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Near-infrared-II fluorescence imaging (NIR-II FI) has become a powerful imaging technique for disease diagnosis owing to its superiorities, including high sensitivity, high spatial resolution, deep imaging depth, and low background interference. Despite the widespread application of conjugated polymer nanoparticles (CPNs) for NIR-II FI, most of the developed CPNs have quite low NIR-II fluorescence quantum yields based on the energy gap law, which makes high-sensitivity and high-resolution imaging toward deep lesions still a huge challenge. This work proposes a nanoengineering strategy to modulate the size of CPNs aimed at optimizing their NIR-II fluorescence performance for improved NIR-II phototheranostics. By adjusting the initial concentration of the synthesized conjugated polymer, a series of CPNs with different particle sizes are successfully prepared via a nanoprecipitation approach. Results show that the NIR-II fluorescence brightness of CPNs gradually amplifies with decreasing particle size, and the optimal CPNs, NP0.2, demonstrate up to a 2.05-fold fluorescence enhancement compared with the counterpart nanoparticles. With the merits of reliable biocompatibility, high photostability, and efficient light-heat conversion, the optimal NP0.2 has been successfully employed for NIR-II FI-guided photothermal therapy both in vitro and in vivo. Our work highlights an effective strategy of nanoengineering to improve the NIR-II performance of CPNs, advancing the development of NIR-II FI in life sciences.
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Nanopartículas , Terapia Fototérmica , Polímeros , Nanopartículas/uso terapéutico , Imagen Óptica/métodos , Fototerapia , Línea Celular TumoralRESUMEN
The adverse effects of chronic heat stress (CHS)-induced fatty liver syndrome on laying hens during the egg-producing stages have been wildly documented. However, until nowadays, the CHS responses of growing laying hens as well as its alleviating effects of vitamin C are rarely reported. In this study, 12-wk-old laying hens were subjected to CHS at 36 °C for 10 h/d for 3 wk with or without dietary supplementation of 300 mg/kg vitamin C. Results showed that CHS significantly impaired the growth performances and the liver functions of birds, as characterized by reduced feed intake and body weight, increased hepatic lipid accumulation and serum concentrations of TG, ALT, and AST, as well as the abnormal expression patterns of the lipid metabolism-related genes. Vitamin C supplementation successfully mitigated the lipid accumulation, while showing no alleviating effect on the serum contents of ALT or AST, which are two key indicators of liver functions. Metabolomic analysis based on UPLC-Q-TOF/MS identified 173 differential metabolites from the HS and HSV group samples, and they are mainly enriched in the pathways related to the cellular components, vitamin and amino acid metabolism and energy substance metabolism. The results indicate that CHS-induced hepatic lipid deposition in growing laying hens is effectively alleviated by dietary supplementation of vitamin C, which is probably resulted from the alterations of hepatocellular metabolic patterns.
Chronic heat stress (CHS)-induced fatty liver syndrome (FLS) is one of the major problems faced in poultry industry. However, the heat stress response as well as the alleviating strategies for growing laying hens is rarely concerned until nowadays. In this study, 12-wk-old laying hens were subjected to the CHS condition with or without dietary supplementation of 300 mg/kg vitamin C, we found that CHS can also remarkably impair the growth performance and liver functions and induce the hepatic lipid metabolism disorders in the growing laying hens. Vitamin C supplementation successfully mitigated the hepatic lipid accumulation, while showed no alleviating effect on the liver functions. Metabolomic analysis further identified 173 differential metabolites between CHS and HSV groups, which are mainly enriched in the pathways including the cellular components, vitamin and amino acid metabolism and the energy substance metabolism. The results suggest that vitamin C supplementation can effectively alleviate the hepatic lipid deposition in growing laying hens under CHS probably through altering their energy metabolism patterns.
