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1.
Aesthetic Plast Surg ; 48(10): 1889-1898, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38409347

RESUMEN

BACKGROUND: Forehead augmentation have become popular aesthetic procedures among Asians in recent years. However, the use of polyetheretherketone (PEEK) patient-specific implant (PSI) in the facial contouring surgery for aesthetic considerations is not well documented in the existing studies. The purpose of this study was to develop a novel method for forehead augmentation and assess the clinical outcomes and complications in patients who underwent forehead augmentation with PEEK PSI assisted by endoscopy. METHODS: The PEEK PSIs were fabricated using the virtual surgical planning (VSP) and the computer-aided manufacturing (CAM) for each patient, preoperatively. The implant pockets were dissected in the subperiosteal plane, and PEEK PSIs were placed in their designed position and fixed assisting by endoscopy via small incision within the hairline. All patients were asked to complete the FACE-Q questionnaire before and 6 months after the operation. Pre- and postoperative demographics, photographs, and other clinical data of patients were collected and analyzed. RESULTS: 11 patients underwent forehead augmentation were enrolled in this study. All procedures were completed successfully with the help of endoscope. The average patient age was 30.63 ± 2.54 years. The mean thickness and size of PEEK PSI were 4.44 ± 1.77 mm and 38.43 ± 22.66 cm2, respectively. The mean operative time was 83.00 ± 29.44 min, and the mean postoperative follow-up period was 11.00 ± 6.50 months. No implant exposure, extrusion or removal were reported. The FACE-Q scores of patients in satisfaction with the forehead increased from 47.64 ± 7.15 to 78.81 ± 6.35. CONCLUSIONS: PEEK PSIs can be prefabricated to achieve accurate remodeling of the frontal contour with good esthetic outcomes. The endoscope provides direct and magnified vision, which allow easy access to the supraorbital rim and lateral edge of the eyebrow arch and confirming the position of the implants without damaging nerves and vessels. Endoscopic-assisted forehead augmentation with PEEK PSI is safe and effective. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Benzofenonas , Endoscopía , Estética , Frente , Cetonas , Polietilenglicoles , Polímeros , Humanos , Adulto , Femenino , Frente/cirugía , Endoscopía/métodos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Materiales Biocompatibles , Estudios de Cohortes , Prótesis e Implantes
2.
Aesthetic Plast Surg ; 47(3): 1111-1118, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36941453

RESUMEN

BACKGROUND: Several genioplasty techniques can narrow the width of the chin. Nevertheless, patients with a broad and short chin who received these methods were unsatisfied with the outcomes. The goal of this study was to analyze the clinical outcomes of modified M-shaped genioplasty for broad, flat and short chin deformity. METHODS: Thirty-eight patients with broad, flat and short chins were included in this study from January 2019 to December 2021. The preoperative design was performed individually according to the data of the chin and the patient's desire of final chin shape. Narrowing and vertical elongating genioplasty was performed for all the patients with modified M-shaped genioplasty under general anesthesia according to the preoperative designs. All patients have completed the FACE-Q preoperatively and 3 months postoperatively. The results were evaluated by clinical appearances and FACE-Q scores. RESULTS: The vertical lengthening of the chin was 2-5 mm, with an average of 3.02 mm. The horizontal narrowing width was 3-6 mm, with an average of 5.6 mm. FACE-Q scores in satisfaction with the chin increased significantly from 35.34 ± 9.57 to 72.95 ± 6.81. There were no severe complications took place during the time frame of 3-24 months postoperatively. CONCLUSIONS: The modified M-shaped genioplasty preserved the bone structure in the midsymphyseal area and suprahyoid muscular attachments as far as possible, and the bone segments may be repositioned quickly. This technique produced reliable and esthetically satisfying results in correcting a short, flat and broad chin, with altered vertical length, slope, width and protrusion three-dimensionally. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Mentoplastia , Osteotomía , Humanos , Mentoplastia/métodos , Mentón/cirugía , Osteotomía/métodos , Medicina Basada en la Evidencia , Anestesia General , Mandíbula/cirugía
3.
Aesthetic Plast Surg ; 2023 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-37626139

