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This study aims to optimize the conditions for the formation of neutrophil extracellular traps(NETs) in vitro, so as to establish a relatively stable experimental research platform. Different conditions were compared, including commonly used laboratory animals(rats and mice) and a variety of cell sources(bone marrow neutrophils and peripheral blood neutrophils separated by percoll density gradient centrifugation). Different inducers like lipopolysaccharide(LPS) and phorbol 12-myristate 13-acetate(PMA) were used for induction in vitro. Myeloperoxidase(MPO)/citrullinated histone H3(CitH3)/DAPI immunofluorescence and cell free DNA(cf-DNA) content determination were used for comprehensive evaluation to screen the optimal conditions for the formation of NETs induced in vitro. Furthermore, the stability of the selected conditions for inducing the formation of NETs in vitro was evaluated by tetramethylpyrazine(TMP), an active component in Chinese herbal medicines. The results showed that coated poly-D-lysine(PDL) induced the formation of NETs in bone marrow neutrophils of mice to a certain extent. Both LPS and PMA significantly up-regulated the protein levels of MPO and CitH3 in mouse bone marrow neutrophils and elevated the cfDNA level in the supernatant of rat peripheral blood neutrophils. The cfDNA level in the PMA-induced group increased more significantly than that in the LPS-induced group(P<0.05). The results of immunofluorescence staining showed that the expression of MPO and CitH3 in mouse bone marrow neutrophils, rat bone marrow neutrophils, and rat peripheral blood neutrophils were significantly increased after PMA induction, especially in rat peripheral blood neutrophils. TMP significantly down-regulated the protein levels of MPO, CitH3, and neutrophil elastase(NE) in rat peripheral blood neutrophils induced by PMA. In conclusion, treating the peripheral blood neutrophils of rats with PMA is the optimal condition for inducing the formation of NETs in vitro. This study provides an optimal platform for in vitro studies based on NETs and a basis for studying the effects of traditional Chinese medicines targeting NETs.
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Trampas Extracelulares , Neutrófilos , Peroxidasa , Trampas Extracelulares/efectos de los fármacos , Trampas Extracelulares/metabolismo , Animales , Neutrófilos/efectos de los fármacos , Neutrófilos/citología , Ratones , Ratas , Peroxidasa/metabolismo , Peroxidasa/genética , Acetato de Tetradecanoilforbol/farmacología , Masculino , Lipopolisacáridos/farmacología , Ratas Sprague-Dawley , Histonas/metabolismo , Histonas/genética , HumanosRESUMEN
Design the electrocatalysts without noble metal is still a challenge for oxygen evolution reaction (OER) in acid media. Herein, we reported the manganese (Mn) doping method to decrease the concentration of oxygen vacancy (VO) and form the Mn-O structure adjacent octahedral sites in spinel NiCo2O4-δ (NiMn1.5Co3O4-δ), which highly enhanced the activity and stability of spinel NiCo2O4-δ with a low overpotential (η) of 280â mV at j=10â mA cm-2 and long-term stability of 80â h in acid media. The isotopic labelling experiment based on differential electrochemical mass spectrometry (DEMS) clearly demonstrated the lattice oxygen in NiMn1.5Co3O4-δ is more stable due to strong Mn-O bond and shows synergetic adsorbate evolution mechanism (SAEM) for acid OER. Density functional theory (DFT) calculations reveal highly increased oxygen vacancy formation energy (EVO) of NiCo2O4-δ after Mn doping. More importantly, the highly hydrogen bonding between Mn-O and *OOH adsorbed on adjacent Co octahedral sites promote the formation of *OO from *OOH due to the greatly enhanced charge density of O in Mn substituted sites.
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OBJECTIVES: To investigate the changes in the serum levels of oxidized phospholipids (OxPLs) and endothelial nitric oxide synthase (eNOS) and their association with coronary artery disease (CAL) in children in the acute stage of Kawasaki disease (KD), as well as the clinical significance of OxPLs and eNOS. METHODS: A prospective study was conducted on 95 children in the acute stage of KD (KD group). According to the presence of absence of CAL, the KD group was further divided into a CAL subgroup and a non-CAL (NCAL) subgroup. Thirty children with fever due to lower respiratory tract infection were enrolled as the fever group. Thirty healthy children who underwent physical examination were enrolled as the healthy control group. The above groups were compared in terms of general information and serum levels of OxPLs, eNOS and other laboratory indexes, and the correlation between OxPLs level and eNOS level was analyzed. RESULTS: The KD group had a significantly higher level of OxPLs and a significantly lower level of eNOS compared with the fever group and the healthy control group (P<0.05). After treatment, the children with KD had a significantly decreased OxPLs level and a significantly increased eNOS level (P<0.05). Compared with the NCAL subgroup, the CAL subgroup had a significantly higher level of OxPLs and a significantly lower level of eNOS (P<0.05). Among the children of KD, the level of OxPLs was negatively correlated with that of eNOS (rs=-0.353, P<0.05). CONCLUSIONS: Serum OxPLs and eNOS in the acute stage of KD may be involved in the development of CAL in children with KD, and therefore, they may be used as the biomarkers to predict CAL in these children.
