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1.
Br J Haematol ; 204(6): 2342-2350, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38400570

RESUMEN

A chemotherapy-based mobilization regimen in patients who mobilize poorly, based on etoposide, cytarabine and pegfilgrastim (EAP), has recently been introduced. The aim of this prospective study was to investigate the efficacy and safety of the EAP regimen in patients with poorly mobilizing multiple myeloma (MM) or lymphoma. This single-arm clinical trial was performed at eight public hospitals in China and was registered as a clinical trial (NCT05510089). The inclusion criteria were; (1) diagnosis of MM or lymphoma, (2) defined as a 'poor mobilizer' and (3) aged 18-75 years. The EAP regimen consisted of etoposide 75 mg/m2/day on days 1-2, cytarabine 300 mg/m2 every 12 h on days 1-2 and pegfilgrastim 6 mg on day 6. The primary endpoint of the study was the ratio of patients achieving adequate mobilization (≥2.0 × 106 CD34+ cells/kg). From 1 September 2022 to 15 August 2023, a total of 58 patients were enrolled, 53 (91.4%) achieved adequate mobilization, while 41 (70.7%) achieved optimal mobilization with a median number of cumulative collected CD34+ cells was 9.2 (range 2.1-92.7) × 106/kg and the median number of apheresis per patient of 1.2. The median time from administration of the EAP regimen to the first apheresis was 12 days. Approximately 8.6% of patients required plerixa for rescue, which was successful. Twelve (20.7%) of the 58 patients suffered grade 2-3 infections, while 25 (43.1%) required platelet transfusions. The duration of neutrophil and platelet engraftment was 11 days. In conclusion, these results suggest that the EAP mobilization regimen might be a promising option for poorly mobilizing patients with MM or lymphoma.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Citarabina , Etopósido , Filgrastim , Movilización de Célula Madre Hematopoyética , Linfoma , Mieloma Múltiple , Polietilenglicoles , Humanos , Filgrastim/administración & dosificación , Filgrastim/uso terapéutico , Citarabina/administración & dosificación , Citarabina/uso terapéutico , Persona de Mediana Edad , Polietilenglicoles/administración & dosificación , Femenino , Masculino , Etopósido/administración & dosificación , Etopósido/uso terapéutico , Adulto , Linfoma/tratamiento farmacológico , Linfoma/terapia , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/terapia , Estudios Prospectivos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Movilización de Célula Madre Hematopoyética/métodos , Adulto Joven , Adolescente
2.
Proc Natl Acad Sci U S A ; 118(8)2021 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-33558418

RESUMEN

The expansion of anatomically modern humans (AMHs) from Africa around 65,000 to 45,000 y ago (ca. 65 to 45 ka) led to the establishment of present-day non-African populations. Some paleoanthropologists have argued that fossil discoveries from Huanglong, Zhiren, Luna, and Fuyan caves in southern China indicate one or more prior dispersals, perhaps as early as ca. 120 ka. We investigated the age of the human remains from three of these localities and two additional early AMH sites (Yangjiapo and Sanyou caves, Hubei) by combining ancient DNA (aDNA) analysis with a multimethod geological dating strategy. Although U-Th dating of capping flowstones suggested they lie within the range ca. 168 to 70 ka, analyses of aDNA and direct AMS 14C dating on human teeth from Fuyan and Yangjiapo caves showed they derive from the Holocene. OSL dating of sediments and AMS 14C analysis of mammal teeth and charcoal also demonstrated major discrepancies from the flowstone ages; the difference between them being an order of magnitude or more at most of these localities. Our work highlights the surprisingly complex depositional history recorded at these subtropical caves which involved one or more episodes of erosion and redeposition or intrusion as recently as the late Holocene. In light of our findings, the first appearance datum for AMHs in southern China should probably lie within the timeframe set by molecular data of ca. 50 to 45 ka.


