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Objective: To determine how a combination of auricular acupuncture, acupoint application and the Doula instrument affects numerical rating scale (NRS) scores, labour time of puerperae and the Apgar scores of newborns during natural delivery. Methods: This is a retrospective study. From January 2021 to December 2022, clinical data were collected from 90 healthy primiparae who completed natural delivery at Baoding Maternal and Child Health Hospital. They were divided into two groups based on different perinatal intervention methods. While the Doula instrument was used for the control group's perinatal intervention, the study group received a combination of auricular acupuncture, acupoint application and the Doula instrument during their perinatal period. Results: The NRS score of the study group was lower than that of the control group, demonstrating that their intergroup difference is statistically significant (P < 0.05). The incubation period, the active phase of the first stage of labour and the time of the second and third stages of work are shorter in the study group than in the control group (P < 0.05). Intergroup comparison of their one and five minutes Apgar scores demonstrates no statistically significant differences (P > 0.05). Expression levels in the study group are higher than in the control group five minutes after delivery (P < 0.05). Conclusions: In this case, a perinatal intervention comprising auricular acupuncture, acupoint application and the Doula instrument was used for puerperae undergoing natural delivery.
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The rapid development of advanced material science boosts novel chemical analytical technologies for effective pretreatment and sensitive sensing applications in the fields of environmental monitoring, food security, biomedicines, and human health. Ionic covalent organic frameworks (iCOFs) emerge as a class of covalent organic frameworks (COFs) with electrically charged frames or pores as well as predesigned molecular and topological structures, large specific surface area, high crystallinity, and good stability. Benefiting from the pore size interception effect, electrostatic interaction, ion exchange, and recognizing group load, iCOFs exhibit the promising ability to extract specific analytes and enrich trace substances from samples for accurate analysis. On the other hand, the stimuli response of iCOFs and their composites to electrochemical, electric, or photo-irradiating sources endows them as potential transducers for biosensing, environmental analysis, surroundings monitoring, etc. In this review, we summarized the typical construction of iCOFs and focused on their rational structure design for analytical extraction/enrichment and sensing applications in recent years. The important role of iCOFs in the chemical analysis was fully highlighted. Finally, the opportunities and challenges of iCOF-based analytical technologies were also discussed, which may be beneficial to provide a solid foundation for further design and application of iCOFs.
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Estructuras Metalorgánicas , Humanos , Cromatografía de Gases , Suplementos Dietéticos , Electricidad , Monitoreo del Ambiente , IonesRESUMEN
OBJECTIVES: In the early stage of sepsis, identifying high-risk paediatric patients with a poor prognosis and providing timely and adequate treatment are critical. This study aimed to evaluate the effect of average body temperature within 24 hours of admission on the short-term prognosis of paediatric patients with sepsis. DESIGN: A retrospective cohort study. SETTING: A single-centre, tertiary care hospital in China, containing patient data from 2010 to 2018. PARTICIPANTS: 1144 patients with sepsis were included. INTERVENTION: None. PRIMARY AND SECONDARY OUTCOME MEASURES: The main outcome measure was in-hospital mortality, which was defined as death from any cause during hospitalisation. The secondary outcome was the length of hospital stay. RESULTS: The LOWESS method showed a roughly 'U'-shaped relationship between body temperature on the first day and in-hospital mortality. Multivariate logistic regression showed that severe hypothermia (OR 14.72, 95% CI 4.84 to 44.75), mild hypothermia (OR 3.71, 95% CI 1.26 to 10.90), mild hyperthermia (OR 3.41, 95% CI 1.17 to 9.90) and severe hyperthermia (OR 5.15, 95% CI 1.84 to 14.43) were independent risk factors for in-hospital mortality. Compared with other variables, the Wald χ2 value of temperature on the first day minus the degree of freedom was the highest. CONCLUSIONS: Whether hypothermic or hyperthermic, the more abnormal the temperature on the first day is, the higher the risk of in-hospital death in children with sepsis.