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Síndrome Mucocutáneo Linfonodular , Óxido Nítrico Sintasa de Tipo III , Fosfolípidos , Humanos , Síndrome Mucocutáneo Linfonodular/sangre , Masculino , Femenino , Óxido Nítrico Sintasa de Tipo III/sangre , Preescolar , Lactante , Estudios Prospectivos , Enfermedad Aguda , Fosfolípidos/sangre , Oxidación-Reducción , Niño , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/etiologíaRESUMEN
Typical wide-band gap cathode interlayer materials are difficulty in reducing interface recombination without limiting charge transport in perovskite solar cells (PSCs). Here, a lead-doped titanium-oxo cluster protected by S-containing ligands is introduced at the interface of perovskite and SnO2 . By in situ heating, the cluster is transformed into PbSO4 -PbTi3 O7 heterostructure. The oxygen atoms from sulfate ion in heterostructure connect with iodine from perovskite to boost interfacial electron extraction and reduce charge recombination. While the yielded metallic interface between PbSO4 and PbTi3 O7 promotes the electron transport across the interface. Finally, an efficiency as high as 24.2 % for the modified PSC is obtained. The heterostructure well-stabilize the interface of perovskite and SnO2 , to greatly improve the device stability. This work provides a novel strategy to prepare wide-band gap cathode interlayer by directional transformation of heterometallic oxo clusters.
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GPM6A is a glycoprotein in endothelial cells, and its biological function in the development of hepatocellular carcinoma (HCC) is unknown. Through Affymetrix gene expression microarray and bioinformatic analysis, very low GPM6A expression was found in HCC tissue. The present study aims to explore the function and regulatory mechanism of GPM6A in HCC development and progression. Levels of GPM6A expression in HCC specimens from different disorders and various hepatoma cell lines were determined, and its role on cell proliferation was evaluated in hepatoma cells stably overexpressing GPM6A. Modulation of a specific microRNA (miRNA) on its expression and function was evaluated with miRNA mimetic transfection. Herein, it is reported that much lower GPM6A levels were found in HCC tissues than pericancerous liver tissues and correlated to a poor prognosis. GPM6A overexpression inhibited cell proliferation, suppressed colony formation, migration and invasion in two hepatoma cell types. Available evidence does not support that genetic and epigenetic dysregulation contributes significantly to GPM6A inactivation in HCC. Additional findings demonstrated that miR-96-5p acted directly on the 3'-UTR of the GPM6A gene and significantly decreased its mRNA and protein levels. MiR-96-5p transfection promoted proliferation, migration and invasion of SMMC-7721 and MHCC-97H hepatoma cells; whereas the function of oncogenic microRNA-96 was significantly inhibited in GPM6A-overexpressed hepatoma cells. In conclusion, GPM6A expression in HCC is commonly suppressed regardless its base disease types, and its low expression in HCC tissues is most likely attributed to upregulated miR-96-5p. GPM6A may function as a valuable biomarker for HCC progression and prognosis.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Humanos , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Células Endoteliales/metabolismo , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , MicroARNs/metabolismo , Proliferación Celular/genética , Regiones no Traducidas 3' , ARN Mensajero , Biomarcadores , Movimiento Celular/genética , Glicoproteínas de Membrana/metabolismo , Proteínas del Tejido Nervioso/metabolismoRESUMEN
OBJECTIVE: To evaluate the influence of post-label delay times (PLDs) on the performance of 3D pseudo-continuous arterial spin labeling (pCASL) magnetic resonance imaging for characterizing parotid gland tumors and to explore the optimal PLDs for the differential diagnosis. MATERIALS AND METHOD: Fifty-eight consecutive patients with parotid gland tumors were enrolled, including 33 patients with pleomorphic adenomas (PAs), 16 patients with Warthin's tumors (WTs), and 9 patients with malignant tumors (MTs). 3D pCASL was scanned for each patient five times, with PLDs of 1025 ms, 1525 ms, 2025 ms, 2525 ms, and 3025 ms. Tumor blood flow (TBF) was calculated, and compared among different PLDs and tumor groups. Performance of TBF at different PLDs was evaluated using receiver operating characteristic analysis. RESULTS: With an increasing PLD, TBF tended to gradually increase in PAs (p < 0.001), while TBF tended to slightly increase and then gradually decrease in WTs (p = 0.001), and PAs showed significantly lower TBF than WTs at all 5 PLDs (p < 0.05). PAs showed significantly lower TBF than MTs at 4 PLDs (p < 0.05), except at 3025 ms (p = 0.062). WTs showed higher TBF than MTs at all 5 PLDs; however, differences did not reach significance (p > 0.05). Setting a TBF of 64.350 mL/100g/min at a PLD of 1525 ms, or a TBF of 23.700 mL/100g/min at a PLD of 1025 ms as the cutoff values, optimal performance could be obtained for differentiating PAs from WTs (AUC = 0.905) or from MTs (AUC = 0.872). CONCLUSIONS: Short PLDs (1025 ms or 1525 ms) are suggested to be used in 3D pCASL for characterizing parotid gland tumors in clinical practice. KEY POINTS: ⢠With 5 different PLDs, 3D pCASL can reflect the variation of blood flow in parotid gland tumors. ⢠3D pCASL is useful for characterizing PAs from WTs or MTs. ⢠Short PLDs (1025 ms or 1525 ms) are suggested to be used in 3D pCASL for characterizing parotid gland tumors in clinical practice.
