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OBJECTIVE: In this study, the three-dimensional relationship between the optimal puncture needle path and the lumbar spinous process was discussed using digital technology. Additionally, the positioning guide plate was designed and 3D printed in order to simulate the surgical puncture of specimens. This plate served as an important reference for the preoperative simulation and clinical application of percutaneous laser decompression (PLD). METHOD: The CT data were imported into the Mimics program, the 3D model was rebuilt, the ideal puncture line N and the associated central axis M were developed, and the required data were measured. All of these steps were completed. A total of five adult specimens were chosen for CT scanning; the data were imported into the Mimics program; positioning guide plates were generated and 3D printed; a simulated surgical puncture of the specimens was carried out; an X-ray inspection was carried out; and an analysis of the puncture accuracy was carried out. RESULTS: (1) The angle between line N and line M was 42°~55°, and the angles between the line M and 3D plane were 1°~2°, 5°~12°, and 78°~84°, respectively; (2) As the level of the lumbar intervertebral disc decreases, the distance from point to line and point to surface changes regularly; (3) The positioning guide was designed with the end of the lumbar spinous process and the posterior superior iliac spine on both sides as supporting points. (4) Five specimens were punctured 40 times by using the guide to simulate surgical puncture, and the success rate was 97.5%. CONCLUSION: By analyzing the three-dimensional relationship between the optimal puncture needle path and the lumbar spinous process, the guide plate was designed to simulate surgical puncture, and the individualized safety positioning of percutaneous puncture was obtained.
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Imagenología Tridimensional , Vértebras Lumbares , Agujas , Punciones , Tomografía Computarizada por Rayos X , Humanos , Imagenología Tridimensional/métodos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Punciones/métodos , Tomografía Computarizada por Rayos X/métodos , Descompresión Quirúrgica/métodos , Descompresión Quirúrgica/instrumentación , Impresión Tridimensional , Adulto , Punción Espinal/métodos , Punción Espinal/instrumentación , Rayos LáserRESUMEN
PURPOSE: Acute lung injury (ALI) is a fatal acute inflammatory illness with restricted therapeutic choices clinically. Piperlongumine (PL) is recognized as an alkaloid separated from Piper longum L, which was suggested to exhibit multiple pharmacological activities (e.g., anti-inflammatory activity). However, the effects of PL on LPS-triggered ALI and its anti-inflammatory target remain unclear. This paper intended to assess the roles of PL in LPS-triggered ALI, as well as its underlying mechanism and target. METHODS: In vivo, ALI was induced by intratracheal injection of LPS to evaluate protective effects of PL and assessed by the changes of histopathological. In vitro, the anti-inflammatory activity and mechanism of PL were investigated by ELISA, RT-qPCR, transcription factor enrichment analysis, Western blotting and Immunofluorescence assay. The binding affinity of PL to MD2 was analyzed using computer docking, surface plasmon resonance, ELISA and immunoprecipitation assay. RESULTS: It was reported here that PL treatment alleviated LPS-induced pulmonary damage, inflammatory cells infiltration and inflammatory response in mice. In culture cells, PCR array showed that PL significantly inhibited LPS-induced inflammatory cytokines, chemokines, and type I IFNs genetic expression, along with the inhibition of TAK1 and TBK1 pathway. It is noteworthy that PL is capable of straightly binding to MD2 and inhibiting MD2/TLR4 complex formation and TLR4 dimerization. CONCLUSIONS: As revealed from this study, PL directly binding to MD2 to block cytokines expression by inhibiting the activation of TAK1 and TBK1 pathway, which then exerted its pulmonary protective activity. Accordingly, PL may act as an underlying candidate for treating LPS-triggered ALI.
