ABSTRACT
The structural characteristics of fucoidans exhibit species and regional diversity. Previous studies have demonstrated that Laminaria japonica- and Ascophyllum nodosum-derived fucoidans have type I and type II fucosyl chains, respectively. These chemical differences may contribute to distinct hypolipidemic effects and mechanisms of action. Chemical analysis demonstrated that the percentage contents of sulfate, glucuronic acid, and galactose were higher in L. japonica-derived fucoidans than those of A. nodosum-derived fucoidans. In hyperlipidemic apolipoprotein E-deficient mice, both A. nodosum- and L. japonica-derived fucoidans significantly decreased the plasma and hepatic levels of total cholesterol and triglyceride, leading to the reduction of atherosclerotic plaques. Western blotting experiments demonstrated that these fucoidans significantly enhanced the expression and levels of scavenger receptor B type 1, cholesterol 7 alpha-hydroxylase A1, and peroxisome proliferator-activated receptor (PPAR)-α, contributing to circulating lipoprotein clearance and fatty acid degradation, respectively. Differentially, L. japonica-derived fucoidan significantly increased the LXR/ATP-binding cassette G8 signaling pathway in the small intestine, as revealed by real-time quantitative PCR, which may lead to further cholesterol and other lipid excretion. Collectively, these data are useful for understanding the hypolipidemic mechanisms of action of seaweed-derived fucoidans, and their potential application for the prevention and/or treatment of atherosclerotic cardiovascular diseases.
Subject(s)
Apolipoproteins E , Ascophyllum , Hypolipidemic Agents , Laminaria , Polysaccharides , Animals , Laminaria/chemistry , Ascophyllum/chemistry , Mice , Polysaccharides/pharmacology , Polysaccharides/chemistry , Hypolipidemic Agents/pharmacology , Apolipoproteins E/genetics , Male , Mice, Inbred C57BL , Triglycerides/blood , Triglycerides/metabolism , Cholesterol/blood , Cholesterol/metabolism , Mice, Knockout , PPAR alpha/metabolism , PPAR alpha/genetics , Hyperlipidemias/drug therapy , Hyperlipidemias/metabolism , Plant Extracts/pharmacology , Plant Extracts/chemistry , Liver/metabolism , Liver/drug effects , Humans , Edible SeaweedsABSTRACT
Dairy cows undergo dramatic physiological changes during the transition from late pregnancy to early lactation, which make them vulnerable to metabolic stress and immune dysfunction. The objective of this study was to evaluate the effects of a commercial beta-1,3-glucan product (Aleta™, containing 50% beta-1,3-glucan) on productivity, immunity and antioxidative status in transition cows. Fifty-four multiparous Holstein cows received a control diet or a diet supplemented with 5 or 10 g of beta-1,3-glucan per cow per day from 21 days before expected calving to 21 days after parturition. Blood samples were collected at day -21, 1, and 21 relative to calving. Colostrum and milk were collected at day 1 and 21 after calving, respectively. Data showed that supplementation with beta-1,3-glucan had no effect on milk composition, but increased milk production. Beta-1,3-glucan treatment also improved the milk quality, as shown by reduced milk somatic cell count and increased immunoglobulin levels in colostrum. Notably, beta-1,3-glucan markedly reduced serum levels of pro-inflammatory cytokines and C-reactive protein, while elevated serum immunoglobulin levels, indicating its immunity enhancement in transition cows. Moreover, beta-1,3-glucan addition reduced the serum malondialdehyde level and enhanced the activities of serum superoxide dismutase and catalase, which enhanced the antioxidative capacity in transition cows. In summary, supplementation with beta-1,3-glucan improves productivity, immunity and antioxidative status in transition dairy cows.