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Adenolinfoma , Adenoma Pleomórfico , Neoplasias de la Parótida , Adenolinfoma/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Glándula Parótida , Neoplasias de la Parótida/diagnóstico por imagen , Marcadores de SpinRESUMEN
Chronic administration of methamphetamine (METH) leads to physical and psychological dependence. It is generally accepted that METH exerts rewarding effects via competitive inhibition of the dopamine transporter (DAT), but the molecular mechanism of METH addiction remains largely unknown. Accumulating evidence shows that mitochondrial function is important in regulation of drug addiction. In this study, we investigated the role of Clk1, an essential mitochondrial hydroxylase for ubiquinone (UQ), in METH reward effects. We showed that Clk1+/- mutation significantly suppressed METH-induced conditioned place preference (CPP), accompanied by increased expression of DAT in plasma membrane of striatum and hippocampus due to Clk1 deficiency-induced inhibition of DAT degradation without influencing de novo synthesis of DAT. Notably, significantly decreased iron content in striatum and hippocampus was evident in both Clk1+/- mutant mice and PC12 cells with Clk1 knockdown. The decreased iron content was attributed to increased expression of iron exporter ferroportin 1 (FPN1) that was associated with elevated expression of hypoxia-inducible factor-1α (HIF-1α) in response to Clk1 deficiency both in vivo and in vitro. Furthermore, we showed that iron played a critical role in mediating Clk1 deficiency-induced alteration in DAT expression, presumably via upstream HIF-1α. Taken together, these data demonstrated that HIF-1α-mediated changes in iron homostasis are involved in the Clk1 deficiency-altered METH reward behaviors.
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Metanfetamina , Animales , Cuerpo Estriado/metabolismo , Homeostasis , Hierro/metabolismo , Metanfetamina/farmacología , Ratones , Ratas , RecompensaRESUMEN
BACKGROUND: The distinction between solitary inflammatory lesion and solitary lung cancer remains a challenge because of their considerable overlapping computed tomography (CT) imaging features. PURPOSE: This study aimed to verify whether spectral CT parameters can differentiate solitary lung cancer from solitary inflammatory lesions and to find their correlations with lesion size. METHODS: A total of 78 patients with solitary lung lesions were included in our study. All of them underwent enhanced CT scans with Gemstone Spectral Imaging (GSI) mode, which was one of the dual-energy imaging technologies. According to maximum diameter (Dmax) of the lesion, regions of interest were collected and divided into inflammatory (group I: <3 cm [IA], n = 17; ≥3 cm [IB], n = 14) and cancer groups (group II: <3 cm [IIA], n = 20; ≥3 cm [IIB], n = 27). Computed tomography values (HU40keV, HU70keV), effective atomic number (Zeff), iodine concentration (IC), normalized IC (NIC), and spectral curve slopes (λ30, λ40) of each region of interest were calculated. The NIC was defined as the IC ratio of the lesion to the descending aorta. Mann-Whitney U test was used for intergroup (I vs II, IA vs IIA, IB vs IIB) and intragroup (IA vs IB, IIA vs IIB) comparisons, and receiver operating characteristic curve analysis was performed. Correlation analysis was applied to find the relationship between Dmax and GSI parameters. RESULTS: No significant correlation was found between GSI parameters and Dmax in the inflammatory group, whereas inverse correlations were found in the cancer group. Gemstone spectral imaging parameters (except HU70keV) of group IIA were significantly higher than those of group IIB. There were significant differences in HU40keV, IC, NIC, λ30, and λ40 between groups IB and IIB under both arterial and venous phase (P values < 0.05), whereas the area under the curve for λ30 under venous phase was largest, and sensitivity and specificity were 96.32% and 85.71%, respectively. However, only HU40keV and HU70keV values under the arterial phase of IIA were significantly higher than those of IA. CONCLUSIONS: Quantitative parameters of GSI demonstrated an inverse correlation with the lesion size of solitary lung cancer, and GSI parameters can be new ways to differentiate solitary lung cancer from solitary inflammatory lesions.
