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Despite the development of several anticancer treatments, there remains a need for new drugs that can overcome resistance and reduce side effects. While the medicinal herb Hydrocotyle umbellata (H. umbellata) has been used to relieve pain and inflammation, its antitumor properties have not yet been explored. In this study, we investigated the anticarcinogenic potential of H. umbellata extract (HUE) and its major components, as well as the underlying molecular mechanisms. Our results showed that HUE inhibited the growth of various tumor cell lines, including B16F10, without affecting non-cancer cells. Furthermore, HUE was effective in treating and preventing tumor growth in mice. Our mechanistic studies revealed that HUE inhibited cellular respiration, thereby reducing tumor cell proliferation. When combined with 2-deoxy-D-glucose, HUE demonstrated an enhanced anticancer effect by increasing the rate apoptosis. Analysis of the ethyl acetate and n-butanol fractions of HUE identified 1,3,4-trihydroxy-2-butanyl-α-d-glucopyranoside and caffeoylquinic acid derivatives as the major components responsible for the observed anticancer effects. In conclusion, our findings suggest that HUE and its two major components have the potential to be developed as effective therapeutic agents for a wide range of tumors by targeting cancer cell metabolism.
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BACKGROUND: Whether deep learning models using clinical data and brain imaging can predict the long-term risk of major adverse cerebro/cardiovascular events (MACE) after acute ischaemic stroke (AIS) at the individual level has not yet been studied. METHODS: A total of 8590 patients with AIS admitted within 5 days of symptom onset were enrolled. The primary outcome was the occurrence of MACEs (a composite of stroke, acute myocardial infarction or death) over 12 months. The performance of deep learning models (DeepSurv and Deep-Survival-Machines (DeepSM)) and traditional survival models (Cox proportional hazards (CoxPH) and random survival forest (RSF)) were compared using the time-dependent concordance index ([Formula: see text] index). RESULTS: Given the top 1 to all 60 clinical factors according to feature importance, CoxPH and RSF yielded [Formula: see text] index of 0.7236-0.8222 and 0.7279-0.8335, respectively. Adding image features improved the performance of deep learning models and traditional models assisted by deep learning models. DeepSurv and DeepSM yielded the best [Formula: see text] index of 0.8496 and 0.8531 when images were added to all 39 relevant clinical factors, respectively. In feature importance, brain image was consistently ranked highly. Deep learning models automatically extracted the image features directly from personalised brain images and predicted the risk and date of future MACEs at the individual level. CONCLUSIONS: Deep learning models using clinical data and brain images could improve the prediction of MACEs and provide personalised outcome prediction for patients with AIS. Deep learning models will allow us to develop more accurate and tailored prognostic prediction systems that outperform traditional models.
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Isquemia Encefálica , Aprendizaje Profundo , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/diagnóstico por imagen , Isquemia Encefálica/diagnóstico por imagen , PronósticoRESUMEN
Affinity-based ultrafiltration-mass spectrometry coupled with ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry was utilised for the structural identification of direct tyrosinase ligands from a crude Pseudolysimachion rotundum var. subintegrum extract. False positives were recognised by introducing time-dependent inhibition in the control for comparison. The P. rotundum extract contained nine main metabolites in the UPLC-QTOF-MS chromatogram. However, four metabolites were reduced after incubation with tyrosinase, indicating that these metabolites were bound to tyrosinase. The IC50 values of verproside (1) were 31.2 µM and 197.3 µM for mTyr and hTyr, respectively. Verproside showed 5.6-fold higher efficacy than that of its positive control (kojic acid in hTyr). The most potent tyrosinase inhibitor, verproside, features a 3,4-dihydroxybenzoic acid moiety on the iridoid glycoside and inhibits tyrosinase in a time-dependent and competitive manner. Among these three compounds, verproside is bound to the active site pocket with a docking energy of -6.9 kcal/mol and four hydrogen bonding interactions with HIS61 and HIS85.