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Hipertermia Inducida , Hipotermia , Sepsis , Humanos , Niño , Estudios Retrospectivos , Mortalidad Hospitalaria , Enfermedad Crítica/terapia , Sepsis/terapia , Hipertermia , Unidades de Cuidados IntensivosRESUMEN
A general and adaptable method is proposed to reliably extract quantitative information from smartphone images of microfluidic sensors. By analyzing and processing the color information of selected standard substances, the influence of light conditions, device differences, and human factors could be significantly reduced. Machine learning and multivariate fitting methods were proved to be effective for chroma correction, and a key element was the training of sample size and the fitting form, respectively. A custom APP was developed and validated using a high-sensitivity chromium ion quantification paper chip. The average chroma deviations under different conditions were reduced by more than 75% in RGB color space, and the concentration test error was reduced by more than half compared with the commonly used method. The proposed approach could be a beneficial supplement to existing and potential colorimetry-based detection methods.
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Nine compounds were isolated and elucidated from this species, among which, two new compounds (1, 2) and seven known compounds (3-9). Their structures were determined by means of extensively spectroscopic analysis including HR-ESI-MS, 1H NMR, 13C NMR, HSQC and HMBC. The bioactivities evaluation was referred to the cytotoxic assay on four human tumor cell lines of the ethanol extract, different fractions and 6 compounds. The results demonstrated that the dichloromethane fraction showed the strongest cytotoxicity, followed by the ethyl acetate fraction. Compounds 4 and 6 had significant effects on SMMC-7721 and Hela cells.
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Antineoplásicos , Smilax , Humanos , Células HeLa , Smilax/química , Línea Celular Tumoral , Antineoplásicos/farmacología , Fitoquímicos/farmacología , Fitoquímicos/análisis , Extractos Vegetales/farmacología , Extractos Vegetales/químicaRESUMEN
This study aimed to investigate the effect of Jiaotai Pills on protein expression in the hippocampus of the rat model of chronic unpredictable mild stress(CUMS)-induced depression by quantitative proteomics and explore the anti-depression mechanism of Jiaotai Pills. The SD rats were randomized into control, model, Jiaotai Pills, and fluoxetine groups(n=8). Other groups except the control group were subjected to CUMS modeling for 4 weeks. After 4 weeks of continuous administration, the changes of behavior and pathological morphology of the hippocampal tissue were observed. Proteins were extracted from the hippocampal tissue, and bioinformatics analysis was performed for the differentially expressed proteins(DEPs) identified by quantitative proteomics. Western blot was employed to verify the key DEPs. The results showed that Jiaotai Pills significantly alleviated the depression behaviors and hippocampal histopathological changes in the rat model of CUMS-induced depression. A total of 5 412 proteins were identified in the hippocampus of rats, including 65 DEPs between the control group and the model group and 35 DEPs between the Jiaotai Pills group and the model group. There were 16 DEPs with the same trend in the Jiaotai Pills group and the control group, which were mainly involved in sphingolipid, AMPK, and dopaminergic synapse signaling pathways. The Western blot results of Ppp2r2b, Cers1, and Ndufv3 in the hippocampus were consistent with the results of proteomics. In conclusion, Jiaotai Pills may play an anti-depression role by modulating the levels of Ppp2r2b, Cers1, Ndufv3 and other proteins and regulating sphingolipid, AMPK, and dopaminergic synapse signaling pathways.