Subject(s)
Antioxidants/metabolism , Dietary Supplements , Immunity/drug effects , beta-Glucans/pharmacology , Animals , Cattle , Cell Count/veterinary , Colostrum , Diet/veterinary , Female , Glucans/metabolism , Glucans/pharmacology , Lactation , Malondialdehyde/blood , Milk/cytology , PregnancyABSTRACT
Objectives of this study were to evaluate the alleviating effects of a commercial beta-1,3-glucan product (Aleta, containing 50% beta-1,3-glucan, Kemin Industries) on metabolic stress in transition Holstein cows as reflected by circulating metabolites and enzymes. Fifty-four multiparous Holstein cows were randomly allocated to three groups with 18 cows each. Cows in each group received a commercial basal diet or the basal diet supplemented with Aleta calculated to supply 5 or 10 g of Aleta per cow per day. Blood samples were collected at day -21, 1, and 21 relative to calving for determination of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDLC), very low density lipoprotein (VLDL), glucose, insulin, ß-hydroxybutyric acid (BHBA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamyl transpeptidase (GGT), and non-esterified fatty acid (NEFA). Supplementation with Aleta markedly elevated serum concentrations of TG, TC, HDLC, LDL-C and VLDL, implying its positive effect on lipid metabolism in transition dairy cows. Aleta treatment significantly decreased the serum concentrations of NEFA and BHBA, but markedly elevated the serum concentrations of glucose and insulin. Also, Aleta treatment significantly elevated the dry matter intake and milk production in postpartum cows, indicating the alleviating effect of Aleta on negative energy balance in transition cows. Moreover, Aleta treatment significantly reduced the serum activities of AST, ALT and GGT, indicating its hepatoprotective effect on transition cows. These results suggest that Aleta supplementation may help to improve fat metabolism disorder initiated by negative energy balance in transition dairy cows.
Subject(s)
Cattle/blood , Dietary Supplements , beta-Glucans/pharmacology , 3-Hydroxybutyric Acid/blood , Animal Feed , Animals , Cattle/metabolism , Diet/veterinary , Energy Metabolism , Fatty Acids, Nonesterified/blood , Female , Glucose , Insulin/blood , Lactation , Lipid Metabolism , Postpartum Period/metabolismABSTRACT
Background: Antinuclear antibodies (ANAs) can be detected in about 30% of patients with primary immune thrombocytopenia (ITP), yet their relationship with treatment response to rituximab remains elusive.Methods: we retrospectively reviewed the clinical records of hospitalized adult ITP patients who were treated with rituximab from three medical centers across China. Rituximab was given intravenously at 100â mg weekly for 4 weeks, or at a single dose of 375â mg/m2. All included patients had their ANAs tested before rituximab treatment.Results: A total of 287 patients fulfilled the inclusion criteria and were eligible for analysis. ANAs were positive in 98 (34.1%) of the included patients. The incidence of overall response and complete response (CR) in ANA-positive patients was significantly higher than that in ANA-negative patients (overall response: 76.5% vs. 55.0%, P < 0.001; CR: 46.9% vs. 29.1%, P = 0.003). However, sustained response (SR) rates in ANA-positive patients at 6, 12 and 24 months were all lower compared with ANA-negative patients (all P < 0.05). The overall duration of response (DOR) estimated by Kaplan-Meier analysis in ANA-negative patients was greater than that in ANA-positive patients (P < 0.001).Conclusion: ITP patients with positive ANA test were likely to achieve a better initial response to rituximab treatment, while their long-term outcome was unfavorable. Therefore, ANA test could be useful for predicting rituximab response in ITP.
Subject(s)
Antineoplastic Agents, Immunological/therapeutic use , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Rituximab/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Immunological/pharmacology , Female , Humans , Male , Middle Aged , Retrospective Studies , Rituximab/pharmacology , Young AdultABSTRACT
OBJECTIVE: To investigate the preventive and therapeutic effects of endothelial progenitor cells on monocrotaline-induced hepatic vein occlusion disease in mice. METHODS: C57BL/6 mice were randomly divided into 3 groups: saline group (n=15), monocrotaline group (n=15), and endothelial progenitor cell infusion group (n=15). Liver function (TBIL, ALT, AST), liver index, and serum levels of TNF-α and IL-6 were measured on the 8th day after intragastric administration. Hepatic sinusoidal endothelial cells, hepatic central venous endothelial cells and hepatocytes were observed by both HE and immunohistochemical staining. Hepatic fibrosis was observed by Masson's trichrome staining. RESULTS: By the light microscopy, the liver of the monocrotaline group showed moderate to the severe injuries of hepatic sinusoidal and central venous endothelial cells, and hepatic venous congestion. Masson staining showed moderate to severe hepatic fibrosis of central vein and hepatic sinus. In the endothelial progenitor cell group, hepatic sinusoidal and central venous endothelial cell injuries, and the fibrosis of central hepatic vein and hepatic sinus were mild to moderate. Hepatic venous congestion was reduced in comparison with that in the mice of the monocrotaline group. Compared with the endothelial progenitor cell group, the liver index was higher, the liver function was more abnormal, and the serum expression levels of TNF-α and IL-6 were higher in the monocrotaline group. CONCLUSION: The monocrotaline-induced damage of hepatic sinusoidal and central venous endothelial cells is an linitiating factor for hepatic vein occlusive disease. Infusion of endothelial progenitor cells can play a role in preventing and treating hepatic vein occlusion.
