RESUMEN
Polyamide 56 (PA56) has gained significant attention in the academic field due to its remarkable mechanical and thermal properties as a highly efficient and versatile biobased material. Its superior moisture absorption property also makes it a unique advantage in the realm of fiber textiles. However, despite extensive investigations on PA56's molecular and aggregate state structure, as well as processing modifications, little attention has been paid to its polymerization mechanism. Herein, the influence of temperature and time on PA56's polycondensation reaction is detailed studied by end-group titration and carbon nuclear magnetic resonance (NMR) techniques. The reaction kinetics equations for the pre-polymerization and vacuum melt-polymerization stages of PA56 are established, and possible side reactions during the polycondensation process are analyzed. By optimizing the reaction process based on kinetic characteristics, PA56 resin with superior comprehensive properties (melting temperature of 252.6 °C, degradation temperature of 371.6 °C, and tensile strength of 75 MPa) is obtained. The findings provide theoretical support for the industrial production of high-quality biobased PA56.
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Nylons , Nylons/química , Polimerizacion , TemperaturaRESUMEN
PURPOSE: To apply propensity score matching to evaluate the impact of peripapillary staphylomas (PPS) on vascular and structural characteristics in the myopic eyes. METHODS: This was a prospective, cross-sectional study. Forty-one control eyes and 41 eyes with PPS were analyzed. The eyes were selected using propensity score matching analysis based on the age and axial length. All subjects underwent ophthalmologic examinations for assessing vessel and structure parameters using swept-source optical coherence tomography (SS-OCT), OCT angiography, color fundus photography, and ocular biometry. RESULTS: As compared with control eyes, the eyes with PPS had shallower anterior chamber depth (3.61 ± 0.24 mm vs 3.77 ± 0.24 mm, P = 0.004), higher intraocular pressure (IOP) (16.59 ± 2.88 mmHg vs 14.53 ± 2.45 mmHg, P = 0.002), and higher myopic spherical equivalent (- 11.52 ± 3.22D vs - 9.88 ± 2.20D, P = 0.009). while corneal curvature and lens thickness between the two groups were not statistically different. Compared with control eyes, increased macular deep vessel density, reduced macular choriocapillaris and radial peripapillary capillary, and thinning retinal layer, ganglion cell complex, choroidal layer as well as the superior and inferior peripapillary retinal nerve fiber layer were observed in eyes with PPS, apart from larger disc area, parapapillary atrophy area, and degree of disc rotation. Logistic regression analysis revealed that the IOP (P = 0.046), disc rotation (P = 0.003), and average peripapillary choroidal thickness (P = 0.009) were associated with the presence of PPS. CONCLUSION: Close association of PPS with exacerbation of myopia and anatomical alterations was observed which not only affected the eye posterior segment but also the anterior segments. We further identified significant reductions in the radial peripapillary capillary and macular choroidal perfusion with the increase in macular deep retinal flow blood of myopic eyes with PPS. Higher IOP, thinner peripapillary choroidal thickness, and rotated optic disc were risk factors for the presence of PPS.