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Glucósidos Iridoides , Monofenol Monooxigenasa , Humanos , Cromatografía Liquida , GlicósidosRESUMEN
Asthma is a chronic inflammatory lung disease that causes respiratory difficulties. Black ginseng extract (BGE) has preventative effects on respiratory inflammatory diseases such as asthma. However, the pharmacological mechanisms behind the anti-asthmatic activity of BGE remain unknown. To investigate the anti-asthmatic mechanism of BGE, phorbol 12-myristate 13-acetate plus ionomycin (PMA/Iono)-stimulated mouse EL4 cells and ovalbumin (OVA)-induced mice with allergic airway inflammation were used. Immune cells (eosinophils/macrophages), interleukin (IL)-4, -5, -13, and serum immunoglobulin E (IgE) levels were measured using an enzyme-linked immunosorbent assay. Inflammatory cell recruitment and mucus secretion in the lung tissue were estimated. Protein expression was analyzed via Western blotting, including that of inducible nitric oxide synthase (iNOS) and the activation of protein kinase C theta (PKCθ) and its downstream signaling molecules. BGE decreased T helper (Th)2 cytokines, serum IgE, mucus secretion, and iNOS expression in mice with allergic airway inflammation, thereby providing a protective effect. Moreover, BGE and its major ginsenosides inhibited the production of Th2 cytokines in PMA/Iono-stimulated EL4 cells. In EL4 cells, these outcomes were accompanied by the inactivation of PKCθ and its downstream transcription factors, such as nuclear factor of activated T cells (NFAT), nuclear factor kappa B (NF-κB), activator of transcription 6 (STAT6), and GATA binding protein 3 (GATA3), which are involved in allergic airway inflammation. BGE also inhibited the activation of PKCθ and the abovementioned transcriptional factors in the lung tissue of mice with allergic airway inflammation. These results highlight the potential of BGE as a useful therapeutic and preventative agent for allergic airway inflammatory diseases such as allergic asthma.
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Antiasmáticos , Asma , Hipersensibilidad , Panax , Animales , Ratones , Antiasmáticos/farmacología , Antiasmáticos/uso terapéutico , Interleucina-4/metabolismo , Asma/metabolismo , Pulmón/metabolismo , Citocinas/metabolismo , Hipersensibilidad/metabolismo , Transducción de Señal , Inflamación/metabolismo , Inmunoglobulina E , Panax/metabolismo , Ovalbúmina , Ratones Endogámicos BALB C , Modelos Animales de EnfermedadRESUMEN
The recently defined type of cell death ferroptosis has garnered significant attention as a potential new approach to cancer treatment owing to its more immunogenic nature when compared with apoptosis. Ferroptosis is characterized by the depletion of glutathione (GSH)/glutathione peroxidase-4 (GPx4) and iron-dependent lipid peroxidation. Diplacone (DP), a geranylated flavonoid compound found in Paulownia tomentosa fruit, has been identified to have anti-inflammatory and anti-radical activity. In this study, the potential anticancer activity of DP was explored against A549 human lung cancer cells. It was found that DP induced a form of cytotoxicity distinct from apoptosis, which was accompanied by extensive mitochondrial-derived cytoplasmic vacuoles. DP was also shown to increase mitochondrial Ca2+ influx, reactive oxygen species (ROS) production, and mitochondrial permeability transition (MPT) pore-opening. These changes led to decreases in mitochondrial membrane potential and DP-induced cell death. DP also induced lipid peroxidation and ATF3 expression, which are hallmarks of ferroptosis. The ferroptosis inhibitors ferrostatin-1 and liproxstatin-1 were effective in counteracting the DP-mediated ferroptosis-related features. Our results could contribute to the use of DP as a ferroptosis-inducing agent, enabling studies focusing on the relationship between ferroptosis and the immunogenic cell death of cancer cells.
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Ferroptosis , Humanos , Necrosis por Permeabilidad de la Transmembrana Mitocondrial , Frutas/metabolismo , Muerte Celular/fisiología , Especies Reactivas de Oxígeno/metabolismo , Glutatión/metabolismo , Peroxidación de Lípido , Poro de Transición de la Permeabilidad Mitocondrial/metabolismoRESUMEN
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease which causes breathing problems. YPL-001, consisting of six iridoids, has potent inhibitory efficacy against COPD. Although YPL-001 has completed clinical trial phase 2a as a natural drug for COPD treatment, the most effective iridoid in YPL-001 and its mechanism for reducing airway inflammation remain unclear. To find an iridoid most effectively reducing airway inflammation, we examined the inhibitory effects of the six iridoids in YPL-001 on TNF or PMA-stimulated inflammation (IL-6, IL-8, or MUC5AC) in NCI-H292 cells. Here, we show that verproside among the six iridoids most strongly suppresses inflammation. Both TNF/NF-κB-induced MUC5AC expression and PMA/PKCδ/EGR-1-induced IL-6/-8 expression are successfully reduced by verproside. Verproside also shows anti-inflammatory effects on a broad range of airway stimulants in NCI-H292 cells. The inhibitory effect of verproside on the phosphorylation of PKC enzymes is specific to PKCδ. Finally, in vivo assay using the COPD-mouse model shows that verproside effectively reduces lung inflammation by suppressing PKCδ activation and mucus overproduction. Altogether, we propose YPL-001 and verproside as candidate drugs for treating inflammatory lung diseases that act by inhibiting PKCδ activation and its downstream pathways.