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Proteínas Quinasas Activadas por AMP , Depresión , Medicamentos Herbarios Chinos , Ratas , Animales , Ratas Sprague-Dawley , Depresión/tratamiento farmacológico , Proteínas Quinasas Activadas por AMP/metabolismo , Proteómica , Hipocampo , Estrés Psicológico/metabolismo , Esfingolípidos/metabolismo , Modelos Animales de EnfermedadRESUMEN
OBJECTIVE: To investigate the molecular mechanism underlying the anti-hepatic fibrosis activity of ethyl acetate fraction Dicliptera chinensis (L.) Juss. (EDC) in human hepatic stellate cells (HSCs) in vitro and in a carbon tetrachloride (CCl4)-induced hepatic fibrosis mouse model in vivo. METHODS: For in vitro study, HSCs were pre-treated with platelet-derived growth factor (10 ng/mL) for 2 h to ensure activation and treated with EDC for 24 h and 48 h, respectively. The effect of EDC on HSCs was assessed using cell counting kit-8 assay, EdU staining, transmission electron microscopy, immunofluorescence staining, and Western blot, respectively. For in vivo experiments, mice were intraperitoneally injected with CCl4 (2 ° L/g, adjusted to a 25% concentration in olive oil), 3 times per week for 6 weeks, to develop a hepatic fibrosis model. Forty 8-week-old male C57BL/6 mice were divided into 4 groups using a random number table (n=10), including control, model, positive control and EDC treatment groups. Mice in the EDC and colchicine groups were intragastrically administered EDC (0.5 g/kg) or colchicine (0.2 mg/kg) once per day for 6 weeks. Mice in the control and model groups received an equal volume of saline. Biochemical assays and histological examinations were used to assess liver damage. Protein expression levels of α -smooth muscle actin (α -SMA) and microtubule-associated protein light chain 3B (LC3B) were measured by Western blot. RESULTS: EDC reduced pathological damage associated with liver fibrosis, downregulated the expression of α -SMA and upregulated the expression of LC3B (P<0.05), both in HSCs and the CCl4-induced liver fibrosis mouse model. The intervention of bafilomycin A1 and rapamycin in HSCs strongly supported the notion that inhibition of autophagy enhanced α -SMA protein expression levels (P<0.01). The results also found that the levels of phosphoinositide (PI3K), p-PI3K, AKT, p-AKT, mammalian target of rapamycin (mTOR), p-mTOR, and p-p70S6K all decreased after EDC treatment (P<0.05). CONCLUSIONS: EDC has anti-hepatic fibrosis activity by inducing autophagy and might be a potential drug to be further developed for human liver fibrosis therapy.
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Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Acetatos , Animales , Autofagia , Tetracloruro de Carbono , Células Estrelladas Hepáticas , Hígado/patología , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Quinasas S6 Ribosómicas 70-kDa , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
BACKGROUND: Multi-modal therapy has attracted increasing attention as it provides enhanced effectiveness and potential stimulation of the immune community. However, low accumulation at the tumor sites and quick immune clearance of the anti-tumor agents are still insurmountable challenges. Hypothetically, cancer cell membrane (CCM) can homologously target the tumor whereas multi-modal therapy can complement the disadvantages of singular therapies. Meanwhile, moderate hyperthermia induced by photothermal therapy can boost the cellular uptake of therapeutic agents by cancer cells. RESULTS: CCM-cloaked indocyanine green (ICG)-incorporated and abraxane (PTX-BSA)-loaded layered double hydroxide (LDH) nanosheets (LIPC NSs) were fabricated for target efficient photo-chemotherapy of colorectal carcinoma (CRC). The CCM-cloaked LDH delivery system showed efficient homologous targeting and cytotoxicity, which was further enhanced under laser irradiation to synergize CRC apoptosis. On the other hand, CCM-cloaking remarkably reduced the uptake of LDH NSs by HEK 293T cells and macrophages, implying mitigation of the side effects and the immune clearance, respectively. In vivo data further exhibited that LIPC NSs enhanced the drug accumulation in tumor tissues and significantly retarded tumor progression under laser irradiation at very low therapeutic doses (1.2 and 0.6 mg/kg of ICG and PTX-BSA), without observed side effects on other organs. CONCLUSIONS: This research has demonstrated that targeting delivery efficiency and immune-escaping ability of LIPC NSs are tremendously enhanced by CCM cloaking for efficient tumor accumulation and in situ generated hyperthermia boosts the uptake of LIPC NSs by cancer cells, a potential effective way to improve the multi-modal cancer therapy.
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Antineoplásicos/farmacología , Biomimética , Hidróxidos/farmacología , Hidróxidos/uso terapéutico , Nanocompuestos/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Femenino , Células HEK293 , Humanos , Hidróxidos/química , Hipertermia Inducida , Ratones , Ratones Endogámicos BALB C , Nanocompuestos/química , Neoplasias , Fototerapia , Escape del TumorRESUMEN
Cancer vaccines based on DNA encoding oncogenes have shown great potential in preclinical studies. However, the efficacy of DNA vaccines is limited by their weak immunogenicity because of low cellular internalisation and insufficient activation of dendritic cells (DCs). Calcium phosphate (CP) nanoparticles (NPs) are biodegradable vehicles with low toxicity and high loading capacity of DNA but suffer from stability issues. Here we employed adenosine triphosphate (ATP) as a dual functional agent, i.e. stabiliser for CP and immunological adjuvant, and applied the ATP-modified CP (ACP) NPs to the DNA vaccine. ACP NP-enhanced cellular uptake and improved transfection efficiency of DNA vaccine, and further showed the ability to activate DCs that are critical for them to prime T cells in cancer immunotherapy. As a result, a higher level of antigen-specific antibody with stronger tumour growth inhibition was achieved in mice immunised with the ACP-DNA vaccine. Overall, this one-step synthesised ACP NPs are an efficient nano-delivery system and nano-adjuvant for cancer DNA vaccines.
