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Post-Traumatic Stress Disorder (PTSD) is a chronic mental disorder characterized by symptoms of panic and anxiety, depression, impaired cognitive functioning, and difficulty in social interactions. While the effect of the traditional Chinese medicine artemisinin (AR) on PTSD is unknown, its therapeutic benefits have been demonstrated by studies on models of multiple neurological disorders. This study aimed to extend such findings by investigating the effects of AR administration on a rat model of PTSD induced by a regimen of single prolonged stress (SPS). After rats were subjected to the SPS protocol, AR was administered and its impact on PTSD-like behaviors was evaluated. In the present study, rats were subjected to a multitude of behavioral tests to evaluate behaviors related to anxiety, memory function, and social interactions. The expression of hippocampal synaptic plasticity-related proteins was detected using Western blot and immunofluorescence. The ultrastructure of synapses was observed under transmission electron microscopy. The apoptosis of hippocampal neurons was examined with Western blot, TUNEL staining, and HE staining. The results showed that AR administration alleviated the PTSD-like phenotypes in SPS rats, including behavior indicative of anxiety, cognitive deficits, and diminished sociability. AR administration was further observed to improve synaptic plasticity and inhibit neuronal apoptosis in SPS rats. These findings suggest that administering AR after the onset of severe traumatic events may alleviate anxiety, cognitive deficits, and impaired social interaction, improve synaptic plasticity, and diminish neuronal apoptosis. Hence, the present study provides evidence for AR's potential as a multi-target agent in the treatment of PTSD.
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INTRODUCTION: Hyperphosphatemia in chronic kidney disease (CKD) patients is positively associated with mortality. Ferric citrate is a potent phosphorus binder that lowers serum phosphorus level and improves iron metabolism. We compared its efficacy and safety with active drugs in Chinese CKD patients with hemodialysis. METHODS: Chinese patients undergoing hemodialysis were randomized into two treatment groups in a 1:1 ratio, receiving either ferric citrate or sevelamer carbonate, respectively, for 12 weeks. Serum phosphorus levels, calcium concentration, and iron metabolism parameters were evaluated every 2 weeks. Frequency and severity of adverse events were recorded. RESULTS: 217 (90.4%) patients completed the study with balanced demographic and baseline characteristics between two groups. Ferric citrate decreased the serum phosphorus level to 0.59 ± 0.54 mmol/L, comparable to 0.56 ± 0.62 mmol/L by sevelamer carbonate. There was no significant difference between two groups (p > 0.05) in the proportion of patients with serum phosphorus levels reaching the target range, the response rate to the study drug, and the changes of corrected serum calcium concentrations, and intact-PTH levels at the end of treatment. The change of iron metabolism indicators in the ferric citrate group was significantly higher than those in the sevelamer carbonate group. There are 47 (40.5%) patients in the ferric citrate group, and 26 (21.3%) patients in the sevelamer carbonate group experienced drug-related treatment emergent adverse events (TEAEs); most were mild and tolerable. Common drug-related TEAEs were gastrointestinal disorders, including diarrhea (12.9 vs. 2.5%), fecal discoloration (14.7 vs. 0%), and constipation (1.7 vs. 7.4%) in ferric citrate and sevelamer carbonate group. CONCLUSION: Ferric citrate capsules have good efficacy and safety in the control of hyperphosphatemia in adult patients with CKD undergoing hemodialysis. Efficacy is not inferior to sevelamer carbonate. The TEAEs were mostly mild and tolerated by the patients.
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Hiperfosfatemia , Insuficiencia Renal Crónica , Adulto , Humanos , Hiperfosfatemia/tratamiento farmacológico , Hiperfosfatemia/etiología , Sevelamer/efectos adversos , Calcio , Quelantes/efectos adversos , Diálisis Renal/efectos adversos , Compuestos Férricos/efectos adversos , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/tratamiento farmacológico , Fósforo , Hierro/uso terapéutico , ChinaRESUMEN
Introduction: With the increasingly serious problem of bacterial drug resistance caused by NDM-1, it is an important strategy to find effective inhibitors to assist ß-lactam antibiotic treatment against NDM-1 resistant bacteria. In this study, PHT427 (4-dodecyl-N-1,3,4-thiadiazol-2-yl-benzenesulfonamide) was identified as a novel NDM-1 inhibitor and restored the susceptibility of meropenem against Enterobacteriaceae producing NDM-1. Methods: We used a high throughput screening model to find NDM-1 inhibitor in the library of small molecular compounds. The interaction between the hit compound PHT427 and NDM-1 was analyzed by fluorescence quenching, surface plasmon resonance (SPR) assay, and molecular docking analysis. The efficacy of the compound in combination with meropenem was evaluated by determining the FICIs of Escherichia coli BL21(DE3)/pET30a(+)-bla NDM-1 and Klebsiella pneumoniae clinical strain C1928 (producing NDM-1). In addition, the mechanism of the inhibitory effect of PHT427 on NDM-1 was studied by site mutation, SPR, and zinc supplementation assays. Results: PHT427 was identified as an inhibitor of NDM-1. It could significantly inhibit the activity of NDM-1 with an IC50 of 1.42 µmol/L, and restored the susceptibility of meropenem against E. coli BL21(DE3)/pET30a(+)-bla NDM-1 and K. pneumoniae clinical strain C1928 (producing NDM-1) in vitro. The mechanism study indicated that PHT427 could act on the zinc ions at the active site of NDM-1 and the catalytic key amino acid residues simultaneously. The mutation of Asn220 and Gln123 abolished the affinity of NDM-1 by PHT427 via SPR assay. Discussion: This is the first report that PHT427 is a promising lead compound against carbapenem-resistant bacteria and it merits chemical optimization for drug development.