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Miopía , Disco Óptico , Humanos , Estudios Transversales , Estudios Prospectivos , Puntaje de Propensión , Miopía/complicaciones , Miopía/diagnóstico , Disco Óptico/irrigación sanguínea , Tomografía de Coherencia Óptica/métodosRESUMEN
OBJECTIVE: To investigate the microvasculature and structural characteristics of the eyes of myopic patients and their association with posterior staphyloma (PS). METHODS: This was a retrospective, case-control study comprising of 106 eyes from 72 individuals. Using 1:1 matching of axial length (AL) of their eyes, patients were allocated into a PS group or no posterior staphyloma (NPS) group. All patients were examined using ultra-widefield fundus imaging, optical coherence tomography angiography, and ocular biometry to acquire microvasculature and microstructure parameters. RESULTS: The anterior chamber depth (ACD) of the PS group was significantly different from that of the NPS group (3.56 mm vs 3.76 mm, P < 0.001), as was 1ens thickness (3.72 mm vs 3.57 mm, P = 0.005) and spherical equivalent (SE)(-10.11D vs -8.80D, P = 0.014). The PS group had reduced choriocapillaris flow, subfoveal choroidal thickness (SFCT), and a thinner retinal layer compared with the NPS group. No difference in retinal blood flow between the two groups was observed. The PS group exhibited a smaller disc area (15082.89 vs 17,043.32, P = 0.003) and angle α between temporal retinal arterial vascular arcades (113.29°vs 128.39°, P = 0.003), a larger disc tilt ratio (1.41 vs 1.24, P < 0.001) and parapapillary atrophy (PPA) area (13840.98 vs 8753.86, P = 0.020), compared with the NPS group. Multivariate regression analysis indicated that disc tilt ratio (P = 0.031) and SFCT (P = 0.015) were significant predictors of PS. In addition, PS (P = 0.049), AL (P = 0.003), corneal refractive power (P < 0.001), ACD (P = 0.022), relative lens position (P = 0.045), and disc area (P = 0.011) were significant predictors of SE. CONCLUSIONS: PS was found to be closely linked to a reduction in choriocapillaris perfusion and anatomical abnormalities including posterior and anterior segments. Furthermore, PS exacerbated the progression of myopia.
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Miopía , Enfermedades de la Esclerótica , Estudios de Casos y Controles , Humanos , Microvasos , Miopía/diagnóstico , Estudios Retrospectivos , Enfermedades de la Esclerótica/diagnóstico , Tomografía de Coherencia ÓpticaRESUMEN
Aconitine, the main component in Radix Aconiti Lateralis Preparata, not only exerts the anti-tumor effect on Hepatocellular Carcinoma (HCC) but also damages on immune system. In the present study, Crude Monkshood Polysaccharide (CMP), another one natural composition component originated from the same herbal with aconitine, combined with aconitine to investigate the effects on HCC and immunity in vitro and in vivo. The combination of CMP and aconitine enhanced the ability of the immunocyte to kill the tumor cell in vitro and had an additive effect on anti-HCC in vivo. Aconitine-CMP in combination improved the spleen weights, spleen index, thymus weights, thymus index. Elevated CD4+ T and CD8+ T cells and macrophages in spleen, decreased serum IL-6 level and increased serum IFN-γ and TNF-α levels were observed in mice treated with the combination of aconitine and CMP compare with control group (P<0.05). Our results showed that the combination of aconitine and CMP exerts anti-tumor effect by directly killing tumor cells and enhancing the anti-tumor immune responses, which further implies that chemotherapy drugs combined with Chinese medicine immunopotentiator maybe a feasible and effective strategy for HCC.
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Aconitina/farmacología , Aconitum , Carcinoma Hepatocelular/inmunología , Proliferación Celular/efectos de los fármacos , Neoplasias Hepáticas/inmunología , Extractos Vegetales/farmacología , Adyuvantes Inmunológicos/farmacología , Animales , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Técnicas In Vitro , Interferón gamma/efectos de los fármacos , Interferón gamma/inmunología , Interferón gamma/metabolismo , Interleucina-6/inmunología , Interleucina-6/metabolismo , Neoplasias Hepáticas/metabolismo , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Ratones , Trasplante de Neoplasias , Tamaño de los Órganos/efectos de los fármacos , Polisacáridos/farmacología , Bazo/efectos de los fármacos , Bazo/inmunología , Bazo/patología , Timo/efectos de los fármacos , Timo/inmunología , Timo/patología , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Factor de Necrosis Tumoral alfa/inmunología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Lysyl oxidase (LOX) is involved in fibrosis by catalyzing collagen cross-linking. Previous work observed that Triptolide (TPL) alleviated radiation-induced pulmonary fibrosis (RIPF), but it is unknown whether the anti-RIPF effect of TPL is related to LOX. In a mouse model of RIPF, we found that LOX persistently increased in RIPF which was significantly lowered by TPL. Excessive LOX aggravated fibrotic lesions in RIPF, while LOX inhibition mitigated RIPF. Irradiation enhanced the transcription and synthesis of LOX by lung fibroblasts through IKKß/NFκB activation, and siRNA knockdown IKKß largely abolished LOX production. By interfering radiation induced IKKß activation, TPL prevented NFκB nuclear translocation and DNA binding, and potently decreased LOX synthesis. Our results demonstrate that the anti-RIPF effect of TPL is associated with reduction of LOX production which mediated by inhibition of IKKß/NFκB pathway.