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Lesión Pulmonar Aguda , Lipopolisacáridos , Ratones , Animales , Lipopolisacáridos/farmacología , Receptor Toll-Like 4/metabolismo , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/patología , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismo , Pulmón/patología , Antiinflamatorios/farmacología , Citocinas/metabolismo , FN-kappa B/metabolismoRESUMEN
BACKGROUND: Plants in the genus Artemisia are rich in active ingredients and specialized metabolites. Many of these compounds, especially flavonoids, have potential medicinal and nutritional applications, and are of growing interest to scientists due to their wide range of pharmacological and biological activities. Artemisia cultivars are commonly used as raw materials for medicine, food, and moxibustion in China. However, most of the metabolites produced by Artemisia species have not been identified, and few studies have addressed differences in active compounds between species and cultivars. RESULTS: We here investigated two Artemisia cultivars, 'Nanyangshiyong' (NYSY) and 'Nanyangyaoyong' (NYYY), which are commonly used in foods and moxibustion, respectively. NYSY and NYYY were confirmed to be Artemisia argyi cultivars. Total flavonoids contents and antioxidant activities were higher in NYYY than in NYSY. A total of 882 metabolites were identified in the samples; most of the potentially medicinally active compounds, especially flavonoids (e.g., flavone, flavonol, isoflavone, and anthocyanin), were up-regulated in NYYY compared to NYSY. Furthermore, most of the genes related to flavonoids biosynthesis were up-regulated in NYYY. Correlation analysis was used to identify putative members of transcription factor families that may regulate genes encoding key flavonoids biosynthesis enzymes. CONCLUSIONS: We found that the antioxidant activities and flavonoids contents significantly varied between two Artemisia cultivars of the same species. We also uncovered metabolomic and transcriptomic evidence of the molecular phenomena underlying those differences in flavonoids contents between the two Artemisia cultivars. This study provides a wealth of data for future utilization and improvements of Artemisia cultivars, and highlights a need to study the specific metabolite profiles of plants that are used in foods and medicines.
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Artemisia , Artemisia/genética , Artemisia/metabolismo , Flavonoides/metabolismo , Transcriptoma , Antioxidantes/metabolismo , Perfilación de la Expresión GénicaRESUMEN
Slow charge kinetics and unfavorable CO2 adsorption/activation strongly inhibit CO2 photoreduction. In this study, a strain-engineered Cs3 Bi2 Br9 /hierarchically porous BiVO4 (s-CBB/HP-BVO) heterojunction with improved charge separation and tailored CO2 adsorption/activation capability is developed. Density functional theory calculations suggest that the presence of tensile strain in Cs3 Bi2 Br9 can significantly downshift the p-band center of the active Bi atoms, which enhances the adsorption/activation of inert CO2 . Meanwhile, in situ irradiation X-ray photoelectron spectroscopy and electron spin resonance confirm that efficient charge transfer occurs in s-CBB/HP-BVO following an S-scheme with built-in electric field acceleration. Therefore, the well-designed s-CBB/HP-BVO heterojunction exhibits a boosted photocatalytic activity, with a total electron consumption rate of 70.63 µmol g-1 h-1 , and 79.66% selectivity of CO production. Additionally, in situ diffuse reflectance infrared Fourier transform spectroscopy reveals that CO2 photoreduction undergoes a formaldehyde-mediated reaction process. This work provides insight into strain engineering to improve the photocatalytic performance of halide perovskite.
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It is technically challenging to reversibly tune the layer number of 2D materials in the solution. Herein, a facile concentration modulation strategy is demonstrated to reversibly tailor the aggregation state of 2D ZnIn2 S4 (ZIS) atomic layers, and they are implemented for effective photocatalytic hydrogen (H2 ) evolution. By adjusting the colloidal concentration of ZIS (ZIS-X, X = 0.09, 0.25, or 3.0 mg mL-1 ), ZIS atomic layers exhibit the significant aggregation of (006) facet stacking in the solution, leading to the bandgap shift from 3.21 to 2.66 eV. The colloidal stacked layers are further assembled into hollow microsphere after freeze-drying the solution into solid powders, which can be redispersed into colloidal solution with reversibility. The photocatalytic hydrogen evolution of ZIS-X colloids is evaluated, and the slightly aggregated ZIS-0.25 displays the enhanced photocatalytic H2 evolution rates (1.11 µmol m-2 h-1 ). The charge-transfer/recombination dynamics are characterized by time-resolved photoluminescence (TRPL) spectroscopy, and ZIS-0.25 displays the longest lifetime (5.55 µs), consistent with the best photocatalytic performance. This work provides a facile, consecutive, and reversible strategy for regulating the photo-electrochemical properties of 2D ZIS, which is beneficial for efficient solar energy conversion.