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Interleucina-6 , Enfermedad Pulmonar Obstructiva Crónica , Animales , Humanos , Ratones , Células Epiteliales/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Interleucina-6/metabolismo , Iridoides/farmacología , Iridoides/uso terapéutico , Iridoides/metabolismo , Pulmón/metabolismo , FN-kappa B/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Proteína Quinasa C-delta/metabolismoRESUMEN
Background and Objectives: Recent studies revealed that the extremely low activity of serum alanine aminotransferase (ALT) is associated with frailty and contributes to increased mortality after acute physical stress. We aimed to investigate whether the extremely low activity of serum ALT (<10 U/L) at the time of diagnosis can be used to predict overall-cause mortality in elderly patients that underwent percutaneous coronary intervention (PCI) after acute coronary syndrome (ACS) diagnosis. Materials and Methods: A retrospective medical record review was performed on 1597 patients diagnosed with ACS who underwent PCI at a single university hospital from February 2014 to March 2020. The associations between the extremely low activity of serum ALT and mortality were assessed using a stepwise Cox regression (forward: conditional). Results: A total of 210 elderly patients were analyzed in this study. The number of deaths was 64 (30.5%), the mean survival time was 25.0 ± 18.9 months, and the mean age was 76.9 ± 7.6 years. The mean door-to-PCI time was 74.0 ± 20.9 min. The results of stepwise Cox regression analysis showed that the extremely low activity of serum ALT (adjusted hazard ratio: 5.157, 95% confidence interval: 3.001-8.862, p < 0.001) was the independent risk factor for long-term overall-cause mortality in the elderly who underwent PCI after ACS diagnosis. Conclusions: The extremely low activity of serum ALT at ACS diagnosis is a significant risk factor for increased long-term overall-cause mortality in the elderly who underwent PCI after ACS diagnosis. It is noteworthy that a simple laboratory test at the time of diagnosis was found to be a significant risk factor for mortality.
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Síndrome Coronario Agudo , Intervención Coronaria Percutánea , Anciano , Anciano de 80 o más Años , Humanos , Síndrome Coronario Agudo/mortalidad , Alanina Transaminasa/sangre , Intervención Coronaria Percutánea/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
In this work, we develop an environmental-friendly approach to produce organic-inorganic hybrid MAPbBr3(MA = CH3NH3) perovskite nanocrystals (PeNCs) and PMMA-MAPbBr3NC films with excellent compression-resistant PL characteristics. Deionized water is used as the solvent to synthesize MAPbBr3powder instead of conventionally-used hazardous organic solvents. The MAPbBr3PeNCs derived from the MAPbBr3powder exhibit a high photoluminescence quantum yield (PLQY) of 93.86%. Poly(methyl methacrylate) (PMMA)-MAPbBr3NC films made from the MAPbBr3PeNCs retain â¼97% and â¼91% of initial PL intensity after 720 h aging in ambient environment at 50 °C and 70 °C, respectively. The PMMA-MAPbBr3NC films also exhibit compression-resistant photoluminescent characteristics in contrast to the PMMA-CsPbBr3NC films under a compressive stress of 1.6 MPa. The PMMA-MAPbBr3NC film integrated with a red emissive film and a blue light emitting source achieves an LCD backlight of â¼114% color gamut of National Television System Committee (NTSC) 1953 standard.
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The bioactive components of Canavalia lineata (Thunb.) DC pods were investigated using bioactivity-guided isolation, and the chemical structures of flavonoids 1-3, isoflavonoid derivatives 4-11, and phenolic compounds 12 and 13 were identified by comparing NMR, MS, and CD spectral data with previously reported spectroscopic data. Compounds 1-13 were evaluated for their anti-inflammatory effects on LPS-stimulated RAW264.7 macrophages. Among these compounds, the isoflavonoid derivative cajanin (7) exhibited the most potent anti-inflammatory activity (IC50 of NO = 19.38 ± 0.05 µM; IC50 of IL-6 = 7.78 ± 0.04 µM; IC50 of TNF-α = 26.82 ± 0.11 µM), exerting its anti-inflammatory effects by suppressing the activation and nuclear translocation of the transcription factor NF-κB by phosphorylating IκB and p65. These results suggested that cajanin (7) may be a potential candidate for improving the treatment of inflammatory diseases.