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Ácido Ascórbico , Suplementos Dietéticos , Animales , Femenino , Ácido Ascórbico/farmacología , Suplementos Dietéticos/análisis , Dieta/veterinaria , Metabolismo de los Lípidos , Pollos/fisiología , Vitaminas/metabolismo , Respuesta al Choque Térmico , Hígado/metabolismo , Lípidos , Alimentación Animal/análisisRESUMEN
A simple yet powerful D-A type-based NIR-II fluorophore (MTF) with mitochondria targeting was constructed. This mitochondrial targeting dye MTF exhibited not only a photothermal effect but also photodynamic performance, and was further fabricated with DSPE-mPEG to generate nanodots for in vivo experiments, achieving strong NIR-II fluorescence tracing of tumors and impressive NIR-II image-guided photodynamic therapy (PDT) and photothermal therapy (PTT).
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Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Terapia Fototérmica , Diagnóstico por Imagen , Mitocondrias , Fototerapia , Línea Celular TumoralRESUMEN
A multifunctional semiconducting nanoagonist with high photothermic conversion efficiency (86.2%) and alkyl radical generation ability was developed. The nanoagonist demonstrated excellent anticancer performance through NIR-II light-triggered photothermic/thermodynamic combinational therapy both in vitro and in vivo.
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Nanopartículas , Fototerapia , Línea Celular Tumoral , Terapia Combinada , TermodinámicaRESUMEN
Lake eutrophication remains a serious environmental problem of global significance, and phosphorus (P) plays a key role in lake eutrophication. Internal P loading, as a result of P release from sediments, is gathering more and more recognition as an important source governing the P availability in these ecosystems. Anoxic condition can promote the release of P associated with Fe oxides, which has already been a consensus. However, it is still unknown whether the anoxic conditions induced by eutrophication act to intensify or weaken the regeneration of organic P (Porg) in sediments. We selected the Hongfeng Reservoir, a typical sub-deep lake, to study the regeneration behaviours of C and P in the sediments buried before and after eutrophication. The results showed that Porg did not significantly increase with the rapid increase in organic C (Corg) since eutrophication occurred. Furthermore, the organic C/P ratio was much higher in sediments buried after eutrophication than in those buried before, which indicated that Porg regeneration had been significantly enhanced since eutrophication occurred. Based on C/P ratios, our estimation suggested that the Porg regeneration and P release from sediment to water approximately enhanced 45.2% ± 8.7% and 34.5% ± 9.8%, respectively. Elevated primary productivity (algae) and the corresponding hypoxic/anoxic condition, both caused by eutrophication, promoted P biogeochemical cycle in the sub-deep reservoir. This study further verifies the significant contribution of regenerated Porg to the internal P load, and highlights the importance of controlling P release from sediments in order to restore clear water ecosystems in sub-deep lakes or reservoirs.
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Fósforo , Contaminantes Químicos del Agua , China , Ecosistema , Monitoreo del Ambiente , Eutrofización , Sedimentos Geológicos , Lagos , Fósforo/análisis , Agua , Contaminantes Químicos del Agua/análisisRESUMEN
In this study, melanin from wild Auricularia auricula (WAA) was isolated using an ultra-high pressure (UHP)-assisted extraction method, and the physicochemical properties and antioxidant activity of WAA melanin were investigated. Under the optimized extraction conditions of a solid/liquid ratio of 1:30, a UHP of 450 MPa, a 22-min pressure holding time, a 1-mol/L NaOH concentration, and acid precipitation for 8 h, the WAA melanin extraction yield was 7.9 ± 0.16%. Moreover, the results showed that the surface of WAA melanin lacked structural order. Most melanin showed an average diameter of 1000 nm. WAA melanin had strong absorption at a wavelength of 210 nm and displayed typical characteristic absorption peaks. Moreover, WAA melanin contained 48.51% C, 6.88% H, 5.26% N, 0.45% S, and 38.90% O and may be a 3,4-dihydroxyphenylalanine melanin. An analysis of physicochemical properties showed that WAA melanin had good stability toward heat, light, and low concentrations of reducing agents and oxidizing agents. Furthermore, WAA melanin presented certain free radical scavenging activity. This study demonstrates that wild A. auricula melanin may have potential applications in the cosmetic or food industries as a natural antioxidant.