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BACKGROUND: A new antibacterial compound powder of amoxicillin (AMO)/Radix Scutellaria extract (RSE) was developed, and its pharmacokinetics were determined in pigs following oral administration. RESULTS: The MIC ranges of AMO against Escherichia coli, Staphylococcus aureus and Streptococcus were 1-8 µg/mL, 0.5-4 µg/mL and 0.5-64 µg/mL, respectively. The MIC ranges of RSE against E. coli, S. aureus, and Streptococcus were greater than 2.5 mg/mL, 0.156-2.5 mg/mL, and greater than 2.5 mg/mL, respectively. For S. aureus, the combined drug susceptibility test showed that AMO and RSE had an additive or synergistic effect. The results of compatibility test, the excipient screening test and the drug quality control test showed that the formulation had stable quality and uniform properties under the test conditions. Two studies were conducted to investigate the pharmacokinetics of the compound product in pigs. First, the pharmacokinetics of the AMO-RSE powder were compared with those of their respective single products. The results showed no significant change in the main pharmacokinetic parameters when either component was removed from the compound formulation; thus, AMO and RSE have no pharmacokinetic interaction in pigs. Second, pigs were orally administered three different doses of AMO-RSE powder. The Cmax and AUC increased proportionally with increasing p.o. dose; thus, the λz, t1/2λ, MRT, and Tmax were unchanged for the doses of 10, 20, and 30 mg/kg AMO and the doses of 5, 10, and 15 mg/kg BCL, showing that AMO/baicalin in AMO-RSE powder showed linear pharmacokinetic characteristics in pigs. CONCLUSIONS: The combined drug sensitivity test of AMO and RSE against S. aureus showed that the combination was additive or synergistic. Pharmacokinetic studies indicated that AMO and BCL do not interfere with each other in pigs when used in a compound formulation. The pharmacokinetic parameters remained unchanged regardless of the dose for p.o. administration, indicating linear pharmacokinetic properties over the tested dose range. The quality of the AMO-RSE powder was good and stable, providing a foundation for its clinical application in veterinary medicine. Further bioavailability, PK/PD and clinical trials are still needed to determine the final dosage regimen.
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Amoxicilina , Scutellaria , Animales , Porcinos , Escherichia coli , Polvos , Staphylococcus aureus , Extractos Vegetales/farmacologíaRESUMEN
People spend increasing amounts of time at home, yet the indoor home environment remains understudied in terms of potential exposure to toxic trace metals. We evaluated trace metal (and metalloid) concentrations (As, Cu, Cr, Mn, Ni, Pb, and Zn) and health risks in indoor dust from homes from 35 countries, along with a suite of potentially contributory residential characteristics. The objective was to determine trace metal source inputs and home environment conditions associated with increasing exposure risk across a range of international communities. For all countries, enrichments compared to global crustal values were Zn > Pb > Cu > As > Cr > Ni; with the greatest health risk from Cr, followed by As > Pb > Mn > Cu > Ni > Zn. Three main indoor dust sources were identified, with a Pb-Zn-As factor related to legacy Pb sources, a Zn-Cu factor reflecting building materials, and a Mn factor indicative of natural soil sources. Increasing home age was associated with greater Pb and As concentrations (5.0 and 0.48 mg/kg per year of home age, respectively), as were peeling paint and garden access. Therefore, these factors form important considerations for the development of evidence-based management strategies to reduce potential risks posed by indoor house dust. Recent findings indicate neurocognitive effects from low concentrations of metal exposures; hence, an understanding of the home exposome is vital.
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Metaloides , Metales Pesados , Oligoelementos , China , Polvo/análisis , Monitoreo del Ambiente , Humanos , Metaloides/análisis , Medición de Riesgo , Oligoelementos/análisisRESUMEN
Drug-induced liver and kidney damage is an emergent clinical issue that should be addressed. Rosmarinic acid (RA) has obvious anti-inflammatory and antioxidant effects, so we evaluated the anti-inflammatory and antioxidant effects of RA pretreatment on serum and liver and kidney tissues of cisplatin (CP)-treated mice and explored the possible mechanisms. The results showed that RA pretreatment effectively downregulated the serum, liver, and kidney levels of ALT, AST, BUN, and CRE and the inflammatory factors IL-1ß, IL-6, and TNF-α, and simultaneously enhanced the total antioxidant capacity of the liver and kidney. RA pretreatment significantly reduced the levels of MPO, MDA, and NO in liver and kidney tissue, inhibited the mRNA expression of IL-1ß, IL-6, and TNF-α in liver and kidney tissue, activated the Nrf2 signaling pathway, and upregulated the mRNA expression of downstream target genes. Our findings show that RA could effectively prevent and alleviate acute liver and kidney injury caused by CP.