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Canavalia , Lipopolisacáridos , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Inflamación/tratamiento farmacológico , Lipopolisacáridos/farmacología , Macrófagos , Ratones , FN-kappa B/farmacología , Óxido Nítrico/farmacología , Células RAW 264.7RESUMEN
(1) Background: Progression of chronic obstructive pulmonary disease (COPD) leads to irreversible lung damage and inflammatory responses; however, biomarker discovery for monitoring of COPD progression remains challenging. (2) Methods: This study evaluated the metabolic mechanisms and potential biomarkers of COPD through the integrated analysis and receiver operating characteristic (ROC) analysis of metabolic changes in lung, plasma, and urine, and changes in morphological characteristics and pulmonary function in a model of PPE/LPS-induced COPD exacerbation. (3) Results: Metabolic changes in the lungs were evaluated as metabolic reprogramming to counteract the changes caused by the onset of COPD. In plasma, several combinations of phenylalanine, 3-methylhistidine, and polyunsaturated fatty acids have been proposed as potential biomarkers; the α-aminobutyric acid/histidine ratio has also been reported, which is a novel candidate biomarker for COPD. In urine, a combination of succinic acid, isocitric acid, and pyruvic acid has been proposed as a potential biomarker. (4) Conclusions: This study proposed potential biomarkers in plasma and urine that reflect altered lung metabolism in COPD, concurrently with the evaluation of the COPD exacerbation model induced by PPE plus LPS administration. Therefore, understanding these integrative mechanisms provides new insights into the diagnosis, treatment, and severity assessment of COPD.
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Lipopolisacáridos , Enfermedad Pulmonar Obstructiva Crónica , Animales , Biomarcadores/metabolismo , Modelos Animales de Enfermedad , Lipopolisacáridos/metabolismo , Pulmón/metabolismo , Ratones , Equipo de Protección Personal , Enfermedad Pulmonar Obstructiva Crónica/diagnósticoRESUMEN
A biological photoinduced fermentation process provides an alternative to traditional hydrogen productions. In this study, biohydrogen production was investigated at near IR region coupled to a near-field enhancement by silica-core gold-shell nanoparticles (NPs) over a range of acetate concentrations (5-40 mM) and light intensities (11-160 W/m2). The kinetic data were modeled using modified Monod equations containing light intensity effects. The yields of H2 and CO2 produced per acetate were determined as 2.31 mol-H2/mol-Ac and 0.83 mol-CO2/mol-Ac and increased to 4.38 mmol-H2/mmol-Ma and 2.62 mmol-CO2/mmol-Ma when malate was used. Maximum increases in H2 and CO2 productions by 115% and 113% were observed by adding NPs without affecting the bacterial growth rates (6.1-8.2 mg-DCM/L/hour) while the highest hydrogen production rate was determined as 0.81 mmol/L/hour. Model simulations showed that the energy conversion efficiency increased with NPs concentration but decreased with the intensity. Complete hydrogenation application was demonstrated with toxic 2-chlorobiphenyl using Pd catalysts.
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Signal transducer and activator of transcription 3 (STAT3) is aberrantly activated in many human cancers. We tried to find STAT3 inhibitors from natural sources and found that Xanthium fruit extracts decreased phosphorylation of STAT3-Y705. 8-Epi-xanthatin (EXT) was isolated from the extracts. When DU145 cancer cells were treated with EXT, p-STAT3-Y705 was decreased with an IC50 of 3.2 µM. EXT decreased the expression of STAT3 target genes, such as cyclin A, cyclin D1, and BCL-2, and induced PARP cleavage, indicating apoptotic cell death. Downregulation of EXT-induced p-STAT3-Y705 was rescued by pretreating DU145 cells with antioxidants, such as N-acetyl-L-cysteine (NAC), indicating that reactive oxygen species (ROS) were involved in the EXT-induced inhibition of STAT3 activation. Furthermore, we proved the association of EXT with STAT3 protein by using a drug affinity responsive target stability (DARTS) assay and a cellular thermal shift assay (CETSA). EXT inhibited proliferation of DU145 cells with a GI50 of 6 µM and reduced tumor growth in mice xenografted with DU145 cells. Immunoblotting showed that phosphorylation of STAT3-Y705 was lower in EXT-treated tumor tissue than in control tissues. Collectively, we found that EXT binds to, and inhibits, STAT3 activation and could be a lead compound for anticancer therapy.