Subject(s)
Endothelial Progenitor Cells , Hepatic Veno-Occlusive Disease , Animals , Hepatic Veins , Liver , Mice , Mice, Inbred C57BL , MonocrotalineABSTRACT
OBJECTIVE: To analyze the effective components of Chinese medicine (CM) contained in Chaihu Shugan Powder (, CSP) in the treatment of depressive disorders and to predict its anti-depressant mechanism by network pharmacology. METHODS: Absorption, distribution, metabolism, excretion, and toxicity calculation method was used to screen the active components of CSP. Traditional Chinese Medicine System Pharmacological Database Analysis Platform and text mining tool (GoPuMed database) were used to predict and screen the active ingredients of CSP and anti-depressive targets. Through Genetic Association Database, Therapeutic Target Database, and PharmGkb database targets for depression were obtained. Cytoscape3.2.1 software was used to establish a network map of the active ingredients-targets of CSP, and to analyze gene function and metabolic pathways through Database for Annotation, Visualization and Integrated Discovery and the Omicshare database. RESULTS: The 121 active ingredients and 15 depression-related targets which were screened from the database can exert antidepressant effects by improving the neural plasticity, growth, transfer condition and gene expression of neuronal cell, and the raise of the expression of gap junction protein. The 15 targets passed 14 metabolic pathways, mainly involved in the regulation of neurotransmitters (5-hydroxytryptamine, dopamine and epinephrine), inflammatory mediator regulation of TRP channels, calcium signaling pathway, cyclic adenosine monophosphate signaling pathway and neuroactive ligand-receptor interaction and other signal channels to exert anti-depressant effects. CONCLUSION: This article reveals the possible mechanism of CSP in the treatment of depression through network pharmacology research, and lays a foundation for further target studies.
Subject(s)
Antidepressive Agents/pharmacology , Depression/drug therapy , Drugs, Chinese Herbal/pharmacology , Antidepressive Agents/chemistry , Drugs, Chinese Herbal/chemistry , Humans , Metabolic Networks and Pathways/drug effects , PowdersABSTRACT
A chemical investigation of Cynanchum mongolicum (Maxim.) Kom. identified 8 compounds. On the basis of spectroscopic data, they were determined to be 3 alkaloids and 5 sinapoyl esters, among which were two previously undescribed compounds (1 and 2). The inhibitory effects of the isolated compounds against four human tumor cell lines were evaluated in vitro by MTT assays, which revealed moderate inhibitory effects with IC50 values < 50 mM, in particularly, three antofine analogues have showed significant antitumor activities with IC50 values < 0.1 mM, which was obviously better than the 5-fluorouracil and potential to be used as cancer drugs.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Cynanchum/chemistry , Phytochemicals/chemistry , Alkaloids/chemistry , Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Indoles/chemistry , Indoles/pharmacology , Molecular Structure , Phenanthrolines/chemistry , Phenanthrolines/pharmacology , Phytochemicals/pharmacologyABSTRACT
In this work, a rapid high-performance liquid chromatography method was developed to efficiently purify anthocyanin from Nitraria tangutorum based on reversed-phase column. A new anthocyanin was purified from N. tangutorum and elucidated on the basis of extensive spectroscopic analysis, including one- and two-dimensional nuclear magnetic resonance, as well as high-resolution mass spectrometry (HR-MS) data. The new anthocyanin was elucidated as cyanidin 3-[2â³-(6â´-coumaroyl)-glucosyl]-glucoside.
