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Silver nanoparticles (AgNPs) by green synthesis from fungi polysaccharides are attracting increasing attention owing to their distinctive features and special applications in numerous fields. In this study, a cost-effective and environmentally friendly biosynthesizing AgNPs method with no toxic chemicals involved from the fruiting body polysaccharide of Phlebopus portentosus (PPP) was established and optimized by single factor experiment and response surface methodology. The optimum synthesis conditions of polysaccharide-AgNPs (PPP-AgNPs) were identified to be the reaction time of 140 min, reaction temperature of 94 °C, and the PPP: AgNO3 ratio of 1:11.5. Formation of PPP-AgNPs was indicated by visual detection of colour change from yellowish to yellowish brown. PPP-AgNPs were characterized by different methods and further evaluated for biological activities. That the Ultraviolet-visible (UV-Vis.) spectroscopy displayed a sharp absorption peak at 420 nm confirmed the formation of AgNPs. Fourier transform infrared (FTIR) analysis detected the presence of various functional groups. The lattice indices of (111), (200), (220), and (331), which indicated a faced-centered-cubic of the Ag crystal structure of PPP-AgNPs, was confirmed by X-ray diffraction (XRD) and the particles were found to be spherical through high resolution transmission electron microscopy (HRTEM). Energy dispersive X-ray spectroscopy (EDS) determined the presence of silver in PPP-AgNPs. The percentage relative composition of elements was determined as silver (Ag) 82.5 % and oxygen (O) 17.5 % for PPP-AgNPs, and did not exhibit any nitrogen peaks. The specific surface area of PPP-AgNPs was calculated to be 0.5750 m2/g with an average pore size of 24.33 nm by BET analysis. The zeta potential was -4.32 mV, which confirmed the stability and an average particle size of 64.5 nm was calculated through dynamic light scattering (DLS). PPP-AgNPs exhibited significant free radical scavenging activity against DPPH with an IC50 value of 0.1082 mg/mL. The MIC values of PPP-AgNPs for E. coli, S. aureus, C. albicans, C. glabrata, and C. parapsilosis are 0.05 mg/mL. The IC50 value of the inhibition of PPP-AgNPs against α-glucosidase was 11.1 µg/mL, while the IC50 values of PPP-AgNPs against HepG2 and MDA-MB-231 cell lines were calculated to be 14.36 ± 0.43 µg/mL and 40.05 ± 2.71 µg/mL, respectively. According to the evaluation, it can be concluded that these green-synthesized and eco-friendly PPP-AgNPs are helpful to improve therapeutics because of significant antioxidant, antimicrobial, antidiabetic, and anticancer properties to provide new possibilities for clinic applications.
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Antiinfecciosos , Nanopartículas del Metal , Plata/química , Antioxidantes/farmacología , Antioxidantes/química , Staphylococcus aureus , Hipoglucemiantes/farmacología , Nanopartículas del Metal/química , Escherichia coli , Extractos Vegetales/química , Antiinfecciosos/química , Espectrometría por Rayos X , Polisacáridos/farmacología , Antibacterianos/farmacologíaRESUMEN
A column prepared using a unique three-membered phenanthrene skeleton of rosin has complementary selectivity to a C18 column for some separation tasks. In this study, propylene pimaric acid (16-hydroxyethyl acrylate-34-n-butyl) ester (BRB) and propylene pimaric acid (16-hydroxyethyl acrylate-34-dodecyl) ester (BRLA) were used as functional ligands to prepare two novel stationary phases, namely BRB@SiO2 and BRLA@SiO2, through a "thiol-ene" click chemistry reaction. The characterization results of Fourier transform infrared spectroscopy, thermogravimetric analysis, nitrogen adsorption-desorption measurements, and contact angle tests showed that the BRB@SiO2 and BRLA@SiO2 stationary phases were successfully prepared. In addition, the performance of the columns was evaluated using the Tanaka test and hydrophobic subtraction model, which showed that the stationary phases exhibited typical reversed-phase chromatography performance and good hydrophobicity, hydrophobic selectivity, and steric selectivity. The changes in the retention of Panax notoginseng saponins on a column under different chromatographic conditions (acetonitrile content, flow rate, and column temperature) were investigated. The separation effect of BRB@SiO2 and BRLA@SiO2 columns on P. notoginseng saponins was better than that of the C18 column and the BRLA@SiO2 column could replace the C18 column for the detection of P. notoginseng saponins.