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Diterpenos/farmacología , Proteínas de la Matriz Extracelular/antagonistas & inhibidores , Quinasa I-kappa B/antagonistas & inhibidores , Fenantrenos/farmacología , Proteína-Lisina 6-Oxidasa/antagonistas & inhibidores , Fibrosis Pulmonar/tratamiento farmacológico , Traumatismos por Radiación/tratamiento farmacológico , Animales , Diterpenos/administración & dosificación , Relación Dosis-Respuesta a Droga , Compuestos Epoxi/administración & dosificación , Compuestos Epoxi/farmacología , Proteínas de la Matriz Extracelular/biosíntesis , Femenino , Quinasa I-kappa B/metabolismo , Inyecciones Intravenosas , Ratones , Ratones Endogámicos C57BL , Estructura Molecular , Fenantrenos/administración & dosificación , Proteína-Lisina 6-Oxidasa/biosíntesis , Fibrosis Pulmonar/metabolismo , Traumatismos por Radiación/metabolismo , Relación Estructura-ActividadRESUMEN
Glucose triggers glucagon-like peptide (GLP)-1 secretion from L cells involving several glucose sensors including sodium-glucose transporter (SGLT)1, glucose transporter (GLUT)2, and sweet taste receptors (STRs). This study investigated the effects of different glucose concentrations on GLP-1 secretion, intracellular concentrations of Ca2+ and cAMP, glucose uptake, and protein levels of SGLT1, GLUT2, and STRs in STC-1 cells. Low glucose (5.6 mM) increased GLP-1 secretion, intracellular Ca2+ concentration, and SGLT1 protein level compared with glucose-free group. GLP-1 secretion and intracellular Ca2+ concentration triggered by low glucose were inhibited by the SGLT1 inhibitor. GLP-1 secretion or intracellular Ca2+ concentration in high-glucose (25, 100, 200 mM) groups was significantly higher than that of low-glucose group. Elevation of cAMP level was observed in concentration-dependent manner, and decreased glucose uptake was observed in 100 or 200 mM glucose group. High glucose increased protein levels of STRs and GLUT2 in comparison to low-glucose group. GLP-1 secretion and intracellular levels of Ca2+ and cAMP triggered by high glucose were inhibited in the presence of the GLUT2 or STR inhibitor. These results suggest that SGLT1 is dominantly responsible for GLP-1 secretion triggered by low glucose, and that STRs and GLUT2 are involved in GLP-1 secretion induced by high glucose.
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Células Enteroendocrinas , Línea Celular , Péptido 1 Similar al Glucagón , GlucosaRESUMEN
Maintenance of glucose homeostasis is reciprocally regulated by insulin and glucagon-like peptide-1 (GLP-1). We previously reported that GLP-1 secretion in response to an oral glucose load was impaired following an administration of 3-deoxyglucosone (3DG), an independent factor associated with the development of pre-diabetes. Here we investigated the effects of 3DG on insulin signaling and insulin-induced GLP-1 secretion under high-glucose conditions in the enteroendocrine L cell line STC-1. STC-1 cells were exposed to 3DG (80, 300, and 1000 ng/ml) in the presence of 10-7 M insulin and 25 mM glucose. GLP-1 secretion was determined by ELISA, glucose uptake was monitored with 2-NBDG (2-(N(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxyglucose), glucose consumption was detected by glucoseoxidase, and protein expression of insulin signaling molecules was examined by western blot. Results showed a decrease in insulin-induced GLP-1 secretion and insulin receptor phosphorylation after 3DG treatment. Concomitantly, 3DG treatment inhibited insulin-induced phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway activation. In the presence, but not absence, of insulin, 3DG treatment decreased insulin-stimulated glucose consumption. Inhibition of PI3K with Wortmannin attenuated insulin-induced increment in glucose transporter 2 (GLUT2) expression and 2-NBDG uptake. Accordingly, insulin-induced increase in GLUT2 expression and 2-NBGD uptake was significantly inhibited by 3DG treatment. 3DG-mediated reduction in GLUT2 expression contributes to the attenuation of insulin-induced GLP-1 secretion under high-glucose conditions in part through the insulin-PI3K/Akt/GLUT2 pathway in STC-1 cells. We conclude that 3DG interferes with insulin signaling and attenuates insulin action on glucose-induced GLP-1 secretion in STC-1 cells.
