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Type 3 resistant starch from Canna edulis (Ce-RS3) is an insoluble dietary fiber which could improve blood lipids in animals, but clinically robust evidence is still lacking. We performed a double-blind randomized controlled trial to assess the effects of Ce-RS3 on lipids in mild hyperlipidemia. One hundred and fifteen patients were included followed the recruitment criteria, and were randomly allocated to receive Ce-RS3 or placebo (native starch from Canna edulis) for 12 weeks (20â¯g/day). In addition to serum lipids, complete blood counts, serum inflammatory factors, antioxidant indexes, and dietary survey, 16â¯S rRNA sequencing technique was utilized to analyze the gut microbiota alterations. Targeted quantitative metabolomics (TQM) was used to detect metabolite changes. Compared with the placebo, Ce- RS3 significantly decreased levels of total cholesterol, lowdensity lipoprotein cholesterol, and non-high-density lipoprotein cholesterol, and increased the glutathione peroxidase. Based on the 16â¯S rRNA sequencing, TQM, the correlation analysis, as well as the Kyoto Encyclopedia of Genes (KEGG) and Genomes and Human Metabolome Database (HMDB) analysis, we found that Ce-RS3 could increase the abundances of genera Faecalibacterium and Agathobacter, while reduce the abundances of genera norank_f_Ruminococcaceae and Christensenellaceae_R-7_ group to regulate phenylalanine metabolism, which could reduce the fatty acid biosynthesis and fatty acid elongation in the mitochondria to lower blood lipids. Conclusively, we firstly confirmed the feasibility of Ce-RS3 for clinical application, which presents a novel, effective therapy for the mild hyperlipidemia. (Chictr. org. cn. Clinical study on anti-mild hyperlipidemia of Canna edulis RS3 resistant starch, ID Number: ChiCTR2200062871).
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Microbioma Gastrointestinal , Hiperlipidemias , Humanos , Microbioma Gastrointestinal/efectos de los fármacos , Método Doble Ciego , Masculino , Persona de Mediana Edad , Hiperlipidemias/tratamiento farmacológico , Hiperlipidemias/sangre , Hiperlipidemias/microbiología , Femenino , Adulto , Lípidos/sangre , Almidón Resistente , Almidón , Hipolipemiantes/uso terapéutico , Hipolipemiantes/farmacología , AncianoRESUMEN
Liposomes (LPs) are a delivery system for stabilizing pharmaceuticals with limited use due to their propensity to congregate and fuse. A proposed method of addressing these problems is polymer coating. In this study, the potential of octadecylamine (ODA)-coated liposomes and carboxymethyl chitosan (CMCS/ODA-LPs) for enhancing Wacao pentacyclic triterpene saponin (WPTS) transport capacity was investigated. CMCS/ODA-LPs were produced by electrostatic adsorption and thin-film hydration. Response surface methodology (RSM) was employed to enhance the process and encapsulation efficiency (EE) for optimum drug encapsulation efficiency. The synthesized WPTS-CMCS/ODA-LPs were uniformly dispersed in a circular shape, and during 14 days of storage at 4 °C, the particle size and morphology did not significantly change. Vesicle size, zeta potential, polydispersity index (PDI), and entrapment efficiency (%) were 179.1 ± 7.31 nm, -29.6 ± 1.35 mV, 0.188 ± 0.052, and 75.62 ± 0.43, respectively. The hemolysis test revealed that WPTS-CMCS/ODA-LPs were sufficiently biocompatible. Compared to WPTS-LPs, WPTS-CMCS/ODA-LPs consistently showed a much more significant cytotoxic effect on cancer cells. Early and WPTS-CMCS/ODA-LPs-induced apoptosis resulted in almost seven times more cell death than the control. Compared to physiological pH 7.3, the pH-sensitive CMCS coupled LPs increased drug release at acidic pH 6.5. These findings suggest the efficacy of pH-sensitive CMCS/ODA-LPs as a medication delivery method for WPTS.