Asunto(s)
Arqueología , Cuevas/química , ADN Antiguo/análisis , Fósiles , Sedimentos Geológicos/análisis , Migración Humana/historia , Datación Radiométrica/métodos , China , Historia Antigua , Humanos
3.
Molecules ; 29(10)2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38792212

RESUMEN

Lignanoids are an active ingredient exerting powerful antioxidant and anti-inflammatory effects in the treatment of many diseases. In order to improve the efficiency of the resource utilization of traditional Chinese medicine waste, Magnolia officinalis Rehder & E.H.Wilson residue (MOR) waste biomass was used as raw material in this study, and a series of deep eutectic solvents (ChUre, ChAce, ChPro, ChCit, ChOxa, ChMal, ChLac, ChLev, ChGly and ChEG) were selected to evaluate the extraction efficiency of lignanoids from MORs. The results showed that the best conditions for lignanoid extraction were a liquid-solid ratio of 40.50 mL/g, an HBD-HBA ratio of 2.06, a water percentage of 29.3%, an extract temperature of 337.65 K, and a time of 107 min. Under these conditions, the maximum lignanoid amount was 39.18 mg/g. In addition, the kinetics of the extraction process were investigated by mathematic modeling. In our antioxidant activity study, high antioxidant activity of the lignanoid extract was shown in scavenging four different types of free radicals (DPPH, ·OH, ABTS, and superoxide anions). At a concentration of 3 mg/mL, the total antioxidant capacity of the lignanoid extract was 1.795 U/mL, which was equal to 0.12 mg/mL of Vc solution. Furthermore, the antibacterial activity study found that the lignanoid extract exhibited good antibacterial effects against six tested pathogens. Among them, Staphylococcus aureus exerted the strongest antibacterial activity. Eventually, the correlation of the lignanoid extract with the biological activity and physicochemical properties of DESs is described using a heatmap, along with the evaluation of the in vitro hypoglycemic, in vitro hypolipidemic, immunomodulatory, and anti-inflammatory activity of the lignanoid extract. These findings can provide a theoretical foundation for the extraction of high-value components from waste biomass by deep eutectic solvents, as well as highlighting its specific significance in natural product development and utilization.


Asunto(s)
Antioxidantes , Biomasa , Magnolia , Magnolia/química , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/aislamiento & purificación , Disolventes Eutécticos Profundos/química , Lignina/química , Lignina/farmacología , Lignina/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Animales
4.
Macromol Rapid Commun ; 44(18): e2300211, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37294875

RESUMEN

In recent years, as a class of advanced additive manufacturing (AM) technology, photocurable 3D printing has gained increasing attention. Based on its outstanding printing efficiency and molding accuracy, it is employed in various fields, such as industrial manufacturing, biomedical, soft robotics, electronic sensors. Photocurable 3D printing is a molding technology based on the principle of area-selective curing of photopolymerization reaction. At present, the main printing material suitable for this technology is the photosensitive resin, a composite mixture consisting of a photosensitive prepolymer, reactive monomer, photoinitiator, and other additives. As the technique research deepens and its application gets more developed, the design of printing materials suitable for different applications is becoming the hotspot. Specifically, these materials not only can be photocured but also have excellent properties, such as elasticity, tear resistance, fatigue resistance. Photosensitive polyurethanes can endow photocured resin with desirable performance due to their unique molecular structure including the inherent alternating soft and hard segments, and microphase separation. For this reason, this review summarizes and comments on the research and application progress of photocurable 3D printing of photosensitive polyurethanes, analyzing the advantages and shortcomings of this technology, also offering an outlook on this rapid development direction.


Asunto(s)
Poliuretanos , Impresión Tridimensional
5.
Acta Radiol ; 64(8): 2446-2454, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37551019