Subject(s)
Anthocyanins , Magnoliopsida , Chromatography, High Pressure Liquid , Fruit , Molecular StructureABSTRACT
Effects of hardness and the pH value of water in a water pool on PEG-based nonionic surfactant dyeing of cotton fiber with reactive dyes in a heptane reverse micelle system were investigated in terms of the color yield, reflectance, CIE L*a*b* value, and unlevelness. Results reveal that the effect of the water-pool pH value on the color yield and reflectance are more significant than the effect of hardness in the water pool. The dyed fabrics under an alkaline water-pool condition obtain a lower color yield and higher reflectance percentage than those under acidic and nearly neutral conditions. The increase of hardness in a water pool has higher influence on unlevelness of dyed samples than the increase or decrease of the pH value in a water pool. The changes in hardness and the pH value in a water pool did not result in a significant change in CIE L*a*b* values of dyed specimens, and no chromatic change was found in dyed fabrics. Excellent washing fastness results of the dyed fabrics, guaranteeing adequate removal of unfixed dyes, assure accuracy of the results in a spectrophotometric measurement.
ABSTRACT
Jerusalem artichoke (JA, Helianthus tuberosus L.) has been researched extensively due to its wide range of uses, but there are limited studies on its flowers. In this study, we report the first detailed phytochemical study on JA flowers, which yielded 21 compounds. Compound 4 was identified as a major water-soluble yellow pigment of JA flowers. In addition, the methanol extract of JA flowers and the isolates were evaluated for their antioxidant and α-glucosidase inhibitory activities. Among the tested compounds, compound 13 showed the strongest ABTS+ free radical scavenging activity with SC50 value of 2.30 ± 0.13 µg/mL, and compound 6 showed most potent α-glucosidase inhibitory activity with inhibition rate of 60.0% ± 10.3% at a concentration of 250 µg/mL. Results showed that methanol extract of JA flowers exhibited antioxidant and α-glucosidase inhibitory activities which could be attributed to its phenolic ingredients including chlorogenic acid derivatives, flavonoids and phenols.
Subject(s)
Antioxidants/isolation & purification , Flowers/chemistry , Glycoside Hydrolase Inhibitors/isolation & purification , Helianthus/chemistry , Plant Extracts/chemistry , Antioxidants/analysis , Antioxidants/chemistry , Chlorogenic Acid/analogs & derivatives , Chlorogenic Acid/analysis , Flavonoids/analysis , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Phenols/analysis , Phenols/chemistry , Plant Extracts/analysis , alpha-GlucosidasesABSTRACT
Malignant gliomas are treated with temozolomide (TMZ) at present, but often exhibit resistance to this agent. Cancer-initiating cells (CICs) have been suggested to lead to TMZ resistance. The mechanisms underlying CICs-based TMZ resistance are not fully understood. MicroRNAs (miRNAs) have been demonstrated to serve important roles in tumorigenesis and TMZ resistance. In the present study, a sphere forming assay and western blot analysis were performed to detect the formation of CICs and fibroblast activation protein α (FAP-α) protein expression. It was revealed that TMZ resistance promoted the formation of CICs and upregulated FAP-α expression in glioblastoma cells. Over-expressing FAP-α was also demonstrated to promote TMZ resistance and induce the formation of CICs in U251MG cells. In addition, using a reverse transcription-quantitative polymerase chain reaction, it was observed that miR-204 was downregulated in U251MG-resistant (-R) cells. miR-204 expression negatively correlated with the FAP-α levels in human glioblastoma tissues, and it may inhibit the formation of CICs and reverse TMZ resistance in U251MG-R cells. Therefore, it was concluded that miR-204 reversed temozolomide resistance and inhibited CICs phenotypes by degrading FAP-α in glioblastoma.
ABSTRACT
Candida albicans cells homozygous at the mating-type locus stochastically undergo the white-to-opaque switching to become mating-competent. This switching is regulated by a core circuit of transcription factors organized through interlocking feedback loops around the master regulator Wor1. Although a range of distinct environmental cues is known to induce the switching, the pathways linking the external stimuli to the central control mechanism remains largely unknown. By screening a C. albicans haploid gene-deletion library, we found that SAC7 encoding a GTPase-activating protein of Rho1 is required for the white-to-opaque switching. We demonstrate that Sac7 physically associates with Rho1-GTP and the constitutively active Rho1G18V mutant impairs the white-to-opaque switching while the inactive Rho1D124A mutant promotes it. Overexpressing WOR1 in both sac7Δ/Δ and rho1 G18V cells suppresses the switching defect, indicating that the Sac7/Rho1 module acts upstream of Wor1. Furthermore, we provide evidence that Sac7/Rho1 functions in a pathway independent of the Ras/cAMP pathway which has previously been positioned upstream of Wor1. Taken together, we have discovered new regulators and a signaling pathway that regulate the white-to-opaque switching in the most prevalent human fungal pathogen C. albicans.