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Yodo , Neoplasias Pulmonares , Neumonía , Humanos , Pulmón/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Tomografía Computarizada por Rayos X/métodosRESUMEN
NOD-like receptor protein 3 (NLRP3) promotes the inflammatory response during progression of nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). This study aimed to further delineate the role of NLRP3 in NASH development by abolishing its expression in mice. A high-fat and calorie diet plus high fructose and glucose in drinking water (HFCD-HF/G) was used to establish NASH in both wild-type (WT) and NLRP3 knock-out (KO) mice. Hepatocellular injury, hepatic steatosis and fibrosis, as well as inflammatory response and insulin resistance in the liver and epidydimal white adipose tissue (eWAT) were determined. Elevated body weight, liver weight and serum alanine transaminase level, increased hepatic triglyceride accumulation and collagen deposition, and worsened systemic insulin resistance were observed in Nlrp3-/- mice compared to WT mice under HFCD-HF/G feeding. Upregulated hepatic transcription of tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1), and enhanced infiltration of inducible nitric oxide synthase-positive (iNOS+) M1 macrophages were also documented in HFCD-HF/G-fed Nlrp3-/- mice in comparison to HFCD-HF/G-fed WT mice. Moreover, transcription of TNF-α and MCP-1 and infiltration of iNOS+ M1 macrophages were increased in the liver of Nlrp3-/- mice under control diet. NLRP3 deficiency did not attenuate, but instead aggravated NASH development under HFCD-HF/G feeding. The worsened extent of NASH might be attributed to enhanced hepatic MCP-1 expression and M1 macrophage infiltration in Nlrp3-/- mice. Our study points to additional caution when NLRP3 blockade is considered as a therapeutic strategy in the treatment of human NASH.
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Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Enfermedad del Hígado Graso no Alcohólico/etiología , Animales , Colágeno/metabolismo , Dieta Alta en Grasa/efectos adversos , Fructosa/efectos adversos , Glucosa/efectos adversos , Resistencia a la Insulina , Metabolismo de los Lípidos , Hígado/inmunología , Hígado/metabolismo , Masculino , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Lysophosphatidic acid receptor 5 (LPAR5) is involved in mediating thyroid cancer progression, but the underlying mechanism needs to be further revealed. In this study, we confirmed that LPAR5 is upregulated in papillary thyroid carcinoma (PTC), especially in BRAF-like PTC, by analyzing The Cancer Genome Atlas (TCGA) database and performing immunohistochemistry assay in human thyroid cancer tissues. LPAR5-specific antagonist TC LPA5 4 treatment inhibited CGTH-W3, TPC-1, B-CPAP, and BHT-101 cell proliferation, CGTH-W3 and TPC-1 cell migration significantly. In vivo, TC LPA5 4 treatment could delay CGTH-W3 xenograft growth in nude mice. We also found that LPAR5-specific antagonist TC LPA5 4, PI3K inhibitor wortmannin, or mTOR inhibitor rapamycin pretreatment abrogated phosphorylation of Akt and p70S6K1 stimulated by LPA in CGTH-W3 and TPC-1 cells. Stimulating CGTH-W3 cells transfected with pEGFPC1-Grp1-PH fusion protein with LPA resulted in the generation of phosphatidylinositol (3,4,5)-triphosphate, which indicates that PI3K was activated by LPA directly. The p110ß-siRNA instead of p110α-siRNA transfection abrogated the increase of levels of phosphorylated Akt and S6K1 stimulated by LPA. Furthermore, immunoprecipitation assay confirmed an interaction between LPAR5 and p110ß. Overall, we provide new insights that the downregulation of LPAR5 decreased the proliferation and migration phenotype via the PI3K/Akt pathway. Inhibition of LPAR5 or the PI3K/Akt signal may be a novel therapeutic strategy for treating thyroid cancer.