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Antioxidantes , Factor 2 Relacionado con NF-E2 , Ratones , Animales , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Antioxidantes/metabolismo , Cisplatino/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/metabolismo , FN-kappa B/metabolismo , Riñón , Transducción de Señal , Hígado , Antiinflamatorios/farmacología , ARN Mensajero/metabolismo , Ácido RosmarínicoRESUMEN
BACKGROUND: Cigarette smoke is well known to worsen asthma symptoms in asthmatic patients and to make them refractory to treatment, but the underling molecular mechanism is unclear. We hypothesized that cigarette smoke can reduce the expression of HDAC2 in asthma and the process was achieved by activating the PI3K-δ/Akt signaling pathway. We further hypothesized that roxithromycin (RXM) can alleviate the impacts by cigarette smoke. METHODS: A murine model of asthma induced by ovalbumin (OVA) and cigarette smoke has been established. The infiltration of inflammatory cells and inflammatory factors was examined in this model. Finally, we evaluated the expression of HDAC2, Akt phosphorylation levels, and the effects of RXM treatment on the model described earlier. RESULTS: Cigarette smoke exposure reduced HDAC2 protein expression by enhancing the phosphorylation of Akt in PI3K-δ/Akt signaling pathway. Furthermore, RMX reduced the airway inflammation and improved the level of expression of HDAC2 in the cigarette smoke-exposed asthma mice. CONCLUSIONS: This study provides a novel insight into the mechanism of cigarette smoke exposure in asthma and the effects of RXM treatment on this condition. These results may be helpful for treating refractory asthma and emphasizing the need for a smoke-free environment for asthmatic patients.
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Antiasmáticos/uso terapéutico , Antibacterianos/uso terapéutico , Asma/tratamiento farmacológico , Histona Desacetilasa 2/metabolismo , Nicotiana , Roxitromicina/uso terapéutico , Humo/efectos adversos , Alérgenos , Animales , Antiasmáticos/farmacología , Antibacterianos/farmacología , Asma/genética , Asma/metabolismo , Asma/patología , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Modelos Animales de Enfermedad , Eosinófilos/inmunología , Femenino , Histona Desacetilasa 2/genética , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Ratones Endogámicos BALB C , Neutrófilos/inmunología , Ovalbúmina , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Roxitromicina/farmacologíaRESUMEN
The care of 40 patients with primary liver cancer with obstructive jaundice treated with liver puncture bile drainage or biliary stent implantation was reported. Treated with the interventional therapy, patients were observed closely to identify symptoms of hepatic encephalopathy and pain; diet care was well performed. Bile drainage tube and skin acre were performed carefully. Liver function, bilirubin and other biochemical indicators were monitored; occurrence of bleeding, acute pancreatitis, biliary tract infection, leakage of ascites around drainage tube and other complication were observed with good discharge instruction. After this operation, three rounds of liver had poor function, and hepatic encephalopathy and death occurred during hospitalisation. Seven patients had bloody bile drainage fluid after operation; eight had increased blood amylase; nine had biliary infection and four had leakage of ascites around the drainage tube. After positive treatment and care, the situation was improved with varied degrees of jaundice increase.