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Aspidopterys obcordata var. obcordata, a medicinal plant endemic to China, is a narrowly distributed species and wild resources are extremely limited. To evaluate the genetic variability and degree of genetic divergence of A. obcordata var. obcordata, and to make rational scientific decisions on its harvest and germplasm conservation, we collected 122 samples from across nearly all of its distribution area and studied genetic diversity using inter-simple sequence repeats (ISSRs), sequence-related amplified polymorphisms (SRAPs), and a method combining the two techniques. The results revealed the high genetic diversity of A. obcordata var. obcordata, mainly due to its intra-population diversity, and the top two populations with the highest levels of intra-population diversity were ML and DH, individuals of which can serve as excellent germplasm candidates during the processing of germplasm screening and conservation. In general, the combining method was prior to the ISSR analyses and SRAP analyses results, except for a slight difference in the genetic structure of individual populations. Therefore, we suggest that a combination analysis of the two marker methods is ideal for evaluating the genetic diversity and genetic relationships of A. obcordata var. obcordata.
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Variación Genética , Genética de Población , Malpighiaceae/genética , China , Análisis por Conglomerados , Marcadores Genéticos , Geografía , Medicina Tradicional China , Repeticiones de Microsatélite , Filogenia , Plantas Medicinales/genética , Polimorfismo Genético , Análisis de Componente PrincipalRESUMEN
BACKGROUND: Patient-derived organoid (PDO) models are highly valuable and have potentially widespread clinical applications. However, limited information is available regarding organoid models of non-small cell lung cancer (NSCLC). This study aimed to characterize the consistency between primary tumors in NSCLC and PDOs and to explore the applications of PDOs as preclinical models to understand and predict treatment response during lung cancer. METHODS: Fresh tumor samples were harvested for organoid culture. Primary tumor samples and PDOs were analyzed via whole-exome sequencing. Paired samples were subjected to immunohistochemical analysis. There were 26 antineoplastic drugs tested in the PDOs. Cell viability was assessed using the Cell Titer Glo assay 7-10 days after drug treatment. A heatmap of log-transformed values of the half-maximal inhibitory concentrations was generated on the basis of drug responses of PDOs through nonlinear regression (curve fit). A total of 12 patients (stages I-III) were enrolled, and 7 paired surgical tumors and PDOs were analyzed. RESULTS: PDOs retained the histological and genetic characteristics of the primary tumors. The concordance between tumors and PDOs in mutations in the top 20 NSCLC-related genes was >80% in five patients. Sample purity was significantly and positively associated with variant allele frequency (Pearson r = 0.82, P = 0.0005) and chromosome stability. The in vitro response to drug screening with PDOs revealed high correlation with the mutation profiles in the primary tumors. CONCLUSIONS: PDOs are highly credible models for detecting NSCLC and for prospective prediction of the treatment response for personalized precision medicine. KEY POINTS: Lung cancer organoid models could save precious time of drug testing on patients, and accurately select anticancer drugs according to the drug sensitivity results, so as to provide a powerful supplement and verification for the gene sequencing.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Evaluación Preclínica de Medicamentos/métodos , Genómica/métodos , Neoplasias Pulmonares/genética , Organoides/patología , Anciano , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana EdadRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Bergenin is a well-known active compound that exhibits antioxidant, antiarrhythmic, hepatoprotective, and anti-inflammatory activities. However, the resource reserve of Rodgersia sambucifolia, one of the main raw materials for extracting bergenin, have sharply declined, and the bergenin content in different germplasms differs vastly, resulting in a serious shortage of the market supply of