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Panax notoginseng , Saponinas , Dióxido de Silicio/química , Panax notoginseng/química , Ésteres , Interacciones Hidrofóbicas e HidrofílicasRESUMEN
Background: The application of medical image three-dimensional (3D) reconstruction technology can provide intuitive 3D image data support for accurate preoperative evaluation, surgical planning, and operation safety. However, there is still a lack of high-quality evidence to support whether 3D reconstruction technology is more advantageous in liver resection. Therefore, this study systematically evaluated the clinical effects of 3D reconstruction and two-dimensional (2D) image-assisted hepatectomy. Methods: Databases were searched to collect published clinical studies on 3D reconstruction technology and 2D image-assisted liver resection. Data were extracted from the database construction to March 2022 and the risk of bias in the included studies was evaluated. Meta-analysis was performed using RevMan5.3 software. Results: A total of 13 clinical studies were included, including 1616 patients, 795 in the 2D group and 819 in the 3D group. The meta-analysis showed that the incidence of postoperative complications was lower in the 3D group than in the 2D group (OR = 0.64, 95% CI = 0.49-0.83, P=0.001) and also reduced operation time (SMD = -0.51, 95% CI = -0.74â¼-0.27, P < 0.0001), decreased intraoperative blood loss (SMD = -63.85, 95% CI = -98.66-29.04, P=0.0003), decreased incidence of postoperative liver failure (OR = 2.42, 95% CI = 0.99-5.95, P=0.05), decreased postoperative recurrence rate (OR = 0.29, 95% CI = 0.16-0.53, P < 0.0001), and increased postoperative survival rate (OR = 2.19, 95% CI = 1.49-3.23, P < 0.0001). Conclusions: Current data suggest that 3D reconstruction-assisted hepatectomy can reduce intraoperative blood loss, postoperative complications, and recurrence, and improve postoperative survival. Therefore, the 3D reconstruction technique is worthy of application and promotion in assisted liver resection.
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Polycystic ovary syndrome (PCOS) is a common endocrine disease in women, potentially causing ovarian infertility for women at gestational age. Huatan Tongjing Decoction is commonly used to treat PCOS; however, the involved molecular mechanism has not been fully understood. In this study, the active components of Huatan Tongjing Decoction and potentially targeted proteins were downloaded from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. PCOS-related genes were accessed from Malacards database. STRING database was utilized to construct a protein-protein interaction (PPI) network based on the PCOS-related genes and the predicted targets. Subsequently, the PPI network was subjected to Random walk with restart (RWR). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on top 50 genes with the high affinity scores to the drug targets. Subsequently, based on the predicted drug components and targets, a component-gene interaction network was constructed. Finally, the most central drug targets were selected, and the corresponding compounds were subjected to molecular docking and dynamic simulations to examine their bindings. The 122 main active components and 246 potential targets of Huatan Tongjing Decoction were obtained from TCMSP, and a total of 259 nodes and 1919 interactions were acquired from the PPI network. The top 50 genes were mainly enriched in response to peptide hormone function and PI3K-Akt signaling pathway. Molecular docking and dynamic simulations predicted that MMP-quercetin interaction played an important role in the treatment of PCOS using Huatan Tongjing Decoction. Luteolin and quercetin in Huatan Tongjing Decoction potentially bound MMP9 and served as active components. This study preliminarily suggested the efficacy of Huatan Tongjing Decoction against PCOS in molecular degree.