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Movimiento Celular/fisiología , Proliferación Celular/fisiología , Fosfatidilinositol 3-Quinasa Clase Ia/metabolismo , Receptores del Ácido Lisofosfatídico/metabolismo , Neoplasias de la Tiroides/metabolismo , Neoplasias de la Tiroides/patología , Animales , Dominio Catalítico/fisiología , Línea Celular Tumoral , Regulación hacia Abajo/fisiología , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Transducción de Señal/fisiología , Cáncer Papilar Tiroideo/metabolismo , Cáncer Papilar Tiroideo/patologíaRESUMEN
BACKGROUND: To evaluate the feasibility of using simultaneous multi-slice (SMS) readout segmentation of long variable echo-trains (RESOLVE) diffusion-weighted imaging (DWI) to assess parotid gland tumors, compared with conventional RESOLVE DWI. METHODS: From September 2018 to December 2018, 20 consecutive patients with parotid tumors who underwent MRI scan for pre-surgery evaluation were enrolled. SMS-RESOLVE DWI and conventional RESOLVE DWI were scanned with matched imaging parameters, respectively. The scan time of two DWI sequences was recorded. Qualitative (anatomical structure differentiation, lesion display, artifact, and overall image quality) and quantitative (apparent diffusion coefficient, ADC; ratio of signal-to-noise ratio, SNR ratio; ratio of contrast-to-noise ratio, CNR ratio) assessments of image quality were performed, and compared between SMS-RESOLVE DWI and conventional RESOLVE DWI by using Paired t-test. Two-sided P value less than 0.05 indicated significant difference. RESULTS: The scan time was 3 min and 41 s for SMS-RESOLVE DWI, and 5 min and 46 s for conventional RESOLVE DWI. SMS-RESOLVE DWI produced similar qualitative image quality with RESOLVE DWI (anatomical structure differentiation, P = 0.164; lesion display, P = 0.193; artifact, P = 0.330; overall image quality, P = 0.083). Meanwhile, there were no significant difference on ADCLesion (P = 0.298), ADCMasseter (P = 0.122), SNR ratio (P = 0.584) and CNR ratio (P = 0.217) between two DWI sequences. CONCLUSION: Compared with conventional RESOLVE DWI, SMS-RESOLVE DWI could provide comparable image quality using markedly reduced scan time. SMS could increase the clinical usability of RESOLVE technique for DWI of parotid gland.
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Imagen de Difusión por Resonancia Magnética/métodos , Imagen Eco-Planar/métodos , Neoplasias de la Parótida/diagnóstico por imagen , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Adulto , Anciano , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
PURPOSE: To assess the added value of susceptibility-weighted imaging (SWI) to diffusion-weighted imaging (DWI) in the characterization of parotid gland tumors. METHODS: Seventy-eight patients with pathologically confirmed parotid gland tumors, who underwent DWI and SWI for pre-surgery evaluation, were enrolled. Apparent diffusion coefficient (ADC) and degree of intratumoral susceptibility signal intensity (ITSS) were measured and compared between benign and malignant groups, and among pleomorphic adenoma (PA), Warthin tumor (WT) and malignant tumor (MT). Independent sample t test, one-way analysis of variance and receiver operating characteristic curve analysis were used for statistical analyses. RESULTS: Benign parotid gland tumor showed a significantly higher mean ADC value than malignant tumors (0.836 ± 0.350 vs 0.592 ± 0.163, p = 0.001). Setting an average ADC value of 0.679 as the cut-off value, optimal differentiating performance could be obtained (AUC, 0.700; sensitivity, 62.69%; specificity, 81.82%) for differentiating malignant from benign tumors. PA showed significantly higher mean ADC and less ITSS than WT (ADC, p < 0.001; ITSS, p = 0.033) and MT (ADC, p < 0.001; ITSS, p = 0.024), while the difference between WT and MT was not significant (ADC, p = 0.826; ITSS, p = 0.539). After integration with ITSS, the diagnostic performance of ADC was improved for differentiating PA from WT (AUC 0.921 vs 0.873) and from MT (AUC 0.906 vs 0.882). CONCLUSION: SWI could provide added information to DWI and serve as a supplementary imaging marker for the characterization of parotid gland tumors.