Subject(s)
Candida albicans/physiology , Candidiasis/microbiology , GTPase-Activating Proteins/metabolism , Phenotype , rho GTP-Binding Proteins/metabolism , Amino Acid Sequence , Candida albicans/ultrastructure , Diploidy , GTPase-Activating Proteins/chemistry , GTPase-Activating Proteins/genetics , Gene Expression Regulation, Fungal , Haploidy , Mutation , Protein Binding , rho GTP-Binding Proteins/chemistry , rho GTP-Binding Proteins/geneticsABSTRACT
The aim of the present study was to investigate the therapeutic potential of a double suicide gene, thymidine kinase (TK) combined with cytosine deaminase (CD), mediated by generation of 5-polyamidoamine dendrimers (G5-PAMAM-D) on human Tenon's capsule fibroblasts (HTFs) as an anti-scarring agent. The pAcGFP1-Hyg-TK-CD plasmid was transfected into HTFs, and reverse-transcription polymerase chain reaction (RT-PCR) was used to detect TK-CD expression. MTT cell proliferation assay was used to evaluate the cytotoxic effects of ganciclovir (GCV) and 5-flurocytosine (5-FC) on HTFs. The optimal concentration of GCV and 5-FC in TK-CD transfected HTFs (HTF-TK-CD) was selected by accessing the lowest and highest cytotoxicity caused, respectively. The morphological changes of transfected HTFs following treatment with GCV and 5-FC were observed by light and transmission electron microscopy. Results demonstrated that the double suicide gene TK-CD mediated by the G5-PAMAM-D delivery system was successfully expressed in HTFs as determined by RT-PCR. A concentration of 3 µg/ml GCV and 200 µg/ml 5-FC was identified as optimal for these prodrugs. The growth rate and number of HTF-TK-CD cells decreased following treatment with GCV and 5-FC as revealed by light microscopy. Additionally, the prodrugs GCV and 5-FC not only demonstrated toxicity on transfected HTFs but also exerted a 'bystander effect'. The present study illustrated that the double suicide gene TK-CD delivery mediated by G5-PAMAM-D was effective in reducing HTF proliferation and inducing cell apoptosis. Furthermore, TK-CD delivery mediated by G5-PAMAM-D may be used as an anti-scarring agent and provide a therapeutic potential for patients requiring glaucoma filtration surgery.
ABSTRACT
Iron is an essential nutrient for nearly all organisms, but iron overdose is toxic. The human commensal-pathogenic fungus Candida albicans traverses host niches with markedly different iron availability. During systemic infection, C. albicans must activate the high-affinity iron permease Ftr1 to acquire iron sequestered by the host's iron-withholding defense and suppresses iron uptake while residing in the iron-rich gut to avoid toxicity. Ftr1 associates with a ferroxidase to form an iron transporter. C. albicans contains four permeases and five ferroxidase homologs, suggesting 20 possible subunit combinations. Here, we investigated the iron-dependent expression, cellular localization and interacting partners of all permeases and ferroxidases and the significance of each subunit for gastrointestinal colonization and systemic infection in mice. We uncovered three distinct patterns of iron-dependent expression and highly flexible ferroxidase-permease partnerships, which underlie a dynamic iron transport system that can be deftly tuned according to iron availability. We found functional differentiation as well as redundancy among the ferroxidases and permeases during both gastrointestinal colonization and bloodstream infection. We propose that C. albicans possesses a sophisticated iron acquisition and utilization system befitting its commensal-pathogenic lifestyle. Our findings reveal new possibilities for medical intervention of C. albicans infection.
Subject(s)
Candida albicans/genetics , Candida albicans/pathogenicity , Ceruloplasmin , Iron/metabolism , Membrane Transport Proteins , Symbiosis/genetics , Animals , Ceruloplasmin/genetics , Ceruloplasmin/metabolism , Female , Gastrointestinal Microbiome , Gene Deletion , Gene Expression Regulation, Fungal , Humans , Ion Transport/physiology , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Mice , Mice, Inbred C57BL , Mutagenesis, Site-Directed , Protein Subunits , VirulenceABSTRACT
The young leaves and shoots of Sibiraea laevigata, known as "Liucha", are used as tea by Tibetans to improve digestion after meals. Long-term consumption of "Liucha" will cause weight loss. In present work, we reported on the isolation and NMR and chemical analysis-based elucidation of seven new sorbitol O-caffeic acid ester derivatives named sorbitol esters A-G (1-7) and eighteen known phenolic compounds from S. laevigata. All of the isolates were evaluated for their antioxidant and α-glucosidase inhibitory activities. Among them sorbitol ester A (1), sorbitol ester D (4), sorbitol ester F (6), sorbitol ester G (7), isoferulic acid (15), methyl caffeate (18), trans-p-hydroxycinnamic acid (19), and kaempferol 3-O-ß-d-(6â³-E-p-coumaroyl)-glucopyranoside (25) showed more potent α-glucosidase inhibitory activity than the clinical drug acarbose.