RESUMEN

BACKGROUND: The optimal treatment for some symptomatic, benign osteopathy lesions is yet to be identified. PURPOSE: To investigate the clinical efficiency of cementoplasty in managing symptomatic, benign osteopathy. MATERIAL AND METHODS: Between June 2006 and January 2020, we retrospectively enrolled 31 patients (10 men, 21 women; mean age = 46.5 ± 16.6 years; age range = 20-85 years), accounting for 34 treatment sites, who underwent percutaneous osteoplasty (14 treatment sites) and percutaneous vertebroplasty (20 treatment sites) with digital subtraction angiography (DSA) or DSA combined with computed tomography (CT). All the participants experienced different degrees of clinical symptoms with benign osteopathy lesions. The technical success of the procedure and occurrence of complications were recorded. Follow-up examinations were conducted to assess the treatment outcome using the MacNab criteria. RESULTS: All the participants had a diagnosis of benign osteopathy lesions before or after the cementoplasty. Surgery was successfully completed in all patients. Cement distributions were diffuse and homogeneous, with the complication of cement leakage occurring in 17.6% (6 of 34) of the lesions. The leakage occurred in the intervertebral disc (n = 1), the intra-articular space (n = 1), and the surrounding soft tissue (n = 4). Analysis of the treatment outcome using the MacNab criteria revealed that all patients showed improvement in their clinical symptoms to some extent and in the quality of life. CONCLUSION: Cementoplasty is an effective treatment for symptomatic, benign osteopathy, with the advantage of favorable clinical outcomes, and low complication rate.


Asunto(s)
Enfermedades Óseas , Cementoplastia , Masculino , Humanos , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Estudios Retrospectivos , Calidad de Vida , Cementoplastia/métodos , Cementos para Huesos/uso terapéutico , Resultado del Tratamiento
6.
Nano Lett ; 22(16): 6516-6522, 2022 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-35943299

RESUMEN

Folic acid (FA) is one of the most widely utilized small-molecule ligands for cancer targeted drug delivery. Natural IgM was recently found to avidly absorb on the surface of FA-functionalized liposomes (FA-sLip), negatively regulating the in vivo performance by efficiently activating complement. Herein, FA-functionalized lipodiscs (FA-Disc) were constructed to successfully circumvent IgM-mediated opsonization and retained binding activity with folate receptors in vivo. The FA moiety along with the bound IgM was restricted to the highly curved rim of lipodiscs, leading to IgM incapability of presenting the membrane-bound conformation to trigger complement activation. The C1q docking, C3 binding, and C5a release were blocked and accelerated blood clearance phenomenon was mitigated of FA-Disc. FA-Disc retained folate binding activity and could effectively target folate receptor positive tumors in vivo. The present study provides a useful solution to avoid the negative regulation by IgM and achieve FA-enabled targeting by exploring disc-shaped nanocarriers.


Asunto(s)
Nanopartículas , Neoplasias , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Ácido Fólico/química , Ácido Fólico/metabolismo , Humanos , Inmunoglobulina M , Liposomas/química , Opsonización
7.
Odontology ; 111(4): 870-882, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36879181

RESUMEN

Periodontal tissue regeneration engineering based on human periodontal ligament stem cells (hPDLSCs) provides a broad prospect for the treatment of periodontal disease. N-Acetyltransferase 10 (NAT10)-catalyzed non-histone acetylation is widely involved in physiological or pathophysiological processes. However, its function in hPDLSCs is still missing. hPDLSCs were isolated, purified, and cultured from extracted teeth. Surface markers were detected by flow cytometry. Osteogenic, adipogenic, and chondrogenic differentiation potential was detected by alizarin red staining (ARS), oil red O staining, and Alcian blue staining. Alkaline phosphatase (ALP) activity was assessed by ALP assay. Quantitative real-time PCR (qRT-PCR) and western blot were used to detect the expression of key molecules, such as NAT10, Vascular endothelial growth factor A (VEGFA), PI3K/AKT pathway, as well as bone markers (RUNX2, OCN, OPN). RNA-Binding Protein Immunoprecipitation PCR (RIP-PCR) was used to detect the N4-acetylcytidine (ac4C) mRNA level. Genes related to VEGFA were identified by bioinformatics analysis. NAT10 was highly expressed in the osteogenic differentiation process with enhanced ALP activity and osteogenic capability, and elevated expression of osteogenesis-related markers. The ac4C level and expression of VEGFA were obviously regulated by NAT10 and overexpression of VEGFA also had similar effects to NAT10. The phosphorylation level of PI3K and AKT was also elevated by overexpression of VEGFA. VEGFA could reverse the effects of NAT10 in hPDLSCs. NAT10 enhances the osteogenic development of hPDLSCs via regulation of the VEGFA-mediated PI3K/AKT signaling pathway by ac4C alteration.