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Glándula Parótida , Neoplasias de la Parótida , Diagnóstico Diferencial , Imagen de Difusión por Resonancia Magnética , Humanos , Glándula Parótida/diagnóstico por imagen , Neoplasias de la Parótida/diagnóstico por imagen , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Cardiac hypertrophy is characterized by an increase in myocyte size in the absence of cell division. This condition is thought to be an adaptive response to cardiac wall stress resulting from the enhanced cardiac afterload. The pathogenesis of heart dysfunction, which is one of the primary causes of morbidity and mortality in elderly people, is often associated with myocardial remodelling caused by cardiac hypertrophy. In order to well understand the potential mechanisms, we described the molecules involved in the development and progression of myocardial hypertrophy. Increasing evidence has indicated that micro-RNAs are involved in the pathogenesis of cardiac hypertrophy. In addition, molecular biomarkers including vascular endothelial growth factor B, NAD-dependent deacetylase sirtuin-3, growth/differentiation factor 15 and glycoprotein 130, also play important roles in the development of myocardial hypertrophy. Knowing the regulatory mechanisms of these biomarkers in the heart may help identify new molecular targets for the treatment of cardiac hypertrophy.
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Biomarcadores/análisis , Cardiomegalia/diagnóstico , Animales , Cardiomegalia/genética , Cardiomegalia/metabolismo , HumanosRESUMEN
BACKGROUND: Limited trials examining the effect of exercise and nutrition supplementation in older people with sarcopenia are available. OBJECTIVES: to assess the impact of resistance exercise program targeting muscle strength and power with and without nutrition supplementation on gait speed, body composition, physical function and quality of life. METHODS: this trial randomized 113 community-dwelling older Chinese adults aged ≥65 and with sarcopenia defined using the Asian Criteria into one of the three groups: exercise program alone, combined-exercise program and nutrition supplement or waitlist control. The exercise program consisted of 90-min group training twice weekly and one-home session weekly for 12 weeks. Participants in the combined group were additionally asked to consume nutrition supplement twice daily for 12 weeks. Both groups were encouraged to keep home exercise after intervention period for another 12 weeks to detect sustained effect. The primary outcome was gait speed. RESULTS: at 12 and 24 weeks, gait speed did not differ significantly between groups. Significant improvement in leg extension, and five-chair stand test occurred in both intervention groups that persisted to 24 weeks. Physical Activity Scale for the Elderly improved in both intervention groups that persisted until 24 weeks only in the combined group. Lower limb muscle and appendicular skeletal muscle mass increased significantly in the combined group but the increase was not sustained to 24 weeks. CONCLUSION: the exercise program with and without nutrition supplementation had no significant effect on the primary outcome of gait speed but improved the secondary outcomes of strength and the five-chair stand test in community-dwelling Chinese sarcopenic older adults. CLINICALTRIALS.GOV IDENTIFIER: NCT02374268.
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Terapia Nutricional , Entrenamiento de Fuerza , Sarcopenia/terapia , Anciano , Composición Corporal , China , Femenino , Marcha , Humanos , Vida Independiente , Masculino , Fuerza Muscular , Terapia Nutricional/métodos , Aptitud Física , Calidad de Vida , Entrenamiento de Fuerza/métodosRESUMEN
The aim of this study is to review the natural course, clinical features, and reproductive prognosis of ovarian tumors associated with hyperandrogenemia. We retrospect 33 patients of ovarian tumors with hyperandrogenemia. Thirty cases (91%) were sex cord-stromal tumors. Sertoli-Leydig cell tumors, Leydig cell tumors, and steroid cell tumors were the most common types. It is not possible, to predict the pathological subtypes based on androgen levels alone. Most of these tumors were solid masses, with an average diameter of 3.9 cm. These tumors are soft or fragile, no clear boundary with normal tissue, thus excision is superior to exfoliation. The average disease course of the top three tumors was 32.6, 35.4, and 67.7 months, respectively. Among 11 married women with a desire to get pregnant, nine cases resumed menstrual periods after surgery and became pregnant naturally. Hyperandrogenemia might predict a better prognosis. The asynchronism of hyperandrogenemia and undetectable tumor may cause irreversible change and emotional depress, the methods of early diagnosis need further study.