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Procedimientos Quirúrgicos del Sistema Biliar , Carcinoma Hepatocelular/complicaciones , Ictericia Obstructiva/cirugía , Neoplasias Hepáticas/complicaciones , Cuidados Posoperatorios/métodos , Complicaciones Posoperatorias/epidemiología , Anciano , Drenaje , Femenino , Encefalopatía Hepática/epidemiología , Humanos , Ictericia Obstructiva/etiología , Masculino , Persona de Mediana Edad , Hemorragia Posoperatoria/epidemiología , StentsRESUMEN
Ulva pertusa lectin 1 (UPL1) is a N-acetyl-D-glucosamine (GlcNAc) binding lectin in marine green alga Ulva pertusa. Exogenous UPL1 colocalized with protein arginine methyltransferase 5 (PRMT5), methylosome protein 50 (MEP50), ß-actin and ß-tubulin, indicating the interaction of UPL1 with the methylosome and cytoskeleton. UPL1 delivery through adenovirus vector (Ad-UPL1) dramatically induced extracellularly regulated protein kinases 1/2 (ERK1/2) phosphorylation in liver cancer cell lines BEL-7404 and Huh7. Signaling pathways including p38 mitogen-activated protein kinase (MAPK), and Akt were also affected by Ad-UPL1 in a cell type dependent manner. MEK1/2 inhibitor U0126, as well as to a lesser extent p38 MAPK inhibitor SB203580 and phosphoinositide 3-kinase (PI3K) inhibitor LY294002, completely eliminated a higher molecular weight isoform of ß-tubulin induced by Ad-UPL1, and significantly enhanced the cytotoxicity of Ad-UPL1 in Huh7 cells, suggesting that the inhibition of MEK1/2, p38 MAPK, and PI3K enhanced antiproliferative effect of Ad-UPL1 possibly through regulating the modification of ß-tubulin. Ad-UPL1 completely inhibited the expression of autophagy-related factor Beclin1, but induced LC3-II expression in Huh7 cells. In addition, Ad-UPL1 significantly enhanced starvation induced survival suppression in Huh7 cells. Our data elucidated intracellular signaling pathways affected by exogenous UPL1, and may provide insights into a novel way of UPL1 delivery through adenovirus vectors combined with survival signaling inhibitors for cancer treatment.
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Adenoviridae/genética , Vectores Genéticos/metabolismo , Lectinas/metabolismo , Transducción de Señal , Ulva/metabolismo , Proteínas ras/metabolismo , Autofagia/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular , Humanos , Espacio Intracelular/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fracciones Subcelulares/metabolismo , Tubulina (Proteína)/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
BACKGROUND: Our previous studies have demonstrated that, through adenovirus mediated gene delivery, various exogenously expressed lectins elicited cytotoxicity to cancer cells, utilizing protein arginine methyltransferase 5 (PRMT5) as a common binding target. METHODS: In the present study, a FLAG tagged Anguilla japonica lectin 1 (AJL1) expression cassette was genetically harbored in a replication-defective adenovirus genome, forming Ad.FLAG-AJL1. The exogenous AJL1-induced cytotoxicity and the underlying mechanisms were analyzed. RESULTS: The exogenous AJL1 suppressed the proliferation of a variety of human cancer cells by inducing apoptosis. Caspase 9, Bcl-2, X-linked inhibitor of apoptosis protein, mitogen-activated protein kinase kinase 1/2-extracellular signal-regulated kinase and p38 mitogen-activated protein kinase were found to be responsible for the exogenous AJL1-induced cytotoxicity. AJL1 was further suggested to regulate PRMT5-E2F-1 pathway, a pathway shared by previously reported marine lectins Dicentrarchus labrax fucose binding lectin and Strongylocentrotus purpuratus rhamnose binding lectin. A localization study revealed that exogenous AJL1 widely distributed in the cell membrane and cytoplasm. CONCLUSIONS: The results of the present study suggest that the PRMT5-E2F-1 pathway may act as a common target for exogenous lectins including AJL1, and the cellular response to exogenous AJL1 may suggest a novel agent for cancer gene therapy. Copyright © 2016 John Wiley & Sons, Ltd.