Asunto(s)
Ligamento Periodontal , Proteínas Proto-Oncogénicas c-akt , Humanos , Proteínas Proto-Oncogénicas c-akt/farmacología , Osteogénesis/genética , Factor A de Crecimiento Endotelial Vascular , Fosfatidilinositol 3-Quinasas , Transducción de Señal , Diferenciación Celular , Células Madre , Células Cultivadas , Proliferación Celular , Acetiltransferasas N-Terminal
8.
Int J Mol Sci ; 24(8)2023 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-37108336

RESUMEN

Nucleocapsid protein (N protein) is an appropriate target for early determination of viral antigen-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We have found that ß-cyclodextrin polymer (ß-CDP) has shown a significant fluorescence enhancement effect for fluorophore pyrene via host-guest interaction. Herein, we developed a sensitive and selective N protein-sensing method that combined the host-guest interaction fluorescence enhancement strategy with high recognition of aptamer. The DNA aptamer of N protein modified with pyrene at its 3' terminal was designed as the sensing probe. The added exonuclease I (Exo I) could digest the probe, and the obtained free pyrene as a guest could easily enter into the hydrophobic cavity of host ß-CDP, thus inducing outstanding luminescent enhancement. While in the presence of N protein, the probe could combine with it to form a complex owing to the high affinity between the aptamer and the target, which prevented the digestion of Exo I. The steric hindrance of the complex prevented pyrene from entering the cavity of ß-CDP, resulting in a tiny fluorescence change. N protein has been selectively analyzed with a low detection limit (11.27 nM) through the detection of the fluorescence intensity. Moreover, the sensing of spiked N protein from human serum and throat swabs samples of three volunteers has been achieved. These results indicated that our proposed method has broad application prospects for early diagnosis of coronavirus disease 2019.


Asunto(s)
COVID-19 , Polímeros , Humanos , Polímeros/química , SARS-CoV-2 , Fluorescencia , COVID-19/diagnóstico , Pirenos/química
9.
Int Wound J ; 20(6): 2233-2240, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36919189

RESUMEN

We conducted a meta-analysis to assess the outcome of prolonged postoperative antibiotics (PA) on wound healing in orthognathic surgery (OS). A systematic literature search up to January 2023 was performed and 1021 related studies were evaluated. The chosen studies comprised 1057 OS subjects who participated in the selected studies' baseline, 446 of them used short-term PA, and 611 used long-term PA. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated to assess the effect of prolonged PA on wound infection after OS by the dichotomous methods with a random or fixed effect model. The short-term PA resulted in significantly higher wound infection (OR, 4.27; 95% CI, 2.97-6.14, P < 0.001) with low heterogeneity (I2  = 27%) compared to the long-term PA in OS. The short-term PA resulted in significantly higher wound infection compared to the long-term PA in OS. Though care should be taken when dealing with the results since a large number of the selected studies had <100 subjects as a sample size.


Asunto(s)
Cirugía Ortognática , Procedimientos Ortopédicos , Infección de Heridas , Humanos , Antibacterianos/uso terapéutico , Infección de la Herida Quirúrgica/tratamiento farmacológico , Cicatrización de Heridas
10.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 45(3): 500-505, 2023 Jun.
Artículo en Zh | MEDLINE | ID: mdl-37407540

RESUMEN

Tissue regeneration is an important engineering method for the treatment of oral soft and hard tissue defects.Growth factors,as one of the three elements of tissue regeneration,are a necessary condition for tissue regeneration.Concentrated growth factor(CGF)is a new generation of blood extract prepared by changing the centrifugal speed on the basis of the preparation of platelet-rich plasma(PRP)and platelet-rich fibrin(PRF).It contains abundant growth factors and a fibrin matrix with a three-dimensional network structure,being capable of activating angiogenesis and promoting tissue regeneration and healing.CGF has been widely used in the repair and regeneration of oral soft and hard tissues.This paper introduces the preparation and composition of CGF and reviews the application of CGF in oral implantation and the regeneration of oral bone tissue,periodontal tissue,and dental pulp tissue.