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Adenosina Trifosfato/química , Adyuvantes Inmunológicos/química , Fosfatos de Calcio/química , Nanopartículas/química , Vacunas de ADN/química , Animales , Reacciones Antígeno-Anticuerpo , Vacunas contra el Cáncer/administración & dosificación , Vacunas contra el Cáncer/química , Vacunas contra el Cáncer/inmunología , Línea Celular Tumoral , Células Dendríticas/citología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Inmunoterapia , Ratones , Ratones Endogámicos C57BL , Neoplasias/terapia , Trasplante Homólogo , Vacunación , Vacunas de ADN/inmunología , Vacunas de ADN/farmacologíaRESUMEN
This study aims to analyze the targets of the effective active ingredients of Scutellariae radix-Coptidis rhizoma drug pair (SCDP) in ulcerative colitis (UC) by network pharmacology and molecular docking and to explore the associated therapeutic mechanism. The effective active ingredients and targets of SCDP were determined from the TCMSP database, and the drug ingredient-target network was constructed using the Cytoscape software. The disease targets related to UC were searched in GeneCards, DisGeNET, OMIM, and DrugBank databases. Then, the drug ingredient and disease targets were intersected to construct a protein-protein interaction network through the STRING database. The Metascape database was used for the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the predicted targets of SCDP for UC. The Autodock software was used for molecular docking between the main active ingredient and the core target to evaluate the binding ability. SCDP has 43 effective active ingredients and 134 intersection targets. Core targets included AKT1, TP53, IL-6, VEGFA, CASP3, JUN, TNF, MYC, EGFR, and PTGS2. GO functional enrichment analysis showed that biological process was mainly associated with a cytokine-mediated signaling pathway, response to an inorganic substance, response to a toxic substance, response to lipopolysaccharide, reactive oxygen species metabolic process, positive regulation of cell death, apoptotic signaling pathway, and response to wounding. KEGG enrichment analysis showed main pathway concentrations were related to pathways in cancer, AGE-RAGE signaling pathway in diabetic complications, bladder cancer, IL-17 signaling pathway, apoptosis, p53 signaling pathway, and PI3K-Akt signaling pathway. The drug active ingredient-core target-key pathway network contains 41 nodes and 108 edges, of which quercetin, wogonin, baicalein, acacetin, oroxylin A, and beta-sitosterol are important active ingredients; PTGS2, CASP3, TP53, IL-6, TNF, and AKT1 are important targets; and the pathways involved in UC treatment include pathways in cancer, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic, apoptosis, IL-17 signaling pathway and herpes simplex infection. The active ingredient has a good binding capacity to the core target. SCDP key active ingredients are mainly quercetin, wogonin, baicalein, acacetin, oroxylin A, and beta-sitosterol, which function mainly by regulating targets, such as PTGS2, CASP3, TP53, IL-6, TNF, and AKT1, and are associated with multiple signaling pathways as pathways in cancer, PI3K-Akt signaling pathway, apoptosis, IL-17 signaling pathways.
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Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, insulin resistance and a systemic pro-inflammatory response. To date, no medications for NAFLD have been approved by relevant governmental agencies. Emerging evidence indicates that innate immune mechanisms are pivotal drivers of inflammation and other pathological manifestations observed in NAFLD. Hyperoside, a flavonoid compound mainly found in medicinal plants, has many biological effects, but the role of hyperoside in the physiological process of NAFLD is poorly defined. This study demonstrated that hyperoside exerts protective effects against high-fat diet (HFD)-induced NAFLD and regulates macrophage polarization in an Nr4A1-dependent manner. After 16 weeks on a HFD, hepatic steatosis, insulin resistance, and inflammatory responses were significantly ameliorated in hyperoside-treated HFD-fed wild-type mice, and hyperoside facilitated the polarization of macrophages from the pro-inflammatory M1 to the anti-inflammatory M2 subtype. Nr4A1 was found to be upregulated in hyperoside-treated HFD-fed mice, and hyperoside did not improve HFD-induced NAFLD or regulate macrophage polarization in Nr4A1-deficient mice. In conclusion, hyperoside may have therapeutic potential in preventing the pathological progression of NAFLD.