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Agaricales , Basidiomycota , Agaricales/química , Antioxidantes/análisis , Antioxidantes/farmacología , Auricularia , Basidiomycota/química , Melaninas/químicaRESUMEN
ABSTRACT: To explore the effects of nutritional support combined with insulin therapy on serum protein, procalcitonin (PCT), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), pentraxin-3 (PTX-3), and serum amylase (AMS) levels in patients with diabetic ketoacidosis complicated with acute pancreatitis.A total of 64 patients with diabetic ketoacidosis complicated with acute pancreatitis admitted to our hospital from January 2018 to February 2019 were enrolled in this prospective study. They were divided into the study group and the control group according to the random number table method, with 32 patients in each group. Patients in the study group were given nutritional support combined with insulin therapy, and patients in the control group were given insulin therapy.There were no significant differences in general data including age, gender, body mass index, course and type of diabetes, acute physiology and chronic health evaluation II, RANSON, CT grades between the 2 groups before treatment (all Pâ>â.05). After 7âdays of treatment, the clinical efficacy of the study group was significantly higher than that of the control group (study group vs control group, 94.44% vs 75.00%, Pâ<â.05). After 7âdays of treatment, the levels of prealbumin and albumin in the study group were significantly higher than those in the control group (Pâ<â.05). After 7âdays of treatment, the levels of PCT, CRP, TNF-α, PTX-3, and AMS in the 2 groups were significantly lower than those before treatment (Pâ<â.05), and the levels of PCT, CRP, TNF-α, PTX-3, and AMS in the study group were significantly lower than those in the control group. After 7âdays of treatment, the levels of IgG, IgM, and IgA in the 2 groups were significantly higher than those before treatment, and the levels of IgG, IgM, and IgA in the study group were significantly higher than those in the control group (Pâ<â.05).Nutritional support combined with insulin is obviously effective in the treatment of diabetic ketoacidosis complicated with acute pancreatitis, which can improve serum protein levels, reduce inflammatory response, improve immune function, and is worthy of clinical application.
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Cetoacidosis Diabética/sangre , Cetoacidosis Diabética/terapia , Insulina/uso terapéutico , Apoyo Nutricional , Pancreatitis/terapia , Enfermedad Aguda , Adulto , Anciano , Amilasas/sangre , Proteína C-Reactiva/análisis , Cetoacidosis Diabética/diagnóstico , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Persona de Mediana Edad , Pancreatitis/complicaciones , Polipéptido alfa Relacionado con Calcitonina/sangre , Polipéptido alfa Relacionado con Calcitonina/efectos de los fármacos , Estudios Prospectivos , Componente Amiloide P Sérico , Factor de Necrosis Tumoral alfa/sangreRESUMEN
OBJECTIVE: To study the effects of psychological intervention combined with dietary guidance on the quality of life and long-term efficacy of Bushen Quyu Decoction in the treatment of patients with advanced ovarian cancer. METHODS: 220 patients with advanced (stages III to IV) ovarian cancer in our hospital from May 2015 to October 2018 were selected and randomly divided into a control group and an observation group, with 110 cases in each group. The patients in the control group received basic nursing care and treatment with Bushen Quyu Decoction, and the patients in the observation group were combined with psychological intervention and dietary guidance on the basis of the treatment of the patients in the control group. The clinical efficacy, nursing satisfaction, treatment compliance, quality of life, negative emotion comparison, and long-term efficacy of the two groups were compared. Moreover, the changes of immune function indexes and the content of tumor markers were compared between the two groups. RESULTS: The total effective rate of treatment in the observation group (64.55%) was higher than that in the control group (31.82%). The nursing satisfaction of the observation group was 94.55%, the nursing satisfaction of the control group was 84.55%, and the difference was statistically significant (p < 0.01). The treatment compliance of the observation group was 98.18%, the treatment compliance of the control group was 82.73%, and the difference was statistically significant (p < 0.0001). After nursing, the Anxiety Self-Rating Scale (SAS) score and Self-Rating Depression Scale (SDS) score of the two groups of patients were decreased (∗p < 0.05), and the score of the observation group decreased more significantly (Δ p < 0.05). After nursing, the scores of the two groups of patients in social/family status, physical function, physiological function, and emotional status increased (∗p < 0.05), and the observation group was significantly higher than the control group (Δ p < 0.05). After nursing, the CD3+, CD4+, CD4+/CD8+ levels of the observation group were significantly higher than the control group (p < 0.05). The CD8+ level of the observation group was significantly lower than the control group (p < 0.05). After nursing, the levels of tumor markers in the two groups were decreased (∗p < 0.05), and the observation group was downregulated more significantly than the control group (Δ p < 0.05). The two-year cumulative survival rate of the observation group was 78.18%, and the two-year cumulative survival rate of the control group was 54.55%. The observation group was significantly higher than the control group (p < 0.05). CONCLUSIONS: Psychological intervention combined with dietary guidance can significantly improve the quality of life and mental state of patients with advanced ovarian cancer, enhance the patient's immune function, reduce the serum tumor markers carcinoembryonic antigen (CEA) and carbohydrate antigen (CA199) levels, and improve survival rate and survival time, which has important clinical significance.