Asunto(s)
Fibrina Rica en Plaquetas , Plasma Rico en Plaquetas , Plasma Rico en Plaquetas/metabolismo , Proliferación Celular , Huesos , Péptidos y Proteínas de Señalización Intercelular/farmacología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Regeneración Ósea
11.
BMC Oral Health ; 21(1): 599, 2021 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-34814909

RESUMEN

BACKGROUND: Periapical periodontitis is a common oral inflammatory disease that affects periapical tissues and is caused by bacteria in the root canal system. The relationship among the local metabolome, the inflammatory grade, and the type and abundance of microorganisms associated with periapical periodontitis is discussed in this study. METHODS: The inflammatory grades of periapical samples from 47 patients with chronic periapical periodontitis in permanent anterior teeth were determined based on the immune cell densities in tissues subjected to haematoxylin and eosin staining. The metabolome was evaluated using ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, followed by principal component analysis and orthogonal partial least squares discriminant analysis. The microbiome was accessed using 16 S rRNA high-throughput sequencing. The differences in the metabolomes and microbiomes of the periapical periodontitis samples were assessed using Spearman's correlation analysis. RESULT: N-acetyl-D-glucosamine, L-tryptophan, L-phenylalanine, and 15 other metabolites were identified by the comparison between samples with severe inflammation and mild or moderate inflammation. Four amino acid metabolism pathways and one sugar metabolism pathway were associated with the inflammatory grade of periapical periodontitis. The abundance of Actinomycetes was negatively correlated with the abundance of glucosamine (GlcN), while the abundance of Tannerella was positively correlated with the abundance of L-methionine. CONCLUSIONS: The local metabolome of periapical periodontitis is correlated with the inflammatory grade. The abundance of the local metabolites GlcN and L-methionine is correlated with the abundance of the major microorganisms Actinomycetes and Tannerella, respectively.


Asunto(s)
Microbiota , Periodontitis Periapical , Humanos , Metaboloma , Proyectos Piloto , Tratamiento del Conducto Radicular
12.
Angew Chem Int Ed Engl ; 59(31): 12756-12761, 2020 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-32343868

RESUMEN

Cancer possesses normoxic and hypoxia microenvironments with different levels of oxygen, needing different efficacies of photothermal and photodynamic therapies. It is important to precisely tune the photothermal and photodynamic effects of phototherapy nano-agents for efficient cancer treatment. Now, a series of copolymeric nanoparticles (PPy-Te NPs) were synthesized in situ by controlled oxidative copolymerization with different ratios of pyrrole to tellurophene by FeCl3 . The photothermal and photodynamic effects of semiconducting nano-agents under the first near-infrared (NIR) irradiation were precisely and systematically tuned upon simply varying the molar ratio of the pyrrole to tellurophene. The PPy-Te NPs were used for cancer treatment in mice, exhibiting excellent biocompatibility and therapeutic effect. This work presents a simple method to tune photothermal and photodynamic therapies effect in semiconducting nano-agents for cancer treatment.


Asunto(s)
Antineoplásicos/uso terapéutico , Nanopartículas/uso terapéutico , Neoplasias/tratamiento farmacológico , Fármacos Fotosensibilizantes/uso terapéutico , Polímeros/uso terapéutico , Pirroles/uso terapéutico , Animales , Antineoplásicos/síntesis química , Antineoplásicos/efectos de la radiación , Línea Celular Tumoral , Rayos Infrarrojos , Ratones , Nanopartículas/química , Nanopartículas/efectos de la radiación , Fotoquimioterapia , Fármacos Fotosensibilizantes/síntesis química , Fármacos Fotosensibilizantes/efectos de la radiación , Terapia Fototérmica , Polimerizacion , Polímeros/síntesis química , Polímeros/efectos de la radiación , Pirroles/síntesis química , Pirroles/efectos de la radiación , Especies Reactivas de Oxígeno/metabolismo
14.
Oral Dis ; 25(7): 1769-1779, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31365165