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Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/metabolismo , Quercetina/análogos & derivados , Animales , Dieta Alta en Grasa , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/metabolismo , Macrófagos/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Miembro 1 del Grupo A de la Subfamilia 4 de Receptores Nucleares/genética , Quercetina/farmacología , Quercetina/uso terapéuticoRESUMEN
With the increased demand for petroleum and petroleum products from all parts of the society, environmental pollution caused by petroleum development and production processes is becoming increasingly serious. Soil pollution caused by petroleum seriously affects environmental quality in addition to human lives and productivity. At present, petroleum in soil is mainly degraded by biological methods. In their natural state, native bacteria in the soil spontaneously degrade petroleum pollutants that enter the soil; however, when the pollution levels increase, the degradation rates decrease, and it is necessary to add nutrients, dissolved oxygen, biosurfactants and other additives to improve the degradation ability of the native bacteria in the soil. The degradation process can also be enhanced by adding exogenous petroleum-degrading bacteria, microbial immobilization technologies, and microbial fuel cell technologies.
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Contaminación por Petróleo , Petróleo , Contaminantes del Suelo , Biodegradación Ambiental , Humanos , Hidrocarburos , Contaminación por Petróleo/análisis , Suelo , Microbiología del Suelo , Contaminantes del Suelo/análisisRESUMEN
BACKGROUND: Gegen Qinlian (GGQL) decoction is a common Chinese herbal compound for the treatment of ulcerative colitis (UC). In this study, we aimed to identify its molecular target and the mechanism involved in UC treatment by network pharmacology and molecular docking. Material and Methods. The active ingredients of Puerariae, Scutellariae, Coptis, and Glycyrrhiza were screened using the TCMSP platform with drug-like properties (DL) ≥ 0.18 and oral availability (OB) ≥ 30%. To find the intersection genes and construct the TCM compound-disease regulatory network, the molecular targets were determined in the UniProt database and then compared with the UC disease differential genes with P value < 0.005 and â£log2 (fold change) | >1 obtained in the GEO database. The intersection genes were subjected to protein-protein interaction (PPI) construction and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. After screening the key active ingredients and target genes, the AutoDock software was used for molecular docking, and the best binding target was selected for molecular docking to verify the binding activity. RESULTS: A total of 146 active compounds were screened, and quercetin, kaempferol, wogonin, and stigmasterol were identified as the active ingredients with the highest associated targets, and NOS2, PPARG, and MMP1 were the targets associated with the maximum number of active ingredients. Through topological analysis, 32 strongly associated proteins were found, of which EGFR, PPARG, ESR1, HSP90AA1, MYC, HSPA5, AR, AKT1, and RELA were predicted targets of the traditional Chinese medicine, and PPARG was also an intersection gene. It was speculated that these targets were the key to the use of GGQL in UC treatment. GO enrichment results showed significant enrichment of biological processes, such as oxygen levels, leukocyte migration, collagen metabolic processes, and nutritional coping. KEGG enrichment showed that genes were particularly enriched in the IL-17 signaling pathway, AGE-RAGE signaling pathway, toll-like receptor signaling pathway, tumor necrosis factor signaling pathway, transcriptional deregulation in cancer, and other pathways. Molecular docking results showed that key components in GGQL had good potential to bind to the target genes MMP3, IL1B, NOS2, HMOX1, PPARG, and PLAU. CONCLUSION: GGQL may play a role in the treatment of ulcerative colitis by anti-inflammation, antioxidation, and inhibition of cancer gene transcription.