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Medicamentos Herbarios Chinos , Hormonas Peptídicas , Síndrome del Ovario Poliquístico , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Humanos , Luteolina , Metaloproteinasa 9 de la Matriz , Simulación del Acoplamiento Molecular , Farmacología en Red , Fosfatidilinositol 3-Quinasas/genética , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/genética , Proteínas Proto-Oncogénicas c-akt , QuercetinaRESUMEN
As green, less toxic, widely available, and site-rich functional ligands, natural products are widely used for the development of chromatographic stationary phases. In this work, a novel stationary phase, cardanol-bonded on silica (CBS) was prepared using γ-glycidoxypropyltrimethoxysilane (KH-560) as the coupling reagent and cardanol as the functional ligand. The synthesized stationary phase was characterized by Fourier transform-infrared spectra (FT-IR), thermogravimetric analysis (TGA), elemental analysis (EA), and N2 adsorption-desorption analysis. The results revealed that cardanol was successfully immobilized on the surface of spherical silica by the ring-opening reaction of the epoxy groups in phenolic hydroxyl. The retention mechanism and chromatographic performance of the CBS column were further evaluated and compared with those of a commercial C18 column using different classes of analytes, e. g., Tanaka standard test mixtures, alkylbenzenes, polycyclic aromatic hydrocarbons (PAHs), phenols, and aromatic positional isomers. The retention of alkylbenzenes under different chromatographic conditions revealed that the CBS column was a typical reversed-phase liquid chromatographic column, similar to the commercial C18 column. From the results of the Tanaka test, it was concluded that CBS could provide various interactions for different solutes e. g., hydrogen bonding and π-π interactions, along with hydrophobic interactions. The synergistic effects resulting from the aromatic rings, the hydroxyl and alkyl linkers in the new stationary phase improved the separation selectivity via multiple retention mechanisms. Based on these interactions, different solute probes such as hydrophobic alkylbenzenes, PAHs, and phenols were successfully separated in the reversed-phase liquid chromatography (RPLC) mode. For example, the aromatic positional isomers o-terthenyl, m-terphenyl, and triphenylene were used to investigate the chromatographic performance of the CBS column. These PHAs were baseline separated with good peak shapes. The resolution of m-terphenyl and triphenylene was as high as 6.81, while the two isomers could not be separated on the C18 column under the same chromatographic conditions. The repeatability and column stability of the CBS column was evaluated, and excellent repeatability and column stability were observed. The relative standard deviations (RSDs) of the retention time, peak area, and peak height for alkylbenzenes with 10 replicate injections were 0.052%-0.079%, 0.104%-0.847%, and 0.081%-0.272%, respectively. Traditional Chinese medicines have contributed notably to the Chinese civilization and human health. However, the complicated chemical compositions, unclear medicinal action mechanisms, and low purification efficiency for the traditional Chinese medicines have limited further development. Therefore it is necessary to establish an efficient, simple and feasible method for the separation and purification of herbal medicines. HPLC has been widely used in traditional Chinese medicines for the separation and detection of various components. In order to explore the CBS column for analysis of the traditional Chinese medicines, the ethanol extracts of fruits of Evodiae fructus and Camptotheca acuminata were used to test the separation performance of this column. The resolution of camptothecin from the preceding and following impurity peaks was 4.23 and 2.71. The resolution between evodiamine and rutaecarpin was 5.43, while the resolution from the adjacencies of impurity peaks was 2.20 and 1.69, respectively. The above mentioned results indicated that the CBS column shows good separation performance for the main active ingredients in the ethanolic extracts of these drugs, this validating its great potential for the analysis of real samples. Overall, the present study not only provides a new approach for the preparation of chromatographic stationary phases but also opens a new possibility for the separation and purification of camptothecin and evodiamine in real samples. This is an extension of the application of cardanol to chromatographic separation materials.
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Hidrocarburos Policíclicos Aromáticos , Dióxido de Silicio , Camptotecina , Cromatografía Líquida de Alta Presión , Interacciones Hidrofóbicas e Hidrofílicas , Fenoles/análisis , Extractos Vegetales , Hidrocarburos Policíclicos Aromáticos/análisis , Dióxido de Silicio/química , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Porcine reproductive and respiratory syndrome virus (PRRSV) infection leads to late-term reproductive failure and respiratory illness that affect the global swine industry. Epigallocatechin gallate (EGCG) is a polyphenolic compound from green tea that exerts antiviral activity against diverse viruses. This study aimed to report an uncharacterized mechanism of how EGCG restricted PRRSV proliferation. EGCG showed no significant effects on cell viability, cell cycle progression, and apoptosis in porcine alveolar macrophages and MARC-145 cells. The treatment of cells with EGCG attenuated the replication of both highly pathogenic and less pathogenic PRRSV in vitro. The viral life cycle analysis demonstrated that EGCG affected PRRSV replication and assembly, but not viral attachment, entry, or release. Interestingly, EGCG treatment abrogated the increased lipid droplets formation and lipid content induced by PRRSV infection. We further demonstrated that EGCG blocked PRRSV-stimulated expression of the key enzymes in lipid synthesis. In addition, EGCG attenuated PRRSV-induced autophagy that is critical for PRRSV proliferation. The supplementation of oleic acid restored PRRSV replication and assembly under EGCG treatment. Together, our results support that EGCG inhibits PRRSV proliferation through disturbing lipid metabolism. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped single-positive-stranded RNA virus that causes acute respiratory distress in piglets and reproductive failure in sows, resulting in huge economic losses to the global swine industry. Several lines of evidence have suggested the crucial roles of lipids in PRRSV proliferation. Our previous report demonstrated that PRRSV activated lipophagy to facilitate viral replication through downregulating the expression of N-Myc downstream-regulated gene 1. The manipulation of lipid metabolism may be a new perspective to prevent PRRSV spread. In the present study, we reported that epigallocatechin-3-gallate (EGCG), the major component of green tea catechins, significantly attenuated PRRSV infection through inhibiting lipid synthesis and autophagy. Given that natural products derived from plants have helped in the prevention and treatment of various infectious diseases, EGCG has a great potential to serve as a safe and environmentally friendly natural compound to treat PRRSV infection.
