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1.
Nano Lett ; 24(23): 6906-6915, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38829311

RESUMEN

Herein, a multifunctional nanohybrid (PL@HPFTM nanoparticles) was fabricated to perform the integration of chemodynamic therapy, photothermal therapy, and biological therapy over the long term at a designed location for continuous antibacterial applications. The PL@HPFTM nanoparticles consisted of a polydopamine/hemoglobin/Fe2+ nanocomplex with comodification of tetrazole/alkene groups on the surface as well as coloading of antimicrobial peptides and luminol in the core. During therapy, the PL@HPFTM nanoparticles would selectively cross-link to surrounding bacteria via tetrazole/alkene cycloaddition under chemiluminescence produced by the reaction between luminol and overexpressed H2O2 at the infected area. The resulting PL@HPFTM network not only significantly damaged bacteria by Fe2+-catalyzed ROS production, effective photothermal conversion, and sustained release of antimicrobial peptides but dramatically enhanced the retention time of these therapeutic agents for prolonged antibacterial therapy. Both in vitro and in vivo results have shown that our PL@HPFTM nanoparticles have much higher bactericidal efficiency and remarkably longer periods of validity than free antibacterial nanoparticles.


Asunto(s)
Antibacterianos , Nanopartículas , Antibacterianos/farmacología , Antibacterianos/química , Animales , Nanopartículas/química , Ratones , Escherichia coli/efectos de los fármacos , Polímeros/química , Indoles/química , Indoles/farmacología , Terapia Fototérmica , Humanos , Staphylococcus aureus/efectos de los fármacos , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/farmacología , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/farmacología
2.
J Chem Inf Model ; 64(14): 5617-5623, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-38980667

RESUMEN

The design of biosequences for biosensing and therapeutics is a challenging multistep search and optimization task. In principle, computational modeling may speed up the design process by virtual screening of sequences based on their binding affinities to target molecules. However, in practice, existing machine-learned models trained to predict binding affinities lack the flexibility with respect to reaction conditions, and molecular dynamics simulations that can incorporate reaction conditions suffer from high computational costs. Here, we describe a computational approach called DeltaGzip that evaluates the free energy of binding in biopolymer-ligand complexes from ultrashort equilibrium molecular dynamics simulations. The entropy of binding is evaluated using the Kolmogorov complexity definition of entropy and approximated using a lossless compression algorithm, Gzip. We benchmark the method on a well-studied data set of protein-ligand complexes comparing the predictions of DeltaGzip to the free energies of binding obtained using Jarzynski equality and experimental measurements.


Asunto(s)
Simulación de Dinámica Molecular , Ligandos , Biopolímeros/química , Biopolímeros/metabolismo , Unión Proteica , Algoritmos , Entropía , Termodinámica , Proteínas/química , Proteínas/metabolismo
3.
BMC Pediatr ; 24(1): 282, 2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38678186

RESUMEN

BACKGROUND: Little has been done to establish biobanks for studying the environment and lifestyle risk factors for diseases among the school-age children. The Minhang Pediatric Biobank (MPB) cohort study aims to identify factors associated with health and diseases of school-aged children living in the urban or suburban area of Shanghai. METHODS: This population-based cohort study was started in all sub-districts/towns of Minhang district of Shanghai in 2014. First-grade students in elementary school were enrolled during the time of their routine physical examinations, with self-administered questionnaires completed by their primary caregivers. Additional information was extracted from multiple health information systems. Urine and saliva samples were collected during the baseline survey and follow-up visits. RESULTS: At the end of 2014 academic year, a total number of 8412 children and their parents were recruited, including 4339 boys and 4073 girls. All the participants completed the baseline survey and physical examination, and 7128 urine and 2767 saliva samples were collected. The five most prevalent childhood diseases in this population were dental caries, bronchitis, pneumonia, asthma and overweight/obese. CONCLUSIONS: The MPB cohort has been successfully established, serving as a useful platform for future research relating to the genetic, environmental and lifestyle risk factors for childhood diseases.