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Apoptosis/genética , Proteínas de Peces/genética , Técnicas de Transferencia de Gen , Lectinas/genética , Proteína-Arginina N-Metiltransferasas/genética , Células A549 , Adenoviridae/genética , Anguilla/metabolismo , Animales , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular Tumoral , Supervivencia Celular/genética , Factor de Transcripción E2F1/genética , Factor de Transcripción E2F1/metabolismo , Proteínas de Peces/metabolismo , Humanos , Lectinas/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Unión Proteica , Proteína-Arginina N-Metiltransferasas/metabolismo , Transducción de Señal/genéticaRESUMEN
OBJECTIVE: To assess the variability of fractional exhaled nitric oxide (FeNO) and to explore the significances of FeNO in the diagnosis and treatment of asthma in pregnant women. METHODS: In a prospective study, 65 healthy pregnant women, 55 asthmatic non-pregnant women, 40 asthmatic pregnant women and 60 healthy non-pregnant women were enrolled in the study from Oct 2012 to Apr 2014.FeNO levels of the 4 groups were compared, and the variability of FeNO in different pregnancy periods of 15 healthy pregnant women were examined.We also analyzed the correlation between the level of FeNO, FEV1% pred, asthma control test (ACT) scores andblood eosinophils in patients of asthmatic pregnant women. RESULTS: The difference in the levels of FeNO between healthy pregnant women (12 ± 6) ppb and healthy non-pregnant women (14 ± 5) ppb were no significant (t = 0.508, P > 0.05) . The levels of FeNO in different pregnancy periods of healthy pregnant women were not significantly different (F = 0.656, P > 0.05). Compared with healthy pregnant women (12 ± 6) ppb, the level of FeNO was significantly higher in asthmatic pregnant patients (43 ± 21) ppb (t = 2.981, P < 0.05) , but the difference of the levels of FeNO between asthmatic non-pregnant (51 ± 32) ppb and pregnant patients (43 ± 21) ppb were no significant (t = 0.366, P > 0.05) . There was no significant correlation between FeNO level and FEV1% pred (r = 0.164, P > 0.05), nor between FeNO level and ACT scores (r = 0.272, P > 0.05) , but there was significant correlation between FeNO level and eosinophils (r = 0.723, P < 0.05). CONCLUSIONS: FeNO level is not influenced by pregnancy and different gestation periods.FeNO level in asthmatic pregnant women is increased, and FeNO is an important examination in the diagnosis of asthma during pregnancy.
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Asma/diagnóstico , Óxido Nítrico/análisis , Complicaciones del Embarazo/diagnóstico , Pruebas Respiratorias , Eosinófilos , Espiración , Femenino , Volumen Espiratorio Forzado , Humanos , Recuento de Leucocitos , Prednisona , Embarazo , Estudios ProspectivosRESUMEN
BACKGROUND: Roxithromycin (RXM) has been widely used in asthma treatment; however, the mechanism has not been fully understood. The aim of our study was to investigate the underlying mechanism of RXM treatment in mediating the effect of transforming growth factor (TGF)-ß1 on airway smooth muscle cells (ASMCs) proliferation and caveolinn-1 expression. METHODS: Firstly, the rat ovalbumin (OVA) model was built according to the previous papers. Rat ASMCs were prepared and cultured, and then TGF-ß1 production in ASMCs was measured by enzyme-linked immunosorbent assay (ELISA). Moreover, the proliferation of ASMCs was determined using cell counting kit (CCK-8) assay. Additionally, the expressions of caveolin-1, phosphorylated-ERK1/2 (p-ERK1/2) and phosphorylated-AKT (p-AKT) in ASMCs treated with or without PD98059 (an ERK1/2 inhibitor), wortannin (a PI3K inhibitor), ß-cyclodextrin (ß-CD) and RXM were measured by Western blot. Finally, data were evaluated using t-test or one-way ANOVA, and then a P value < 0.05 was set as a threshold. RESULTS: Compared with normal control, TGF-ß1 secretion was significantly increased in asthmatic ASMCs; meanwhile, TGF-ß1 promoted ASMCs proliferation (P < 0.05). However, ASMCs proliferation was remarkably inhibited by RXM, ß-CD, PD98059 and wortmannin (P < 0.05). Moreover, the expressions of p-ERK1/2 and p-AKT were increased and peaked at 20 min after TGF-ß1 stimulation, and then suppressed by RXM. Further, caveolin-1 level was down-regulated by TGF-ß1 and up-regulated by inhibitors and RXM. CONCLUSION: Our findings demonstrate that RXM treatment inhibits TGF-ß1-induced activation of ERK and AKT and down-regulation of caveolin-1, which may be the potential mechanism of RXM protection from chronic inflammatory diseases, including bronchial asthma.