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Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Animales , Catequina/análogos & derivados , Línea Celular , Proliferación Celular , Femenino , Metabolismo de los Lípidos , Lípidos , Síndrome Respiratorio y de la Reproducción Porcina/tratamiento farmacológico , Porcinos , TéRESUMEN
BACKGROUND: Zuogui pills (ZGP), a classical prescription of traditional Chinese medicine, have been widely used in the treatment of ovarian aging. Previous studies have demonstrated its efficacy on protecting ovarian aging, and the mechanisms were mostly relevant to inhibiting the apoptosis of follicles and activating the primordial follicles. However, whether ZGP could stimulate the oogonial stem cells (OSCs) to refresh the follicle pool remains poorly understood. PURPOSE: To investigate the effects of ZGP on the stemness of OSCs in cyclophosphamide (Cy)-induced ovarian aging. STUDY DESIGN AND METHODS: Female Sprague-Dawley (SD) rats were randomly divided into 8 groups: control group, model group, ZGP groups (low / high dose groups), estradiol valerate (EV) groups (low / high dose groups), DAPT group and DAPT+ZGP-L group. After modeling with Cy, the ZGP groups and EV groups were treated with ZGP and EV for 8 weeks respectively. Meanwhile, the DAPT groups were treated with DAPT twice a week. Additionally, OSCs were also isolated after modeling, and then treated with drug serum containing ZGP or EV. Ovarian volume and the ratio of weight of total ovaries to the body weight were measured. The serum hormones were measured by ELISA. Quantities and location of OSCs in ovaries were detected by flow cytometry and immunofluorescence. Cell viability was measured by CCK8. And OSCs were identified by immunofluorescence. Biomarkers of germ cells, stem cells and associated to differentiation and meiosis were detected by qPCR and western blot. Proteins in Notch signaling pathway were detected by western blot and immunofluorescence. RESULTS: After treating with ZGP, ovarian volume and the ratio of weight of total ovaries to the body weight increased. ZGP could increase serum AMH and E2 level and decrease serum FSH level. Quantities and cell viability of OSCs increased after ZGP treatment in vivo and in vitro. In addition, treatment with ZGP could increase not only the expression of MVH, Oct4 and DAZL, but also the expression of ZP1 and ZP2. Furthermore, ZGP could up-regulate the expression of Notch intracellular domain (NICD), HES1 and HES5. After blocking the Notch signaling pathway, ZGP could increase not only the expression of NICD, HES1 and HES5, but also the expression of MVH, Oct4, DAZL, ZP1 and ZP3. CONCLUSION: In conclusion, the mechanism of ZGP on treating ovarian aging may be relevant to maintain the stemness of OSCs by up-regulating Notch signaling pathway, which added the mechanism of ZGP on the perspective of OSCs at first time.
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Arcangelisia gusanlung H.S.Lo is widely used as a folk medicine by the Dai and Li peoples. Here, we report the first complete chloroplast (cp) genome sequence for this species based on Illumina paired-end sequencing data. The cp genome was 162,509 bp in length with a small single-copy (SSC) region of 20,852 bp, a large single-copy (LSC) region of 91,449 bp, and two separated inverted region of 25,104 bp. In total, 129 unique genes were identified of this genome, including 84 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The GC contents of this genome is 37.8%. Phylogenetic analysis based on 13 complete cp genomes showed a strong sister relationship with Tinospora cordifolia (Willd.) Miers and Tinospora sinensis (Lour.) Merr. This complete genome of A. gusanlung will provide valuable information to elucidate the mechanism of speciation of Arcangelisia Becc.