Asunto(s)
Bancos de Muestras Biológicas , Humanos , Masculino , Femenino , Niño , China/epidemiología , Estudios de Cohortes , Saliva/química , Factores de Riesgo , Asma/epidemiología , Estilo de Vida , Caries Dental/epidemiología
4.
Ecotoxicol Environ Saf ; 263: 115248, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37441951

RESUMEN

As a new type of environmental pollutant, microplastics have been garnered increasing attention, especially in regard to their effects on the reproductive system. However, researchers have yet to report whether prevention and treatment measures exist for reproductive injury caused by microplastics. The aim of this study was therefore to explore the mechanism of spermatogenic injury induced by polystyrene microplastics (PS-MPs) and the intervention effect of probiotics based on the gut microbiota-testis axis. Mice were orally exposed for 35 days to 5 µm of PS-MPs with a gavage dose was 0.1 mg/day, and the intervention group was given probiotics (Lactobacillus, Bifidobacterium longum, and Enterococcus) orally. Fecal samples were then subjected to 16 S rRNA sequencing analysis, and sperm motion was analyzed by a Hamilton-Thorne Sperm analyzer. The results showed that PS-MPs exposed mice had significant spermatogenic dysfunction and testicular inflammation. In addition, the intestinal microbial structure of exposed mice changed significantly; the abundance of Lactobacillus decreased, and the abundance of Prevotella increased. Furthermore, with fecal microbiota transplantation, the recipient mice showed a significant decrease in sperm quality. However, probiotics supplementation helped inhibit the activation of IL-17A signaling driven by gut microbes, thereby alleviating the inflammatory response and improving sperm quality decline caused by PS-MPs. These results may provide a scientific basis for further understanding of the mechanism of male reproductive damage caused by environmental pollutants such as microplastics and for novel reproductive damage intervention measures.


Asunto(s)
Contaminantes Ambientales , Probióticos , Masculino , Animales , Ratones , Microplásticos , Plásticos , Poliestirenos/toxicidad , Semen , Lactobacillus , Probióticos/farmacología
5.
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
6.
Mediators Inflamm ; 2022: 6206883, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35909660

RESUMEN

Atopic dermatitis (AD) is a chronic skin inflammatory disease associated with immune abnormalities and disrupted skin barrier function. Mesenchymal stem cells (MSCs) have been suggested as an alternative therapeutic option in AD. Stem cells from human exfoliated deciduous teeth (SHEDs) are a unique postnatal stem cell population with high immunomodulatory properties. The aim of this study was to explore the effects of SHEDs on AD in the BALB/c mouse model induced by 2,4-dinitrochlorobenzene (DNCB). SHEDs were administrated intravenously or subcutaneously, and clinical severity, histopathological findings, skin barrier function, and organ indexes were evaluated. Skin tissue cytokine mRNA levels and serum cytokine protein levels were further analysed. SHED administration significantly alleviated AD clinical severity, including dermatitis scores, ear thickness, scratching behaviour, and infiltration of mast cells. In addition, disrupted skin barrier function and enlarged spleens were restored by SHED administration. Further, SHED treatment reduced the levels of IgE, IgG1, and thymic stromal lymphopoietin (TSLP) in the serum and the modulated expression of Th1-, Th2-, and Th17-associated cytokines in skin lesions. In conclusion, SHEDs attenuated AD-like skin lesions in mice by modulating the immune balance and skin barrier function. SHEDs could be a potential new treatment agent for AD.


Asunto(s)
Dermatitis Atópica , Animales , Citocinas/metabolismo , Dermatitis Atópica/tratamiento farmacológico , Dinitroclorobenceno , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Endogámicos BALB C , Piel/metabolismo , Células Madre/metabolismo , Diente Primario
7.
Ecotoxicol Environ Saf ; 237: 113520, 2022 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-35489138

RESUMEN

Microplastics are widely distributed, such as oceans, rivers and the atmosphere, with many opportunities for human exposure and potential health risks. Polystyrene microplastic (PS-MPS) exposure has been found to cause sperm damage to mice; however, the mechanism by which this happens remains unclear. Here, GC-2 cells, a mouse spermatocyte line, were exposed to 5 µm PS-MPS to investigate mitochondrial damage. The results showed that 5 µm PS-MPS decreased ATP content, reduced the mitochondrial membrane potential, damaged the integrity of the mitochondrial genome, and caused an imbalance of homoeostasis between mitochondrial division and fusion. The mitochondrial PINK1/Parkin autophagy pathway was activated. Time-series analysis revealed that PS-MPS damaged the mitochondrial structure through cellular oxidative stress, and mitochondrial function was maintained to some extent after PS-MPS damage. This study revealed the mitochondrial toxicity of polystyrene microplastics, thus providing a basis for understanding the causes of sperm damage by polystyrene microplastics.


Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Animales , Masculino , Ratones , Microplásticos/toxicidad , Estrés Oxidativo , Plásticos/toxicidad , Poliestirenos/toxicidad , Espermatozoides , Contaminantes Químicos del Agua/toxicidad
8.
J Gastroenterol Hepatol ; 36(7): 1843-1850, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33274470

RESUMEN

BACKGROUND AND AIM: Approximately 42-95% of working channels have been reported to show the presence of residual fluid despite endoscope reprocessing. The aim of this study was to design two novel protocols for cleaning residual simethicone and demonstrate its efficiency by evaluating the residual fluid and cleanliness in the working channels of patient-ready duodenoscopes. METHODS: The designed protocol for cleaning residual simethicone was implemented in manual cleaning and/or high-level disinfection (HLD). The residual fluid inside the working channels was estimated by visual inspection. Adenosine triphosphate (ATP) values were evaluated to determine cleanliness after manual cleaning. RESULTS: Manual cleaning with novel simethicone cleaning protocol demonstrated a significant decrease in fluid droplets (14.6 ± 29.9 vs 0 ± 0, P < 0.001) and ATP values (157 ± 196 relative light units [RLUs] vs 52 ± 41 RLUs, P = 0.031). HLD with simethicone cleaning protocol, using either enzymatic detergent with effective for cleaning simethicone or cleaning time set in the automatic endoscope reprocessor program for 8 min, demonstrated significant decrease in the number of fluid droplets. Follow-up after the implementation of the simethicone cleaning protocol showed a significant decrease in fluid droplets (37.4 ± 41.0 vs 2.1 ± 5.5, P = 0.003) and ATP values (271 ± 268 RLUs vs 82 ± 136 RLUs, P = 0.021). CONCLUSIONS: Simethicone cleaning protocol is advantageous for significantly decreasing fluid droplets and ATP values within endoscope working channels. After manual cleaning with the simethicone cleaning protocol, in particular, no retained fluid droplet was observed in patient-ready duodenoscopes.


Asunto(s)
Duodenoscopios , Simeticona , Adenosina Trifosfato , Desinfección , Contaminación de Equipos/prevención & control , Humanos
9.
J Craniofac Surg ; 32(3): 1094-1098, 2021 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-33587527

RESUMEN

PURPOSE: After many years in clinical practice, the authors found that the long-term aesthetics of the upper lip and nose following repair of a unilateral cleft lip deformity using the Huaxi method remained unsatisfactory. The immediate postoperative effect was often good, while the long-term postoperative effect was poor. Therefore, this study aimed to evaluate the characteristics and influencing factors of a modified Huaxi method for repairing unilateral cleft lip over time, and to explore the relationship between immediate and long-term outcomes after cleft lip surgery. METHODS: Patients with unilateral cleft lip who visited the Department of Maxillofacial Surgery of the Stomatological Hospital of Zunyi Medical University from June 2014 to March 2016 were selected. The study group consisted of 51 consecutive patients (30 boys and 21 girls), aged between 3 months and 2 years. Of these, 24 presented with complete unilateral cleft lip (12 wore a nasoalveolar mold as required, 12 did not) and 27 with incomplete unilateral cleft lip (13 wore a nasoalveolar mold as required, 14 did not). Photographs were taken of 51 patients before surgery and immediately, 7 days, and 6 months postoperatively. Various indexes of nasolabial contour of each patient were measured using iWitness photogrammetry, and the slit width; lip height ratio, lip width ratio, nostril width ratio, and nostril height ratio of the healthy side; and degree of deviation of the nasal columella were calculated. RESULTS: Long-term symmetry of lip height and width remained stable postoperatively (P > 0.05), whereas nostril height symmetry was significantly reduced (P > 0.05). Nasal width symmetry and midpoint deviation of the nasal columella were stable in patients with nasoalveolar molding (P > 0.05), but significantly decreased in patients without nasoalveolar molding (P < 0.05). In patients with complete unilateral cleft lip, there was a significant correlation between fissure width and lip width symmetry 6 months postoperatively (r = 0.431, P < 0.05). CONCLUSIONS: The symmetry of the upper lip is satisfactory and stable following surgical repair with the modified Huaxi technique. However, undercorrection of nasal symmetry is commonplace. Fissure width and nasoalveolar molding may influence long-term aesthetics following unilateral cleft lip repair.