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Caveolina 1/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Miocitos del Músculo Liso/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Roxitromicina/farmacología , Factor de Crecimiento Transformador beta1/antagonistas & inhibidores , Animales , Regulación hacia Abajo/efectos de los fármacos , Regulación hacia Abajo/fisiología , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Miocitos del Músculo Liso/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/metabolismo , Factor de Crecimiento Transformador beta1/farmacología , Resultado del TratamientoRESUMEN
Lectins exist widely in marine bioresources such as bacteria, algae, invertebrate animals and fishes. Some purified marine lectins have been found to elicit cytotoxicity to cancer cells. However, there are few reports describing the cytotoxic effect of marine lectins on cancer cells through virus-mediated gene delivery. We show here that a replication-deficient adenovirus-carrying gene encoding Haliotis discus discus sialic acid binding lectin (Ad.FLAG-HddSBL) suppressed cancer cell proliferation by inducing apoptosis, as compared to the control virus Ad.FLAG. A down-regulated level of anti-apoptosis factor Bcl-2 was suggested to be responsible for the apoptosis induced by Ad.FLAG-HddSBL infection. Further subcellular localization studies revealed that HddSBL distributed in cell membrane, ER, and the nucleus, but not in mitochondria and Golgi apparatus. In contrast, a previously reported mannose-binding lectin Pinellia pedatisecta agglutinin entered the nucleus as well, but did not distribute in inner membrane systems, suggesting differed intracellular sialylation and mannosylation, which may provide different targets for lectin binding. Further cancer-specific controlling of HddSBL expression and animal studies may help to provide insights into a novel way of anti-cancer marine lectin gene therapy. Lectins may provide a reservoir of anti-cancer genes.
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Adenoviridae/genética , Apoptosis , Terapia Genética , Neoplasias/terapia , Lectinas Similares a la Inmunoglobulina de Unión a Ácido Siálico/genética , Línea Celular Tumoral , Humanos , Ácido N-Acetilneuramínico/metabolismo , Neoplasias/patologíaRESUMEN
Chitin and its deacetylated form, chitosan, have demonstrated remarkable versatility in the realm of biomaterials. Their exceptional biocompatibility, antibacterial properties, pro- and anticoagulant characteristics, robust antioxidant capacity, and anti-inflammatory potential make them highly sought-after in various applications. This review delves into the mechanisms underlying chitin/chitosan's biological activity and provides a comprehensive overview of their derivatives in fields such as tissue engineering, hemostasis, wound healing, drug delivery, and hemoperfusion. However, despite the wealth of studies on chitin/chitosan, there exists a notable trend of homogeneity in research, which could hinder the comprehensive development of these biomaterials. This review, taking a clinician's perspective, identifies current research gaps and medical challenges yet to be addressed, aiming to pave the way for a more sustainable future in chitin/chitosan research and application.
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Materiales Biocompatibles , Quitina , Quitosano , Ingeniería de Tejidos , Quitosano/química , Quitosano/farmacología , Quitina/química , Humanos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Animales , Ingeniería de Tejidos/métodos , Cicatrización de Heridas/efectos de los fármacos , Sistemas de Liberación de Medicamentos , Antibacterianos/química , Antibacterianos/farmacología , Hemostasis/efectos de los fármacosRESUMEN
IMPORTANCE: messenger RNA (mRNA) vaccines are a key technology in combating existing and emerging infectious diseases. However, the inherent instability of mRNA and the nonspecificity of lipid nanoparticle-encapsulated (LNP) delivery systems result in the need for cold storage and a relatively short-duration immune response to mRNA vaccines. Herein, we develop a novel vaccine in the form of circRNAs encapsulated in LNPs, and the circular structure of the circRNAs enhances their stability. Lyophilization is considered the most effective method for the long-term preservation of RNA vaccines. However, this process may result in irreversible damage to the nanoparticles, particularly the potential disruption of targeting modifications on LNPs. During the selection of lymph node-targeting ligands, we found that LNPs modified with mannose maintained their physical properties almost unchanged after lyophilization. Additionally, the targeting specificity and immunogenicity remained unaffected. In contrast, even with the addition of cryoprotectants such as sucrose, the physical properties of LNPs were impaired, leading to an obvious decrease in immunogenicity. This may be attributed to the protective role of mannose on the surface of LNPs during lyophilization. Freshly prepared and lyophilized mLNP-circRNA vaccines elicited comparable immune responses in both the rabies virus model and the SARS-CoV-2 model. Our data demonstrated that mLNP-circRNA vaccines elicit robust immune responses while improving stability after lyophilization, with no compromise in tissue targeting specificity. Therefore, mannose-modified LNP-circRNA vaccines represent a promising vaccine design strategy.