bergenin. AIM OF THE STUDY: To investigate the influence of genetic diversity and environmental factors on bergenin content in Rodgersia sambucifolia. MATERIALS AND METHODS: Fifty Rodgersia sambucifolia samples with a growth period of 2-3 years were collected from different areas across China and the bergenin content was determined via HPLC. Meanwhile the total genomic DNA was extracted and ISSR was performed. The bergenin content as measured using HPLC and the environmental data gathered from the meteorological stations and field work were combined and analyzed using correlation tests in XLSTAT 2018 to detect the key factors affecting bergenin content. The genetic UPGMA tree constructed based on genetic distances of the 50 samples and the chemical dendrogram constructed according to the distance between the bergenin content were compared to determine the correlation between genetic and chemical differentiation. RESULTS: Among the 50 individuals, bergenin content varied from 2.83 to 12.54%, with the highest content being 4.43-fold that of the lowest content. The survey of the 50 individuals produced a total of 193 amplified bands, 187 of which were polymorphic (96.89%). In the study, bergenin content was positively correlated with annual mean temperature (AMT) (râ¯=â¯0.583, Pâ¯<â¯0.0001) and 1-12 month monthly mean temperature (MMT) (Pâ¯<â¯0.0001). A comparison of the genetic dendrogram with the AHC dendrogram found no corresponding relationship between them. Mantel correlation analyses also showed that there was no significant correlation between them (râ¯=â¯0.144). CONCLUSIONS: There were large differences in bergenin content among different germplasms that were not correlated with the high genetic variation in Rodgersia sambucifolia but were significantly correlated with environmental factors, such as temperature. This study lays the foundation for subsequent superior germplasm selection and artificial breeding of Rodgersia sambucifolia to improve the bergenin content and meet market demands.
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Benzopiranos/metabolismo , Productos Biológicos/metabolismo , Vías Biosintéticas/genética , Variación Genética , Saxifragaceae/metabolismo , Antineoplásicos/aislamiento & purificación , Antineoplásicos/metabolismo , Antioxidantes/aislamiento & purificación , Antioxidantes/metabolismo , Benzopiranos/aislamiento & purificación , Productos Biológicos/aislamiento & purificación , China , ADN de Plantas/genética , ADN de Plantas/aislamiento & purificación , Filogenia , Fitomejoramiento , Saxifragaceae/genética , Semillas/genética , Semillas/metabolismo , TemperaturaRESUMEN
This study is to establish a qualitative method for rapid identification of bile acids in Suis Fellis Pulvis based on UHPLC-LTQ-Orbitrap-MS technology,and an HPLC-ELSD internal standard method for the quantitative determination of two glycine-conjugated BAs in Suis Fellis Pulvis.The chromatographic separation of the UHPLC-LTQ-Orbitrap-MS qualitative analysis was achieved on a Waters Acquity UPLC HSS T_3column(2.1 mm×100 mm,1.8µm),with 0.2%formic acid aqueous solution(A)-acetonitrile(B)as mobile phase ingradient elution.Electrospray ionization(ESI)source was applied and operated in negative ion mode.Quantitative analysis was performed at 30âon a Diamonsil-C_(18)column(4.6 mm×250 mm,5µm).The mobile phase consisted of 0.2%formic acid solution and acetonitrile with gradient elution and the flow rate was 1.0 m L·min~(-1).An ELSD was used with a nitrogen flow-rate of1.4 L·min~(-1)at a drift tube temperature of 60âand the gain was 1.A total of 14 bile acids in Suis Fellis Pulvis were characterized based on the accurate mass measurements,fragmentation patterns,chromatographic retention times,and reference materials.For the quantitative analysis method,the glycohyodeoxycholic acid and glycochenodeoxycholic acid had good linear relationship in the range of26.52-265.20 mg·L~(-1)(r=0.999 8)and 19.84-198.40 mg·L~(-1)(r=0.999 1),respectively.The average recoveries(n=6)were104.1%and 103.1%,and the RSD were 2.0%and 2.4%.The UHPLC-LTQ-Orbitrap-MS technology provides a fast and efficient qualitative analysis method for identification of bile acids in Suis Fellis Pulvis.The HPLC-ELSD internal standard method is accurate and reliable,which has reference value for the quality control of Suis Fellis Pulvis.