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ABCC multidrug resistance-associated proteins (ABCCs/MRPs), a subfamily of ABC transporters, are involved in multiple physiological processes. Although these proteins have been characterized in some plants, limited efforts have been made to address their possible roles in Rehmannia glutinosa, a medicinal plant. Here, we scanned R. glutinosa transcriptome sequences and identified 18 RgABCC genes by in silico analysis. Sequence alignment revealed that the RgABCCs were closely phylogenetically related and highly conserved with other plant ABCCs/MRPs. Subcellular localization revealed that most of the RgABCCs were deposited in vacuoles and a few in plasma membranes. Tissue-specific expression of the RgABCCs indicated significant specific accumulation patterns, implicating their roles in the respective tissues. Differential temporal expression patterns of the RgABCCs exhibited their potential roles during root development. Various abiotic stress and hormone treatment experiments indicated that some RgABCCs could be transcriptionally regulated in roots. Furthermore, the transcription of several RgABCCs in roots was strongly activated by cadmium (Cd), suggesting possible roles under heavy metal stresses. Functional analysis of RgABCC1 heterologous expression revealed that it may increase the tolerance to Cd in yeast, implying its Cd transport activity. Our study provides a detailed inventory and molecular characterization of the RgABCCs and valuable information for exploring their functions in R. glutinosa.
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Transportadoras de Casetes de Unión a ATP/antagonistas & inhibidores , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/biosíntesis , Raíces de Plantas/metabolismo , Rehmannia/metabolismo , Transcriptoma , Transportadoras de Casetes de Unión a ATP/genética , Membrana Celular/genética , Membrana Celular/metabolismo , Proteínas de Plantas/genética , Raíces de Plantas/genética , Rehmannia/genética , Estrés Fisiológico/fisiología , Vacuolas/genética , Vacuolas/metabolismoRESUMEN
CNKI, PubMed and other databases were retrieved to extract eligible randomized controlled trial(RCT) about modified Xuefu Zhuyu Decoction(MXZD) combined with Western medicine(trial group) versus Western medicine alone(control group) in the treatment of leiomyoma. Therefore, a total of 25 RCTs were included, involving 2 328 patients. Bias risk evaluation tool in Cochrane Handbook 5.1.0 was used for evaluating the quality of these RCTs. Meta-analysis was performed for the reported indicators, including total efficiency, serum hormone level [progesterone(P), luteinizing hormone(LH), estradiol(E_2), follicle stimulating hormone(FSH)], uterine size, fibroids size and adverse reactions by using Stata 14.0 software. Meta-analysis showed that the total efficiency(RR=1.21,95%CI[1.17,1.25],P<0.05) of trial group was better than that of control group. Serum hormone level(WMD_P=-3.86,95%CI[-4.31,-3.41],P<0.05; WMD_(LH)=-3.64,95%CI[-4.47,-2.82],P<0.05; WMD_(E_2)=-39.99,95%CI[-53.45,-26.52],P<0.05; WMD_(FSH)=-3.79,95%CI[-4.86,-2.72],P<0.05), uterine size(WMD=-50.02,95%CI[-55.98,-44.06],P<0.05), fibroids size(WMD=-15.79,95%CI[-18.11,-13.46],P<0.05) and adverse reactions(RR=0.65,95%CI[0.48,0.88],P<0.05) of trial group were all lower than those of control group, with statistical significances. Trial sequential analysis(TSA) was performed by using TSA 0.9 software, and showed a reliable therapeutic effect of the experimental group. In short, our study indicated that modified Xuefu Zhuyu Decoction combined with Western medicine had a better therapeutic effect on leiomyoma than Western medicine alone, but more high-quality studies are needed to verify this conclusion in the future.
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Medicamentos Herbarios Chinos , Leiomioma , Medicina , Humanos , Leiomioma/tratamiento farmacológicoRESUMEN
Electronic migration can be tailored by carefully manipulating the local electron donating and withdrawing nature of carbon nitride for charge separation and red-shift emission. A high yield of H2 (5 mmol h-1 g-1) with an apparent quantum yield of 20.98% at 420 nm and a preliminary study on phototherapy by labeling cell membranes are simultaneously provided.