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Colitis Ulcerosa/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Terapia Molecular Dirigida , Colitis Ulcerosa/genética , Regulación hacia Abajo/genética , Evaluación Preclínica de Medicamentos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Chaperón BiP del Retículo Endoplásmico , Ontología de Genes , Humanos , Medicina Tradicional China , Simulación del Acoplamiento Molecular , Mapeo de Interacción de Proteínas , Termodinámica , Regulación hacia Arriba/genéticaRESUMEN
Since late 2010, outbreaks of porcine epidemic diarrhea (PED) have been reported in the swine industry in China. A variant PEDV strain that differs from strain CV777 causes prevalent PEDV infections which commercial vaccines based on CV777 cannot provide complete protection. In this study, we designed a new vaccine based on the epidemic PEDV strain AH2012/12, adjuvanted with flagellin, a mucosal adjuvant that induces mucosal and systemic production of IgA. Three groups of pregnant sows were immunized twice, with a 14-day interval, with PEDV adjuvanted with flagellin, PEDV alone, or PBS before farrowing, and newborn piglets from each group were selected and challenged with PEDV. Immunization with this vaccine elicited high levels of IgG, IgA, and neutralizing antibodies in the serum and colostrum of sows, and newborn piglets were protected against PEDV while suckling. This study should guide the prevention and control strategies for PEDV infection, thereby reducing the losses associated with this virus.
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Infecciones por Coronavirus/veterinaria , Flagelina/administración & dosificación , Virus de la Diarrea Epidémica Porcina/inmunología , Enfermedades de los Porcinos/prevención & control , Vacunas Virales/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Animales , Animales Recién Nacidos , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Línea Celular , Calostro/química , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/prevención & control , Femenino , Flagelina/inmunología , Inmunización , Embarazo , Porcinos , Enfermedades de los Porcinos/patología , Vacunas de Productos Inactivados/inmunología , Vacunas Virales/administración & dosificaciónRESUMEN
A series of seco-sativene sesquiterpenoids (1-11) including two new natural products (2 and 3), four new analogues (4-7), and six known analogues, helminthosporic acid (1), drechslerine A (8), drechslerine B (9), helminthosporol (10), helminthosporal acid (11), and isosativenediol (12), were purified from the endophytic fungus Cochliobolus sativus isolated from a desert plant, Artemisia desertorum. The stereochemistry of helminthosporic acid (1) was established for the first time by X-ray diffraction, and the structures including relative and absolute configurations of these new compounds were determined by NMR and CD spectra together with biosynthetic considerations. Compounds 5-7 are the first seco-sativene sesquiterpenoids possessing a glucose group on C-15, C-15, and C-14, respectively. Compounds 1, 7, 9, and 11 displayed strong phytotoxic effects on corn leaves by producing visible lesions, and helminthosporic acid (1) was shown to promote division of leaves and roots of Arabidopsis thaliana with a dose-dependent relationship.
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Artemisia/microbiología , Ascomicetos/química , Endófitos/química , Sesquiterpenos/química , Sesquiterpenos/farmacología , Arabidopsis , Dicroismo Circular , Espectroscopía de Resonancia Magnética , Estructura Molecular , Hojas de la Planta/efectos de los fármacos , Hojas de la Planta/crecimiento & desarrollo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Plantones/efectos de los fármacos , Espectrofotometría Ultravioleta , Difracción de Rayos X , Zea mays/efectos de los fármacosRESUMEN
Pseudoprotodioscin (PPD), a phytoestrogen isolated from Dioscorea nipponica Makino, is recognized to possess anti-inflammatory and antiadipogenic capacities. However, little is known about the antiatherosclerotic effects of PPD and the underlying mechanisms. Here, the contribution of estrogen receptors (ERs) and inflammation to PPD-mediated amelioration of endothelial dysfunction has been fully assessed. PPD administration alleviated atherosclerotic lesions by lowering total cholesterol in ovariectomized apoE-/- mice fed a high-cholesterol diet. Molecular docking analysis suggested a selective interaction of PPD with ERα. Upon PPD treatment, ERα and endothelial nitric oxide synthase (eNOS) protein levels were increased, whereas cell adhesion molecule and monocyte chemoattractant protein-1 (MCP-1) mRNA levels were suppressed in human umbilical vein endothelial cells (HUVECs) after injury caused by oxidized low-density lipoprotein (ox-LDL). These effects could be abolished by an ERα antagonist or a NOS inhibitor. Whereas, PPD can ERα-independently suppress TNFα expression in peritoneal macrophages upon LPS induction. Estrogen deficiency induced inflammatory phenotypes in perivascular adipose tissue (PAT), which could be partially attenuated by PPD. The increased release of adiponectin in PAT after PPD treatment is in accordance with previous reported data showing that adiponectin exerts anti-inflammatory effects in multiple cell types. ERα-dependent antiadipogenic effects of PPD were also detected in PAT-derived stromal cells. The present study reveals a novel mechanism through which PPD exerts estrogenic and anti-inflammatory properties in atherosclerosis-prone mice. Thus, PPD is a promising compound which has potential therapeutic effects on atherosclerotic cardiovascular diseases in postmenopausal women.