Asunto(s)
Labio Leporino , Fisura del Paladar , Preescolar , Labio Leporino/cirugía , Estética Dental , Femenino , Humanos , Lactante , Labio , Masculino , Tabique Nasal , Nariz/cirugía , Resultado del Tratamiento
10.
BMC Gastroenterol ; 20(1): 181, 2020 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-32517718

RESUMEN

BACKGROUND: Cyanoacrylate alone or in combination with other interventions, can be used to achieve variable rates of success in preventing rebleeding. Our study aims to assess the pooled risk of gastric and esophageal varices rebleeding after an initial treatment with cyanoacrylate alone and/or in combination with other treatments, by a systematic review of the literature and pooled analysis. METHODS: PubMed, EMBASE, SCOPUS, and the Cochrane library were searched for studies that reported the risk of rebleeding during the follow-up period after treatment of gastric or esophageal varices with either cyanoacrylate alone or in combination with other treatments. Standard error, upper and lower confidence intervals at 95% confidence interval for the risk were obtained using STATA Version 15 which was also used to generate forest plots for pooled analysis. The random or fixed effect model was applied depending on the heterogeneity (I2). RESULTS: A total of 39 studies were found to report treatment of either gastric or esophageal varices with either cyanoacrylate alone or in combination with other treatments. When gastric varices are treated with cyanoacrylate alone, the risk of rebleeding during the follow-up period is 0.15(Confidence Interval: 0.11-0.18). When combined with lipiodol; polidocanol or sclerotherapy the rebleeding risks are 0.13 (CI:0.03-0.22), 0.10(CI:0.02-0.19), and 0.10(CI:0.05-0.18), respectively. When combined with percutaneous transhepatic variceal embolization; percutaneous transhepatic variceal embolization; endoscopic ultrasound guided coils; or with ethanolamine, the rebleeding risk are 0.10(CI:0.03-0.17), 0.10(CI:0.03-0.17), 0.07(CI:0.03-0.11) and 0.08(CI:0.02-0.14), respectively. When esophageal varices are treated with cyanoacrylate alone, the risk of rebleeding is 0.29(CI:0.11-0.47). When combined with percutaneous transhepatic variceal embolization; sclerotherapy; or band ligation, the risks of rebleeding are 0.16(CI:0.10-0.22), 0.12(CI:0.04-0.20) and 0.10(CI:0.04-0.24), respectively. When combined with a transjugular intrahepatic portosystemic shunt; or ethanolamine, the risks of rebleeding are 0.06(CI: - 0.01-0.12) and 0.02 (CI: - 0.02-0.05), respectively. CONCLUSION: In treating both gastric and esophageal varices, cyanoacrylate produces better results in terms of lower risk of rebleeding when combined with other treatments than when used alone. The combination of cyanoacrylate with ethanolamine or with endoscopic ultrasound guided coils produces the lowest risk of rebleeding in esophageal and gastric varices, respectively. We call upon randomized trials to test these hypotheses.


Asunto(s)
Quimioprevención/estadística & datos numéricos , Cianoacrilatos/uso terapéutico , Várices Esofágicas y Gástricas/tratamiento farmacológico , Hemorragia Gastrointestinal/tratamiento farmacológico , Adulto , Anciano , Quimioprevención/métodos , Várices Esofágicas y Gástricas/prevención & control , Femenino , Hemorragia Gastrointestinal/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Resultado del Tratamiento
11.
Angew Chem Int Ed Engl ; 59(18): 7235-7239, 2020 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-32061182

RESUMEN

While poly(acyclic orthoester)s (PAOEs) have many appealing features for drug delivery, their application is significantly hindered by a lack of facile synthetic methods. Reported here is a simple method for synthesizing acyclic diketene acetal monomers from diols and vinyl ether, and their polymerization with a diol to first synthesize PAOEs. The PAOEs rapidly hydrolyze at lysosomal pH. With the help of a cationic lipid, ovalbumin, a model vaccine antigen was efficiently loaded into PAOEs nanoparticles using a double emulsion method. These nanoparticles efficiently delivered ovalbumin into the cytosol of dendritic cells and demonstrated enhanced antigen presentation over poly(lactic-co-glycolic acid) (PLGA) nanoparticles. PAOEs are promising vehicles for intracellular delivery of biopharmaceuticals and could increase the utility of poly(orthoesters) in biomedical research.