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Desoxiglucosa/análogos & derivados , Células Enteroendocrinas/metabolismo , Péptido 1 Similar al Glucagón/biosíntesis , Glucosa/metabolismo , Insulina/metabolismo , Transducción de Señal , Animales , Línea Celular , Desoxiglucosa/metabolismo , Transportador de Glucosa de Tipo 2/metabolismo , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor de Insulina/metabolismoRESUMEN
In an effort to develop new drug candidates with enhanced anticancer activity, our team synthesized and assessed the cytotoxicity of a series of novel xanthone derivatives with two longer 3,6-disubstituted amine carbonyl methoxy side chains on either benzene ring in selected human cancer cell lines. An MTT assay revealed that a set of compounds with lower IC50 values than the positive control, 5-FU, exhibited greater anticancer effects. The most potent derivative (XD8) exhibited anticancer activity in MDA-MB-231, PC-3, A549, AsPC-1, and HCT116 cells lines with IC50 values of 8.06, 6.18, 4.59, 4.76, and 6.09µM, respectively. Cell cycle analysis and apoptosis activation suggested that the mechanism of action of these derivatives includes cell cycle regulation and apoptosis induction.
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Antineoplásicos/farmacología , Xantonas/farmacología , Antineoplásicos/síntesis química , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Caspasa 7/metabolismo , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Humanos , Relación Estructura-Actividad , Xantonas/síntesis químicaRESUMEN
Osthole, a natural coumarin derivative, has been shown to have anti-tumor and anti-inflammatory activity. However, the effect of osthole on anti-tumor immune responses in tumor-bearing mice has not yet been reported. In the present study, osthole treatment did not affect the weight and the coefficient of thymus and spleen in tumor-bearing mice with hepatocellular carcinoma (HCC). However, osthole administration significantly elevated the proportion and number of the splenic CD8(+) T cells, the proportion of CD4(+) T and CD8(+) T cells in tumor tissues, and the levels of IL-2 and TNF-α in the serum of HCC tumor-bearing mice. Our results suggested that osthole could promote the activation of the tumor-infiltrating CD4(+) T and CD8(+) T cells, and elevate the proportion of CD4(+) and CD8(+) effector T cells. Osthole treatment also significantly decreased the proportion of CD4(+)CD25(+)Foxp3(+) regulatory T cells in the spleen. Taken together, osthole could enhance the T cell mediated anti-tumor immune responses in the tumor-bearing mice with HCC.
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Adyuvantes Inmunológicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Cumarinas/farmacología , Inmunidad Celular/efectos de los fármacos , Neoplasias Hepáticas Experimentales/tratamiento farmacológico , Animales , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Neoplasias Hepáticas Experimentales/inmunología , Neoplasias Hepáticas Experimentales/patología , Ratones , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/patologíaRESUMEN
The sodium-coupled glucose transporter-1 (SGLT1)-based oral rehydration solution (ORS) used in the management of acute diarrhea does not substantially reduce stool output, despite the fact that glucose stimulates the absorption of sodium and water. To explain this phenomenon, we investigated the possibility that glucose might also stimulate anion secretion. Transepithelial electrical measurements and isotope flux measurements in Ussing chambers were used to study the effect of glucose on active chloride and fluid secretion in mouse small intestinal cells and human Caco-2 cells. Confocal fluorescence laser microscopy and immunohistochemistry measured intracellular changes in calcium, sodium-glucose linked transporter, and calcium-activated chloride channel (anoctamin 1) expression. In addition to enhancing active sodium absorption, glucose increased intracellular calcium and stimulated electrogenic chloride secretion. Calcium imaging studies showed increased intracellular calcium when intestinal cells were exposed to glucose. Niflumic acid, but not glibenclamide, inhibited glucose-stimulated chloride secretion in mouse small intestines and in Caco-2 cells. Glucose-stimulated chloride secretion was not seen in ileal tissues incubated with the intracellular calcium chelater BAPTA-AM and the sodium-potassium-2 chloride cotransporter 1 (NKCC1) blocker bumetanide. These observations establish that glucose not only stimulates active Na absorption, a well-established phenomenon, but also induces a Ca-activated chloride secretion. This may explain the failure of glucose-based ORS to markedly reduce stool output in acute diarrhea. These results have immediate potential to improve the treatment outcomes for acute and/or chronic diarrheal diseases by replacing glucose with compounds that do not stimulate chloride secretion.