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Ácidos Cólicos/análisis , Porcinos , Animales , Cromatografía Líquida de Alta Presión , Control de CalidadRESUMEN
One hitherto unknown 24-nor-13,27-cycloursane-type triterpenoid, lucumic acid A (1), one new 24-nor-ursane triterpenoid, lucumic acid B (2), along with six known triterpenoids were isolated from the ethanol extract of the leaves of Lucuma nervosa. Their structures were established on the basis of spectroscopic data interpretation. Lucumic acid A (1) is the first example of a 24-nor-triterpenoid with a 13,27-cyclopropane ring.
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Ácido Oleanólico/análogos & derivados , Hojas de la Planta/química , Pouteria/química , Triterpenos/aislamiento & purificación , China , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Inhibidores de Glicósido Hidrolasas/farmacología , Estructura Molecular , Ácido Oleanólico/aislamiento & purificación , Ácido Oleanólico/farmacología , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Extractos Vegetales/química , Triterpenos/farmacologíaRESUMEN
This study quantified the fatty acid profile with emphasis on the stereo-specifically numbered (sn) 2 positional distribution in TAG and the composition of main phospholipids at different lactation stages. Colostrum milk (n 70), transitional milk (n 96) and mature milk (n 82) were obtained longitudinally from healthy lactating women in Shanghai. During lactation, total fatty acid content increased, with SFA dominating in fatty acid profile. A high ratio of n-6:n-3 PUFA was observed as 11:1 over lactation due to the abundance of linoleic acid in Chinese human milk. As the main SFA, palmitic acid showed absolute sn-2 selectivity, while oleic acid, linoleic acid and α-linolenic acid, the main unsaturated fatty acids, were primarily esterified at the sn-1 and sn-3 positions. Nervonic acid and C22 PUFA including DHA were more enriched in colostrum with an sn-2 positional preference. A total of three dominant phospholipids (phosphatidylethanolamine (PE), phosphatidylcholine (PC) and sphingomyelin (SM)) were analysed in the collected samples, and each showed a decline in amount over lactation. PC was the dominant compound followed by SM and PE. With prolonged breast-feeding time, percentage of PE in total phospholipids remained constant, but PC decreased, and SM increased. Results from this study indicated a lipid profile different from Western reports and may aid the development of future infant formula more suitable for Chinese babies.
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Calostro/química , Ácidos Grasos/análisis , Leche Humana/química , Fosfolípidos/análisis , Adulto , Pueblo Asiatico , China , Ácidos Docosahexaenoicos/análisis , Ácidos Grasos Omega-3/análisis , Ácidos Grasos Omega-6/análisis , Femenino , Humanos , Lactancia/fisiología , Ácido Linoleico/análisis , Ácido Oléico/análisis , Ácido Palmítico/análisis , Factores de Tiempo , Ácido alfa-Linolénico/análisisRESUMEN
Uncaria macrophylla Wall. is an important Chinese medicinal herb. Rhynchophylline (RIN) and isorhynchophylline (IRN) are its major active compounds. We investigated the influence of genetic differentiation and environmental factors on the RIN and IRN to find the main influencing factors of their contents and lay the foundation for the following cultivation and breeding. We used inter-simple sequence repeat (ISSR) markers to investigate the genetic diversity, and high-performance liquid chromatography (HPLC) to measure the contents of RIN and IRN in 200 samples of U. macrophylla obtained from nine natural populations, and then to analyze the correlation between genetic differentiation, environmental factors of sampling sites and the contents of RIN and IRN. We found that High intra-population (80.05%) and low inter-population (19.95%) genetic diversity existed in the samples of U. macrophylla. To some extent, genetic differentiation and the contents of RIN and IRN had correlation in individual populations (such as JH, MH, XM, and ML). The RIN and IRN contents were significant negatively correlated with the precipitation in May (RIRN = -0.771, p = 0.015) and June (RRIN = -0.814, p = 0.008; RIRN = -0.921, p = 0.000), indicating that precipitation was the main affecting factor of their contents. Interestingly, the analysis results showed that the RIN content had a significant positive correlation (r = 0.585, p = 0.000) with the IRN content (they are isomers); the proportion of RIN had a significant negative correlation with the sum of the two (r = -0.390, p<0.0001), while the proportion of IRN had a significant positive correlation (r = 0.390, p<0.0001). It meant that, with the total quantity of the two compounds increased, the proportion of RIN decreased and the proportion of IRN increased, illustrating that their conversion exist some regularity. Moreover, the content ratio of RIN and IRN was significant positively correlated with the January precipitation (r = 0.716, p = 0.030), implying that January may be the key period for the mutual transformation of RIN and IRN.