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Antineoplásicos Fitogénicos/uso terapéutico , Frutas/química , Furanos/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Factor de Transcripción STAT3/metabolismo , Animales , Antineoplásicos Fitogénicos/farmacología , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Femenino , Furanos/farmacología , Humanos , Masculino , Ratones , Ratones Desnudos , Especies Reactivas de Oxígeno/metabolismo , Transducción de SeñalRESUMEN
Longifolioside A is an iridoid glucoside compound isolated from Pseudolysimachion rotundum var. subintegrum, which has been used in traditional herbal medicines to treat respiratory inflammatory diseases. Logifolioside A is a potent antioxidant; however, its underlying pharmacological mechanisms of action in inflammatory diseases are unknown. Here, we investigated the inhibitory effects of longifolioside A in lipopolysaccharide (LPS)-stimulated toll-like receptor 4 (TLR4) signal transduction systems using human THP-1 macrophages and HEK293 cells stably expressing human TLR4 protein (293/HA-hTLR4). Longifolioside A significantly reduced the release of inflammatory cytokines such as interleukin (IL)-6, -8, and tumor necrosis factor (TNF)-α in LPS-stimulated THP-1 macrophages. Furthermore, longifolioside A inhibited the expression of inflammatory mediator genes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 that produce nitric oxide (NO) and prostaglandin E2 (PGE2), respectively. Longifolioside A suppressed the phosphorylation of PKCδ, IRAK4, IKKα/ß, IκBα, and mitogen-activated protein (MAP) kinases (ERK 1/2 and JNK, but not p38), thereby inactivating the nuclear localization of NF-κB and AP-1, and thus decreasing the expression of inflammatory response genes. Notably, longifolioside A disrupted the interaction between human TLR4 and the TIR domain-containing adaptor protein (TIRAP), an early step during TLR4 activation, thereby reducing IL-8 secretion in 293/HA-hTLR4 cells. This inhibitory effect was comparable to that of TAK-242 (a TLR4 inhibitor, or resatorvid). Our results indicate that longifolioside A prevents inflammatory response by suppressing TLR4 activation required for NF-κB and AP-1 activation.
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Mediadores de Inflamación/metabolismo , Macrófagos/efectos de los fármacos , Proteína Quinasa C-delta/antagonistas & inhibidores , Receptor Toll-Like 4/antagonistas & inhibidores , Citocinas/metabolismo , Activación Enzimática/efectos de los fármacos , Células HEK293 , Humanos , Interleucina-8/metabolismo , Lipopolisacáridos/farmacología , Macrófagos/enzimología , Macrófagos/metabolismo , Glicoproteínas de Membrana/antagonistas & inhibidores , FN-kappa B/metabolismo , Proteína Quinasa C-delta/metabolismo , Receptores de Interleucina-1/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Células THP-1 , Factor de Transcripción AP-1/metabolismoRESUMEN
Ruthenium(II) complexes developed for photodynamic therapy (PDT) are almost exclusively tris-bidentate systems with C2 or D3 symmetry. This is due to the fact that this structural framework commonly produces long-lived excited states, which, in turn, allow for the generation of large amounts of singlet oxygen (1O2) and other reactive oxygen species. Complexes containing tridentate ligands would be advantageous for biological applications as they are generally achiral (D2d or C2v symmetry), which eliminates the possibility of multiple isomers which could exhibit potentially different interactions with chiral biological entities. However, Ru(II) complexes containing tridentate ligands are rarely studied as candidates for photobiological applications, such as PDT, since they almost exclusively exhibit low quantum yields and very short excited-state lifetimes and, thus, are not capable of generating sufficient 1O2 or engaging in electron transfer reactions. Here, we report a proof-of-concept approach to make bis-tridentate Ru(II) complexes useful for PDT applications by altering their photophysical properties through the inclusion of N-heterocyclic carbene (NHC) ligands. Three NHC and two terpyridine ligands were studied to evaluate the effects of structural and photophysical modulations of bis-substituted Ru(II) complexes. The NHC complexes were found to have superior excited-state lifetimes, 1O2 production, and photocytotoxicity. To the best of our knowledge, these complexes are the most potent light-activated bis-tridentate complexes reported.