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Antiinflamatorios/uso terapéutico , Aterosclerosis/tratamiento farmacológico , Diosgenina/análogos & derivados , Estrógenos/uso terapéutico , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Antiinflamatorios/farmacología , Aorta Torácica/efectos de los fármacos , Aorta Torácica/patología , Aorta Torácica/fisiopatología , Apoptosis/efectos de los fármacos , Aterosclerosis/patología , Aterosclerosis/fisiopatología , Células Cultivadas , Quimiocina CCL2/genética , Diosgenina/farmacología , Diosgenina/uso terapéutico , Receptor alfa de Estrógeno/genética , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/genética , Receptor beta de Estrógeno/metabolismo , Estrógenos/farmacología , Femenino , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Malondialdehído/metabolismo , Ratones Noqueados para ApoE , Simulación del Acoplamiento Molecular , Óxido Nítrico Sintasa de Tipo III/metabolismo , Posmenopausia , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Obesity is associated with cancer risk and its link with liver cancer is particularly strong. Obesity causes non-alcoholic fatty liver disease (NAFLD) that could progress to hepatocellular carcinoma (HCC). Chronic inflammation likely plays a key role. We carried out a bioassay in the high-fat diet (HFD)-fed C57BL/6J mice to provide insight into the mechanisms of obesity-related HCC by studying γ-OHPdG, a mutagenic DNA adduct derived from lipid peroxidation. In an 80-week bioassay, mice received a low-fat diet (LFD), high-fat diet (HFD), and HFD with 2% Theaphenon E (TE) (HFD+TE). HFD mice developed a 42% incidence of HCC and LFD mice a 16%. Remarkably, TE, a standardized green tea extract formulation, completely blocked HCC in HFD mice with a 0% incidence. γ-OHPdG measured in the hepatic DNA of mice fed HFD and HFD+TE showed its levels increased during the early stages of NAFLD in HFD mice and the increases were significantly suppressed by TE, correlating with the tumor data. Whole-exome sequencing showed an increased mutation load in the liver tumors of HFD mice with G>A and G>T as the predominant mutations, consistent with the report that γ-OHPdG induces G>A and G>T. Furthermore, the mutation loads were significantly reduced in HFD+TE mice, particularly G>T, the most common mutation in human HCC. These results demonstrate in a relevant model of obesity-induced HCC that γ-OHPdG formation during fatty liver disease may be an initiating event for accumulated mutations that leads to HCC and this process can be effectively inhibited by TE. Cancer Prev Res; 11(10); 665-76. ©2018 AACR.
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Carcinoma Hepatocelular/prevención & control , Aductos de ADN/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Neoplasias Hepáticas Experimentales/prevención & control , Extractos Vegetales/administración & dosificación , Animales , Carcinogénesis/efectos de los fármacos , Carcinogénesis/genética , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/patología , Dieta Alta en Grasa/efectos adversos , Ensayos de Selección de Medicamentos Antitumorales , Incidencia , Hígado/efectos de los fármacos , Hígado/patología , Neoplasias Hepáticas Experimentales/epidemiología , Neoplasias Hepáticas Experimentales/etiología , Neoplasias Hepáticas Experimentales/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Tasa de Mutación , Obesidad/complicaciones , Obesidad/etiología , Obesidad/patología , Extractos Vegetales/química , Polifenoles/administración & dosificación , Té/química , Secuenciación del ExomaRESUMEN
To understand the effects of drought stress on C, N and P stoichiometry in different organs of Ulmus pumila, U. pumila seedlings were grown under suitable water level, mild, moderate and serious water stress treatment, i.e., 80%, 65%, 50% and 35% of field water holding capacity. The results showed that drought stress increased C content in leaves, stems, coarse and fine roots, N content in leaves, stems and coarse roots, and P content in fine roots, but decreased P content in leaves, stems and coarse roots. Moreover, C:N in leaves and stems decreased, while C:P and N:P in leaves, stems and coarse roots increased and in fine roots reduced in response to drought stresses. There were significant correlations of C content among different organs, while N content was not correlated with P content in all organs. Soil water content was negatively related to C content in all organs, N content in leaves, P content and C:N in fine roots, C:P and N:P in leaves, stems and coarse roots. There were positive relationships between the soil water content and N content in fine roots, P content in leaves, stems and coarse roots, C:P and N:P in fine roots. These findings indicated that the absorption and upward translocation of N and P of U. pumila seedlings were influe-nced by drought stress. Nitrogen limitation for the growth of U. pumila seedlings was found. With the increases of drought stress, however, P limitation was gradually enhanced.