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Canales de Cloruro/metabolismo , Cloruros/metabolismo , Glucosa/metabolismo , Íleon/metabolismo , Mucosa Intestinal/metabolismo , Animales , Anoctamina-1 , Transporte Biológico , Células CACO-2 , Calcio/metabolismo , Quelantes/farmacología , Canales de Cloruro/efectos de los fármacos , Impedancia Eléctrica , Humanos , Íleon/efectos de los fármacos , Inmunohistoquímica , Mucosa Intestinal/efectos de los fármacos , Cinética , Masculino , Moduladores del Transporte de Membrana/farmacología , Ratones , Microscopía Confocal , Proteínas de Neoplasias/metabolismo , Sodio/metabolismo , Transportador 1 de Sodio-Glucosa/metabolismoRESUMEN
The tumor vascular system, which is critical to the survival and growth of solid tumors, has been an attractive target for anticancer research. Building on studies that show that some flavonoids have anticancer vascular effects, we developed and analyzed the flavonoid derivative R24 [3, 6-bis (2-oxiranylmethoxy)-9H-xanthen-9-one]. A CAM assay revealed that R24 disrupted neovascular formation; fewer dendrites were detected and overall dendritic length was shorter in the R24-treated chicken embryos. The antiproliferative effect of R24 was measured by MTT assay in A549 (lung cancer), AsPC-1 (pancreatic cancer), HCT-116 (colorectal cancer), and PC-3 (prostate cancer) cell lines. R24 reduced proliferation with an IC50 of 3.44, 3.59, 1.22, and 11.83 µM, respectively. Cell-cycle analysis and Annexin-V/propidium iodide staining showed that R24 induced apoptosis. In addition, R24 regulated intracellular ROS production in a dose-dependent manner. CM-H2DCFDA staining indicated that intracellular ROS production increased with the R24 dose. In summary, we found that R24 exhibits potent antiangiogenic and antiproliferative effects, induces apoptosis, and promotes ROS production.
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Flavonoides/farmacología , Neoplasias/irrigación sanguínea , Neovascularización Patológica/prevención & control , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , HumanosRESUMEN
Optimal triage biodosimetry would include risk stratification within minutes, and it would provide useful triage despite heterogeneous dosimetry, cytokine therapy, mixed radiation quality, race, and age. For regulatory approval, the U.S. Food and Drug Administration (FDA) Biodosimetry Guidance requires suitability for purpose and a validated species-independent mechanism. Circulating cell-free DNA (cfDNA) concentration assays may provide such triage information. To test this hypothesis, cfDNA concentrations were measured in unprocessed monkey plasma using a branched DNA (bDNA) technique with a laboratory developed test. The cfDNA levels, along with hematopoietic parameters, were measured over a 7-day period in Rhesus macaques receiving total body radiation doses ranging from 1 to 6.5 Gy. Low-dose irradiation (0-2 Gy) was easily distinguished from high-dose whole-body exposures (5.5 and 6.5 Gy). Fold changes in cfDNA in the monkey model were comparable to those measured in a bone marrow transplant patient receiving a supralethal radiation dose, suggesting that the lethal threshold of cfDNA concentrations may be similar across species. Average cfDNA levels were 50 ± 40 ng/mL [±1 standard deviation (SD)] pre-irradiation, 120 ± 13 ng/mL at 1 Gy; 242 ± 71 ng/mL at 2 Gy; 607 ± 54 at 5.5 Gy; and 1585 ± 351 at 6.5 Gy (±1 SD). There was an exponential increase in cfDNA concentration with radiation dose. Comparison of the monkey model with the mouse model and the Guskova model, developed using Chernobyl responder data, further demonstrated correlation across species, supporting a similar mechanism of action. The test is available commercially in a Clinical Laboratory Improvement Amendments (CLIA) ready form in the U.S. and the European Union. The remaining challenges include developing methods for further simplification of specimen processing and assay evaluation, as well as more accurate calibration of the triage category with cfDNA concentration cutoffs.