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Hiperandrogenismo/complicaciones , Hiperandrogenismo/diagnóstico , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/diagnóstico , Tumores de los Cordones Sexuales y Estroma de las Gónadas/complicaciones , Tumores de los Cordones Sexuales y Estroma de las Gónadas/diagnóstico , Adolescente , Adulto , Anciano , Andrógenos/sangre , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Preservación de la Fertilidad , Humanos , Hiperandrogenismo/patología , Hiperandrogenismo/cirugía , Persona de Mediana Edad , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Pronóstico , Estudios Retrospectivos , Tumor de Células de Sertoli-Leydig/complicaciones , Tumor de Células de Sertoli-Leydig/diagnóstico , Tumor de Células de Sertoli-Leydig/patología , Tumor de Células de Sertoli-Leydig/cirugía , Tumores de los Cordones Sexuales y Estroma de las Gónadas/patología , Tumores de los Cordones Sexuales y Estroma de las Gónadas/cirugía , Carga Tumoral , Adulto JovenRESUMEN
AMP-activated protein kinase (AMPK) is a central regulator of multiple metabolic pathways. It has been shown that activation of AMPK could inhibit fibroblast proliferation and extracellular matrix (ECM) accumulation, thereby suppressing cardiac fibrosis. Baicalin, the major component found in skullcap, possesses multiple protective effects on the cardiovascular system. However, little is known about the effect of baicalin on cardiac fibrosis and the molecular mechanism by which baicalin exerts its anti-fibrotic effects has not been investigated. In this study, we revealed that baicalin could inhibit cell proliferation, collagen synthesis, fibronectin (FN) and Connective tissue growth factor (CTGF) protein expression in cardiac fibroblasts induced by angiotensin â ¡ (Ang â ¡). It also ameliorated cardiac fibrosis in rats submitted to abdominal aortic constriction (AAC). Moreover, baicalin inhibited transforming growth factor-ß (TGF-ß)/Smads signaling pathway stimulated with Ang â ¡ through activating AMPK. Subsequently, we also demonstrated that baicalin attenuated Ang â ¡-induced Smad3 nuclear translocation, and interaction with transcriptional coactivator p300, but promoted the interaction of p300 and AMPK. Taken together, these results provide the first evidence that the effect of baicalin against cardiac fibrosis may be attributed to its regulation on AMPK/TGF-ß/Smads signaling, suggesting the therapeutic potential of baicalin on the prevention of cardiac fibrosis and heart failure.
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Flavonoides/farmacología , Cardiopatías/prevención & control , Miocardio/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Angiotensina II/farmacología , Animales , Células Cultivadas , Colágeno/metabolismo , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Relación Dosis-Respuesta a Droga , Fibronectinas/metabolismo , Fibrosis , Cardiopatías/inducido químicamente , Ratas , Ratas Sprague-DawleyRESUMEN
PURPOSE: To evaluate the diagnostic performance of histogram parameters derived from diffusion-weighted imaging (DWI) for differentiating malignant from benign parotid gland tumors compared with that of hotspot region of interest (ROI)-based apparent diffusion coefficient (ADC) measurement. METHODS: Our study retrospectively enrolled 60 patients with parotid gland tumors who had undergone DWI scan for pre-treatment evaluation. ADC measurements were performed using hotspot ROI (ADCHS-ROI)-based and histogram-based approach. Histogram parameters included mean (ADCmean), median (ADCmedian), 10th (ADC10), 90th (ADC90) percentiles, skewness and kurtosis of ADC. Mann-Whitney U test, Kruskal-Wallis test with post hoc Dunn-Bonferroni method and receiver operating characteristic (ROC) curve analyses were used for statistical analyses. RESULTS: ADCHS-ROI and ADC histogram parameters showed no significant differences between malignant and benign parotid gland tumors (All Ps > 0.05). Within the sub-group analyses, Warthin's tumors showed the lowest ADCHS-ROI, ADCmean, ADCmedian, ADC10 and ADC90 value, followed by malignant tumors and pleomorphic adenomas (All Ps < 0.05). ADC10 out-performed ADCHS-ROI in differentiating malignant tumors from pleomorphic adenomas (area under curve, 0.890 vs 0.821; sensitivity, 79.31 vs 82.76%; specificity, 90.91 vs 72.73%; P = 0.016), and improved the diagnostic performance in differentiating malignant tumors from Warthin's tumors (area under curve, 1.000 vs 0.965; sensitivity, 100.00 vs 90.91%), although the difference was not significant (P = 0.348). CONCLUSIONS: ADC histogram analysis, especially ADC10, might be a promising imaging biomarker for characterizing parotid gland tumors.