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Nitrilos/química , Procesos Fotoquímicos , Fototerapia , Catálisis , Membrana Celular/metabolismo , Microscopía Electrónica de Transmisión , Espectroscopía de FotoelectronesRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Zuogui Pills (ZGP), which is a classical prescription of Traditional Chinese Medicine (TCM), has been reported to be widely used in the treatment of premature ovarian failure (POF). AIM OF THE STUDY: To investigate the therapeutic effects of ZGP on the treatment of POF induced by chemotherapy, and elucidate the potential molecular mechanism. MATERIALS AND METHODS: Female 8-week-old Sprague-Dawley rats (Nâ¯=â¯54) were randomized to six groups, containing the Control group, Model group, three ZGP groups and Triptorelin group which was served as a positive control. The Triptorelin group received triptorelin injection ten days before model establishment by cyclophosphamide. The three ZGP groups (high dose group, medium dose group and low dose group) were given a daily intragastric administration of ZGP at doses of 3.2, 1.6 and 0.8â¯g/kg for sixty days. We observed the general growth of rats and examed the estrous cycle and the rate of pregnancy, ovarian ultrastructures, follicles and corpora lutea numbers. The serum hormone concentrations were measured by Enzyme-linked immunosorbent assay (ELISA). To explore the molecular mechanism of the effect, gene and protein expression levels of Bax, Bcl-2 and Cyt-c related to apoptosis were determined by quantitative PCR (qPCR), Western Blot and Immunohistochemistry analysis, respectively. RESULTS: After treating with ZGP, though the rate of pregnancy showed no significant difference, the estrous cycle, ovarian ultrastructures, numbers of follicles and corpora lutea were improved significantly. And ZGP led to a significant lower concentration of follicle stimulating hormone (FSH) in the serum, and the concentration of oestradiol (E2) was increased. Furthermore, a significant downregulation of Bax, cytochrome c (Cyt-c), and upregulation of B cell lymphoma/leukemia-2 (Bcl-2) both on gene and protein levels were observed after the administration with ZGP. And effects showed a positive correlation with the dosages. CONCLUSIONS: Our study suggested that ZGP exerted significant effect on POF, which was meditated by inhibiting mitochondria-dependent apoptosis in the follicles.
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Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Mitocondrias/efectos de los fármacos , Folículo Ovárico/efectos de los fármacos , Insuficiencia Ovárica Primaria/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Ciclofosfamida/farmacología , Modelos Animales de Enfermedad , Estradiol/sangre , Ciclo Estral/efectos de los fármacos , Femenino , Hormona Folículo Estimulante/sangre , Masculino , Medicina Tradicional China , Folículo Ovárico/patología , Insuficiencia Ovárica Primaria/patología , Ratas Sprague-Dawley , ComprimidosRESUMEN
The importance of BET protein BRD4 in gene transcription is well recognized through the study of chemical modulation of its characteristic tandem bromodomain (BrD) binding to lysine-acetylated histones and transcription factors. However, while monovalent inhibition of BRD4 by BET BrD inhibitors such as JQ1 blocks growth of hematopoietic cancers, it is much less effective generally in solid tumors. Here, we report a thienodiazepine-based bivalent BrD inhibitor, MS645, that affords spatially constrained tandem BrD inhibition and consequently sustained repression of BRD4 transcriptional activity in blocking proliferation of solid-tumor cells including a panel of triple-negative breast cancer (TNBC) cells. MS645 blocks BRD4 binding to transcription enhancer/mediator proteins MED1 and YY1 with potency superior to monovalent BET inhibitors, resulting in down-regulation of proinflammatory cytokines and genes for cell-cycle control and DNA damage repair that are largely unaffected by monovalent BrD inhibition. Our study suggests a therapeutic strategy to maximally control BRD4 activity for rapid growth of solid-tumor TNBC cells.
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Antineoplásicos/farmacología , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas Nucleares/antagonistas & inhibidores , Factores de Transcripción/antagonistas & inhibidores , Transcripción Genética/efectos de los fármacos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Proteínas de Ciclo Celular , Línea Celular Tumoral , Femenino , Humanos , Subunidad 1 del Complejo Mediador/genética , Subunidad 1 del Complejo Mediador/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Factor de Transcripción YY1/genética , Factor de Transcripción YY1/metabolismoRESUMEN
The removal efficiency of sediment phosphorus (P) with the in-situ synergistic effect of modified bentonite granules (MBG) and Vallisneria spiralis (V. spiralis) in West Lake, Hangzhou, China was investigated for the first time in the study. CMBG-Na10-450 (nitrification (10% Na2CO3)-calcination (450⯰C) combined modification) was prepared and characterized, and the removal effects of sediment P of all fractions with CMBG-Na10-450 and V. spiralis in combination and separately were evaluated in batch experiments. Results showed that CMBG-Na10-450 could promote the growth of V. spiralis, and the residual P of the sediment not adsorbed on CMBG-Na10-450 was changed through root oxygenation and nutrition allocation, and then enhanced the extra P adsorption on CMBG-Na10-450. The combination of MBG and V. spiralis exhibited a synergistic removal effect higher than the summation of MBG and V. spiralis applied separately. The results of microcosm experiments showed that the combination of CMBG-Na10-450 and V. spiralis enhanced the function of P metabolism by increasing the special genus that belongs to the family Erysipelotrichaceae.