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Aminas , Antineoplásicos , Quitosano , Liposomas , Lipopolisacáridos , Tamaño de la PartículaRESUMEN
The performance of Chinese-named entity recognition (NER) has improved via word enhancement or new frameworks that incorporate various types of external data. However, for Chinese NER, syntactic composition (in sentence level) and inner regularity (in character-level) have rarely been studied. Chinese characters are highly sensitive to sentential syntactic data. The same Chinese character sequence can be decomposed into different combinations of words according to how they are used and placed in the context. In addition, the same type of entities usually have the same naming rules due to the specificity of the Chinese language structure. This paper presents a Kcr-FLAT to improve the performance of Chinese NER with enhanced semantic information. Specifically, we first extract different types of syntactic data, functionalize the syntactic information by a key-value memory network (KVMN), and fuse them by attention mechanism. Then the syntactic information and lexical information are integrated by a cross-transformer. Finally, we use an inner regularity perception module to capture the internal regularity of each entity for better entity type prediction. The experimental results show that with F1 scores as the evaluation index, the proposed model obtains 96.51%, 96.81%, and 70.12% accuracy rates on MSRA, resume, and Weibo datasets, respectively.
RESUMEN
Wacao pentacyclic triterpenoid saponins (WPTS) is a newly discovered insulin sensitivity enhancer. It is a powerful hypoglycemic compound derived from Silene viscidula, which has a hypoglycemic effect similar to that of insulin. It can rapidly reduce blood glucose levels, normalizing them within 3 days of administration. However, its mechanism of action is completely different from that of insulin. Thus, we aimed to determine the pharmacological effects and mechanism of activity of WPTS on type 2 diabetes to elucidate the main reasons for its rapid effects. The results showed that WPTS could effectively improve insulin resistance in KKAy diabetic mice. Comparative transcriptomics showed that WPTS could upregulate the expression of insulin resistance-related genes such as glucose transporter type 4 (Glut4), insulin receptor substrate 1 (Irs1), Akt, and phosphoinositide 3-kinase (PI3K), and downregulate the expression of lipid metabolism-related genes such as monoacylglycerol O-acyltransferase 1 (Moat1), lipase C (Lipc), and sphingomyelin phosphodiesterase 4 (Smpd4). The results indicated that the differentially expressed genes could regulate lipid metabolism via the PI3K/AKT metabolic pathway, and it is noteworthy that WPTS was found to upregulate Glut4 expression, decrease blood glucose levels, and attenuate insulin resistance via the PI3K/AKT pathway. Q-PCR and western blotting further validated the transcriptomics findings at the mRNA and protein levels, respectively. We believe that WPTS can achieve a rapid hypoglycemic effect by improving the lipid metabolism and insulin resistance of the diabetic KKAy mice. WPTS could be a very promising candidate drug for the treatment of diabetes and deserves further research.
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Proliferación Celular/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dislipidemias/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Resistencia a la Insulina , Células Secretoras de Insulina/efectos de los fármacos , Saponinas/uso terapéutico , Silene/química , Animales , Western Blotting , Hipoglucemiantes/aislamiento & purificación , Hipoglucemiantes/farmacología , Ratones , Ratones Endogámicos C57BL , Ratones Mutantes , Reacción en Cadena en Tiempo Real de la Polimerasa , Saponinas/aislamiento & purificación , Saponinas/farmacologíaRESUMEN
The relationship between gut microbiota and type 2 diabetes mellitus (T2DM) has drawn increasing attention, and the benefits of various treatment strategies, including nutrition, medication and physical exercise, maybe microbially-mediated. Metformin is a widely used hypoglycemic agent, while resistant starch (RS) is a novel dietary fiber that emerges as a nutritional strategy for metabolic disease. However, it remains unclear as to the potential degree and interactions among gut microbial communities, metabolic landscape, and the anti-diabetic effects of metformin and RS, especially for a novel type 3 resistant starch from Canna edulis (Ce-RS3). In the present study, T2DM rats were administered metformin or Ce-RS3, and the changes in gut microbiota and serum metabolic profiles were characterized using 16S-rRNA gene sequencing and metabolomics, respectively. After 11 weeks of treatment, Ce-RS3 exhibited similar anti-diabetic effects to those of metformin, including dramatically reducing blood glucose, ameliorating the response to insulin resistance and glucose tolerance test, and relieving the pathological damage in T2DM rats. Interestingly, the microbial and systemic metabolic dysbiosis in T2DM rats was effectively modulated by both Ce-RS3 and, to a lesser extent, metformin. The two treatments increased the gut bacterial diversity, and supported the restoration of SCFA-producing bacteria, thereby significantly increasing SCFAs levels. Both treatments simultaneously corrected 16 abnormal metabolites in the metabolism of lipids and amino acids, many of which are microbiome-related. PICRUSt analysis and correlation of SCFAs levels with metabolomics data revealed a strong association between gut microbial and host metabolic changes. Strikingly, Ce-RS3 exhibited better efficacy in increasing gut microbiota diversity with a peculiar enrichment of Prevotella genera. The gut microbial properties of Ce-RS3 were tightly associated with the T2DM-related indexes, showing the potential to alleviate diabetic phenotype dysbioses, and possibly explaining the greater efficiency in improving metabolic control. The beneficial effects of Ce-RS3 and metformin might derive from changes in gut microbiota through altering host-microbiota interactions with impact on the host metabolome. Given the complementarity of Ce-RS3 and metformin in regulation of gut microbiota and metabolites, this study also prompted us to suggest possible "Drug-Dietary fiber" combinations for managing T2DM.
