. Combination with laser irradiation further enhanced the tumor inhibition effect of N/PGEM/dp-16 NPs. In an "early metastatic" pancreatic cancer PANC02 model with small distal tumors, introduction of NLG and dp coating improved the inhibition effect on both primary and distal tumors. Compared to N/PGEM/dp-16, N/PGEM/dp-16 plus laser irradiation further enhanced the inhibition effect on primary tumor, but didn't improve the abscopal antitumor effect. When the initial volume of distal tumor was sufficiently large in a "late metastasis" model, a more dramatic abscopal antitumor effect was achieved, resulting in a significant growth inhibition of both primary tumor and the unirradiated distal tumor. Furthermore, laser irradiation can amplify the immunochemo-NPs-mediated innate and adaptive immune responses in both tumors. This work demonstrated a distal tumor-size dependent abscopal effect, and provided a perspective for future design of more effective immunochemo-PTT nano-formulations for early- and late-stage metastatic tumors.


Asunto(s)
Nanopartículas , Neoplasias , Línea Celular Tumoral , Humanos , Indoles , Neoplasias/terapia , Fototerapia , Terapia Fototérmica , Polímeros , Distribución Tisular
15.
Int J Numer Method Biomed Eng ; 36(5): e3321, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32043311

RESUMEN

The tooth defect is a frequently occurring disease within the field of dental clinic. However, the traditional manual restoration for the defective tooth needs an especially long treatment time, and dental computer aided design and manufacture (CAD/CAM) systems fail to restore the personalized anatomical features of natural teeth. Aiming to address the shortcomings of existed methods, this article proposes an intelligent network model for designing tooth crown surface based on conditional generative adversarial networks. Then, the data set for training the network model is constructed via generating depth maps of 3D tooth models scanned by the intraoral. Through adversarial training, the network model is able to generate tooth occlusal surface under the constraint of the space occlusal relationship, the perceptual loss, and occlusal groove filter loss. Finally, we carry out the assessment experiments for the quality of the occlusal surface and the occlusal relationship with the opposing tooth. The experimental results demonstrate that our method can automatically reconstruct the personalized anatomical features on occlusal surface and shorten the treatment time while restoring the full functionality of the defective tooth.


Asunto(s)
Diente , Diseño Asistido por Computadora , Diseño de Prótesis Dental , Humanos
16.
Shanghai Kou Qiang Yi Xue ; 29(6): 586-590, 2020 Dec.
Artículo en Zh | MEDLINE | ID: mdl-33778823

RESUMEN

PURPOSE: To investigate the effect of firing times on the fatigue properties and failure modes of posterior occlusal veneers made of lithium disilicate glass ceramics. METHODS: According to the number of times of firing (1, 3, 5, 7 times), IPS e.max CAD(IC) and IPS e.max Press(IP) occlusal veneer restorations with a thickness of 1.2mm were prepared, and then cemented to the maxillary molar composite resin dies. Each group was subjected to thermo-mechanical fatigue(TMFT) test (5-55 ℃, 5000 cycles, 30-300 N, 10 Hz, sinusoidal wave, 500 000 cycles) and compressive loading. The maximum force at fracture was recorded. Stereomicroscope and scanning electron microscope(SEM), energy dispersive X-ray spectroscopy(EDX) and X-ray diffraction(XRD) were adopted to analyze the failure modes and microstructural features. Statistical analysis was performed with SPSS 20.0 software package. RESULTS: The highest average loads (N) at fracture for IC groups were (1546.73±192.85) N after one firing time; in IP group, the highest average loads were (1504.46±138.56) N after three firing times. There was no significant difference in the fracture load with different firing times for IC/IP(P>0.05). EDX and XRD analysis showed no significant difference in the composition of two materials. SEM showed that the size of crystal was shorter and the porosity increased after multiple firing. CONCLUSIONS: After repeated firing, the fatigue loading of lithium disilicate glass ceramics has a decreasing trend of fracture load value without any significant difference, and it meets clinical requirements.


Asunto(s)
Porcelana Dental , Coronas con Frente Estético , Cerámica , Resinas Compuestas , Diseño Asistido por Computadora , Fracaso de la Restauración Dental , Análisis del Estrés Dental , Ensayo de Materiales , Propiedades de Superficie
17.
PeerJ ; 8: e9858, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33194358

RESUMEN

Collaborative hunting by complex social groups is a hallmark of large dogs (Mammalia: Carnivora: Canidae), whose teeth also tend to be hypercarnivorous, specialized toward increased cutting edges for meat consumption and robust p4-m1 complex for cracking bone. The deep history of canid pack hunting is, however, obscure because behavioral evidence is rarely preserved in fossils. Dated to the Early Pleistocene (>1.2 Ma), Canis chihliensis from the Nihewan Basin of northern China is one of the earliest canines to feature a large body size and hypercarnivorous dentition. We present the first known record of dental infection in C. chihliensis, likely inflicted by processing hard food, such as bone. Another individual also suffered a displaced fracture of its tibia and, despite such an incapacitating injury, survived the trauma to heal. The long period required for healing the compound fracture is consistent with social hunting and family care (food-sharing) although alternative explanations exist. Comparison with abundant paleopathological records of the putatively pack-hunting Late Pleistocene dire wolf, Canis dirus, at the Rancho La Brea asphalt seeps in southern California, U.S.A., suggests similarity in feeding behavior and sociality between Chinese and American Canis across space and time. Pack hunting in Canis may be traced back to the Early Pleistocene, well before the appearance of modern wolves, but additional evidence is needed for confirmation.