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Pared Celular/metabolismo , Ambiente , Variación Genética , Oxindoles/metabolismo , Uncaria/genética , Uncaria/metabolismo , Pared Celular/química , China , ADN de Plantas , Geografía , Filogenia , Fitoquímicos/metabolismo , Uncaria/química , Uncaria/clasificaciónRESUMEN
Oral drug delivery has attracted substantial attention due to its advantages over other administration routes. Bacillus spores, as oral probiotic agents, are applied widely. In this paper, a novel Bacillus spore-based oral colon targeted carrier loading curcumin was developed for colon cancer treatment. Curcumin was linked covalently with the outer coat of Bacillus spore and folate, respectively (SPORE-CUR-FA). Bacillus spores are capable of delivering drugs to the colon area through gastric barrier, taking the advantage of its tolerance to the harsh conditions and disintegration of the outer coat of spores after germination in the colon. The drug release in vitro and in vivo of SPORE-CUR-FA was investigated. Results showed that SPORE-CUR-FA had the characteristics of colon-targeted drug release. Pharmacokinetic studies confirmed that Bacillus spore-based carriers could efficiently improve the oral bioavailability of curcumin. In vitro and in vivo anti-tumor studies showed that SPORE-CUR-FA had substantial ability for inhibiting colon cancer cells. These findings suggest that this Bacillus spore-based oral drug delivery system has a great potential for the treatment of colon cancer.
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Antineoplásicos/administración & dosificación , Bacillus coagulans , Neoplasias del Colon/tratamiento farmacológico , Curcumina/administración & dosificación , Portadores de Fármacos/administración & dosificación , Ácido Fólico/administración & dosificación , Esporas Bacterianas , Administración Oral , Animales , Antineoplásicos/química , Antineoplásicos/farmacocinética , Curcumina/química , Curcumina/farmacocinética , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Liberación de Fármacos , Ácido Fólico/química , Ácido Fólico/farmacocinética , Células HT29 , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Ratas Sprague-DawleyRESUMEN
Polymeric nanoparticles have been widely investigated as insulin delivery systems for oral administration. However, the toxic nature of many artificial polymers hampers their effective application, creating a demand for the further exploration of alternative natural polymers. In addition, ethnobotanical research has reported that over 800 plant species have a hypoglycemic function, some of which are polymers. For the advantages of both areas to be combined, the aim of this work was to choose an organic hypoglycemic polymer and prepare it into an insulin carrier to build a dual-functional oral insulin delivery system. We found that the insulin loading rate, release mode, thermostability, and both in vitro and in vivo absorption and efficacy varied with the different modifications of polygalacturonic acid (PGLA) nanoparticulate backbones. By in vivo pharmaceutical testing and constantly monitoring the symptoms of type 1 diabetic (T1D) rats, we ascertained the hypoglycemic function of the nanoparticles and showed that overall diabetic symptoms were ameliorated after the long-term daily administration of nanoparticles with no significant damage to organ structure or cell viability.
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Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/química , Insulina/administración & dosificación , Insulina/química , Nanopartículas/administración & dosificación , Nanopartículas/química , Administración Oral , Animales , Péptidos Catiónicos Antimicrobianos/química , Supervivencia Celular/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Humanos , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Quorum sensing of bacteria and its specific gene expression regulation have a very important role in bacterial biofilm formation. LuxS and agr are the key regulatory genes in quorum sensing of Staphylococcus epidermidis, and RNA â ¢ is the effector molecule of agr system. In order to evaluate the effects of sodium houttuyfonate in combination with erythromycin on the transcription level of S. epidermidis, serial dilution method was used to determine the MIC of sodium houttuyfonate, erythromycin and vancomycin on S. epidermidis, and fluorescent quantitative PCR method was used to detect the transcription levels of luxS, agr/RNAâ ¢ in different time periods after treatment on S. epidermidis by sodium houttuyfonate in combination with erythromycin, vancomycin, and erythromycin alone. Our results showed that in treatment by 1/2MIC, 1/4MIC sodium houttuyfonate, 1/2MIC sodium houttuyfonate +1/2MIC erythromycin, 1/4MIC sodium houttuyfonate+1/4MIC erythromycin, and 1/8MIC sodium houttuyfonate+1/8MIC erythromycin for ATCC 35984, they could rapidly up-regulate the expression of luxS of S. epidermidis from the beginning as compared with negative control, with significant differences (P<0.05); furthermore, sodium houttuyfonate can still up-regulate the expression of luxS even after treatment for 6, 12 and 48 h. Sodium houttuyfonate in MIC and 1/2MIC concentration can significantly down-regulate the expression of agr (P<0.05); 1/2MIC sodium houttuyfonate+1/2MIC erythromycin, 1/4MIC sodium houttuyfonate+1/4MIC erythromycin, can also significantly down-regulate the expression of agr in 6 h, 12 h and 24 h(P<0.05). Sodium houttuyfonate in MIC, can significantly down-regulate the expression of RNA â ¢ (P<0.05), and 1/2MIC sodium houttuyfonate+1/2MIC erythromycin can also significantly down-regulate the expression of RNAâ ¢(P<0.05). Therefore, our presented results showed that sodium houttuyfonate in combination with erythromycin can rapidly up-regulate the transcription of luxS of S. epidermidis, and can down-regulate the expression of agr/RNA â ¢ in certain concentrations, and suggested that sodium houttuyfonate in combination of erythromycin could inhibit mutual aggregation between S. epidermidis and biofilm bacteria, inhibit membrane nutrition and formation of water transport channels, prevent separation of bacterial cells in biofilm, and inhibit the formation of bacterial exotoxin of S. epidermidis.