Asunto(s)
Materiales Biocompatibles/síntesis química , Ovalbúmina/inmunología , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/inmunología , Vacunas/inmunología , Presentación de Antígeno/inmunología , Materiales Biocompatibles/química , Citosol/química , Citosol/inmunología , Estructura Molecular , Nanopartículas/química , Ovalbúmina/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/síntesis química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Vacunas/química
12.
Angew Chem Int Ed Engl ; 59(42): 18701-18708, 2020 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-32648353

RESUMEN

Dynamic and on-site analysis of serum from human blood is crucial, however, state-of-the-art blood-assay methods can only collect single or discrete data of physiological analytes; thus, the online reports of the dynamic fluctuation of key analytes remains a great challenge. Here, we propose a novel separation-sensing membrane by constructing a heterogeneous-nanostructured architecture, wherein a surface nanoporous layer continuously extracts serum, while the biosensing nanochannels underneath dynamically recognise biotargets, thereby achieving a continuous testing of vital clinical indices as blood is drawn. By precisely controlling the pore structure and nanoshape of biosensing crystals, this membrane achieved accurate and online glucose and lactate monitoring in patients with a variety of medical conditions within 1 min, which is one order of magnitude faster than state-of-the-art techniques. Moreover, various kinds of bio-recognisers can be introduced into this membrane to accurately detect glutamate, transaminase, and cancer biomarkers.


Asunto(s)
Técnicas Biosensibles/métodos , Glucemia/análisis , Ácido Láctico/sangre , Biomarcadores/sangre , Técnicas Electroquímicas , Humanos , Límite de Detección , Membranas Artificiales , Nanoestructuras/química , Polímeros/química , Pirroles/química
13.
Biochem Biophys Res Commun ; 516(2): 526-532, 2019 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-31230746

RESUMEN

The hepatocellular carcinoma (HCC) is a common and highly aggressive malignancy especially in China. Accumulating data have shown a critical role of long non-coding RNAs (lncRNAs) during cancer progression. However, the function of lncRNA TSLD8 remains elusive. By lncRNA profiling, we identify a novel lncRNA termed TSLD8 in HCC. TSLD8 expression is significantly lowered in HCC tissues and cell lines. TSLD8 facilitates migration and viability in SMMC-7721 and HepG2 cells. Furthermore, TSLD8 can interact with WWOX and protect WWOX from proteasome-mediated degradation. Using PuPGEA-based nanocomplex for gene delivery, we found that co-delivery of TSLD8 and WWOX may exhibit synergistic and additive effects to inhibit HCC progression. PuPGEA-based nanocomplex delivery does not substantially alter the blood chemistries (e.g. alkaline phosphatase, blood urea nitrogen, aspartate aminotransferase, alanine aminotransferase) or initiate immune responses implying a safe strategy. Collectively, our current study has identified a novel tumor suppressive lncRNA TSLD8 which exerts its tumor suppressive function by stabilizing WWOX. Co-delivery of TSLD8 and WWOX via PuPGEA-based nanocomplexes might provide promising therapeutics for eradicating HCC.


Asunto(s)
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , ARN Largo no Codificante/genética , Proteínas Supresoras de Tumor/metabolismo , Oxidorreductasa que Contiene Dominios WW/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Progresión de la Enfermedad , Regulación hacia Abajo/genética , Regulación Neoplásica de la Expresión Génica , Glucanos/química , Humanos , Neoplasias Hepáticas/patología , Nanopartículas/química , Ácidos Polimetacrílicos/química , Estabilidad Proteica , ARN Largo no Codificante/metabolismo , Resultado del Tratamiento
14.
Mol Biol Rep ; 46(3): 3073-3081, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30895561

RESUMEN

OBJECTIVE: To investigate the expression of C-JNK, RANKL and OPG after SP600125 administration in cultured dental follicle cells (DFCs). METHODS: TRAP staining and electron microscope were carried out on day 7 and 9 after coculture of BMMs and DFCs with a ratio of 5:1 in different groups. To determine the effects of SP600125 on the expression of C-JNK, RANKL and OPG mRNA and protein, cultured DFCs were divided into control group, DMSO group and SP600125 groups. Real-time PCR and Western blot analysis were performed to investigate the expression of the mRNA and protein, respectively. RESULTS: TRAP assay indicated that the number of multinucleated osteoclasts in the SP600125 group showed significant decrease compared with that of control (P < 0.05). The expression of JNK protein in the SP600125 groups showed significant decline compared with that of the control group and blank control (P < 0.05). Significant decrease was noticed in the RANKL protein expression with the elevation of SP600125. CONCLUSIONS: SP600125 could inhibit the formation of osteoclast in the coculture system of DFCs and BMMs. After SP600125 treatment, the expression of RANKL and JNK showed a trend of decrease, and the expression of OPG showed gradual increase followed by gradual decrease.