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Bentonita/química , Restauración y Remediación Ambiental , Sedimentos Geológicos/química , Hydrocharitaceae/metabolismo , Lagos/química , Fósforo/aislamiento & purificación , ChinaRESUMEN
This paper describes the design of an 8-channel high voltage stimulator chip for rehabilitation of stroke patients through surface stimulation, which requires high stimulation currents and high compliance voltage. The chip gets stimulation control data through its Serial Peripheral Interface (SPI), and can accordingly generate biphasic stimulation currents with different amplitudes, duration, frequencies and polarities independently for each channel. The current driver is implemented with thick oxide devices with a supply voltage up to 90V. The chip is designed in a 0.35εm X-FAB high voltage process.
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Terapia por Estimulación Eléctrica/instrumentación , Electricidad , Rehabilitación de Accidente Cerebrovascular , Simulación por Computador , Diseño de Equipo , HumanosRESUMEN
Rehmannia glutinosa, a traditional Chinese medicine herb, is unable to grow normally in a soil where the same species has recently been cultivated. The biological basis of this so called "replanting disease" is unknown, but it may involve the action of microRNAs (miRNAs), which are known to be important regulators of plant growth and development. High throughput Solexa/Illumina sequencing was used to generate a transcript library of the R. glutinosa transcriptome and degradome in order to identify possible miRNAs and their targets implicated in the replanting disease. A total of 87,665 unigenes and 589 miRNA families (17 of which have not been identified in plants to date) was identified from the libraries made from a first year (FP) and a second year (SP) crop. A comparison between the FP and SP miRNAs showed that the abundance of eight of the novel and 295 of the known miRNA families differed between the FP and SP plants. Sequencing of the degradome sampled from FP and SP plants led to the identification of 165 transcript targets of 85 of the differentially abundant miRNA families. The interaction of some of these miRNAs with their target(s) is likely to form an important part of the molecular basis of the replanting disease of R. glutinosa.
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Regulación de la Expresión Génica de las Plantas , MicroARNs/genética , Tracheophyta/genética , Transcriptoma , Biología Computacional , Perfilación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Anotación de Secuencia MolecularRESUMEN
OBJECTIVE: To observe the therapeutic efficacy of Chinese medical syndrome typing and treatment combined cold needle puncture drainage operation or unipolar electrocoagulation drilling technique under laparoscope for treating clomiphene-resistant polycystic ovary syndrome (PCOS). METHODS: Forty infertility patients with clomiphene-resistant PCOS were assigned to two groups using stratified random sampling method according to age, infertility time, and body mass index, 20 in each group. Patients in Group A were treated with Chinese medical syndrome typing and treatment combined cold needle puncture drainage operation, while those in Group B were treated with Chinese medical syndrome typing and treatment combined unipolar electrocoagulation drilling technique. After operation Chinese herbal treatment was administered to all patients according to syndrome typing. The serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), androgen (T), estradiol (E2), and prolactin (PRL) were determined before and after operation. The ovulation was monitored. The pregnancy rate and the pregnancy outcomes were recorded after operation. RESULTS: There was no statistical difference in the 3-month spontaneous ovulation rate or the 1-year pregnancy rate (P > 0.05). The levels of LH, T, and PRL were significantly lower after operation than before operation in the two groups (P < 0.05). The menstruation and ovulation were obviously improved after operation. The total ovulation rate was 95% (19/20) in Group A. Successful pregnancy occurred in 15 cases of Group A. Ovarian hyperstimulation syndrome (OHSS) occurred in 1 case of Group A. The total ovulation rate was 90% (18/20) in Group B. Successful pregnancy occurred in 13 cases of Group B. Hypovaria occurred in 1 case of Group B. Luteinized unruptured follicle (LUFS) occurred in 2 cases of Group A and 1 case of Group B. CONCLUSIONS: Chinese medical syndrome typing and treatment combined cold needle puncture drainage operation or unipolar electrocoagulation drilling technique could effectively promote the ovulation. The two methods showed similar therapeutic effects.