RESUMEN

BACKGROUND: Ultrasonic scalpel has been reported to be superior to conventional electrocautery in many studies. However, with respect to transaxillary endoscopic breast augmentation, few studies on the effect of ultrasonic scalpel are available in the literature. METHODS: The medical records of 173 female patients who underwent breast augmentation via endoscopic transaxillary approach from January 2018 to December 2020 were reviewed retrospectively. The patients were divided into two groups according to the implant pocket dissection instruments. In group A, the implant pockets were dissected with conventional electrocautery (EC group) on 81 patients, and in group B, ultrasonic scalpel (US group) was used for implant pockets on 92 patients. All operations were performed by the same senior plastic surgeon and the same surgical team. The operation time, intraoperative blood loss, postoperative total drainage volume, days of drainage, postoperative surgical site pain and hospital stay time of the two groups were compared and analyzed statistically. RESULTS: The average operation time of the US group (83.82 ± 11.57 min) was significantly shorter than that of the EC group (101.40 ± 14.36 min), intraoperative blood loss in the US group was significantly less than that of the EC group (18.67 ± 6.20 ml vs. 21.59 ± 6.44 ml), the mean hospital stay days (2.96 ± 0.69 vs. 4.30 ± 1.11), total drainage volume (122.24 ± 43.81 vs. 232.37 ± 99.15), and duration of drain (2.52 ± 0.54 vs. 3.77 ± 1.10), mean VAS score for surgical site pain on 3 postoperative days (5.08 ± 1.35 vs. 6.51 ± 1.36, 4.08 ± 1.16 vs. 5.40 ± 1.32, 3.04 ± 0.91 vs. 4.06 ± 1.11) were significantly lower in the US group compared to the EC group. CONCLUSIONS: The ultrasonic scalpel reduces operative time, intraoperative blood loss, postoperative drainage, postoperative pain, hospital stay time, and incidence of complications. The ultrasonic scalpel is safe and reliable for transaxillary endoscopic breast augmentation. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

4.
J Am Chem Soc ; 143(3): 1416-1427, 2021 01 27.
Artículo en Inglés | MEDLINE | ID: mdl-33439015

RESUMEN

Targeting SIRT1 signaling pathway could improve glucose aerobic metabolism and mitochondrial biosynthesis to resist cardiac and neurological injuries. Ginsenoside Rc has been identified for targeting mitochondrial function, but how ginsenoside Rc interacts with SIRT1 to regulate energy metabolism in cardiomyocytes and neurons under physiological or ischemia/reperfusion (I/R)-injured conditions has not been clearly investigated. Here, we confirm the interaction of Rc on the residue sites of SIRT1 in promoting its activity. Ginsenoside Rc significantly promotes mitochondrial biogenesis and increases the levels of electron-transport chain complex II-IV in cardiomyocytes and neurons. Meanwhile, ginsenoside Rc pretreatment increases ATP production, glucose uptake, and the levels of hexokinase I/II and mitochondrial pyruvate carrier I/II in both cell models. In addition, ginsenoside Rc activates the PGC1α pathway to induce mitochondrial biosynthesis. More importantly, ginsenoside Rc reduces mitochondrial damage and apoptosis through SIRT1 restoration-mediated reduction of PGC1α acetylation in the I/R-induced cardiac and neuronal models. Collectively, the in vitro and in vivo data indicate that ginsenoside Rc as a SIRT1 activator promotes energy metabolism to improve cardio- and neuroprotective functions under normal and I/R injury conditions, which provides new insights into the molecular mechanism of ginsenoside Rc as a protective agent.


Asunto(s)
Metabolismo Energético/efectos de los fármacos , Ginsenósidos/uso terapéutico , Miocitos Cardíacos/efectos de los fármacos , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Sirtuina 1/metabolismo , Animales , Encéfalo/patología , Glucosa/metabolismo , Masculino , Mitocondrias/metabolismo , Daño por Reperfusión Miocárdica/prevención & control , Miocardio/patología , Miocitos Cardíacos/metabolismo , Neuronas/metabolismo , Fosforilación Oxidativa/efectos de los fármacos , Células PC12 , Ácido Pirúvico/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos
5.
Inorg Chem ; 54(9): 4423-30, 2015 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-25880251