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Bacterias/efectos de los fármacos , Glucemia/efectos de los fármacos , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 2/terapia , Microbioma Gastrointestinal/efectos de los fármacos , Hipoglucemiantes/farmacología , Intestinos/microbiología , Metaboloma , Metformina/farmacología , Almidón Resistente/administración & dosificación , Animales , Bacterias/genética , Bacterias/metabolismo , Biomarcadores/sangre , Glucemia/metabolismo , Cromatografía Liquida , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/etiología , Diabetes Mellitus Experimental/microbiología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/microbiología , Dieta Alta en Grasa , Disbiosis , Ácidos Grasos/sangre , Control Glucémico , Metabolómica , Ratas Sprague-Dawley , Almidón Resistente/metabolismo , Ribotipificación , Espectrometría de Masa por Ionización de Electrospray , Estreptozocina , ZingiberalesRESUMEN
Mutations in autophagy genes can cause familial and sporadic amyotrophic lateral sclerosis (ALS). However, the role of autophagy in ALS pathogenesis is poorly understood, in part due to the lack of cell type-specific manipulations of this pathway in animal models. Using a mouse model of ALS expressing mutant superoxide dismutase 1 (SOD1G93A), we show that motor neurons form large autophagosomes containing ubiquitinated aggregates early in disease progression. To investigate whether this response is protective or detrimental, we generated mice in which the critical autophagy gene Atg7 was specifically disrupted in motor neurons (Atg7 cKO). Atg7 cKO mice were viable but exhibited structural and functional defects at a subset of vulnerable neuromuscular junctions. By crossing Atg7 cKO mice to the SOD1G93A mouse model, we found that autophagy inhibition accelerated early neuromuscular denervation of the tibialis anterior muscle and the onset of hindlimb tremor. Surprisingly, however, lifespan was extended in Atg7 cKO; SOD1G93A double-mutant mice. Autophagy inhibition did not prevent motor neuron cell death, but it reduced glial inflammation and blocked activation of the stress-related transcription factor c-Jun in spinal interneurons. We conclude that motor neuron autophagy is required to maintain neuromuscular innervation early in disease but eventually acts in a non-cell-autonomous manner to promote disease progression.
