RESUMEN
In this study, Spirulina maxima derived pectin nanoparticles (SmPNPs) were synthesized and multiple biological effects were investigated using in vitro and in vivo models. SmPNPs were not toxic to Raw 264.7 cells and zebrafish embryos up to 1 mg/mL and 200 µg/mL, respectively. SmPNPs upregulated Il 10, Cat, Sod 2, Def 1, Def 2, and Muc 1 in Raw 264.7 cells and tlr2, tlr4b, tlr5b, il1ß, tnfα, cxcl8a, cxcl18b, ccl34a.4, ccl34b.4, muc5.1, muc5.2, muc5.3, hamp, cstd, hsp70, cat, and sod1 in the larvae and adult zebrafish, suggesting immunomodulatory activity. Exposure of larvae to SmPNPs followed by challenge with pathogenic bacterium Aeromonas hydrophila resulted a two-fold reduction of reactive oxygen species, indicating reduced oxidative stress compared to that in the control group. The cumulative percent survival of larvae exposed to SmPNPs (50 µg/mL) and adults fed diet supplemented with SmPNPs (4%) was 53.3% and 76.7%, respectively. Topical application of SmPNPs on adult zebrafish showed a higher wound healing percentage (48.9%) compared to that in the vehicle treated group (38.8%). Upregulated wound healing markers (tgfß1, timp2b, mmp9, tnfα, il1ß,ccl34a.4, and ccl34b.4), enhanced wound closure, and restored pigmentation indicated wound healing properties of SmPNPs. Overall, results uncover the multiple bioactivities of SmPNPs, which could be a promising biocompatible candidate for broad range of aquatic and human therapies.
Asunto(s)
Factores Inmunológicos/farmacología , Nanopartículas , Estrés Oxidativo/efectos de los fármacos , Pectinas/farmacología , Células RAW 264.7/efectos de los fármacos , Spirulina/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Pez Cebra , Aeromonas hydrophila/patogenicidad , Animales , Regulación de la Expresión Génica , Factores Inmunológicos/aislamiento & purificación , Ratones , Pectinas/aislamiento & purificación , Células RAW 264.7/inmunología , Células RAW 264.7/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transcriptoma , Pez Cebra/embriología , Pez Cebra/genética , Pez Cebra/inmunología , Pez Cebra/microbiología , Proteínas de Pez Cebra/genética , Proteínas de Pez Cebra/metabolismoRESUMEN
Objective: To explore the relationship between serum 25-hydroxyvitamin D levels and core symptoms of autism spectrum disorder (ASD) in children. Method: In this cross-sectional study, ASD children 4 to 6 years of age who were diagnosed in Department of Developmental and Behavioral Pediatrics, First Hospital of Jilin university from January to May 2017 were assigned to ASD group, and children for routine growth and development assessment in Jilin province were assigned to control group. The two groups were well matched for age and sex, and none of them had received vitamin D supplementation. Serum 25-hydroxyvitamin D levels were measured by HPLC-MS/MS method. The patients of the ASD group were assessed with autism behavior checklist (ABC), childhood autism rating scale (CARS), social response scale (SRS), and autism treatment evaluation checklist (ATEC). The levels of vitamin D were divided into normal(>0.03 ng/L), insufficient (0.01-0.03 ng/L) and deficient (<0.01 ng/L). Levels of serum vitamin D between the two groups were compared by two independent sample t-test, and the difference in the percentages of normal, insufficient and deficient levels of vitamin D was tested by chi-square test, and correlations between vitamin D levels and the total scores or subscales of ABC, CARS, SRS and ATEC were analyzed by Pearson correlation analysis. Result: The 87 subjects in the ASD group included 75 males and 12 females, with a mean (±SD) age of (4.7±0.7) years. The 301 subjects in the control group included 249 males and 52 females, with a mean (±SD) age of (4.8±0.8) years. Serum vitamin D level in ASD children was significantly lower than that of the control group ( (0.021±0.008) vs. (0.036±0.016) ng/L, t=-8.17, P<0.01), and the between-group percentage difference of normal, insufficient and deficient levels of vitamin D was statistically significant (12 (14%) vs. 186 (62%) , 67 (77%) vs. 113 (37%) , 8 (9%) vs. 2 (1%) , χ(2)=72.1, P<0.01). There were negative correlations between serum vitamin D level in ASD children and total ABC score or ABC subscale scores (body behavior, self-care, language and social interaction)(r=-0.531,-0.397,-0.283,-0.248,-0.262, P=0.000, 0.000, 0.007, 0.020, 0.014). There were negative correlations between serum vitamin D level in ASD children and total CARS score and CARS subscale scores (imitation, nonverbal communication and general impression) (r=-0.352, -0.216, -0.248, -0.216, P=0.001, 0.046, 0.021, 0.046). There were negative correlations between serum vitamin D level in ASD children and SRS behavior subscale or ATEC social interaction subscale (r=-0.536, P=0.005, r=-0.400, P=0.014). Conclusion: Serum 25-hydroxyvitamin D level in children with ASD is obviously lower than that in the healthy control group, and there are negative correlations between vitamin D levels and core symptoms of ASD. Trial registration Chinese Clinical Trial Registry, ChiCTR-CCC-13004498.