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ARN Circular , Vacunas , Manosa/química , Vacunas/genética , Inmunidad , Liofilización , ARN Mensajero/genéticaRESUMEN
Although protein subunit vaccines generally have acceptable safety profiles with precise antigenic content, limited immunogenicity can lead to unsatisfactory humoral and cellular immunity and the need for vaccine adjuvants and delivery system. Herein, we assess a vaccine adjuvant system comprising Quillaja Saponaria-21(QS-21) and cobalt porphyrin polymeric micelles that enabling the display of His-tagged antigen on its surface. The nanoscale micelles promote antigen uptake and dendritic cell activation to induce robust cytotoxic T lymphocyte response and germinal center formation. Using the recombinant protein antigens from influenza A and rabies virus, the micelle adjuvant system elicited robust antiviral responses and protected mice from lethal challenge. In addition, this system could be combined with other antigens to induce high titers of neutralizing antibodies in models of three highly pathogenic viral pathogens: Ebola virus, Marburg virus, and Nipah virus. Collectively, our results demonstrate this polymeric micelle adjuvant system can be used as a potent nanoplatform for developing antiviral vaccine countermeasures that promote humoral and cellular immunity.
Asunto(s)
Vacunas Virales , Animales , Ratones , Vacunas Virales/inmunología , Vacunas Virales/administración & dosificación , Micelas , Adyuvantes de Vacunas/administración & dosificación , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/farmacología , Anticuerpos Antivirales/inmunología , Virus de la Rabia/inmunología , Células Dendríticas/inmunología , Polímeros/química , Femenino , Ratones Endogámicos C57BL , Virus de la Influenza A/inmunología , Ratones Endogámicos BALB CRESUMEN
For coal and gangue, intelligent sorting processes for separation, the use of coal and gangue mineral components with different fundamental differences, and the study of different properties of minerals and coal with different scales and density regarding the gray value change law are presented. The results show that the gray value of single minerals and mixed minerals gradually decreases with the increase of their thickness and density. The greater the density of minerals, the smaller the gray value at the same thickness, and the same rule applies to different coal ranks. Via regression analysis methods, the values of the regression equation parameter a of pure minerals for graphite, quartz, kaolinite, and montmorillonite are 59.25, 65.69, 61.61, and 58.02 in the high-energy region, respectively. In the low-energy region, they are 174.95, 177.31, 186.95, and 161.81. For the regression equation parameter of mixed minerals in the form of two mixed minerals (graphite and quartz, kaolinite, or montmorillonite) and three kinds of mineral mixing (graphite-kaolinite and quartz; graphite-montmorillonite and quartz; graphite-kaolinite and montmorillonite), the gray values are 151.12, 156.00, 153.13,152.43, 152.98, and 151.98 in the high-energy region, respectively; in the low-energy region, they are 193.34, 201.34, 192.93, 191.26, 194.68, and 193.08. The phenomenon for the gray range of two kinds of single minerals locates in the range of mixed minerals that was formed from a single mineral observed after the regression equation of mixed mineral was verified by a single mineral, which agrees with the X-ray recognition pattern. In the end, as the density of coking coal, fat coal, and gas coal increases, the gray value decreases, which was in agreement with single- and mixed-mineral analyses.
RESUMEN
Postoperative peritoneal adhesions are common complications caused by abdominal and pelvic surgery, which seriously impact the quality of life of patients and impose additional financial burdens. Using of biomedical materials as physical barriers to completely isolate the traumatic organ and injured tissue is an optimal strategy for preventing postoperative adhesions. However, the limited efficacy and difficulties in the complete degradation or integration of biomedical materials with living tissues restrict the application of these materials. In this study, novel chitin-based crosslinked hydrogels with appropriate mechanical properties and flexibilities were developed using a facile and green strategy. The developed hydrogels simultaneously exhibited excellent biocompatibilities and resistance to nonspecific protein adsorption and NIH/3T3 fibroblast adhesion. Furthermore, these hydrogels were biodegradable and could be completely integrated into the native extracellular matrix. The chitin-based crosslinked hydrogels also effectively inhibited postoperative peritoneal adhesions in rat models of adhesion and recurrence. Therefore, these novel chitin-based crosslinked hydrogels are excellent candidate physical barriers for the efficient prevention of postoperative peritoneal adhesions and provide a new anti-adhesion strategy for biomedical applications.