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Ácidos Nucleicos Libres de Células , Macaca mulatta , Triaje , Animales , Ácidos Nucleicos Libres de Células/sangre , Triaje/métodos , Humanos , Masculino , Ratones , Relación Dosis-Respuesta en la Radiación , Radiometría/métodos , Irradiación Corporal TotalRESUMEN
BACKGROUND: Gastric motility disorder is an increasingly common problem among people with diabetes. Neurotransmitters have been recognized as critical regulators in the process of gastric motility. Previous study has shown that herb pair huanglian-banxia (HL-BX) can improve gastric motility, but the underlying mechanism is still unclear. The aim of this study was to further investigate the role of HL-BX in modulating brain-gut neurotransmission to promote gastric motility in diabetic rats, and to explore its possible mechanism. METHODS: The diabetic rats were divided into five groups. Gastric emptying rate, intestinal propulsion rate, body weight, and average food intake were determined. Substance P (SP), 5- hydroxytryptamine (5-HT), and glucagon-like peptide -1 (GLP-1) in the serum were measured by enzyme-linked immunosorbent assay. Dopamine (DA) and norepinephrine (NE) in the brain were analyzed by high-pressure liquid chromatography with a fluorescence detector. Protein expression of the tissues in the stomach and brain was determined by Western blot. KEY RESULTS: HL-BX reduced average food intake significantly, increased body weight, and improved gastric emptying rate and intestinal propulsion rate. HL-BX administration caused a significant increase in SP, GLP-1, and 5-HT, but a significant decrease in DA and NE. Interestingly, HL-BX regulated simultaneously the different expressions of MAPK and its downstream p70S6K/S6 signaling pathway in the stomach and brain. Moreover, berberine exhibited a similar effect to HL-BX. CONCLUSIONS: These results indicated that HL-BX promoted gastric motility by regulating brain-gut neurotransmitters through the MAPK signaling pathway. HL-BX and MAPK provide a potential therapeutic option for the treatment of gastroparesis.
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Diabetes Mellitus Experimental , Medicamentos Herbarios Chinos , Motilidad Gastrointestinal , Sistema de Señalización de MAP Quinasas , Animales , Masculino , Ratas , Encéfalo/metabolismo , Eje Cerebro-Intestino/fisiología , Diabetes Mellitus Experimental/metabolismo , Medicamentos Herbarios Chinos/farmacología , Motilidad Gastrointestinal/fisiología , Motilidad Gastrointestinal/efectos de los fármacos , Péptido 1 Similar al Glucagón/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/fisiología , Neurotransmisores/metabolismoRESUMEN
BACKGROUND: In recent studies, concentrations of cell-free circulating DNA (cf-DNA) have been correlated with clinical characteristics and prognosis in several diseases. The relationship between cf-DNA concentrations and the acute coronary syndrome (ACS) remains unknown. Moreover, no data are available for the detection cf-DNA in ACS by a branched DNA (bDNA)-based Alu assay. The aim of the present study was to investigate cf-DNA concentrations in ACS and their relationship with clinical features. METHODS: Plasma cf-DNA concentrations of 137 ACS patients at diagnosis, of 60 healthy individuals and of 13 patients with stable angina (SA) were determined using a bDNA-based Alu assay. RESULTS: ACS patients (median 2,285.0, interquartile range 916.4-4,857.3 ng/ml), especially in ST-segment elevation myocardial infarction patients (median 5,745.4, interquartile range 4,013.5-8,643.9 ng/ml), showed a signiï¬cant increase in plasma cf-DNA concentrations compared with controls (healthy controls: median 118.3, interquartile range 81.1-221.1 ng/ml; SA patients: median 202.3, interquartile range 112.7-256.1 ng/ml) using a bDNA-based Alu assay. Moreover, we found positive correlations between cf-DNA and Gensini scoring and GRACE (Global Registry of Acute Coronary Events) scoring in ACS. CONCLUSION: cf-DNA may be a valuable marker for diagnosing and predicting the severity of coronary artery lesions and risk stratification in ACS.