Subject(s)
Antioxidants/analysis , Cinnamates/analysis , Glycoside Hydrolase Inhibitors/analysis , Kaempferols/analysis , Rosaceae/chemistry , Antioxidants/chemistry , Antioxidants/isolation & purification , Cinnamates/isolation & purification , Cinnamates/pharmacology , Glycoside Hydrolase Inhibitors/isolation & purification , Glycoside Hydrolase Inhibitors/pharmacology , Kaempferols/isolation & purification , Kaempferols/pharmacology , Phenols/analysis , Phenols/isolation & purification , Phenols/pharmacology , Plant Leaves/chemistry , Plant Shoots/chemistry , TibetABSTRACT
Nitraria tangutorum Bor., having edible berries, is valued for reputed health benefits in Qinghai-Tibet plateau. The phytochemical research on the fruit juice of N. tangutorum led to the isolation of twenty-six compounds including five new compounds, tangutorids A-D (1, 2, 3a, and 3b), and (3E,5E)-7-O-ß-glucosyl-4-(2-methoxy-2-oxoethyl)hepta-3,5-dienoic acid (15). The structures of these compounds were elucidated through comprehensive spectroscopic analyses. Tangutorids A-F were the first examples of glucose-derived ß-carbolines from natural products. The biogenetic pathways of 1-8 were proposed to involve Pictet-Spengler reactions and described starting from the co-isolated tryptophan (10) and corresponding aldehydes. All isolates were evaluated for their antioxidant and α-glucosidase inhibitory activities. Compounds 21, 22, and 24 showed antioxidant activity with SC50 values ranging from 12.2±1.9 to 30.4±2.7µg/mL, and compound 1 showed strong α-glucosidase inhibitory effect with IC50 value of 63.3±4.6µg/mL.
Subject(s)
Antioxidants/chemistry , Fruit and Vegetable Juices/analysis , Glycoside Hydrolase Inhibitors/chemistry , Magnoliopsida/chemistry , Plant Extracts/chemistry , Antioxidants/isolation & purification , Fruit/chemistry , Glycoside Hydrolase Inhibitors/isolation & purification , Plant Extracts/isolation & purification , Tibet , alpha-Glucosidases/chemistryABSTRACT
A new flavonoid, along with 16 known ones, was separated from the aerial parts of Asterothamnus centrali-asiaticus. Their structures were elucidated by extensive spectroscopic methods, including 1D and 2D NMR techniques and HRESIMS. To confirm the structure of the new compound, computational prediction of its 13C chemical shifts was performed. All of the 17 flavonoids were reported from A. centrali-asiaticus for the first time. In addition, all flavonoids were evaluated for their antioxidant and α-glucosidase inhibitory activities. The results showed that 10 of them exhibited antioxidant activity. Meanwhile, four flavonoids displayed α-glucosidase inhibitory effect with IC50 values ranging from 38.9 to 299.7 µM.