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Alcanos/farmacología , Eritromicina/farmacología , Staphylococcus epidermidis/efectos de los fármacos , Sulfitos/farmacología , Proteínas Bacterianas/metabolismo , Biopelículas , Liasas de Carbono-Azufre/metabolismo , Pruebas de Sensibilidad Microbiana , ARN Bacteriano/metabolismo , Vancomicina/farmacologíaRESUMEN
The therapeutic potential of curcumin (Cur) is hampered by its poor aqueous solubility and low bioavailability. The aim of this study was to determine whether Cur nanoemulsions enhance the efficacy of Cur against prostate cancer cells and increase the oral absorption of Cur. Cur nanoemulsions were developed using the self-microemulsifying method and characterized by their morphology, droplet size and zeta potential. The results showed that the cytotoxicity and cell uptake were considerably increased with Cur nanoemulsions compared to free Cur. Cur nanoemulsions exhibited a significantly prolonged biological activity and demonstrated better therapeutic efficacy than free Cur, as assessed by apoptosis and cell cycle studies. In situ single-pass perfusion studies demonstrated higher effective permeability coefficient and absorption rate constant for Cur nanoemulsions than for free Cur. Our study suggested that Cur nanoemulsions can be used as an effective drug delivery system to enhance the anticancer effect and oral bioavailability of Cur.
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Antineoplásicos Fitogénicos/farmacología , Curcumina/farmacología , Absorción Intestinal/efectos de los fármacos , Nanoestructuras/administración & dosificación , Próstata/efectos de los fármacos , Animales , Antineoplásicos Fitogénicos/farmacocinética , Apoptosis/efectos de los fármacos , Caspasa 3/genética , Caspasa 3/metabolismo , Caspasa 7/genética , Caspasa 7/metabolismo , Ciclo Celular/efectos de los fármacos , Ciclo Celular/genética , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Curcumina/farmacocinética , Duodeno/efectos de los fármacos , Duodeno/metabolismo , Emulsiones , Expresión Génica , Glicerol/química , Humanos , Íleon/efectos de los fármacos , Íleon/metabolismo , Yeyuno/efectos de los fármacos , Yeyuno/metabolismo , Masculino , Nanoestructuras/química , Tamaño de la Partícula , Polietilenglicoles/química , Próstata/metabolismo , Próstata/patología , Ratas , Ratas Wistar , Tensoactivos/químicaRESUMEN
Pulmonary fibrosis is common in a variety of inflammatory lung diseases, such as interstitial pneumonia, chronic obstructive pulmonary disease, and silicosis. There is currently no effective clinical drug treatment. It has been reported that grape seed extracts (GSE) has extensive pharmacological effects with minimal toxicity. Although it has been found that GSE can improve the lung collagen deposition and fibrosis pathology induced by bleomycin in rat, its effects on pulmonary function, inflammation, growth factors, matrix metalloproteinases and epithelial-mesenchymal transition remain to be researched. In the present study, we studied whether GSE provided protection against bleomycin (BLM)-induced mouse pulmonary fibrosis. ICR strain mice were treated with BLM in order to establish pulmonary fibrosis models. GSE was given daily via intragastric administration for three weeks starting at one day after intratracheal instillation. GSE at 50 or 100mg/kg significantly reduced BLM-induced inflammatory cells infiltration, proinflammatory factor protein expression, and hydroxyproline in lung tissues, and improved pulmonary function in mice. Additionally, treatment with GSE also significantly impaired BLM-induced increases in lung fibrotic marker expression (collagen type I alpha 1 and fibronectin 1) and decreases in an anti-fibrotic marker (E-cadherin). Further investigation indicated that the possible molecular targets of GSE are matrix metalloproteinases-9 (MMP-9) and TGF-ß1, given that treatment with GSE significantly prevented BLM-induced increases in MMP-9 and TGF-ß1 expression in the lungs. Together, these results suggest that supplementation with GSE may improve the quality of life of lung fibrosis patients by inhibiting MMP-9 and TGF-ß1 expression in the lungs.