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Esclerosis Amiotrófica Lateral/enzimología , Autofagia , Neuronas Motoras/enzimología , Superóxido Dismutasa-1/metabolismo , Superóxido Dismutasa/metabolismo , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/patología , Animales , Proteína 7 Relacionada con la Autofagia/genética , Proteína 7 Relacionada con la Autofagia/metabolismo , Modelos Animales de Enfermedad , Ratones , Ratones Noqueados , Neuronas Motoras/patología , Superóxido Dismutasa/genética , Superóxido Dismutasa-1/genéticaRESUMEN
Block of neurotransmitter receptors at the neuromuscular junction (NMJ) has been shown to trigger upregulation of the number of synaptic vesicles released (quantal content, QC), a response termed homeostatic synaptic plasticity. The mechanism underlying this plasticity is not known. Here, we used selective toxins to demonstrate that block of α1-containing nicotinic acetylcholine receptors (nAChRs) at the NMJ of male and female mice triggers the upregulation of QC. Reduction of current flow through nAChRs, induced by drugs with antagonist activity, demonstrated that reduction in synaptic current per se does not trigger upregulation of QC. These data led to the remarkable conclusion that disruption of synaptic transmission is not sensed to trigger upregulation of QC. During studies of the effect of partial block of nAChRs on QC, we observed a small but reproducible increase in the decay kinetics of miniature synaptic currents. The change in kinetics was correlated with the increase in QC and raises the possibility that a change in postsynaptic nAChR conformation may be associated with the presynaptic increase in QC. We propose that, in addition to functioning in synaptic transmission, ionotropic muscle nicotonic nAChRs may serve as signaling molecules that participate in synaptic plasticity. Because nAChRs have been implicated in a number of disease states, the finding that nAChRs may be involved in triggering synaptic plasticity could have wide-reaching implications.SIGNIFICANCE STATEMENT The signals that initiate synaptic plasticity of the nervous system are still incompletely understood. Using the mouse neuromuscular junction as a model synapse, we studied how block of neurotransmitter receptors is sensed to trigger synaptic plasticity. Our studies led to the surprising conclusion that neither changes in synaptic current nor spiking of the presynaptic or postsynaptic cell are sensed to initiate synaptic plasticity. Instead, postsynaptic nicotinic acetylcholine receptors (nAChRs), in addition to functioning in synaptic transmission, may serve as signaling molecules that trigger synaptic plasticity. Because nAChRs have been implicated in a number of disease states, the finding that they may mediate synaptic plasticity has broad implications.
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Músculo Esquelético/efectos de los fármacos , Unión Neuromuscular/efectos de los fármacos , Neurotoxinas/farmacología , Antagonistas Nicotínicos/farmacología , Receptores Nicotínicos/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Sinapsis/efectos de los fármacos , Animales , Femenino , Cinética , Masculino , Ratones , Potenciales Sinápticos/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , Vesículas Sinápticas/efectos de los fármacosAsunto(s)
Ansiedad , Depresión , Prurigo , Ideación Suicida , Humanos , Prurigo/psicología , Depresión/psicología , Ansiedad/psicología , Factores de Riesgo , FemeninoRESUMEN
BACKGROUND: The causal link between tobacco smoke exposure (TSE) and numerous severe respiratory system diseases (RSD), including chronic bronchitis, chronic obstructive pulmonary disease, and lung cancer, is well established. However, the pathogenesis of TSE-induced RSD remains incompletely understood. This research aims to detect the pathogenetic mechanisms and potential therapeutic targets of TSE-induced RSD. METHODS: This study employed TSE model which rats were exposed to a concentration of 60% tobacco smoke in a toxicant exposure system for four weeks. Tandem mass tags (TMT) labeled quantitative proteomics combined with off-line high pH reversed-phase fractionation, and nano-liquid chromatography-mass spectrometry method (off-line high pH RPF-nano-LC-MS/MS) were adopted to detect differentially expressed proteins (DEPs) in the lung tissues of the TSE model rats and to compare them with those in control. The accuracy of the results was verified by western blot. RESULTS: Compared with the control group, 33 proteins in the TSE model group's lung tissues showed significant differential expression. Analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways indicated that, several biological pathways, such as the steroid biosynthesis pathway, were involved and played significant roles in the pathogenesis of the experimental group's TSE. CONCLUSIONS: These findings make a crucial contribution to the search for a comprehensive understanding of TSE-induced RSD's pathogenesis, and furthermore provide guidance for the diagnosis and treatment of TSE-induced RSD.
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Pulmón/metabolismo , Proteoma/metabolismo , Proteómica/métodos , Espectrometría de Masas en Tándem/métodos , Contaminación por Humo de Tabaco/efectos adversos , Animales , Exposición a Riesgos Ambientales/efectos adversos , Pulmón/patología , Masculino , Ratas Sprague-Dawley , Enfermedades Respiratorias/etiología , Enfermedades Respiratorias/metabolismo , Nicotiana/químicaRESUMEN
One new monoterpene glycoside (1), one new phenyl glycoside (2), one new caffeoyl derivative (3), were isolated from Scindapsus officinalis (Roxb.) Schott., along with four known compounds (4â»7). Structures of the isolated compounds were elucidated by extensive analysis of spectroscopic data, especially 2D NMR data and comparison with literatures. All isolates were evaluated for anti-inflammatory activity against nitric oxide (NO) production in vitro. Compounds 3 and 7 exhibited moderate inhibitory effects on NO production with IC50 values of 12.2 ± 0.8 and 18.9 ± 0.3 µM, respectively.