RESUMEN

A series of phosphorus-substituted germanium(II) complexes, L(1)GeR [L(1) = CH{(CMe)(2,6-(i)Pr2C6H3N)}2; 2, R = PPh2; 4, R = OPPh2; 5a, R = OP(O)Ph2; 5b, R = OP(O) (O(n)Bu)2; 6a, R = OP(S)Ph2; 6b, R = OP(S)(OEt)2], were synthesized through the direct activation of various organic phosphorus compounds by N-heterocyclic ylide-like germylene 1. These compounds were characterized by IR and NMR spectroscopy, and 4, 5a, 6a, and 6b were further investigated by X-ray crystallography. Interestingly, the reaction of 1 with Ph2P(O)H produced the tricoordinated phosphorus(III) species L(1)GeOPPh2 (4) rather than the expected isomeric product L(1)GeP(O)Ph2. The reaction of 1 with dialkylthiophosphoric acid and diphenylthiophosphinic acid resulted in the products 6a and 6b containing the P═S double bond rather than the P═O double bond.


Asunto(s)
Complejos de Coordinación/química , Germanio/química , Organotiofosfatos/química , Fósforo/química , Cristalografía por Rayos X , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Estereoisomerismo
6.
J Org Chem ; 79(17): 8118-27, 2014 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-25084550

RESUMEN

The first nickel-catalyzed decarboxylative C-P coupling of a wide range of alkenyl acids with various P(O)H compounds, especially for H-phosphonates, has been developed, affording a versatile and efficient tool for the preparation of valuable (E)-1-alkenylphosphonates, (E)-1-alkenylphosphinate oxides, and (E)-1-alkenylphosphine oxides with high stereoselectivity and broad substrate applicability. DFT calculation revealed that the phosphine ligand exhibits better catalytic performance than the nitrogen ligand in the reductive elimination step owing to the stronger nucleophilicity and larger size.


Asunto(s)
Alquenos/química , Níquel/química , Nitrógeno/química , Organofosfonatos/química , Fosfinas/química , Catálisis , Ligandos , Estructura Molecular , Teoría Cuántica , Estereoisomerismo
7.
Wei Sheng Wu Xue Bao ; 54(12): 1471-80, 2014 Dec 04.
Artículo en Zh | MEDLINE | ID: mdl-25876333

RESUMEN

OBJECTIVE: To explore electricity generation and dynamic characteristics of microbial community of microbial fuel cells (MFC) started-up with mixed sludge of aerobic/anaerobic sludge. METHODS: Single-chamber MFCs were constructed and characteristics of microbial community composition and structure were investigated by culture-independent microbial molecular techniques. RESULTS: MFC started up successfully after three cycles' operation, and the maximum output voltage was up to 230 mV. The maximum power density reached 11.15 W/m3 at the outer resistance of 1656 Ω. The structure of microbial community on the anodic biofilm was different from that of seed sludge and microbial diversity reduced. The dominant microbial groups on anodic biofilm were Betaproteobacteria (24.90%), Bacteroidetes (21.30%), Firmicutes (9.70%), Gammaproteobacteria (8.50%), Deltaproteobacteria ( 7.90%), Chloroflexi (4.20%) and Alphaproteobacteria (3.60%). The biofilm-forming microbial genera Zoogloea and Acinetobacter accounted for 5.00% and 3.90% of total community. The abundance of electricity-producing bacteria Geobacter spp. increased from 0.60% in mixed sludge to 2.60% on the biofilm. CONCLUSION: Dominant microbial populations in mixed sludge were selected by long-term acclimation and finally a beneficial microbial group was built on the anodic biofilm. The populations group was helpful to form a functional and active biofilm, which consequently benefited to produce electricity under anaerobic condition by fermenting organic matter.


Asunto(s)
Bacterias/metabolismo , Fuentes de Energía Bioeléctrica , Aguas del Alcantarillado , Biopelículas , Filogenia
8.
Front Genet ; 15: 1408404, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38919952

RESUMEN

Fracture healing is a complex process that involves multiple molecular events, and the regulation mechanism is not fully understood. We acquired miRNA and mRNA transcriptomes of mouse fractures from the Gene Expression Omnibus database (GSE76197 and GSE192542) and integrated the miRNAs and genes that were differentially expressed in the control and fracture groups to construct regulatory networks. There were 130 differentially expressed miRNAs and 4,819 differentially expressed genes, including 72 upregulated and 58 downregulated miRNAs, along with 2,855 upregulated and 1964 downregulated genes during early fracture healing. Gene ontology analysis revealed that most of the differentially expressed genes were enriched in the extracellular matrix (ECM) structure and the ECM organization. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment suggested cell cycle, DNA replication, and mismatch repair were involved in the progression of fracture healing. Furthermore, we constructed a molecular network of miRNAs and mRNAs with inverse expression patterns to elucidate the molecular basis of miRNA-mRNA regulation in fractures. The regulatory network highlighted the potential targets, which may help to provide a mechanistic basis for therapies to improve fracture patient outcomes.