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Antiinflamatorios/uso terapéutico , Antibióticos Antineoplásicos/toxicidad , Bleomicina/toxicidad , Extracto de Semillas de Uva/uso terapéutico , Pulmón/efectos de los fármacos , Fibrosis Pulmonar/prevención & control , Animales , Antiinflamatorios/administración & dosificación , Líquido del Lavado Bronquioalveolar/química , Femenino , Extracto de Semillas de Uva/administración & dosificación , Pulmón/inmunología , Pulmón/patología , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones Endogámicos ICR , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/inmunología , Fibrosis Pulmonar/patología , Pruebas de Función Respiratoria , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Eight wild species in Sect. Moutan DC (tree peony) of the genus Paeonia grown in natural habitats and 1 cultivated specie were investigated to analyze their fatty acid and bioactive phenolic compound profiles. For fatty acid composition, P. ludlowii contained the lowest α-linolenic acid (27.68%) and P. jishanensis contained the highest (51.96 %) content of the 9 species. For phenolic compounds, P. qiui contained the highest resveratrol (2.12 mg/g), P. delavayi contained the highest ß-gentiobiosylpaeoniflorin (26.23 mg/g), and P. ostii contained the highest paeoniflorin (23.66 mg/g). P. ostii was selected to perform a feasibility study because of its relatively high level of α-linolenic acid 46.53%, low in ω-6 to ω-3 ratio of 1:2, and high level of the preferred bioactive phenolic compounds l including paeoniflorin and resveratrol. Physical pressing and refining process were conducted to obtain P. ostii seed oil. It exhibited bland sensory attributes described as slight grassy, very slight nutty, no painty or fishy aroma and slight grassy, slight nutty flavor with a very slight throat catch. Tocol results reported high level in tree peony seed oil 223.5 ± 13.65 mg/100 g with γ-tocopherol 70.1 ± 2.14 mg/100 g, and γ-tocotrienol 149.6 ± 15.83 mg/g. Because of the high total tocol, γ-tocopherol and γ-tocotrienol levels, and tree peony seed oil exhibited better oxidation stability than flaxseed oil even with similar α-linolenic acid levels. In addition, high levels of γ-tocopherol and γ-tocotrienol can introduce therapeutic effects such as antiinflammation and antioxidation. Therefore, this study showed that tree peony seed oil has a great potential to be used in edible oil, nutraceutical supplement, and other health care products.
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Análisis de los Alimentos/métodos , Paeonia/química , Semillas/química , Ácido alfa-Linolénico/análisis , gamma-Tocoferol/análisis , Antioxidantes/análisis , Cromanos/análisis , Estudios de Factibilidad , Glucósidos/análisis , Aceite de Linaza/análisis , Monoterpenos/análisis , Valor Nutritivo , Oxidación-Reducción , Fenoles/análisis , Resveratrol , Especificidad de la Especie , Estilbenos/análisis , Árboles , Vitamina E/análogos & derivados , Vitamina E/análisisRESUMEN
The therapeutic potential of curcumin (Cur) is hampered by its poor aqueous solubility and low bioavailability.The aim of this study was to determine whether Cur nanoemulsions enhance the efficacy of Cur against prostate cancer cells and increase the oral absorption of Cur.Cur nanoemulsions were developed using the self-microemulsifying method and characterized by their morphology,droplet size and zeta potential.The results showed that the cytotoxicity and cell uptake were considerably increased with Cur nanoemulsions compared to free Cur.Cur nanoemulsions exhibited a significantly prolonged biological activity and demonstrated better therapeutic efficacy than free Cur,as assessed by apoptosis and cell cycle studies.In siru single-pass perfusion studies demonstrated higher effective permeability coefficient and absorption rate constant for Cur nanoemulsions than for free Cur.Our study suggested that Cur nanoemulsions can be used as an effective drug delivery system to enhance the anticancer effect and oral bioavailability of Cur.