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Antiinflamatorios/química , Araceae/química , Extractos Vegetales/química , Animales , Antiinflamatorios/farmacología , Supervivencia Celular/efectos de los fármacos , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Ratones , Estructura Molecular , Óxido Nítrico/biosíntesis , Extractos Vegetales/farmacología , Células RAW 264.7RESUMEN
Homeostatic regulation is essential for the maintenance of synaptic strength within the physiological range. The current study is the first to demonstrate that both induction and reversal of homeostatic upregulation of synaptic vesicle release can occur within seconds of blocking or unblocking acetylcholine receptors at the mouse neuromuscular junction. Our data suggest that the homeostatic upregulation of release is due to Ca(2+)-dependent increase in the size of the readily releasable pool (RRP). Blocking vesicle refilling prevented upregulation of quantal content (QC), while leaving baseline release relatively unaffected. This suggested that the upregulation of QC was due to mobilization of a distinct pool of vesicles that were rapidly recycled and thus were dependent on continued vesicle refilling. We term this pool the "homeostatic reserve pool." A detailed analysis of the time course of vesicle release triggered by a presynaptic action potential suggests that the homeostatic reserve pool of vesicles is normally released more slowly than other vesicles, but the rate of their release becomes similar to that of the major pool during homeostatic upregulation of QC. Remarkably, instead of finding a generalized increase in the recruitment of vesicles into RRP, we identified a distinct homeostatic reserve pool of vesicles that appear to only participate in synchronized release following homeostatic upregulation of QC. Once this small pool of vesicles is depleted by the block of vesicle refilling, homeostatic upregulation of QC is no longer observed. This is the first identification of the population of vesicles responsible for the blockade-induced upregulation of release previously described. Significance statement: The current study is the first to demonstrate that both the induction and reversal of homeostatic upregulation of synaptic vesicle release can occur within seconds. Our data suggest that homeostatic upregulation of release is due to Ca(2+)-dependent priming/docking of a small homeostatic reserve pool of vesicles that normally have slow-release kinetics. Following priming, the reserve pool of vesicles is released synchronously with the normal readily releasable pool of synaptic vesicles. This is the first description of this unique pool of synaptic vesicles.
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Homeostasis/fisiología , Plasticidad Neuronal/fisiología , Terminales Presinápticos/metabolismo , Vesículas Sinápticas/metabolismo , Inhibidores de la Liberación de Acetilcolina/farmacología , Animales , Femenino , Homeostasis/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratones Transgénicos , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Unión Neuromuscular/efectos de los fármacos , Unión Neuromuscular/metabolismo , Plasticidad Neuronal/efectos de los fármacos , Terminales Presinápticos/efectos de los fármacos , Vesículas Sinápticas/efectos de los fármacosRESUMEN
Tobacco smoke (TS) is a major causative agent to lead to chronic bronchitis (CB). However the mechanisms of CB induced by TS are unclear. In this report, rats were exposed to different concentrations of TS and the metabolic features of CB were characterized by using a nontargeted metabolic profiling method based on liquid chromatography-mass spectrometry (LC-MS) to detect the altered metabolic patterns in serum from CB rats and investigate the mechanisms of CB. 11 potential biomarkers were identified in serum of rats. Among them, the levels of lysophosphatidylethanolamine (18:1), lysophosphatidic acid (18:1), lysophosphatidylethanolamine (18:0), lysophosphatidylethanolamine (16:0), lysophosphatidylethanolamine (20:4), docosahexaenoic acid, 5-hydroxyindoleacetic acid and 5'-carboxy-γ-tocopherol were higher in TS group compared to control group. Conversely, the levels of 4-imidazolone-5-propionic acid, 12-hydroxyeicosatetraenoic acid and uridine were lower in TS group. The results indicated that the mechanism of CB was related to amino acid metabolism and lipid metabolism, particularly lipid metabolism. In addition, lysophosphatidylethanolamines were proved to be important mediators, which could be used as biomarkers to diagnose CB. These results also suggested that metabolomics was suitable for diagnosing CB and elucidating the possible metabolic pathways of TS-induced CB.