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Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/efectos de la radiación , Línea Celular Tumoral , Complejos de Coordinación/síntesis química , Complejos de Coordinación/efectos de la radiación , ADN/metabolismo , Roturas del ADN de Cadena Simple/efectos de la radiación , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ligandos , Luz , Prueba de Estudio Conceptual , Rutenio/química , Oxígeno Singlete/metabolismoRESUMEN
Upconverting nanoparticles (UCNPs) composed of NaYF4 and doped with photoactive Yb3+ and Er3+ (NaYF4:Yb/Er) are highly desirable for many biological applications, but obtaining stable dispersions of UCNPs is challenging. Traditional synthetic methods often use complicated synthetic steps, produce toxic side products, and require post modifications to make UCNPs more dispersible in aqueous solutions. In this study, we demonstrate that laser ablation in liquid (LAL) is a novel approach to synthesize water-dispersible and -stable UCNPs with advantages of particle-size tuning, in situ coating of UCNPs with capping agents, no use of toxic or high boiling point solvents, and short reaction times. NaYF4:Yb/Er UCNPs were produced through LAL of annealed targets using water as the liquid, and their compositions and properties were investigated at a laser fluence of 0.57 J cm-2-6.22 J cm-2 by direct capping with citric acid and ethylene glycol and by comparing with the UCNPs prepared from the traditional hydrothermal method. Low laser fluences produced polydisperse particles consisting of no photoactive species through a thermal evaporation mechanism, while high laser fluences generated UCNPs with more uniform morphologies and compositions similar to the target material by an explosive ejection mechanism. The inclusion of capping agents during LAL allowed for direct coating of the UCNP surface without the need of post modifications, and the concentrations of capping agents affected the UCNP photoluminescence lifetimes. As compared to the hydrothermal method, the LAL-prepared samples showed better size control and no degradation of the capping agents.
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PURPOSE: Forms of intraoperative neurophysiologic monitoring (IONM), including somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs), have been widely used in the field of neurosurgery. This study aimed to evaluate the diagnostic efficacy of IONM in identifying intraoperative events and predicting postoperative neurologic deficits in neurovascular intervention. METHODS: From January 2013 to December 2016, we retrospectively reviewed patients who underwent neurovascular intervention under general anesthesia with the use of IONM. Associations between significant changes in MEPs or SSEPs which were defined as a decrease more than 50% in amplitude and/or an increase more than 10% in latency and any identifiable intraoperative events and/or postoperative neurologic deficits were determined. The sensitivity and specificity values for both MEPs and SSEPs were calculated. RESULTS: In total, 578 patients (175 men and 403 women) were included. Their mean age was 59.5 years. SSEP changes occurred in 1% (n = 6), and MEP changes occurred in 1.2% (n = 7). Four patients suffered postoperative neurologic deficits, and identifiable intraoperative events were observed in seven patients. Both SSEP and MEP changes were significantly associated with identifiable intraoperative events and/or postoperative neurologic deficits (p < 0.001, Fisher's exact test). The calculated sensitivity and specificity of MEP monitoring were 50 and 99.5%, respectively. The sensitivity and specificity of SSEP monitoring were both 100%. CONCLUSION: Intraoperative SSEP monitoring might be a reliable and sensitive method to surveil neurologic complications during neurovascular intervention. Intraoperative MEP monitoring appears to be feasible. However, it is unclear whether MEP monitoring has any additive benefit over SSEP monitoring.
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Potenciales Evocados Motores/fisiología , Potenciales Evocados Somatosensoriales/fisiología , Monitorización Neurofisiológica Intraoperatoria/métodos , Procedimientos Neuroquirúrgicos/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anestesia General , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Broussonetia papyrifera has been used as a diuretic, tonic and suppressor of edema. Bioactivity-guided fractionation and metabolite investigation of root bark extracts of this plant resulted in the isolation and identification of six 1,3-diphenylpropanes (1, 2, 8, 10, 17, 20), flavanone (3), two chalcones (4, 5), five flavans (6, 11, 14-16), dihydroflavonol (7) and five flavonols (9, 12, 13, 18, 19), including five new compounds (5, 7, 8, 19, 20) that inhibit NO production in LPS-induced RAW264.7 cells. The structures of compounds 1-20 were elucidated on the basis of spectroscopic data (1D and 2D NMR, MS, MS/MS, and HRMS). In particular, compounds 3, 5, 7, 12, and 20 exhibited significant inhibitory effects on the NO, iNOS, and pro-inflammatory cytokine (TNF-α and IL-6) production. Therefore, this study suggests that the flavonoid-rich products of B. papyrifera, including the new compounds, could be valuable candidates for the development of pharmaceuticals or functional foods in the prevention and treatment of anti-inflammatory disease.