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BACKGROUND: To create an animal model for diabetic ulcers with semi-Yin and semi-Yang (SYSY) syndrome and to study the pathological and metabolic features of SYSY syndrome. METHODS: Firstly, based on the clinical characteristics of the SYSY syndrome of diabetic ulcer, an animal model of diabetic ulcers with SYSY syndrome being full-thickness skin defects was created by injecting streptozotocin (STZ) intraperitoneally, infecting with Staphylococcus aureus, and gastrically administering senna. Secondly, the content and distribution patterns of collagen fibers, the expression of neutrophils and macrophage markers, angiogenesis, and the expression of IL-1ß and IL-10 in the rats with Yang syndrome, Yin syndrome, and SYSY syndrome of diabetic ulcers at different time points were detected. Representative traditional Chinese medicine (TCM) ointment of Yang syndrome, Yin syndrome, and SYSY syndrome was used to treat this animal model. The above indexes in each treatment group were detected. Finally, metabonomics was used to detect and analyze the changes of differential metabolites related to macrophage metabolism in Yang, Yin, and SYSY syndromes at different time points. RESULTS: An animal model of diabetic ulcers with SYSY syndrome was established. The pathological features of the SYSY syndrome group were chronic low-grade inflammatory reactions. On the third day, the SYSY syndrome group displayed lower expression of CD16, CD68, CD163, IL-1ß, and metabolites related to M1-type macrophages compared with other groups. On the seventh day, the SYSY syndrome group showed lower expression of CD31, IL-10, myeloperoxidase, and metabolites related to M2-type macrophages. Treatment with Chong He Ointment, a representative TCM ointment for SYSY syndrome, reversed the expression levels of these indexes and promoted wound healing in the SYSY group. CONCLUSION: SYSY syndrome presents a persistent pathological state of low inflammation, which may be caused by an insufficient activation of the M1-type metabolic pathway in macrophages in the early acute inflammatory stage, resulting in the incomplete clearance of pathogens and debris and continuous stimulation of macrophages to initiate the M1-type metabolic pathway. CD163, CD31, IL-10, and citric acid can be used as potential specific markers for the recovery and progression of SYSY syndrome.
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To obtain activated fractions, the ethanol extract (EE) of Hericium erinaceus was fractionated to get petroleum ether fraction (PEF), chloroform fraction (CF), ethyl acetate fraction (EAF) and n-butanol fraction (NF). Total phenol content (TPC) and total flavonoid content (TFC) in the fractions were determined, and the phenolic compounds were characterized and quantitated using liquid chromatography-electrospray ionization-mass spectrometry. Meanwhile, in vitro antioxidant and antihyperglycemic activities of extracts were evaluated respectively based on their 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging abilities as well as α-amylase and α-glucosidase inhibitory abilities. Finally, the inhibition modes of extracts on α-amylase and α-glucosidase were detected by kinetic assay. The results showed that TPC, TFC, and the content of phenolic compounds in the extracts were different. EAF contained the highest contents of both TPC and TFC and exhibited strongest inhibitory effects on α-amylase and α-glucosidase, with half maximal inhibitory concentration (IC50) values of 0.47 ± 0.02 and 0.63 ± 0.01 mg/mL, respectively. However, CF showed the highest scavenging abilities on DPPH and ABTS radicals, with IC50 values of 2.30 ± 0.12 and 1.72 ± 0.06 mg/mL, respectively. Correlation analysis showed that the high antihyperglycemic ability of EAF may be related to ferulic acid, whereas cinnamic acid may be responsible for the high antioxidant ability of CF. Furthermore, all fractions were found to exert inhibition on α-amylase and α-glucosidase in mixed-type and competitive manners, respectively. Overall, these results suggest that H. erinaceus has a potential effect on antihyperglycemic and antioxidant activity.