RESUMEN

OBJECTIVES: This study aimed to investigate the role of JAK2-STAT3 (Janus kinase 2/signal transducer and activator of transcription 3) in periapical disease caused by Enterococcus faecalis, as well as the correlation between lipoteichoic acid (LTA) in E. faecalis and the activity of the JAK2-STAT3 signaling pathway and osteoclast formation. MATERIALS AND METHODS: A rat model of periapical periodontitis induced by E. faecalis was established. Periapical bone resorption was confirmed by HE staining. The expression of JAK2, p-JAK2, STAT3, and p-STAT3 was assessed with immunohistochemical staining. Osteoclasts were observed through enzyme histochemical staining. LTA acted on mouse osteoclast precursor cells (RAW264.7 cells); a JAK2 inhibitor (AG490) was used to inhibit the JAK2-STAT3 pathway in RAW264.7 cells. The expression of proteins in the JAK2-STAT3 pathway and TRAP (tartrate resistant acid phosphatase) in RAW264.7 cells was also detected. RESULTS: Rat periapical periodontitis was successfully established and bone resorption peaked at day 21. The expression of critical components in the JAK2-STAT3 pathway increased with the progression of inflammation. LTA promoted the differentiation of RAW264.7 cells into osteoclasts. NFATc1 was highly expressed and was inhibited by AG490. CONCLUSIONS: JAK2-STAT3 signaling pathway plays an important role in the process of periapical bone resorption and osteoclastogenesis.


Asunto(s)
Resorción Ósea , Enterococcus faecalis/fisiología , Janus Quinasa 2/metabolismo , Osteoclastos/fisiología , Osteogénesis , Periodontitis Periapical/fisiopatología , Factor de Transcripción STAT3/metabolismo , Animales , Regulación de la Expresión Génica , Janus Quinasa 2/genética , Ratones , Osteoclastos/microbiología , Periodontitis Periapical/etiología , Ratas , Factor de Transcripción STAT3/genética , Transducción de Señal
15.
Mediators Inflamm ; 2019: 8767529, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31427888

RESUMEN

Chronic apical periodontitis is characterized by alveolar bone absorption in the apical region and is the result of the participation of various inflammatory mediators. Studies have shown that the Bruton tyrosine kinase- (Btk-) phospholipase Cγ2 (PLCγ2) signaling pathway plays an important role in bone absorption, but it is unknown whether it plays a role in apical periodontitis bone destruction. Therefore, this study verified the role of Btk and PLCγ2 in bone resorption of apical periodontitis by in vivo and in vitro experiments. In the in vivo experiment, a mice model of apical periodontitis was established; apical bone resorption was confirmed by the numbers of osteoclasts and HE staining. Btk, PLCγ2, and nuclear factor of activated T-cells 1 (NFATc-1) were detected by immunohistochemical staining. In the in vitro experiment, lipopolysaccharides (LPS) were used to stimulate osteoclast precursor cell RAW264.7 to establish an inflammatory microenvironment and detect osteoclast differentiation. By silencing Btk, the expression of Btk, PLCγ2, and NFATc-1 was detected by real-time qPCR and Western blot, and osteoclastogenesis was detected by enzyme histochemical staining to further confirm the role of Btk in bone resorption. It was found that the expression of Btk, PLCγ2, and NFATc-1 changed significantly with the progression of inflammation and bone destruction, indicating that Btk and PLCγ2 may be involved in the progression of inflammation in apical periodontitis and bone absorption. In vitro experiments confirmed that the differentiation of osteoclasts and the expression of PLCγ2 and NFATc-1 were significantly inhibited after silencing Btk expression, but osteoclast precursor cells could be differentiated due to the proinflammatory factor lipopolysaccharide. This study demonstrates that Btk and PLCγ2 are key factors involved in the apical inflammatory response and bone destruction.