Subject(s)
Antioxidants/isolation & purification , Asteraceae/chemistry , Flavonoids/isolation & purification , Glycoside Hydrolase Inhibitors/isolation & purification , Plant Components, Aerial/chemistry , Antioxidants/chemistry , Antioxidants/pharmacology , Flavonoids/chemistry , Flavonoids/pharmacology , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/pharmacologyABSTRACT
Whole tumor cell lysates (TCL) have been implemented as tumor antigens for cancer vaccine development, although clinical outcomes of TCL-based antitumor immunotherapy remain unsatisfactory. In order to improve the efficacy of TCL-based vaccines, biomaterials have been employed to enhance antigen delivery and presentation. Here, we have developed chitosan nanoparticles (CTS NPs) with surface mannose (Man) moieties for specific dendritic cells (DCs) targeting (Man-CTS NPs). The Man-CTS NPs were then loaded with TCL generated from B16 melanoma cells (Man-CTS-TCL NPs) for in vitro and in vivo assessment. Potency of the Man-CTS-TCL NPs as cancer vaccine was also assessed in vivo by immunization of mice with Man-CTS-TCL NPs followed by re-challenge with B16 melanoma cell inoculation. We have shown here that Man-CTS-TCL NPs promote bone marrow-derived dendritic cells (BMDCs) maturation and antigen presentation in vitro. In vivo evaluation further demonstrated that the Man-CTS-TCL NPs were readily taken up by endogenous DCs within the draining lymph node (DLN) following subcutaneous administration accompanied by increasing in serum IFN-γ and IL-4 levels. Tumor growth was also significantly delayed in mice primed with Man-CTS-TCL NPs vaccine, attributable at least in part to cytotoxic T lymphocytes response. Moreover, Man-CTS-TCL NPs vaccine also exhibited therapeutic effects in mice with melanoma. Thus, we report here the Man-CTS-TCL NPs as effective anti-tumor vaccine for cancer immunotherapy.
Subject(s)
Antigens, Neoplasm/therapeutic use , Cancer Vaccines/therapeutic use , Chitosan/chemistry , Dendritic Cells/immunology , Drug Carriers/chemistry , Melanoma, Experimental/therapy , Nanoparticles/chemistry , Animals , Antigens, Neoplasm/administration & dosage , Antigens, Neoplasm/immunology , Cancer Vaccines/administration & dosage , Cancer Vaccines/immunology , Cell Line, Tumor , Female , Immunotherapy , Melanoma, Experimental/immunology , Melanoma, Experimental/pathology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BLABSTRACT
BACKGROUND: A case-control study was conducted to evaluate the influence of interleukin (IL)-17A and -17F gene polymorphisms on the risk of primary chronic immune thrombocytopenia (ITP). METHODS: The study included 146 Chinese chronic ITP patients and 137 healthy controls. IL-17A G197A and IL-17F A7488G polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: No significant difference in frequencies of IL-17A G197A genotypes and alleles was found between ITP patients and healthy controls, whereas frequencies of IL-17F A7488G allele A were significantly higher in ITP patients than that in healthy controls (31.85% vs. 18.98%; P<0.01). More specifically, patients with ITP had significantly higher frequencies of the IL-17F A7488G AA and AG genotypes compared with healthy controls (AA: 17.12% vs. 9.49%, P=0.02; AG: 29.46% vs. 18.98%, P=0.02). Logistic regression analysis revealed that AA and AG genotypes of IL-17F A7488G were associated with increased risk of ITP (AA: odds ratio (OR)=2.33, 95% CI 1.11-4.89; AG: OR=2.03, 95% CI 1.14-3.61). CONCLUSIONS: Our results suggest that SNPs in IL-17F A7488G but not IL-17A are associated with the development of chronic ITP in China.
Subject(s)
Asian People/genetics , Genetic Predisposition to Disease , Interleukin-17/genetics , Polymorphism, Single Nucleotide/genetics , Purpura, Thrombocytopenic, Idiopathic/genetics , Adult , Alleles , Case-Control Studies , Demography , Female , Gene Frequency , Humans , Male , Risk FactorsABSTRACT
In fungi, the Nim1 protein kinases, such as Gin4, are important regulators of multiple cell cycle events, including the G2-M transition, septin assembly, polarized growth and cytokinesis. Compelling evidence has linked some key functions of Gin4 with the large C-terminal non-kinase region which, however, is poorly defined. By systematically dissecting and functionally characterizing the non-kinase region of Gin4 in the human fungal pathogen Candida albicans, we report the identification of three new domains with distinct functions: a lipid-binding domain (LBD), a septin-binding domain (SBD) and a nucleolus-associating domain (NAD). The LBD and SBD are indispensable for the function of Gin4, and they alone could sufficiently restore septin ring assembly in GIN4-null mutants. The NAD localizes to the periphery of the nucleolus and physically associates with Cdc14, the ultimate effector of the mitotic exit network. Gin4 mutants that lack the NAD are defective in spindle orientation and exit mitosis prematurely. Furthermore, we show that Gin4 is a substrate of Cdc14. These findings provide novel insights into the roles and mechanisms of Nim1 kinases in the regulation of some crucial cell cycle events.