9.
Nat Commun ; 15(1): 446, 2024 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-38199985

RESUMEN

Patients with corticosteroid-refractory acute graft-versus-host disease (aGVHD) have a low one-year survival rate. Identification and validation of novel targetable kinases in patients who experience corticosteroid-refractory-aGVHD may help improve outcomes. Kinase-specific proteomics of leukocytes from patients with corticosteroid-refractory-GVHD identified rho kinase type 1 (ROCK1) as the most significantly upregulated kinase. ROCK1/2 inhibition improved survival and histological GVHD severity in mice and was synergistic with JAK1/2 inhibition, without compromising graft-versus-leukemia-effects. ROCK1/2-inhibition in macrophages or dendritic cells prior to transfer reduced GVHD severity. Mechanistically, ROCK1/2 inhibition or ROCK1 knockdown interfered with CD80, CD86, MHC-II expression and IL-6, IL-1ß, iNOS and TNF production in myeloid cells. This was accompanied by impaired T cell activation by dendritic cells and inhibition of cytoskeletal rearrangements, thereby reducing macrophage and DC migration. NF-κB signaling was reduced in myeloid cells following ROCK1/2 inhibition. In conclusion, ROCK1/2 inhibition interferes with immune activation at multiple levels and reduces acute GVHD while maintaining GVL-effects, including in corticosteroid-refractory settings.


Asunto(s)
Enfermedad Injerto contra Huésped , Quinasas Asociadas a rho , Humanos , Animales , Ratones , Quinasas Asociadas a rho/genética , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Transducción de Señal , FN-kappa B , Corticoesteroides/farmacología , Corticoesteroides/uso terapéutico
10.
Environ Sci Pollut Res Int ; 30(46): 102790-102802, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37672159

RESUMEN

Air pollution is a major public health problem that can lead to conjunctivitis. This study aimed to explore the associations between air pollutants and outpatient visits for conjunctivitis in Hangzhou, China. This study collected data on 50,772 patients with conjunctivitis and the concentrations of six air pollutants from February 1, 2014, to August 31, 2018. A time series analysis using a generalized additive model (GAM) was conducted. We found that the risk of conjunctivitis was related to the air pollutants PM2.5, PM10, SO2, NO2, and O3, which had concentration hysteresis effects. The risk of conjunctivitis increased by 1.009 (95% confidence interval (CI): 1.003, 1.014), 1.011 (95% CI: 1.008, 1.015), 1.238 (95% CI: 1.186, 1.292), 1.028 (95% CI: 1.019, 1.038), and 1.013 (95% CI: 1.008, 1.017) for every 10 µg/m3 increase in PM2.5, PM10, SO2, NO2, and O3 concentrations, respectively. The lag effects of SO2 and NO2 were stronger than those of particulate matter. Females exposed to PM10, PM2.5, SO2, and O3 had a higher risk of conjunctivitis than males, while males exposed to NO2 had a nearly identical risk of conjunctivitis as females. People aged 19-59 were more likely to suffer from conjunctivitis. The risk of conjunctivitis caused by PM10, SO2, and O3 was highest in the transitional season, while the risk caused by NO2 was highest in the winter season. In conclusion, females and middle-aged adults were at higher risk of conjunctivitis. People were more susceptible to conjunctivitis during the transitional season. These findings highlight the importance of atmospheric pollution governance and reference for public health measures.

11.
iScience ; 25(4): 104064, 2022 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-35355522

RESUMEN

Photocatalysis under UV/visible light irradiation has emerged as one of the green methodologies for solar energy utilization and organic synthesis. These photocatalytic processes are typically initiated by one-photon-absorbing metal complexes or organic dyes. Nevertheless, the intrinsic restrictions of UV/visible light irradiation, such as shallow penetration in reaction solutions, competing absorption by substrates, and limited coverage of the solar spectrum, call for the development of innovative photocatalysts functioning under longer wavelength irradiation. Herein, we report a ruthenium complex containing a metal-organic framework, MOF-Ru1, which can drive diverse organic reactions under 740 nm light irradiation following the two-photon absorption (TPA) process. Various organic transformations such as energy transfer, reductive, oxidative, and redox neutral reactions were realized using this heterogeneous hybrid photocatalyst. Overall, MOF-Ru1 represents an intriguing TPA photocatalyst active under near-infrared light irradiation, paving a way for the efficient utilization of low-energy light and convenient photocatalyst recycling because of phase separation.