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Bronquitis Crónica/sangre , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas/métodos , Metabolómica/métodos , Nicotiana/efectos adversos , Humo/efectos adversos , Animales , Biomarcadores/sangre , Bronquitis Crónica/inducido químicamente , Femenino , Humanos , Lisofosfolípidos/sangre , Lisofosfolípidos/química , Masculino , Ratas , Ratas Sprague-Dawley , Nicotiana/químicaRESUMEN
In this work, dummy molecularly imprinted polymers with high selectivity and affinity to capsaicin and dihydrocapsaicin are designed using N-vanillylnonanamide as a dummy template. The performance of dummy molecularly imprinted polymers and nonimprinted polymers was evaluated using adsorption isotherms, adsorption kinetics, and selective recognition capacity. Dummy molecularly imprinted polymers were found to exhibit good site accessibility, taking just 20 min to achieve adsorption equilibrium; they were also highly selective toward capsaicin and dihydrocapsaicin. We successfully used dummy molecularly imprinted polymers as a specific sorbent for selectively enriching capsaicin and dihydrocapsaicin from chili pepper samples. In a scaled-up experiment, the selective recovery of capsaicinoids was calculated to be 77.8% using solid-phase extraction. To the best of our knowledge, this is the first example of the use of N-vanillylnonanamide as a dummy template in molecularly imprinted polymers to simultaneously enrich capsaicin and dihydrocapsaicin.
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Capsaicina/análogos & derivados , Capsaicina/aislamiento & purificación , Capsicum/química , Extractos Vegetales/aislamiento & purificación , Polímeros/química , Extracción en Fase Sólida/métodos , Adsorción , Capsaicina/química , Impresión Molecular , Extractos Vegetales/química , Polímeros/síntesis química , Extracción en Fase Sólida/instrumentaciónRESUMEN
OBJECTIVE: To observe the morphology of hypertrophic scar tissue and explore the expressions and distribution of vascular endothelial growth factor (VEGF) and transforming growth factor beta activated kinase 1(TAK1 )in these tissues. METHOD: Hematoxylin-eosin staining, Masson staining,immunofluorescence,and real-time polymerase chain reaction were used to detect the localization and expression of VEGF and TAK1 in 15 hypertrophic scar tissues and 10 normal skin tissues. RESULTS: Morphological observation showed that the dermal fibroblasts in hypertrophic scar were disorderly and densely arranged (compared to the normal skin). Immunofluorescence displayed that the expressions of VEGF and TAK1 in hypertrophic scar tissue were higher than in normal skin tissues. Real-time polymerase chain reaction showed the mRNA expressions of both VEGF and TAK1 were significantly higher in hypertrophic scar tissue than in normal tissue (P<0.01, P<0.05,respectively). CONCLUSIONS: Hypertrophic scar tissue has higher collagen fibrosis degree and higher TAK1 and VEGF expressions than the normal skin. VEGF and TAK1 can be used as the reference indicators for the diagnosis and differential diagnosis of hypertrophic scar and serve as new therapeutic targets.
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Cicatriz Hipertrófica , Forma de la Célula , Colágeno , Fibroblastos , Humanos , Quinasas Quinasa Quinasa PAM , Factor de Crecimiento Transformador beta , Factor A de Crecimiento Endotelial VascularRESUMEN
The aim of this paper was to seek an efficient method to preparative separation of alkaloid compounds from Aconitum coreanum (Guanbaifu), a well-known traditional Chinese medicinal plant for heart disease. Seven alkaloid compounds were successfully purified by pH-zone-refining counter-current chromatography with two-phase solvent system of petroleum ether-ethyl acetate-methanol-water (5:5:1:9, v/v/v/v), 10 mM triethylamine in upper phase and 10 mM hydrochloric acid in lower phase. From 3.5 g of crude extract, 356 mg of Guanfu base I, 578 mg of Guanfu base A, 74 mg of atisine, 94 mg of Guanfu base F, 423 mg of Guanfu base G, 67 mg of Guanfu base R and 154 mg of Guanfu base P were obtained with the purity of 96.40%, 97.2%, 97.5%, 98.1%, 98.9%, 98.3% and 98.4%. Their chemical structures were identified by TOF-MS and 1H-NMR. This study indicated that pH-zone-refining counter-current chromatography was an efficient method for separating the kind of alkaloids with low absorbance values.