Asunto(s)
Trastorno del Espectro Autista/tratamiento farmacológico , Suplementos Dietéticos , Vitamina D/análogos & derivados , Pueblo Asiatico , Trastorno del Espectro Autista/complicaciones , Trastorno del Espectro Autista/psicología , Trastorno Autístico , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Autocuidado , Espectrometría de Masas en Tándem , Vitamina D/sangre , Vitamina D/uso terapéutico , VitaminasRESUMEN
We explored the effects of icariin on the expression of estrogen receptor (ER), vascular endothelial growth factor (VEGF), and kinase insert domain receptor (KDR) in the endometrial cells of the thin endometrium. Primary endometrial cells were obtained and divided into a blank control group, a high-, a middle-, and a low-dose icariin groups, as well as an estrogen treatment group to undergo cellular identification by immunocytochemistry. The expression levels of ER, VEGF, and its receptor were estimated by western blotting. The expression levels of ER, VEGF, and KDR gradually increased from the control group to the estrogen (E2) treatment and icariin treatment groups; the differences were statistically significant. However, the differences were not statistically significant among the different icariin dose groups. The endometrium may be thickened by icariin treatment by increasing the expression levels of ER, VEGF, and KDR in endometrial cells.
Asunto(s)
Endometrio/metabolismo , Flavonoides/farmacología , Receptores de Estrógenos/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Adulto , Células Cultivadas , Evaluación Preclínica de Medicamentos , Endometrio/efectos de los fármacos , Endometrio/patología , Estradiol/farmacología , Femenino , Humanos , Trastornos de la Menstruación/tratamiento farmacológico , Trastornos de la Menstruación/metabolismo , Adulto JovenRESUMEN
Natural products have long been regarded as excellent sources for drug discovery given their structural diversity and wide variety of biological activities. Accordingly, the identification of the molecular targets of natural products is an important aspect of current drug discovery, as knowledge regarding a compound's molecular targets will greatly aid drug development and design. In this review, we will explore genomic, proteomic, and computational approaches to the elucidation of these mechanisms and the implications of these approaches for the target profiling of natural products. The recent applications of target profiling of natural products will also be reviewed.
Asunto(s)
Productos Biológicos/química , Productos Biológicos/metabolismo , Biología Computacional , Evaluación Preclínica de Medicamentos , Genómica , Humanos , Preparaciones Farmacéuticas/química , Preparaciones Farmacéuticas/metabolismo , ProteómicaRESUMEN
The Tibetan herb Potentilla anserina L. has been widely used in China for many thousands of years to treat hepatitis-B. Bioassay-guided fractionation of the ethanol extract of the rhizomes led to the isolation of a triterpenoid saponin (TS) that was determined to be 2alpha,3beta,19alpha-trihydroxyurs-12-en-28-oic acid beta-D-glucopyranosyl ester. Using models of HBV infection, this compound was evaluated for its effect on HBV antigene expression in the 2.2.15 cell line in vitro and anti-hepatitis B virus (HBV) activities in Peking ducklings in vivo. Results showed that it could decrease the expression levels of HBsAg, HBeAg and HBVDNA in the 2.2.15 cell culture and the inhibitory effect was not due to the cytotoxity of the triterpenoid saponin. The antiviral study in vivo on Peking ducklings also demonstrated that this compound inhibits duck hepatitis B virus (DHBV) DNA replication.