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Antioxidantes/farmacología , Hericium/química , Hipoglucemiantes/farmacología , Antioxidantes/aislamiento & purificación , Inhibidores de Glicósido Hidrolasas/farmacología , Humanos , Hipoglucemiantes/aislamiento & purificaciónRESUMEN
To improve the production of mycelial biomass and intracellular polysaccharide (IPS), the culture medium composition and culture condition were respectively optimized by response surface methodology and one-factor-at-a-time methodology. The impact of fermentation process on the transcription of genes involved in IPS synthesis was evaluated using quantitative reverse transcription PCR (qRT-PCR). The yield of biomass and IPS were increased by 150% and 177% under the optimized fermentation process, respectively. Moreover, the optimization of fermentation process significantly increased the transcription of genes involved in IPS synthesis, especially pgm-1, ugp, and pgi. This is the first exploration of gene transcription profile for IPS synthesis of Auricularia auricula-judae under submerged fermentation. These results could provide a potential tool for fermentation process optimization and transcriptional regulation of IPS biosynthesis in A. auricula-judae.
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Auricularia/genética , Auricularia/metabolismo , Genes Fúngicos , Polisacáridos/biosíntesis , Transcripción Genética , Auricularia/crecimiento & desarrollo , Medios de Cultivo , Fermentación , Fosfoglucomutasa/genética , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Development of near-infrared-II (NIR-II) light responsive nano-agents with high photothermal stability, high photothermal conversion efficiency (PCE), and excellent biocompatibility for photoacoustic (PA) imaging-guided photothermal therapy (PTT) is of tremendous significance. In spite of the superiority of organic semiconducting polymer nanoparticles (OSPNs) in PA imaging-guided PTT, the limited absorption in the first NIR (NIR-I) window and metastable nanostructure of OSPNs resulting from commonly used preparation methods based on nanoprecipitation or reprecipitation compromise their in vivo phototheranostic performance. Herein we design and synthesize a novel NIR-II absorbing organic semiconducting polymer amphiphile (OSPA) to enhance the structural stability of OSPNs. With prominent optical properties, low toxicity, and a suitable size, OSPA not only efficiently labels and kills cancer cells under NIR-II irradiation but also accumulates at the tumor of living mice upon intravenous injection, allowing efficient NIR-II light-triggered phototheranostics toward tumor. The developed OSPA has promising potential for fabricating multifunctional nanoplatforms to enable multimodal theranostics.
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Nanopartículas , Técnicas Fotoacústicas , Polímeros , Nanomedicina Teranóstica , Animales , Rayos Infrarrojos , Ratones , Fototerapia , SemiconductoresRESUMEN
Hydrogen sulfide (H2S) is a versatile modulator in mitochondria and involved in numerous diseases caused by mitochondrial dysfunction. Therefore, many efforts have been made to develop fluorescent probes for mitochondrial H2S detection. However, these cationic small molecule probes are inapplicable for in vivo imaging because of the shallow tissue penetration and poor biostability. Herein, a ratiometric upconversion luminescence nanoprobe with an acid-activated targeting strategy is developed for detecting and bioimaging of mitochondrial H2S. The merocyanine triphenylamine-merocyanine (TPAMC)-modified upconversion nanophosphors, acting as the targeting and response component, are encapsulated into a pH-sensitive husk, composed of 1,2-distearoyl- sn-glycero-3-phosphoethanolamine- N-[methoxy-(poly(ethylene glycol))-2000] (DSPE-PEG) and poly(l-histidine)- b-PEG, which improved the nanoprobe's stability during transport in vivo. Under lysosomal pH, the PEG shell is interrupted and the targeting sites are exposed to further attach to mitochondria. Taking advantage of the luminescence resonance energy transfer process between TPAMC and upconversion nanophosphors, the ratiometric detection of mitochondrial H2S can be achieved with high selectivity and sensitivity. Cellular testing reveals the precise targeting to mitochondria via a lysosome delivery process. Importantly, the nanoprobe can be used for monitoring mitochondrial H2S levels in living cells and colon cancer mouse models.