Asunto(s)
Imagen de Difusión por Resonancia Magnética/métodos , Glándula Parótida/diagnóstico por imagen , Neoplasias de la Parótida/diagnóstico , Adulto , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de las Parótidas/diagnóstico , Curva ROC , Estudios RetrospectivosRESUMEN
BACKGROUND/AIMS: Spinal cord injury (SCI) is a common and devastating disease, which results in systemic inflammatory response syndrome and secondary lung injury. Mitochondrial dysfunction and inflammation are closely related to lung injury in diverse disease models. No studies have demonstrated the effects of mitochondrial targeted peptide SS-31 in a mouse model of SCI-induced lung injury. METHODS: Immediately after injury, mice in the treatment groups received a daily, single-dose intraperitoneal injection of SS-31 and for the next 2 days. The sham and SCI groups also received a daily single dose of vehicle (DMSO and 0.9% NaCl, 1: 3). The lung tissue of mice was examined after SCI, and tissue damage, apoptosis, inflammation, and mitochondrial dysfunction were recorded. RESULTS: SS-31 treatment attenuated lung edema and tissue damage. Furthermore, SS-31 treatment reduced apoptosis of alveolar type II cells, the number of total macrophages and M1 macrophages, and neutrophil infiltration. Moreover, SS-31 treatment attenuated reactive oxygen species levels, reversed mitochondrial dysfunction and inhibited NLRP3 inflammasome activation. CONCLUSIONS: Collectively, our results demonstrate that SS-31 attenuates mitochondrial dysfunction, controls inflammatory responses, and alleviates the severity of lung damage in a mouse model of SCI-induced lung injury.
Asunto(s)
Inflamación/prevención & control , Lesión Pulmonar/prevención & control , Oligopéptidos/uso terapéutico , Sustancias Protectoras/uso terapéutico , Traumatismos de la Médula Espinal/complicaciones , Animales , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Interleucina-1beta/metabolismo , Pulmón/metabolismo , Pulmón/patología , Lesión Pulmonar/etiología , Macrófagos/citología , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Microscopía Fluorescente , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Infiltración Neutrófila/efectos de los fármacos , Oligopéptidos/farmacología , Sustancias Protectoras/farmacología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The reaction of uranyl nitrate with terephthalic acid (H2TP) under hydrothermal conditions in the presence of an organic base, 1,3-(4,4'-bispyridyl)propane (BPP) or 4,4'-bipyridine (BPY), provided four uranyl terephthalate compounds with different entangled structures by a pH-tuning method. [UO2(TP)1.5](H2BPP)0.5·2H2O (1) obtained in a relatively acidic solution (final aqueous pH, 4.28) crystallizes in the form of a noninterpenetrated honeycomb-like two-dimensional network structure. An elevation of the solution pH (final pH, 5.21) promotes the formation of a dimeric uranyl-mediated polycatenated framework, [(UO2)2(µ-OH)2(TP)2]2(H2BPP)2·4.5H2O (2). Another new polycatenated framework with a monomeric uranyl unit, [(UO2)2(TP)3](H2BPP) (3), begins to emerge as a minor accompanying product of 2 when the pH is increased up to 6.61, and turns out to be a significant product at pH 7.00. When more rigid but small-size BPY molecules replace BPP molecules, [UO2(TP)1.5](H2BPP)0.5 (4) with a polycatenated framework similar to 3 was obtained in a relatively acidic solution (final pH, 4.81). The successful preparation of 2-4 represents the first report of uranyl-organic polycatenated frameworks derived from a simple H2TP linker. A direct comparison between these polycatenated frameworks and previously reported uranyl terephthalate compounds suggests that the template and cavity-filling effects of organic bases (such as BPP or BPY), in combination with specific hydrothermal conditions, promote the formation of uranyl terephthalate polycatenated frameworks.
RESUMEN
Amidine is a notable nitrogen-containing structural motif found in bioactive natural products and pharmaceuticals. Herein, a novel rhodium(I)-catalyzed tandem reaction of readily accessible azides with isonitriles and boronic acids via a carbodiimide intermediate is achieved. This protocol offers an alternative approach toward N-sulfonyl-, N-acyl-, and N- phosphoryl-functionalized, as well as general N-aryl and N-alkyl amidines with broad substrate scope. In addition, functionalized guanidines can also been synthesized when amines are used instead. The accomplishment of estrone-derived amidine and glibenclamide bioisosteres further reveals the practical utility of this strategy.