12.
Front Chem ; 6: 395, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30238003

RESUMEN

Removal of sulfanilic acid (SA) from water is an urgent but still challenging task. Herein, we developed a low pressure electrochemical membrane filtration (EMF) system for SA decontamination using RuO2-TiO2@Ti/PVDF composite membrane to serve as not only a filter but also an anode. Results showed that efficient removal of SA was achieved in this EMF system. At a charging voltage of 1.5 V and a electrolyte concentration of 15 mM, flow-through operation with a hydraulic retention time (HRT) of 2 h led to a high SA removal efficiency (80.4%), as expected from the improved contact reaction of this compound with ROS present at the anode surface. Cyclic voltammetry (CV) analysis indicated that the direct anodic oxidation played a minor role in SA degradation. Electron spin resonance (ESR) spectra demonstrated the production of •OH in the EMF system. Compared to the cathodic polarization, anodic generated ROS was more likely responsible for SA removal. Scavenging tests suggested that adsorbed •OH on the anode (>•OH) played a dominant role in SA degradation, while O2•- was an important intermediate oxidant which mediated the production of •OH. The calculated mineralization current efficiency (MCE) of the flow-through operated system 29.3% with this value much higher than that of the flow-by mode (5.1%). As a consequence, flow-through operation contributed to efficient oxidation of SA toward CO2 and nontoxic carboxylic acids accounting for 71.2% of initial C. These results demonstrate the potential of the EMF system to be used as an effective technology for water decontamination.

13.
ChemSusChem ; 11(4): 743-752, 2018 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-29240294

RESUMEN

RuPx nanoparticles (NPs) encapsulated in uniform N,P-codoped hollow carbon nanospheres (RuPx @NPC) have been synthesized through a facile route in which aniline-pyrrole copolymer nanospheres are used to disperse Ru ions followed by a gas phosphorization process. The as-prepared RuPx @NPC exhibits a uniform core-shell hollow nanospherical structure with RuPx NPs as the core and N,P-codoped carbon (NPC) as the shell. This strategy integrates many advantages of hollow nanostructures, which provide a conductive substrate and the doping of a nonmetal element. At high temperatures, the obtained thin NPC shell can not only protect the highly active phase of RuPx NPs from aggregation and corrosion in the electrolyte but also allows variation in the electronic structures to improve the charge-transfer rate greatly by N,P codoping. The optimized RuPx @NPC sample at 900 °C exhibits a Pt-like performance for the hydrogen evolution reaction (HER) and long-term durability in acidic, alkaline, and neutral solutions. The reaction requires a small overpotential of only 51, 74, and 110 mV at 10 mA cm-2 in 0.5 m H2 SO4 , 1.0 m KOH, and 1.0 m phosphate-buffered saline, respectively. This work provides a new way to design unique phosphide-doped carbon heterostructures through an inorganic-organic hybrid method as excellent electrocatalysts for HER.


Asunto(s)
Hidrógeno/química , Nanosferas/química , Compuestos de Rutenio/química , Carbono , Conductividad Eléctrica , Técnicas Electroquímicas/métodos , Calor , Nitrógeno , Fósforo/química
14.
J Colloid Interface Sci ; 513: 151-160, 2018 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-29145018