Asunto(s)
Infecciones por Hepadnaviridae/tratamiento farmacológico , Virus de la Hepatitis B del Pato/efectos de los fármacos , Hepatitis Viral Animal/tratamiento farmacológico , Fitoterapia , Potentilla/química , Saponinas/farmacología , Triterpenos/uso terapéutico , Animales , Antivirales/farmacología , Carcinoma Hepatocelular/virología , Línea Celular Tumoral , Replicación del ADN/efectos de los fármacos , ADN Viral/efectos de los fármacos , Patos , Anticuerpos Antihepatitis/sangre , Antígenos de la Hepatitis/sangre , Humanos , Neoplasias Hepáticas/virología , Extractos Vegetales/uso terapéutico , Rizoma/química , Saponinas/aislamiento & purificación , Saponinas/uso terapéutico , Triterpenos/aislamiento & purificación , Triterpenos/farmacologíaRESUMEN
Two new flavanes, named daphneflavan B (1) and daphneflavan C (2), along with two known biflavonoids, daphnodorin D(1) (3) and daphnodorin D(2) (4), were isolated from the roots of Daphne tangutica Maxim. Their structures were established on the basis of chemical, physicochemical, and spectroscopic evidences. Two compounds 3 and 4 were noted to have the most marked antitumor activity in vivo assay.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Daphne/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Plantas Medicinales/química , Animales , Antineoplásicos Fitogénicos/química , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Femenino , Flavonoides/química , Ratones , Estructura Molecular , Raíces de Plantas/químicaRESUMEN
Two new phenolic constituents, daphnenone (1) and daphneone (2), were isolated from the stem bark of Daphne odora Thunb. var. marginata. Their structures were established on the basis of spectroscopic analysis. Compounds 1 and 2 were tested for cytotoxic activity by MTT assays on five human tumour cell lines, K562, A549, MCF-7, LOVO and HepG2. Compound 1 showed obvious cytotoxic activity against all the five cell lines.
Asunto(s)
Antineoplásicos Fitogénicos/química , Daphne/química , Cetonas/química , Fenoles/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Formazáns/metabolismo , Humanos , Concentración 50 Inhibidora , Células K562 , Cetonas/aislamiento & purificación , Cetonas/farmacología , Resonancia Magnética Nuclear Biomolecular , Fenoles/aislamiento & purificación , Fenoles/farmacología , Corteza de la Planta/química , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Espectrometría de Masa por Ionización de Electrospray , Espectrofotometría Infrarroja , Espectrofotometría Ultravioleta , Sales de Tetrazolio/metabolismoRESUMEN
Neuromedin U is a neuropeptide prominently expressed in the upper gastrointestinal tract and central nervous system. Recently, GPR66/FM-3 (NmU-R1) was identified as a specific receptor for neuromedin U. A BLAST search of the GenBank(TM) genomic database using the NmU-R1 cDNA sequence revealed a human genomic fragment encoding a G protein-coupled receptor that we designated NmU-R2 based on its homology to NmU-R1. The full-length NmU-R2 cDNA was subsequently cloned, stably expressed in 293 cells, and shown to mobilize intracellular calcium in response to neuromedin U. This response was dose-dependent (EC(50) = 5 nm) and specific in that other neuromedins did not induce a calcium flux in receptor-transfected cells. Expression analysis of human NmU-R2 demonstrated its mRNA to be most highly expressed in central nervous system tissues. Based on these data, we conclude that NmU-R2 is a novel neuromedin U receptor subtype that is likely to mediate central nervous system-specific neuromedin U effects.