Asunto(s)
Antracenos/farmacología , Saco Dental/citología , Saco Dental/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Osteoprotegerina/genética , Proteínas Proto-Oncogénicas c-jun/genética , Ligando RANK/genética , Animales , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Células Cultivadas , Técnicas de Cocultivo , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteoblastos/ultraestructura , Ratas
15.
Molecules ; 24(18)2019 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-31505837

RESUMEN

Cistanche tubulosa is a traditional Chinese herbal medicine that is widely used to regulate immunity, and phenylethanol glycosides (CPhGs) are among the primary components responsible for this activity. However, the application of CPhGs is negatively affected by their poor absorption and low oral utilization. Targeted drug delivery is an important development direction for pharmaceutics. Previous studies have indicated that CPhGs could block the conduction of the signaling pathways in TGF-ß1/smad and inhibit the activation of hepatic stellate cells (HSCs). The aim of this study was to evaluate the anti-hepatic fibrosis effect of CPhG liposomes by inhibiting HSC activation, promoting apoptosis, blocking the cell cycle, suppressing the conduction of signaling pathways in focal adhesion kinase(FAK)/phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt), and determining their in vitro hepatoprotective activity. In vitro release studies demonstrated that CPhG liposomes have a sustained release effect compared to drug CPhGs. HSC proliferation was inhibited after treatment with the CPhG liposomes (29.45, 14.72, 7.36 µg/mL), with IC50 values of 42.54 µg/mL in the MTT assay. Different concentrations of the CPhG liposomes could inhibit HSC proliferation, promote apoptosis, and block the cell cycle. The MTT method showed an obvious inhibition of HSC proliferation after CPhG liposome and Recombinant Rat Platelet-derived growth factor-BB(rrPDGF-BB) treatment. The levels of collagen-1, metallopeptidase inhibitor 1 (TIMP-1), α smooth muscle actin (α-SMA), and phosphorylated PI3K/Akt were downregulated, and matrix metalloproteinase-1 (MMP-1) was upregulated, by pretreatment with different concentrations of CPhG liposomes. Moreover, 29.45 µg/mL of CPhG liposomes could decrease the expression of the FAK protein and the phosphorylated PI3K and Akt protein downstream of FAK by overexpression of the FAK gene. This experiment suggests that CPhG liposomes may inhibit the activation of HSCs by inhibiting FAK and then reducing the expression of phosphorylated Akt/PI3K, thereby providing new insights into the application of CPhGs for liver fibrosis.


Asunto(s)
Cistanche/química , Sistemas de Liberación de Medicamentos , Glicósidos/farmacología , Alcohol Feniletílico/farmacología , Animales , Apoptosis/efectos de los fármacos , Becaplermina/química , Becaplermina/genética , Becaplermina/farmacología , Proliferación Celular/efectos de los fármacos , Quinasa 1 de Adhesión Focal/genética , Regulación de la Expresión Génica/efectos de los fármacos , Glicósidos/química , Células Estrelladas Hepáticas/efectos de los fármacos , Humanos , Inmunidad/efectos de los fármacos , Liposomas/química , Liposomas/farmacología , Medicina Tradicional China , Alcohol Feniletílico/química , Fosfatidilinositol 3-Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/genética , Ratas
16.
Arch Biochem Biophys ; 646: 72-79, 2018 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-29621521

RESUMEN

The deregulation of Bcl2L12 expression in cancer has been recognized, but the causative factors are unknown. Histone acetyltransferases (HAT) play critical roles in the regulation gene transcription. This study tests a hypothesis that the aberrant activities of HAT induce deregulation of Bcl2L12 in nasopharyngeal cancer (NPC). In this study, human NPC tissues were collected from the clinic. The expression of Bcl2L12 and HATs in NPC cells was analyzed by real time RT-PCR and Western blotting. NPC cell apoptosis was analyzed by flow cytometry. The results showed that by screening the subtypes of HAT, the levels of HAT1 were uniquely higher in NPC as compared with non-cancer nasopharyngeal tissue. The levels of Bcl2L12 in NPC cells were positively correlated with HAT1. HAT1 involved in the STAT5 binding to the Bcl2L12 promoter. HAT1 increased the expression of Bcl2L12. Bcl2L12 mediated the effects of HAT1 on suppressing NPC cell apoptosis. Absorption of the HAT1 shRNA plasmid-carrying liposomes induced NPC cell apoptosis. In conclusion, inhibition of HAT1 can induce NPC cell apoptosis via increasing Bcl2L12 expression, which can be a potential therapy for NPC treatment.