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Carbono/química , Sequías , Nitrógeno/química , Fósforo/química , Ulmus , China , Hojas de la Planta , Raíces de Plantas , Plantones , AguaRESUMEN
The bimolecular gas-phase reaction of ground-state atomic silicon (Si; 3P) with disilane (Si2H6; 1A1g) was explored under single-collision conditions in a crossed molecular beam machine at a collision energy of 21 kJ mol-1. Combined with electronic structure calculations, the results suggest the formation of Si3H4 isomer(s) along with molecular hydrogen via indirect scattering dynamics through Si3H6 collision complex(es) and intersystem crossing from the triplet to the singlet surface. The nonadiabatic reaction dynamics can synthesize the energetically accessible singlet Si3H4 isomers in overall exoergic reaction(s) (-93 ± 21 kJ mol-1). All reasonable reaction products are either cyclic or hydrogen-bridged suggesting extensive isomerization processes from the reactants via the initially formed collision complex(es) to the fragmenting singlet intermediate(s). The underlying chemical dynamics of the silicon-disilane reaction are quite distinct from the isovalent carbon-ethane system that does not depict any reactivity at all, and open the door for an unconventional gas phase synthesis of hitherto elusive organosilicon molecules under single-collision conditions.
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Objective To observe the effect of clopidogrel on plasma protein binding rates of gin- senoside Rg1. Methods Concentrations of ginsenoside Rg1 were measured in fetal bovine serum and phosphate buffered solution (PBS). Samples were randomly divided into ginsenoside Rg1 groups (low: 0.4; middle: 1. 0; high 5. 0 mg/L, respectively) and clopidogrel combined ginsenoside Rg1 groups (low: 0. 4 mg/L +2. 0 mg/L clopidogrel; middle: 1. 0 mg/L +2. 0 mg/L clopidogrel; high: 5. 0 mg/L +2. 0 mg/L clo- pidogrel). The effect of clopidogrel on plasma protein binding rates of ginsenoside Rgl was observed u- sing equilibrium dialysis. Then 3-dimensional structure of bovine serum albumin (BSA) was constructed using homology modeling. On this basis, binding effect of small compounds (ginsenoside Rg1 and clopi- dogrel) and BSA was observed using molecular docking method. Results The serum protein binding rate was 11. 2% ±2. 1% in the low dose ginsenoside Rg1 group, 13. 4% ±2. 2% in the middle dose ginsenoside Rgl group, and 14. 6% ±1. 4% in the high dose ginsenoside Rg1 group, respectively. It was 6. 5% ±2. 3% in the clopidogrel combined low dose ginsenoside Rg1 group, 9. 2% ±1. 5% in the clopi- dogrel combined middle dose ginsenoside Rg1 group, 12.1% ± 1. 7% in the clopidogrel combined high dose ginsenoside Rg1 group, respectively. They were lower in clopidogrel combined ginsenoside Rg1 groups than in ginsenoside Rg1 groups with statistical difference (P <0. 05). Results of molecular doc- king showed that competitive binding effect existed between compounds (ginsenoside Rg1 and clopi- dogrel) and BSA. Conclusion Results of equilibrium dialysis and molecular docking comprehensively in- dicated clopidogrel had effect on plasma protein binding rate of ginsenoside Rg1.