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Aconitum/química , Diterpenos/aislamiento & purificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Distribución en Contracorriente , Diterpenos/química , Medicamentos Herbarios Chinos/química , Compuestos Heterocíclicos de 4 o más Anillos/química , Compuestos Heterocíclicos de 4 o más Anillos/aislamiento & purificación , Concentración de Iones de Hidrógeno , Solventes/químicaRESUMEN
As one of the most important components of Panax ginseng, ginsenoside Rg1 has certain anti-aging effects, improving the activity of learning and memory. Studies have showed that ginsenoside Rg1 improves the memory impairment associated with Alzheimer's disease (AD). In this study, the effects of ginsenoside Rg1 were investigated through the activity of toll-like receptor (TLR) 3, TLR4 and their signaling transduction pathways in amyloid ß peptide 25-35 (Aß25-35) induced AD cell model. Thus we investigated several critical components of the TLR pathway. The neuroglial cell line NG108-15 was stimulated with or without Aß25-35, while different concentrations of ginsenoside Rg1 were administered. After 24 h, tumor necrosis factor-α (TNF-α), interferon-ß (IFN-ß) in cell supernatant and inducible nitric oxide synthase (iNOS) in cell lysate supernatant were measured with enzyme-linked immunosorbent assays (ELISAs). The mRNA and protein expression of TLR3, TLR4, nuclear factor kappa B (NF-κB) and tumor necrosis factor receptor-associated factor-6 (TRAF-6) were detected by real-time PCR and western blot methods, respectively. The experimental results showed that Aß25-35 could markedly raise the level of TNF-α, IFN-ß and iNOS, and increase the expressions of mRNA and TLR3, TLR4, NF-κB and TRAF-6 protein in the NG108-15 cells. At the same time, the ginsenoside Rg1 significantly reduced the expressions of proteins and mRNA of TLR3, TLR4, NF-κB and TRAF-6, and down-regulated the levels of TNF-α, IFN-ß of cell supernatant and iNOS of cell lysate supernatant in a concentration-dependent manner. In conclusion, ginsenoside Rg1 has good activity for suppressing the signaling transduction pathway of TLR3 and TLR4, and decreasing the inflammation factors induced by Aß25-35 in NG108-15 cells, and this may be the mechanism of ginsenoside Rg1 action in AD treatment, but more studies are needed to identify its specificity.
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Enfermedad de Alzheimer/tratamiento farmacológico , Regulación de la Expresión Génica/efectos de los fármacos , Ginsenósidos/farmacología , Mediadores de Inflamación/metabolismo , Neuroglía/metabolismo , Receptor Toll-Like 3/metabolismo , Receptor Toll-Like 4/metabolismo , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/toxicidad , Animales , Western Blotting , Células Cultivadas , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Interferones/metabolismo , Ratones , FN-kappa B/metabolismo , Neuroglía/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II/metabolismo , Panax/química , Fragmentos de Péptidos/toxicidad , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Receptor Toll-Like 3/genética , Receptor Toll-Like 4/genética , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Tibetan Herbal medicine has its own complete theory based on five sources doctrine. And the theories of "Liuwei", "Baxing" and "Shiqi Gongxiao" formed the basic core components of the property theory of Tibetan medicine. However, books and literature of Tibetan medicine have never been systematically expounded and discussed about it specially which thus will limit the further development of Tibetan medicine theory. In this thesis, we firstly introduced three basic core components of the property theory-the "Liu Wei", "Baxing", and "Shiqi Gongxiao" and their interactions as well. At the same time, the links and similarities between the theory of Tibetan medicine and Chinese medicine theory were compared. The job of the thesis done above is to lay the foundation for further systematic reveal and development of Tibetan medicine theory.