RESUMEN

MoO42-@aniline-pyrrole (MoO42-@polymer) spheres as precursors have been used to synthesize unique core-shell nanostructure consisting of molybdenum carbide and molybdenum phosphide composites encapsulated into uniformly dual N, P-doped carbon shells (Mo2C/MoP@NPC) through a facile two-step strategy. Firstly, porous core-shell N-doped Mo2C@C (Mo2C@NC) nanospheres have been synthesized with ultrafine Mo2C nanoparticles as core and ultrathin NC as shell by a annealing route. Secondly, Mo2C/MoP@NPC has been obtained maintaining intact spherical-like morphology through a phosphidation reaction in high temperature. The synergistic effect of Mo2C and MoP may reduce the strong MoH bonding energy of pure Mo2C and provide a fast hydrogen release process. In addition, the dual N, P-doped carbon matrix as shell can not only improve the electroconductivity of catalysts but also prevent the corrosion of Mo2C/MoP nanoparticles during the electrocatalytic process. When used as HER cathode in acids, the resulting Mo2C/MoP@NPC shows excellent catalytic activity and durability, which only needs an overpotential of 160 mV to drive 10 mA cm-2. Moreover, it also exhibits better HER performance in basic and neutral media with the need for overpotentials of only 169 and 228 mV to achieve 10 mA cm-2, respectively. This inorganic-organic combination of Mo-based catalysts may open up a new way for water-splitting to produce large-scale hydrogen.

15.
Nat Med ; 24(3): 282-291, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29431743

RESUMEN

Individuals with acute myeloid leukemia (AML) harboring an internal tandem duplication (ITD) in the gene encoding Fms-related tyrosine kinase 3 (FLT3) who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) have a 1-year survival rate below 20%. We observed that sorafenib, a multitargeted tyrosine kinase inhibitor, increased IL-15 production by FLT3-ITD+ leukemia cells. This synergized with the allogeneic CD8+ T cell response, leading to long-term survival in six mouse models of FLT3-ITD+ AML. Sorafenib-related IL-15 production caused an increase in CD8+CD107a+IFN-γ+ T cells with features of longevity (high levels of Bcl-2 and reduced PD-1 levels), which eradicated leukemia in secondary recipients. Mechanistically, sorafenib reduced expression of the transcription factor ATF4, thereby blocking negative regulation of interferon regulatory factor 7 (IRF7) activation, which enhanced IL-15 transcription. Both IRF7 knockdown and ATF4 overexpression in leukemia cells antagonized sorafenib-induced IL-15 production in vitro. Human FLT3-ITD+ AML cells obtained from sorafenib responders following sorafenib therapy showed increased levels of IL-15, phosphorylated IRF7, and a transcriptionally active IRF7 chromatin state. The mitochondrial spare respiratory capacity and glycolytic capacity of CD8+ T cells increased upon sorafenib treatment in sorafenib responders but not in nonresponders. Our findings indicate that the synergism of T cells and sorafenib is mediated via reduced ATF4 expression, causing activation of the IRF7-IL-15 axis in leukemia cells and thereby leading to metabolic reprogramming of leukemia-reactive T cells in humans. Therefore, sorafenib treatment has the potential to contribute to an immune-mediated cure of FLT3-ITD-mutant AML relapse, an otherwise fatal complication after allo-HCT.


Asunto(s)
Factor de Transcripción Activador 4/genética , Factor 7 Regulador del Interferón/genética , Interleucina-15/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Tirosina Quinasa 3 Similar a fms/genética , Animales , Linfocitos T CD8-positivos/inmunología , Reprogramación Celular/genética , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/genética , Enfermedad Injerto contra Huésped/patología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Ratones , Sorafenib/administración & dosificación , Sorafenib/efectos adversos , Secuencias Repetidas en Tándem/genética , Trasplante Homólogo/efectos adversos
17.
Nanoscale ; 9(34): 12353-12363, 2017 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-28654107

RESUMEN

In situ cathodic activation (ISCA) of V-incorporated NixSy nanowires supported on nickel foam (VS/NixSy/NF) can be realized in an alkaline hydrogen evolution reaction (HER) process, which provides not only clearly enhanced activity but also ultrahigh stability for HER. The ISCA process is continuous linear sweep voltammetry (LSV) on VS/NixSy/NF as a cathodic electrode with gradually enhanced HER activity. The activated VS/NixSy/NF (A-VS/NixSy/NF) demonstrates enhanced HER activity with an overpotential of 125 mV to drive 10 mA cm-2, which is much lower than that of other samples. It may be predicted that the ISCA-derived amorphous VOOH film covering on A-VS/NixSy/NF accelerates the HER process, and NiOOH may protect active sites from decaying, leading to excellent activity and structural stability. However, for single metal sulfides, the ISCA process of nickel or vanadium sulfides is not available, implying that the synergistic effect between Ni and V of VS/NixSy/NF may be the key to drive ISCA in alkaline HER. In addition, its ultra-high stability confirms that the stable active sites and nanostructures of A-VS/NixSy/NF are derived from ISCA. Therefore, the ISCA of V-incorporated transition metal sulfides in the alkaline HER process may be a facile and promising method to obtain efficient electrocatalysts.