Asunto(s)
Histona Acetiltransferasas/metabolismo , Proteínas Musculares/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Adulto , Apoptosis/genética , Línea Celular Tumoral , Regulación hacia Abajo , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Células HEK293 , Histona Acetiltransferasas/genética , Humanos , Liposomas/metabolismo , Masculino , Persona de Mediana Edad , Proteínas Musculares/genética , Neoplasias Nasofaríngeas/genética , Plásmidos , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas c-bcl-2/genética , ARN Interferente Pequeño/genética , Factor de Transcripción STAT5/metabolismo , Regulación hacia Arriba
17.
Artif Organs ; 41(5): 461-469, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27925229

RESUMEN

The treatment of long-segment tracheal defect requires the transplantation of effective tracheal substitute, and the tissue-engineered trachea (TET) has been proposed as an ideal tracheal substitute. The major cause of the failure of segmental tracheal defect reconstruction by TET is airway collapse caused by the chondromalacia of TET cartilage. The key to maintain the TET structure is the regeneration of chondrocytes in cartilage, which can secrete plenty of cartilage matrices. To address the problem of the chondromalacia of TET cartilage, this study proposed an improved strategy. We designed a new cell sheet scaffold using the poly(lactic-co-glycolic acid) (PLGA) and poly(trimethylene carbonate) (PTMC) to make a porous membrane for seeding cells, and used the PLGA-PTMC cell-scaffold to pack the decellularized allogeneic trachea to construct a new type of TET. The TET was then implanted in the subcutaneous tissue for vascularization for 2 weeks. Orthotopic transplantation was then performed after implantation. The efficiency of the TET we designed was analyzed by histological examination and biomechanical analyses 4 weeks after surgery. Four weeks after surgery, both the number of chondrocytes and the amount of cartilage matrix were significantly higher than those contained in the traditional stem-cell-based TET. Besides, the coefficient of stiffness of TET was significantly larger than the traditional TET. This study provided a promising approach for the long-term functional reconstruction of long-segment tracheal defect, and the TET we designed had potential application prospects in the field of TET reconstruction.


Asunto(s)
Condrogénesis , Dioxanos/química , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Polímeros/química , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Tráquea/trasplante , Animales , Cartílago/citología , Cartílago/fisiología , Cartílago/ultraestructura , Células Cultivadas , Condrocitos/citología , Ácido Láctico/química , Trasplante de Células Madre Mesenquimatosas/métodos , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Conejos , Regeneración , Tráquea/lesiones , Tráquea/ultraestructura
18.
Cell Physiol Biochem ; 40(5): 944-952, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27941347

RESUMEN

BACKGROUND: Osteotome sinus floor elevation is a less invasive approach to augment an insufficient alveolar bone at the posterior maxilla for dental implantation. However, this approach has some limitations due to the lack of sinus lift tools available for clinical use and the small transcrestal access to the maxillary sinus floor. We recently invented shape-memory Ni/Ti alloy wire containing tube elevators for transcrestal detaching maxillary sinus mucosa, and developed goat ex vivo models for direct visualizing the effectiveness of detaching sinus mucosa in real time during transcrestal maxillary sinus floor elevation. METHODS: We evaluated our invented elevators, namely elevator 012 and elevator 014, for their effectiveness for transcrestal detaching maxillary sinus mucosa using the goat ex vivo models. We measured the length of sinus mucosa detached in mesial and distal directions or buccal and palatal directions, and the space volume created by detaching maxillary sinus mucosa in mesial, distal, buccal and palatal directions using the invented elevators. RESULTS: Elevator 012 had a shape-memory Ni/Ti alloy wire with a diameter of 0.012 inch, while elevator 014 had its shape-memory Ni/Ti alloy wire with a diameter of 0.014 inch. Elevator 012 could detach the goat maxillary sinus mucosa in the mesial or distal direction for 12.1±4.3 mm, while in the buccal or palatal direction for 12.5±6.7 mm. The elevator 014 could detach the goat maxillary sinus mucosa for 23.0±4.9 mm in the mesial or distal direction, and for 19.0±8.1 mm in the buccal or palatal direction. An average space volume of 1.7936±0.2079 ml was created after detaching the goat maxillay sinus mucosa in both mesial/distal direction and buccal/palatal direction using elevator 012; while the average space volume created using elevator 014 was 1.8764±0.2366 ml. CONCLUSION: Both two newly invented tube elevators could effectively detach the maxillary sinus mucosa on the goat ex vivo sinus models. Moreover, elevator 014 has advantages over the elevator 012 for the capability to detach sinus mucosa.