Asunto(s)
Agammaglobulinemia Tirosina Quinasa/metabolismo , Periodontitis Periapical/metabolismo , Fosfolipasa C gamma/metabolismo , Animales , Resorción Ósea/metabolismo , Diferenciación Celular/fisiología , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos C57BL , Osteoclastos/metabolismo , Osteoclastos/fisiología , Células RAW 264.7 , Transducción de Señal/fisiología
16.
Angew Chem Int Ed Engl ; 58(17): 5577-5581, 2019 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-30838761

RESUMEN

Tracking membrane-interacting molecules and visualizing their conformational dynamics are key to understanding their functions. It is, however, challenging to accurately probe the positions of a molecule relative to a membrane. Herein, a single-molecule method, termed LipoFRET, is reported to assess interplay between molecules and liposomes. It takes advantage of FRET between a single fluorophore attached to a biomolecule and many quenchers in a liposome. This method was used to characterize interactions between α-synuclein (α-syn) and membranes. These results revealed that the N-terminus of α-syn inserts into the membrane and spontaneously transitions between different depths. In contrast, the C-terminal tail of α-syn is regulated by calcium ions and floats in solution in two conformations. LipoFRET is a powerful tool to investigate membrane-interacting biomolecules with sub-nanometer precision at the single-molecule level.


Asunto(s)
Liposomas/metabolismo , Lípidos de la Membrana/metabolismo , Nanotecnología/métodos , Humanos
17.
Drug Dev Ind Pharm ; 44(2): 329-337, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29113503

RESUMEN

The objective of this study was to investigate the effect of crystalline state and a formulation of self-nanoemulsifying drug delivery system (SNEDDS) on oral bioavailability of 6-benzyl-1-benzyloxymethyl-5-iodouracil (W-1), a novel non-nucleoside reverse transcriptase inhibitor, in rats. The crystalline states of W-1 were characterized by scanning electron microscope (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). The SNEDDS was formulated by medium-chain lipids, characterized by droplet particle size. The plasma concentrations of W-1 were measured by high performance liquid chromatography (HPLC). The results indicated that W-1 compound were presented as crystalline forms, A and B, the degree of crystallization in form B was higher than that in form A. The SNEDDS of W-1 displayed a significant increase in the dissolution rate than W-1 powder. Furthermore, after oral administration of W-1 (100 mg/kg), the pharmacokinetic parameters of form A, form B, and W-1 SNEDDS were as follows: AUC0-t 526.4 ± 123.5, 305.1 ± 58.5 and 2297 ± 451 ng h/mL (p < .05, when W-1 SNEDDS were compared with either form A or form B), respectively. With SNEDDS formulation, the relative bioavailabilities were enhanced by 4.36-fold and 7.53-fold over the form A and form B of W-1, respectively. In conclusion, the present results suggested that the crystalline states of W-1 might lead to the lower oral bioavailability, and SNEDDS formulation is a promising strategy of improving bioavailability, in spite of that crystalline states usually carry small lot-to-lot variability.


Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/farmacocinética , Emulsiones/química , Nanopartículas/química , Uracilo/análogos & derivados , Administración Oral , Animales , Fármacos Anti-VIH/química , Área Bajo la Curva , Rastreo Diferencial de Calorimetría , Química Farmacéutica , Cristalización , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Semivida , Lípidos/química , Masculino , Tasa de Depuración Metabólica , Tamaño de la Partícula , Polietilenglicoles/química , Ratas , Ratas Sprague-Dawley , Tensoactivos/química , Uracilo/administración & dosificación , Uracilo/química , Uracilo/farmacocinética , Difracción de Rayos X
18.
Anal Chem ; 88(17): 8355-8, 2016 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-27417635

RESUMEN

Graphitic C3N4 (g-C3N4) nanosheets are a type of emerging graphene-like carbon-based nanomaterials with high fluorescence and large specific surface areas that hold great potential for biosensor applications. However, current g-C3N4 based biosensors have prevailingly been limited to coordination with metal ions, and it is of great significance to develop new designs for g-C3N4 nanosheets based biosensors toward biomarkers of general interest. We report the development of a novel g-C3N4 nanosheet-based nanosensor strategy for highly sensitive, single-step and label-free detection of tyrosinase (TYR) activity and its inhibitor. This strategy relies on the catalytic oxidation of tyrosine by TYR into melanin-like polymers, which form a nanoassembly on the g-C3N4 nanosheets and quench their fluorescence. This strategy was demonstrated to provide excellent selectivity and superior sensitivity and to enable rapid screening for TYR inhibitors. Therefore, the developed approach might create a useful platform for diagnostics and drugs screening for TYR-based diseases including melanoma cancer.