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Síndrome Coronario Agudo/diagnóstico , ADN/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Angina Estable/diagnóstico , Biomarcadores/metabolismo , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Medición de RiesgoRESUMEN
In the wake of the 9/11 terrorist attacks and the recent Level 7 nuclear event at the Fukushima Daiichi plant, there has been heightened awareness of the possibility of radiological terrorism and accidents and the need for techniques to estimate radiation levels after such events. A number of approaches to monitoring radiation using biological markers have been published, including physical techniques, cytogenetic approaches, and direct, DNA-analysis approaches. Each approach has the potential to provide information that may be applied to the triage of an exposed population, but problems with development and application of devices or lengthy analyses limit their potential for widespread application. We present a post-irradiation observation with the potential for development into a rapid point-of-care device. Using simple mitochondrial proteomic analysis, we investigated irradiated and nonirradiated murine mitochondria and identified a protein mobility shift occurring at 2-3 Gy. We discuss the implications of this finding both in terms of possible mechanisms and potential applications in bio-radiation monitoring.
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Radioisótopos de Cesio/efectos adversos , Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Proteómica , Traumatismos por Radiación/diagnóstico , Terrorismo , Irradiación Corporal Total/efectos adversos , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Mitocondrias/efectos de la radiación , Traumatismos por Radiación/metabolismo , Monitoreo de RadiaciónRESUMEN
Tumor hypoxia is probably the most important not yet measurable factor that predicts the outcome of cancer therapy. Hypoxic tumors are resistant to radiation, chemotherapy, and surgery. They signal tumor cells to grow, invade, survive cytotoxic-factor assault, and increase metastatic activity. Therapies aimed at reversing hypoxia-related treatment resistance or normalizing hypoxia are proven effective with level 1 evidence. The weak link remains the lack of satisfactory methods of measurement of tumor oxygenation.
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Hipoxia/tratamiento farmacológico , Neoplasias/irrigación sanguínea , Neoplasias/metabolismo , Oxígeno/análisis , Medicina de Precisión , Humanos , Neoplasias/terapiaRESUMEN
This study investigated, at the molecular level, mitochondrial responses to radiation. In three mouse strains, we found the following: (1) mitochondrial response to calcium stress was associated with a strain's susceptibility to γ-radiation; (2) γ-radiation increased this calcium stress response in a dose-responsive manner; (3) the mitochondrial DNA (mtDNA) copy number in the liver of the radiosensitive mouse strain was significantly lower, as compared to that of the radioresistant strain; (4) adenine nucleotide translocase (ANT) mRNA copy numbers were significantly lower in the radiosensitive strain; (5) the F1 offspring (BC/C57M) of radiosensitive females mated with radioresistant males exhibited a significant difference in calcium stress response from that of the radiation-resistant strain, but the reverse cross did not exhibit this difference; and (6) only those mitochondria extracted from the livers of irradiated BC/C57M mice exhibited a heightened calcium stress response. We propose that a genetic change in ANT and a postirradiation change involving either mtDNA-encoded protein replacement or altered mtDNA association fit these data.