Asunto(s)
Seno Maxilar/efectos de los fármacos , Membrana Mucosa/efectos de los fármacos , Níquel/farmacología , Elevación del Piso del Seno Maxilar/métodos , Titanio/farmacología , Animales , Estudios de Factibilidad , Femenino , Cabras , Masculino
19.
J Sep Sci ; 39(16): 3130-6, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27465269

RESUMEN

Hydrophobic charge-induction chromatography is a new technology for antibody purification. To improve antibody adsorption capacity of hydrophobic charge-induction resins, new poly(glycidyl methacrylate)-grafted hydrophobic charge-induction resins with 5-aminobenzimidazole as a functional ligand were prepared. Adsorption isotherms, kinetics, and dynamic binding behaviors of the poly(glycidyl methacrylate)-grafted resins prepared were investigated using human immunoglobulin G as a model protein, and the effects of ligand density were discussed. At the moderate ligand density of 330 µmol/g, the saturated adsorption capacity and equilibrium constant reached the maximum of 140 mg/g and 25 mL/mg, respectively, which were both much higher than that of non-grafted resin with same ligand. In addition, effective pore diffusivity and dynamic binding capacity of human immunoglobulin G onto the poly(glycidyl methacrylate)-grafted resins also reached the maximum at the moderate ligand density of 330 µmol/g. Dynamic binding capacity at 10% breakthrough was as high as 76.3 mg/g when the linear velocity was 300 cm/h. The results indicated that the suitable polymer grafting combined with the control of ligand density would be a powerful tool to improve protein adsorption of resins, and new poly(glycidyl methacrylate)-grafted hydrophobic charge-induction resins have a promising potential for antibody purification applications.


Asunto(s)
Cromatografía/instrumentación , Inmunoglobulina G/aislamiento & purificación , Ácidos Polimetacrílicos/química , Sefarosa/química , Adsorción , Bencimidazoles/química , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Inmunoglobulina G/química , Cinética , Ligandos , Resinas Sintéticas/química
20.
Int J Mol Sci ; 17(4): 557, 2016 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-27089334

RESUMEN

Yersinia ruckeri is the etiologic agent of enteric red mouth disease (ERM), a severe fish disease prevailing in worldwide aquaculture industries. Here we report for the first time the complete genome of Y. ruckeri (Yersinia ruckeri) SC09, a highly virulent strain isolated from Ictalurus punctatus with severe septicemia. SC09 possesses a single chromosome of 3,923,491 base pairs, which contains 3651 predicted protein coding sequences (CDS), 19 rRNA genes, and 79 tRNA genes. Among the CDS, we have identified a Ysa locus containing genes encoding all the components of a type III secretion system (T3SS). Comparative analysis suggest that SC09-Ysa share extensive similarity in sequence, gene content, and gene arrangement with Salmonella enterica pathogenicity island 1 (SPI1) and chromosome-encoded T3SS from Yersinia enterocolitica biotype 1B. Furthermore, phylogenetic analysis shown that SC09-Ysa and SPI1-T3SS belong on the same branch of the phylogenetic tree. These results suggest that SC09-Ysa and SPI1-T3SS appear to mediate biological function to adapt to specific hosts with a similar niche, and both of them are likely to facilitate the development of an intracellular niche. In addition, our analysis also indicated that a substantial part of the SC09 genome might contribute to adaption in the intestinal microenvironment, including a number of proteins associated with aerobic or anaerobic respiration, signal transduction, and various stress reactions. Genomic analysis of the bacterium offered insights into the pathogenic mechanism associated with intracellular infection and intestinal survivability, which constitutes an important first step in understanding the pathogenesis of Y. ruckeri.


Asunto(s)
Enfermedades de los Peces/microbiología , Ictaluridae/microbiología , Yersiniosis/veterinaria , Yersinia ruckeri/genética , Animales , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Mapeo Cromosómico , Enfermedades de los Peces/patología , Genoma Bacteriano , Islas Genómicas , Familia de Multigenes , Oncorhynchus mykiss/microbiología , Filogenia , ARN Bacteriano/genética , ARN Bacteriano/metabolismo , Transducción de Señal , Sistemas de Secreción Tipo II/genética , Sistemas de Secreción Tipo II/metabolismo , Sistemas de Secreción Tipo III/genética , Sistemas de Secreción Tipo III/metabolismo , Yersiniosis/microbiología , Yersinia ruckeri/patogenicidad , Yersinia ruckeri/fisiología
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