Asunto(s)
Inhibidores Enzimáticos/farmacología , Melaninas/química , Monofenol Monooxigenasa/antagonistas & inhibidores , Monofenol Monooxigenasa/metabolismo , Nanopartículas/química , Nanotecnología , Nitrilos/química , Polímeros/química , Humanos , Monofenol Monooxigenasa/análisis , Espectrometría de Fluorescencia
19.
J Environ Sci (China) ; 35: 12-19, 2015 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-26354687

RESUMEN

Transport behaviors of graphene oxide nanoparticles (GONPs) in saturated porous media were examined as a function of the presence and concentration of anionic surfactant (SDBS) and non-ionic surfactant (Triton X-100) under different ionic strength (IS). The results showed that the GONPs were retained obviously in the sand columns at both IS of 50 and 200mmol/L, and they were more mobile at lower IS. The presence and concentration of surfactants could enhance the GONP transport, particularly as observed at higher IS. It was interesting to see that the GONP transport was surfactant type dependent, and SDBS was more effective to facilitate GONP transport than Triton X-100 in our experimental conditions. The advection-dispersion-retention numerical modeling followed this trend and depicted the difference quantitatively. Derjaguin-Landau-Verwey-Overbeek (DLVO) interaction calculations also were performed to interpret these effects, indicating that secondary minimum deposition was critical in this study.


Asunto(s)
Grafito/análisis , Nanopartículas/análisis , Octoxinol/química , Óxidos/análisis , Tensoactivos/química , Monitoreo del Ambiente , Modelos Teóricos , Concentración Osmolar , Porosidad , Dióxido de Silicio/química
20.
Pancreatology ; 14(2): 87-90, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24650959

RESUMEN

BACKGROUND AND AIMS: Refractory chronic pancreatitis has been proposed as a challenge for endoscopists following routine single plastic stenting. However, data on the efficacy and safety of further endoscopic stenting are still controversial. The current systematic review aimed to assess the efficacy and safety of placement of fully covered self-expandable metal stent (FCSEMS) and multiple plastic stents. METHODS: Databases including MEDLINE, EMBASE, the Cochrane Library, CBM, CNKI, VIP, and WANFANG Database were used to search relevant trials. Published studies were assessed by using well-defined inclusion and exclusion criteria. The process was independently performed by two investigators. RESULTS: A total of 5 studies provided data of 80 patients. Forest plots and publication bias were not carried out because few studies were relevant and screened studies were all case series. The technical success rate was 100% both in placement of FCSEMS and multiple plastic stents. The functional success rate after placement of FCSEMS was 100%, followed by multiple plastic stents (94.7%). Complications occurred 26.2% after FCSEMS placement, which was not described in detail in multiple plastic stents. The stent migration rate was 8.2% for FCSEMS and 10.5% for multiple plastic stents. Reintervention rate was 9.8% for FCSEMS and 15.8% for multiple plastic stents. Pain improvement rate was 85.2% for FCSEMS and 84.2% for multiple plastic stents. CONCLUSIONS: FCSEMS appeared to be no significant difference with multiple plastic stents in treatment of refractory chronic pancreatitis. We need to develop more investigations.


Asunto(s)
Materiales Biocompatibles , Metales , Conductos Pancreáticos/cirugía , Pancreatitis/cirugía , Plásticos , Stents , Enfermedad Crónica , Constricción Patológica/terapia , Humanos , Complicaciones Posoperatorias/epidemiología , Diseño de Prótesis , Reoperación/estadística & datos numéricos , Stents/efectos adversos
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