Asunto(s)
Medicina Tradicional China/métodos , Síndrome del Ovario Poliquístico/terapia , Adulto , Clomifeno/farmacología , Resistencia a Medicamentos , Electrocoagulación , Femenino , Hormona Folículo Estimulante/análisis , Humanos , Medicina Integrativa , Laparoscopía , Hormona Luteinizante/análisis , Embarazo , Prolactina/análisisRESUMEN
Three new holostan-type triterpene glycosides, arguside F (1), impatienside B (2), and pervicoside D (3), together with a known saponin, holothurin B ( 4) were isolated from the sea cucumber Holothuria (Microthele) axiloga H. L. Clark. On the basis of spectroscopic data and chemical reactions, the structures of the new compounds were elucidated. Compound 2 showed significant antifungal activities against six strains (1 < or = MIC(80) < or = 4 microg/mL). The stereochemistry of holothurin B (4) isolated from the title sea cucumber was also solved through X-ray diffraction analysis.
Asunto(s)
Antifúngicos/farmacología , Hongos/efectos de los fármacos , Glicósidos/farmacología , Holothuria/química , Triterpenos/farmacología , Animales , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Glicósidos/química , Glicósidos/aislamiento & purificación , Triterpenos/química , Triterpenos/aislamiento & purificaciónRESUMEN
We aimed to assess the effects of traditional Chinese medicine; marine (MT) and kuhuang (KH), either alone or in combination, on the early graft function of the recipients and overall patient survival rate after liver transplantation (LT) by using diammonium glycyrrhizinate (DG) as a positive control. A total of 151 subjects undergoing LT were included in this prospective study. According to the different regimens given in the first two post-transplant weeks, they were divided into DG group (n = 49), DG + KH group (n = 36), MT group (n = 42) and MT + KH group (n = 24). The graft function in the early post-transplant period and patient survival rate were examined. During the first two post-transplant weeks, there was no significant difference in total bilirubin, alanine transaminase, aspartate transaminase, serum creatinine, and prothrombin time between MT group and DG group. Patient survivals in these two groups were also similar. Compared to DG group, DG + KH group showed a significantly lower total bilirubin value on post-transplant day 5 (3.2 +/- 2.1 mg/dL vs. 5.7 +/- 5.6 mg/dL, p < 0.01) and day 7 (2.8 +/- 1.8 mg/dL vs. 5.8 +/- 6.1 mg/dL, p < 0.01), and higher patient survival. There was no significant difference between DG + KH group and MT + KH group. In conclusion, MT provides an alternative to DG after LT. The combination of MT and KH is highly effective in decreasing the total blirubin in the early post-transplant period and improving patient survival.
Asunto(s)
Alcaloides/farmacología , Bilirrubina/metabolismo , Medicamentos Herbarios Chinos/farmacología , Riñón/efectos de los fármacos , Trasplante de Hígado/fisiología , Hígado/efectos de los fármacos , Sustancias Protectoras/farmacología , Quinolizinas/farmacología , Adulto , Creatinina/sangre , Quimioterapia Combinada , Femenino , Ácido Glicirrínico/farmacología , Humanos , Hígado/metabolismo , Trasplante de Hígado/mortalidad , Magnoliopsida , Masculino , Persona de Mediana Edad , Fitoterapia , Estudios Prospectivos , Protrombina/metabolismo , Transferasas/metabolismo , MatrinasRESUMEN
Four new holostan-type triterpene glycosides, marmoratoside A ( 1), 17 alpha-hydroxy impatienside A ( 2), marmoratoside B ( 3), 25-acetoxy bivittoside D ( 4), together with two known triterpene glycosides, impatienside A ( 5) and bivittoside D ( 6), were isolated from the sea cucumber Bohadschia Marmorata Jaeger. On the basis of spectroscopic analyses, including two-dimensional NMR techniques, and chemical reactions, the structures of the new triterpene glycosides were elucidated. Compounds 1, 2, 5, and 6 exhibited significant antifungal activity against six strains (0.70 < or = MIC (80) < or = 2.81 microM).