18.
Chem Commun (Camb) ; 52(8): 1582-1585, 2016 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-26609643

RESUMEN

Two newly discovered linear compounds tetraboronate and boroxine stabilized by digermylene are reported, which feature a B4O5 chain and a B3O3 ring, respectively. DFT calculations reveal that not only can digermylene stabilize the electron-deficient boron centers, but also increase the energies of the LUMOs of the boron moiety. Our results provide a hint for the development of boronate covalent organic frameworks.

19.
Oncol Lett ; 10(4): 2390-2394, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26622857

RESUMEN

Increased platelet heterogeneity has been reported in myeloproliferative neoplasms (MPN) with thrombocytosis. However, whether abnormal thrombopoiesis occurs in patients with chronic myeloid leukemia (CML) who have normal platelet counts, remains unclear. In order to explore this question, 25 patients with CML with normal platelet counts (CML-N), 40 patients with CML with elevated platelet counts (CML-E) and 33 healthy adults were recruited. The association of platelet count with mean platelet volume (MPV), platelet large cell ratio (P-LCR) and platelet distribution width (PDW) was examined. Bone marrow smears were also reviewed to assess the proliferation and abnormal lobation of megakaryocytes. The results showed that the two CML groups exhibited higher MPV, P-LCR and PDW values than those of the controls (P<0.05). Furthermore, the CML-N group was more heterogeneous in terms of thrombopoiesis than the CML-E group, as demonstrated by a higher PDW (P<0.05) and higher ratio of multinucleated dysmegakaryocytes (12.17 vs. 4.69%; χ2=29.79; P=0.000). In addition, no correlation between platelet count and MPV, P-LCR or PDW was observed in the CML-N group (r=-0.102, -0.051 and -0.049, and P=0.619, 0.828 and 0.810, respectively). The results suggested that patients in the CML-N group have more heterogeneous thrombopoiesis of megakaryocytes and platelets, and that apparently normal platelet counts may mask the abnormal thrombopoiesis in these patients.

20.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 31(10): 1387-90, 1395, 2015 Oct.
Artículo en Zh | MEDLINE | ID: mdl-26429541

RESUMEN

OBJECTIVE: To study the frequency of CD14⁺HLA-DR(-/low) myeloid-derived suppressor cells (MDSCs) in the peripheral blood of chronic hepatitis B (CHB) patients and the relationship with biochemical characteristics, viral load and liver pathology. METHODS: The frequency of CD14⁺HLA-DR(-/low) MDSCs in the peripheral blood of 96 patients with CHB and 20 healthy control cases were detected by flow cytometry. Ultrasound-guided liver biopsies as well as HBV-related serological tests were performed in HBV-infected individuals to analyze the biochemical characteristics, viral load and pathology. The data were assessed using Spearman correlation analysis. RESULTS: The frequency of the peripheral blood CD14⁺HLA-DR(-/low) MDSCs in the 96 CHB cases was (6.03 ± 0.09)%, which was significantly higher than that of the 20 healthy control cases (1.87 ± 0.05)%. The group of HBeAg positive cases had a significantly higher frequency of the peripheral blood CD14⁺HLA-DR(-/low) MDSCs compared with the group of HBeAg negative cases and the healthy control group. The frequency of CD14⁺HLA-DR(-/low) MDSCs in the peripheral blood was negatively correlated with serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. There was no correlation between the frequency of peripheral blood CD14⁺HLA-DR(-/low) MDSCs and HBV load. The frequency of CD14⁺HLA-DR(-/low) MDSCs in the peripheral blood was negatively correlated with the liver inflammation grade, but not related with the fibrosis stage in patients with CHB. CONCLUSION: The frequency of CD14⁺HLA-DR(-/low) MDSCs is negatively correlated with the inflammation of CHB.


Asunto(s)
Antígenos HLA-DR/análisis , Hepatitis B Crónica/inmunología , Inflamación/inmunología , Receptores de Lipopolisacáridos/análisis , Células Mieloides/inmunología , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Antígenos e de la Hepatitis B/análisis , Humanos
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