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Colorantes/química , Sulfuro de Hidrógeno/química , Lisosomas/química , Mitocondrias/metabolismo , Animales , Transporte Biológico , Sistemas de Liberación de Medicamentos , Colorantes Fluorescentes/química , Células HCT116 , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Luminiscencia , Células MCF-7 , Espectroscopía de Resonancia Magnética , Ratones , Trasplante de Neoplasias , Fósforo/química , Polietilenglicoles/química , Sensibilidad y Especificidad , Fracciones SubcelularesRESUMEN
To observe the efficacy of compound Dendrobium on Sprague Dawley rats (SD) hypertension model induced by "dietary disorders" and its relevant mechanism, totally 50 SD rats were fed with high-sugar, high-fat diet and alcohol for four weeks. According to the blood pressure after modeling, the rats were divided into model group, valsartan group (8 mg·kg⻹), low, medium and high-dose Dendrobium candidum compound groups (1.65, 3.30, 5.00 g·kg⻹), with 10 rats in each group, and the other 10 SD rats were also taken as the normal group. After four weeks of treatment, blood pressure was measured. Orbital blood was collected for the determination of serum cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL), calculation of atherosclerosis index (AI). Nitric acid reductase method was used to detect serum nitric oxide (NO); the levels of serum endothelin-1 (ET-1) and intercellular adhesion molecule-1 (ICAM-1) were measured by ELISA. The rats were put to death after the last administration, and the protein expressions of PI3K/AKT/eNOS in thoracic aorta of rats in each group were detected by Western blot. The aorta was separated and stained with hematoxylin-eosin (HE) to observe the changes in the endothelium and blood vessels in the thoracic aorta. Masson staining was used to observe the formation of aortic collagen. The expressions of nitric oxide synthase (eNOS) and ICAM-1 in aortic endothelial cells were observed by immunohistochemistry. In contrast, the results show D. candidum compound can significantly reduce the blood pressure in hypertensive rats, increase HDL-c, and reduce AI, while increasing serum NO content, decreasing ET-1 and ICAM-1 levels and promoting PI3K/AKT/NOS protein expressions. The lesion degree of the D. candidum compound group was reduced, and the collagen deposition was significantly reduced. Meanwhile, D. candidum compound can significantly increase the expression of eNOS, and reduce the formation of ICAM-1.Therefore, D. candidum compound has an obvious antihypertensive effect on hypertensive rats, which may be related to the increase in PI3K/AKT/eNOS signaling pathways and NO generation, the inhibition of the secretion of ICAM-1 and ET-1, the protection of the vascular endothelium and the improvement of aortic disease.