18.
J Food Sci ; 85(10): 3237-3243, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32860245

RESUMEN

A flaxseed oil carboxymethyl chitosan-decorated proliposome system was fabricated in this research. The physicochemical characteristics, stability, and in vitro release behaviors of flaxseed oil were studied and compared with that of flaxseed oil-loaded liposomes. The results of dynamic light scattering, transmission electron microscopy, and oxidation stability indicated that the storage stability of proliposomes was better. After 28 days of storage, the peroxide value of flaxseed oil-loaded liposomes (20.1 meq/kg) was significantly (P < 0.05) higher than that of flaxseed oil-loaded proliposomes (9.0 meq/kg); the thiobarbituric acid reactive substances in the former (0.53 mmol/kg) was also higher than that in the latter (0.27 mmol/kg). The in vitro release behavior of flaxseed oil indicated the proliposomes were more stable in the simulated gastrointestinal fluids. Therefore, the flaxseed oil-loaded proliposome system could be a promising vehicle for delivery flaxseed oil in food industry. PRACTICAL APPLICATION: A flaxseed oil-loaded proliposome delivery system was fabricated in this research. Their physical and oxidation stability of flaxseed oil were improved, and the in vitro cumulative release of flaxseed oil was delayed compared with flaxseed oil liposomes. This system may provide an effective strategy for the flaxseed oil encapsulation in the food industry.


Asunto(s)
Quitosano/análogos & derivados , Preparaciones de Acción Retardada/química , Portadores de Fármacos/química , Aceite de Linaza/química , Liposomas/química , Quitosano/química , Composición de Medicamentos , Estabilidad de Medicamentos , Oxidación-Reducción , Tamaño de la Partícula
19.
Medicine (Baltimore) ; 99(35): e21825, 2020 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-32871904

RESUMEN

OBJECTIVE: To conduct a meta-analysis evaluating the effect of combining traditional Chinese medicine (TCM) with Western medicine in treating hepatitis C, and to provide an evidence-based medical strategy. METHODS: Randomized controlled trials (RCTs) comparing the effect of pegylated interferon (Peginterferon) combined with ribavirin (PR) alone and its combination with TCM were manually retrieved from the Weipu Information Resources System (VIP), Wan Fang Database, PubMed, and the Chinese Journal Full Text Database (CNKI). Studies meeting the inclusion criteria were selected and analyzed using the Review Manager 5.3 software. Suitable tests were also performed to determine the quality, heterogeneity, and sensitivity of the studies included in the meta-analysis. RESULTS: Twenty-eight RCTs met the inclusion criteria. The combination therapy or intervention group showed significantly greater HCV-RNA negative rate post-treatment compared to the monotherapy or the control group (P < .05). In addition, the serum levels of the liver function indicators alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB) were significantly improved after the combination therapy compared to PR alone (P < .05), while total bilirubin (TB) and r-glutamyltransferase (GGT) levels were not affected by TCM (P > .05). Finally, the parameters of liver fibrosis were also reduced by the combination therapy more effectively than the monotherapy. CONCLUSION: The combination of TCM and PR can improve the Comprehensive Clinical Efficacy of hepatitis C and have a better negative rate of HCV-RNA with a better benefit in the liver function. The effect of TCM + PR is better than that of PR alone in treating hepatitis C.


Asunto(s)
Antivirales/uso terapéutico , Hepatitis C/terapia , Medicina Tradicional China , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Bilirrubina/sangre , Terapia Combinada , Quimioterapia Combinada , Hepacivirus/genética , Humanos , Interferón-alfa/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Polietilenglicoles/uso terapéutico , ARN Viral/sangre , Proteínas Recombinantes/uso terapéutico , Ribavirina/uso terapéutico , Albúmina Sérica , gamma-Glutamiltransferasa/sangre
20.
Opt Express ; 17(26): 23684-9, 2009 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-20052079

RESUMEN

The effects of the lattice pitch of GaN and polymer square-lattice photonic crystal (2PhC) on the diffracted transmission were studied by using rigorous coupled wave analysis (RCWA). Besides the first-order Bragg diffraction, higher-order diffractions from large pitches of PhC are also significant to the light extraction improvement. Three different diffraction mechanisms are illustrated through wave vector analysis. The enhancement factors of integrated transmission are obtained from a wide range of pitches with micro-scale for both GaN and polymer 2PhC. The experimental angular-resolved transmission on a transparent polymer sample of 2 microm pitch 2PhC is comparable to the simulation.


Asunto(s)
Galio/química , Polímeros/química , Refractometría/métodos , Cristalización/métodos , Luz , Ensayo de Materiales , Fotones , Dispersión de Radiación
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