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Mitocondrias Hepáticas/metabolismo , Mitocondrias Hepáticas/efectos de la radiación , Animales , Calcio/metabolismo , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Femenino , Rayos gamma/efectos adversos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Mitocondrias Hepáticas/genética , Translocasas Mitocondriales de ADP y ATP/metabolismo , Permeabilidad , Tolerancia a RadiaciónRESUMEN
In this study, we compared two in vitro collagen production assays ([(3)H]-proline incorporation and Sirius Red) for their ability to determine the pattern shift from soluble to deposited collagen. The effect of the antifibrotic agent, triptolide (TPL), on collagen production was also studied. The results showed that: (1) 48 h after NIH 3T3 (murine embryo fibroblast) and HFL-1(human fetal lung fibroblast) were exposed to transforming growth factor-beta 1 (TGF-ß), there was an increase in soluble collagen in the culture medium; (2) on day 4, soluble collagen declined, whereas deposited collagen increased; (3) Sirius Red was easier to use than [(3)H]-proline incorporation and more consistently reflected the collagen pattern shift from soluble to deposited; (4) the in vitro Sirius Red assay took less time than the in vivo assay to determine the effect of TPL. Our results suggest that: (a) the newly synthesized soluble collagen can sensitively evaluate an agent's capacity for collagen production and (b) Sirius Red is more useful than [(3)H]-proline because it is easier to use, more convenient, less time consuming, and does not require radioactive material.
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Compuestos Azo , Bioensayo , Colágeno/metabolismo , Embrión de Mamíferos/metabolismo , Feto/metabolismo , Fibroblastos/metabolismo , Pulmón/metabolismo , Animales , Antineoplásicos Alquilantes/farmacología , Células Cultivadas , Colorantes , Diterpenos/farmacología , Embrión de Mamíferos/citología , Embrión de Mamíferos/efectos de los fármacos , Compuestos Epoxi/farmacología , Feto/citología , Feto/efectos de los fármacos , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Humanos , Pulmón/citología , Pulmón/efectos de los fármacos , Ratones , Células 3T3 NIH , Fenantrenos/farmacología , Prolina/metabolismo , Factor de Crecimiento Transformador beta/farmacologíaRESUMEN
Although glycoproteins possess a variety of functional and structural roles in intracellular and intercellular activities, the effect of ionizing radiation (IR) on glycosylation is largely unknown. To explore this effect, we established a sandwich assay in which PHA-L, a phytohaemagglutinin that agglutinates leukocytes, was used as a coating layer to capture glycoproteins containing complex oligosaccharides; the bound glycoproteins were then measured. C57BL/6 mice were exposed to 0, 3, 6, or 10 Gy, and the plasma was collected at 6, 12, 18, 24, 48, 72, or 168 h and then analyzed for galactose/N-acetylgalactosamine (Gal/GalNAc) containing proteins. We found that (1) the sandwich assay accurately measured the level of glycoproteins, (2) 6-12 h after IR, the amount of glycoproteins containing GalNAc increased, and (3) at 72 and 168 h, 10 Gy was associated with a decrease in Gal/GalNAc. These IR-induced alterations might relate to the release of glycoproteins into the blood and the damage of the proteins and genes that are related to the glycosylation process.
Asunto(s)
Acetilgalactosamina/sangre , Galactosa/sangre , Glicoproteínas/sangre , Glicosilación/efectos de la radiación , Manosa/sangre , Irradiación Corporal Total , Acetilgalactosamina/análogos & derivados , Animales , Ensayo de Inmunoadsorción Enzimática , Masculino , Ratones , Ratones Endogámicos C57BL , Fitohemaglutininas/metabolismoRESUMEN
Various members of the fibroblast growth factor (FGF) family mitigate radiation-induced damage. We designed and synthesized the binding domain peptide of FGF-2 (FGF-P) with a dimer form resistant to peptidase and examined its mitigatory effect on murine bone marrow cells. NIH Swiss mice were exposed to different doses of total body irradiation (TBI) and treated with ten doses of 5 mg/kg FGF-P. We achieved the following results: (1) FGF-P stimulated the growth of bone marrow cells harvested from mice exposed to 3 Gy; (2) on day 25 after 6 Gy TBI, the number of leukocytes and granulocytes was higher in the FGF-P group than in the vehicle-alone group; (3) FGF-P significantly increased the number of pro-B and pre-B cells; and (4) FGF-P treatment in vivo increased the long-term hematopoietic stem cells (LT-HSC) in bone marrow. These data reveal the underlying mechanism by which FGF-P rescued a significant percentage of the exposed mice. The increase of LT-HSC in bone marrow leads to a concomitant increase of pro-B and pre-B cells followed by leukocytes and granulocytes, which in turn enhance immunity against infection.