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Dendrobium/química , Hipertensión/tratamiento farmacológico , Transducción de Señal , Animales , Dieta Alta en Grasa , Carbohidratos de la Dieta , Óxido Nítrico/sangre , Óxido Nítrico Sintasa de Tipo III/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Melatonin, the major pineal secretory product, has a significant impact on the female reproductive system. Recently, the beneficial effects of melatonin on mammalian oocyte maturation and embryonic development have drawn increased attention. However, the exact underlying mechanisms remain to be fully elucidated. This study demonstrates that supplementing melatonin to in vitro maturation (IVM) medium enhances IVM rate, lipid droplets (LDs) accumulation as well as triglyceride content in porcine oocytes. Decrease of mitochondrial membrane potential, mitochondrial respiratory chain complex IV activity as well as mitochondrial reactive oxygen species (mROS) content indicated that melatonin induced a decrease of mitochondrial activity. The copy number of mitochondrial DNA (mtDNA) which encodes essential subunits of oxidative phosphorylation (OXPHOS), was not affected by melatonin. However, the expression of mtDNA-encoded genes was significantly down-regulated after melatonin treatment. The DNA methyltransferase DNMT1, which regulates methylation and expression of mtDNA, was increased and translocated into the mitochondria in melatonin-treated oocytes. The inhibitory effect of melatonin on the expression of mtDNA was significantly prevented by simultaneous addition of DNMT1 inhibitor, which suggests that melatonin regulates the transcription of mtDNA through up-regulation of DNMT1 and mtDNA methylation. Increase of triglyceride contents after inhibition of OXPHOS indicated that mitochondrial quiescence is crucial for LDs accumulation in oocytes. Taken together, our results suggest that melatonin-induced reduction in mROS production and increase in IVM, and LDs accumulation in porcine oocytes is mediated by mitochondrial quiescence.
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Metabolismo Energético/efectos de los fármacos , Técnicas de Maduración In Vitro de los Oocitos , Gotas Lipídicas/efectos de los fármacos , Melatonina/farmacología , Mitocondrias/efectos de los fármacos , Oocitos/efectos de los fármacos , Animales , Células Cultivadas , ADN (Citosina-5-)-Metiltransferasas/genética , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Metilación de ADN , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Complejo IV de Transporte de Electrones/metabolismo , Femenino , Regulación de la Expresión Génica , Gotas Lipídicas/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Oocitos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sus scrofa , Triglicéridos/metabolismoRESUMEN
Blood pressure variability (BPV) is associated with the development and progression of severe target organ damage (TOD). This study aims to evaluate the protective effect of paeoniflorin enriched extract from Radix Paeoniae Alba (PG) on BPV and TOD in spontaneously hypertensive rats (SHR). All SHR were orally treated with distilled water, metoprolol (MP, 20 mg/kg), and PG (PG-H, 90 mg/kg or PG-L, 30 mg/kg) for a single time or daily for 7 weeks. The 24-hour dynamic blood pressure was monitored and then calculated BPV including long- and short-term systolic blood pressure variability (SBPV), diastolic blood pressure variability (DBPV), mean blood pressure variability (MBPV), and heart rate variability (HRV) as well as the 24-hour-SBP, 24-hour-DBP, and 24-hour-MBP. The protective effects of PG on TOD were observed by histopathologic and biochemical detection. The results indicated that long- and short-term SBPV, DBPV, MBPV, and HRV as well as 24-hour-SBP, 24-hour-DBP, and 24-hour-MBP showed no significant changes after single-dose administration of PG and significantly decreased after administration with PG for 7 weeks. PG could also markedly improve the damage of aorta, heart, kidney, and brain. This study suggested that PG could notably reduce BPV, stabilize blood pressure, and mitigate TOD in SHR.