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Antiinflamatorios/farmacología , Broussonetia/química , Flavonoides/farmacología , Corteza de la Planta/química , Animales , Antiinflamatorios/aislamiento & purificación , Supervivencia Celular/efectos de los fármacos , Ciclooxigenasa 2/genética , Relación Dosis-Respuesta a Droga , Flavonoides/aislamiento & purificación , Expresión Génica/efectos de los fármacos , Interleucina-6/antagonistas & inhibidores , Lipopolisacáridos , Medicina Tradicional Coreana , Ratones , Estructura Molecular , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/genética , Células RAW 264.7 , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
To investigate the relation of physical functions to health-related quality of life (HRQOL), physical activity and fatness of patients during breast cancer treatment within 1 year after surgery. We retrospectively reviewed the patients with breast cancer at the cancer rehabilitation clinic within 1 year after surgery. Physical function assessment included aerobic capacity, muscle strength, flexibility and oedema. Physical activity was assessed using the International Physical Activity Questionnaire-Short Form, and HRQOL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. Stepwise multivariate linear regression analysis was used to find the association factors. Of the physical functions in subjects, aerobic capacity was 88.64% compared to predictive value. The mean overall QOL was 60.82 ± 20.98. The mean physical activity was 2,245.49 ± 3,687.66 MET/week and 39 patients (41.5%) were inactive. As the results of stepwise multivariate linear regression analysis, aerobic capacity was a significant factor of HRQOL and physical activity. The impairment of physical functions affects the HRQOL of patients within 1 year after breast cancer surgery. Among the physical functions, the decrease in aerobic capacity was significantly associated with the decrease in the overall QOL of the patients.
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Neoplasias de la Mama/fisiopatología , Tolerancia al Ejercicio/fisiología , Ejercicio Físico/fisiología , Fuerza Muscular/fisiología , Calidad de Vida , Actividades Cotidianas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Composición Corporal/fisiología , Neoplasias de la Mama/psicología , Neoplasias de la Mama/cirugía , Ejercicio Físico/psicología , Fatiga/fisiopatología , Fatiga/psicología , Femenino , Estado de Salud , Humanos , Mastectomía Radical Modificada/estadística & datos numéricos , Mastectomía Segmentaria/estadística & datos numéricos , Persona de Mediana Edad , Complicaciones Posoperatorias/fisiopatología , Complicaciones Posoperatorias/psicología , Estudios RetrospectivosRESUMEN
Fluorescent carbon nanodots (CNDs) were synthesized in oxidized and reduced forms and were analyzed at the single-particle level. Images of single CNDs at different excitation energies revealed significant heterogeneity in the lower energy trap sites between particles. We observed that a high percentage of reduced CND particles transitioned between multiple fluorescence intensity levels indicative of multichromophoric systems. Despite this behavior, individual CNDs exhibit single-step photobleaching and transient blinking to the background level suggesting single-molecule behavior.
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Cerebrolysin concentrate is a medication whose main active ingredient is brain-derived neurotrophic factor. It has been reported to help in the restoration of cognitive function and overall physical function after brain injuries. We present the case of a 72-year-old man with severe oral apraxia due to a left middle cerebral artery ischemic stroke involving the left insular cortex. He was being tube fed due to severe oral apraxia with cognitive decline that made it difficult for him to even imitate simple oral movements. The patient initially had impaired consciousness and cognitive function. He also had limited physical activity due to acute stroke complications, such as hemorrhagic transformation of cerebral infarction, and required bed rest until 23 days after onset. The patient received intravenous cerebrolysin concentrate in addition to intensive rehabilitation therapy from 23 days after onset. After rehabilitation and administration of cerebrolysin concentrate, there was a marked recovery within a short period of time to the point where oral intake of a regular diet was possible, indicating a significant improvement in oral apraxia. It is a notable example of the potential therapeutic effect of cerebrolysin concentrate for post-stroke oral apraxia.