RESUMEN
In order to find out the composition, characteristics and traditional utilization characteristics of Dai medicine and promote the rational protection, inheritance and utilization of the resources and traditional knowledge of Dai medicine in China, the resources of traditional Dai medicine have been investigated systematically and the traditional knowledge of Dai medicine have been analyzed in the article. We found out that there were altogether 1 077 kinds of traditional Dai medicine in China and among which 272 were the first time recorded in the condition of Dai folk medical uses. There were 1 053 plant medicines which belong to 169 family and 694 genus. These plant medicines mainly distributed in the southern, west southern and east southern area of Yunnan province, the southern area of Guangxi, Guangdong, Guizhou, Sichuan, Fujian province and tropical, subtropical district as Taiwan, and more than 94.49% plant medicines could be found in Yunnan province. From the point of plant life form, they were major herbaceous or shrubby plants; When it is used as medicinal part, root and rhizome of plants account for the highest proportion, the next were whole plant and leaves. From nature, flavor and channel tropism points of view, the largest proportion of Dai medicines were cool, bitter-tasted and possesses water element. In terms of treatment of disease types, most of the drugs can treat gastrointestinal diseases, next were drugs that could be used to treat upper respiratory infection, traumatological and rheumatic diseases, urinary infection, gynecological diseases, hepatopathy, puerperium fever and diseases caused by poisonous insects and beast of prey bite. The study revealed that the resources of traditional Dai medicine and traditional knowledge of application were abundant in China, but the resources of traditional Dai medicine and traditional knowledge of application were faced with the risk of gradually reduce and loss. The article suggested that we should take measures to strengthen the study of protection and utilization of important traditional Dai medicine and endangered resources along with the protection and transmission of traditional knowledge of Dai nationalistic medicine.
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Medicina Tradicional , Fitoterapia , Plantas Medicinales , China , Humanos , InvestigaciónRESUMEN
Cu-pyropheophytin a, the major Cu-pigment of Cu-chlorophyll, was determined in edible oil by high-resolution mass spectrometry with a high-performance liquid chromatography-quadrupole (HPLC-Q)-Orbitrap system and by HPLC coupled with a photodiode-array detector. Respective limit of detection and limit of quantification levels of 0.02 µg/g and 0.05 µg/g were obtained. Twenty-nine commercial oil products marked as olive oil, grapeseed oil and blended oil, all sourced directly from a food company that committed adulteration with Cu-chlorophyll, were investigated. In this company, four green dyes illegally used in oils were seized during factory investigation by the health authorities. The food additive Cu-pyropheophytin a was found in all confiscated samples in concentrations between 0.02 and 0.39 µg/g. Survey results of another 235 commercial oil samples manufactured from other companies, including olive pomace oil, extra virgin olive oil, olive oil, grapeseed oil and blended oil, indicated high positive incidences of 63%, 39%, 44%, 97% and 8%, respectively, with a concentration range between 0.02 and 0.54 µg/g. High Cu-chlorophyll concentrations are indications for fraudulent adulteration of oils.
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Clorofilidas/análisis , Grasas Insaturadas en la Dieta/análisis , Colorantes de Alimentos/análisis , Contaminación de Alimentos , Inspección de Alimentos/métodos , Aceites de Plantas/química , Clorofila/análogos & derivados , Clorofila/análisis , Cromatografía Líquida de Alta Presión , Grasas Insaturadas en la Dieta/economía , Industria de Procesamiento de Alimentos/economía , Frutas/química , Guías como Asunto , Residuos Industriales/análisis , Residuos Industriales/economía , Límite de Detección , Aceite de Oliva/química , Aceite de Oliva/economía , Aceite de Oliva/normas , Feofitinas/análisis , Fotometría , Aceites de Plantas/normas , Semillas/química , Espectrofotometría Ultravioleta , Taiwán , Espectrometría de Masas en Tándem , Vitis/químicaRESUMEN
In the present work, a quantitative 1H Nuclear Magnetic Resonance (qHNMR) was established for purity assessment of six aryltetralin lactone lignans. The validation of the method was carried out, including specificity, selectivity, linearity, accuracy, precision, and robustness. Several experimental parameters were optimized, including relaxation delay (D1), scan numbers (NS), and pulse angle. 1,4-Dinitrobenzene was used as internal standard (IS), and deuterated dimethyl sulfoxide (DMSO-d6) as the NMR solvent. The purities were calculated by the area ratios of H-2,6 from target analytes vs. aromatic protons from IS. Six aryltetralin lactone lignans (deoxypodophyllotoxin, podophyllotoxin, 4-demethylpodophyllotoxin, podophyllotoxin-7'-O-ß-d-glucopyranoside, 4-demethylpodophyllotoxin-7'-O-ß-d-glucopyranoside, and 6''-acetyl-podophyllotoxin-7'-O-ß -d-glucopyranoside) were analyzed. The analytic results of qHNMR were further validated by high performance liquid chromatography (HPLC). Therefore, the qHNMR method was a rapid, accurate, reliable tool for monitoring the purity of aryltetralin lactone lignans.