Asunto(s)
Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Medicina Tradicional de Asia Oriental , Plantas Medicinales/química , Humanos , FitoterapiaRESUMEN
In this study, acylated porous Canna edulis starch with varying degrees of substitution (DS) were prepared and employed for stabilizing Pickering emulsions. Subsequently, the fermentation characteristics of them were investigated. Enzymatically produced porous starch (PS) was esterified with acetic, propionic, butyric, or valeric anhydrides, yielding acetylated (PSA-0.116), propionylated (PSP-0.163), butyrylated (PSB-0.304), and valerylated PS (PSV-0.462) with different DS. Scanning electron microscopy revealed the presence of pores and surface micro-particles in the modified PS, confirming successful esterification through characteristic peaks in 1H NMR and a CO peak at 1736 cm-1 in the FT-IR spectrum. With increasing DS, starch exhibited reduced crystallinity (PSV, 26.61 %), elevated resistant starch content (PSV, 91.63 %), and a higher contact angle (PSV, 87.13°). Acylated PS particles effectively stabilized Pickering emulsions. Pickering emulsions stabilized by acylated PS with higher DS exhibited higher emulsification index and smaller droplet sizes. In vitro fermentation of acylated PS and corresponding stabilized Pickering emulsions fostered short-chain fatty acid production, boosted the relative abundance of beneficial bacteria (Bifidobacterium, Prevotella, etc.) while inhibited the growth of harmful bacteria (Escherichia-Shigella, Comamonas, etc.), maintaining the intestinal microbiota balance. These findings support the potential applications of acylated PS and corresponding stabilized Pickering emulsions in functional foods and drug delivery.
Asunto(s)
Emulsiones , Heces , Fermentación , Almidón , Almidón/química , Almidón/metabolismo , Porosidad , Acilación , Heces/microbiología , Arecaceae/químicaRESUMEN
Introduction: Resistant starch (RS) has garnered attention for its health benefits, including modulating the gut microbiota and promoting the production of short-chain fatty acids (SCFAs). Methods: This study investigates structural changes of type 3 resistant starch from Canna edulis (CE) during in vitro simulated digestion and explores its health-relevant properties using healthy individuals' fecal microbiota. Results: CE, prepared with a RS content of 59.38%, underwent a comprehensive analysis employing X-ray diffraction (XRD), fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). During simulated digestion, XRD analysis demonstrated a significant rise in CE's relative crystallinity from 38.92 to 49.34%. SEM illustrated the transition of CE from a smooth to a rough surface, a notable morphological shift. Post-digestion, CE was introduced into microbial fermentation. Notably, propionic acid and valeric acid levels significantly increased compared to the control group. Furthere more, beneficial Bifidobacterium proliferated while pathogenic Escherichia-Shigella was suppressed. When comparing CE to the well-known functional food fructo-oligosaccharide (FOS), CE showed a specific ability to support the growth of Bifidobacterium and stimulate the production of short-chain fatty acids (SCFAs) without causing lactic acid accumulation. Discussion: CE demonstrates potential as a functional health food, with implications for gut health enhancement and SCFAs production.
RESUMEN
In developing type 3 resistant starch (RS3) from Canna edulis for use as functional food ingredients, we investigated the synthesis of C. edulis RS3 nanoparticles. Simultaneously, we explored the potential of C. edulis short-chain amylose (SCA)-based RS3 nanoparticles (RS3N) as a targeted delivery system, with a specific focus on colon targeting, yielding promising insights. Our study revealed that the degree of polymerization (DP) of C. edulis SCA, particularly the chains of DP 36- 100, exhibited a robust correlation with the particle size and physicochemical characteristics of C. edulis SCA-based RS3N. Additionally, recrystallization temperature variation (4, 25, and 45 °C) significantly influenced the self-assembly behavior of C. edulis SCA, with the preparation at 4 °C resulting in more uniform particle size distributions. In further expanding the scope of applications for C. edulis SCA-based RS3N, we harnessed the potential of Fe3O4 and curcumin (CUR) as guest molecules to assess drug encapsulation and colon-targeting capabilities. Incorporating Fe3O4 into the self-assembly system led to the production of magnetic RS3N, confirming the successful encapsulation of Fe3O4 within C. edulis SCA-based RS3N. Furthermore, in vitro experiments have demonstrated that CUR-RS3N was stable in the gastrointestinal tract and gradually released curcumin with fermentation in the colonic environment. Collectively, these findings provide invaluable insights into the intricate self-assembly behavior of C. edulis SCA with varying fine structures and recrystallization temperatures during RS3N formation. Moreover, they underscore the colon-targeted properties of C. edulis SCA-based RS3N, opening promising avenues for its application within the food industry, particularly in advanced controlled drug delivery systems.