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The aim of this study was to identify an adequate formulation for a poorly soluble lead molecule (BI-A) that would achieve sufficiently high plasma concentrations after oral administration in dogs to enable a robust cardiovascular safety pharmacology assessment in telemetry-instrumented conscious dogs during lead optimization in drug discovery. A spray-dried dispersion of BI-A (BI-A-SDD) containing a 1:2 ratio of BI-A and hydroxypropyl methylcellulose acetate succinate-LF was prepared using a Büchi spray dryer B-90 (B-90). Physical form characterization, an in vitro dissolution test and a preliminary pharmacokinetic (PK) study following oral administration of BI-A-SDD were performed. Thereafter, effects on cardiovascular parameters in conscious, chronically-instrumented dogs were investigated for 24h after a single oral dose (5, 10, and 50mg/kg) using a modified Latin square cross-over study design. The BI-A-SDD powder was confirmed to be amorphous and was stable as an aqueous suspension for at least 4h. The BI-A-SDD suspension provided a greater rate and extent of dissolution than the crystalline BI-A suspension and the supersaturation was maintained for at least 4h. In PK studies the Cmax of the BI-A-SDD formulation (25.4µM; 77-fold the projected efficacious Cmax of 0.33µM) was 7.5-fold higher than the Cmax observed using oral administration of a 10% hydroxypropyl-ß-cyclodextrin formulation at 100mg/kg in dogs (3.4µM). In conscious, chronically-instrumented dogs, the doses tested and plasma concentrations achieved were sufficient to enable a robust safety pharmacology evaluation. Multiple off-target hemodynamic effects were detected including acute elevations in aortic blood pressure (up to 22% elevation in systolic and diastolic blood pressure) and tachycardia (68% elevation in heart rate), results that were confirmed in other in vivo models. These results led to a deprioritization of BI-A. The study demonstrated that a spray-dried dispersion, prepared using the B-90 in drug discovery, enhanced the oral exposure of a poorly water-soluble molecule, BI-A, and thereby enabled its evaluation in safety pharmacology studies that ultimately resulted in deprioritization of BI-A from a pool of lead compounds.
Asunto(s)
Evaluación Preclínica de Medicamentos/métodos , Hemodinámica/efectos de los fármacos , Metilcelulosa/análogos & derivados , Polvos/efectos adversos , Polvos/farmacocinética , Suspensiones/efectos adversos , Suspensiones/farmacocinética , Administración Oral , Animales , Perros , Relación Dosis-Respuesta a Droga , Composición de Medicamentos , Liberación de Fármacos , Femenino , Masculino , Metilcelulosa/química , Modelos Animales , Tamaño de la Partícula , Polvos/química , Polvos/farmacología , Tecnología de Sensores Remotos , Solubilidad , Suspensiones/química , Suspensiones/farmacologíaRESUMEN
Rhubarb is often used in Chinese herbal medicine for the treatment of systemic inflammatory response syndrome (SIRS). Emodin is the main active constituent of rhubarb. This study was performed to investigate the in vitro effects of emodin and dexamethasone on peritoneal macrophage (pMΦ) phagocytosis and the expression of intercellular adhesion molecule-3 (ICAM-3). A total of 40 Sprague-Dawley (SD) rats were randomly divided into sham surgery (n=10) and model groups (n=30). After 24 h, pMΦs were harvested and the model group was randomly divided into three subgroups (n=10 rats/subgroup): the 5 µg/ml emodin, 0.1 µmol/ml dexamethasone and control groups. The drugs were administered following macrophage (MΦ) adhesion for 24 h. pMΦ phagocytosis was significantly increased in the emodin group compared to that in the control group. Moreover, pMΦ phagocytosis was significantly increased in the emodin group compared to that in the dexamethasone group. The expression of ICAM-3 was significantly increased in the emodin group compared to that in the control group. The expression of ICAM-3 was significantly increased in the emodin group compared to that in the dexamethasone group. The expression of ICAM-3 was significantly increased in the emodin and dexamethasone groups compared to that in the control group. pMΦ phagocytosis and ICAM-3 expression were significantly increased following emodin treatment compared to those in the control and dexamethasone groups, indicating that emodin may enhance pMΦ phagocytosis and apoptotic cell clearance by altering ICAM-3 expression.
RESUMEN
In order to detect the trench oil the authors built a trench oil rapid detection system based on laser induced fluorescence detection technology. This system used 355 nm laser as excitation light source. The authors collected the fluorescence spectrum of a variety of edible oil and fried cooking oil (a kind of trench oil) and then set up a fluorescence spectrum database by taking advantage of the trench oil detection system It was found that the fluorescence characteristics of fried cooking oil and common edible oil were obviously different. Then it could easily realize the oil recognition and trench oil rapid detection by using principal component analysis and BP neural network, and the overall recognition rate could reach as high as 97.5%. Experiments showed that laser induced fluorescence spectrum technology was fast, non-contact, and highly sensitive. Combined with BP neural network, it would become a new technique to detect the trench oil.