Astragalus polysaccharides (APS) possess multiple immunomodulatory activities. Due to its high molecular weight, orally administration of APS is not easily absorbed into the blood stream, and how APS ...exerts its capacity in vivo is still not well elucidated. We assume that enteric mucosal immune response might trigger the immune regulation of APS, and our previous studies demonstrated that APS had regulatory activity on intraepithelial lymphocytes (IELs). Therefore, this study aimed to investigate the functions of APS on intestinal intraepithelial γδT cells, a major subset in IELs and an essential component of maintaining homeostasis and immune regulation in enteric mucosa. Results showed that APS could promote proliferation and function of intestinal intraepithelial γδT cells in vitro, the IFN-γ, FasL and GrB mRNA levels in γδT cells were all significantly increased. Moreover, APS also improved the activity of intestinal intraepithelial γδT cells in vivo, as cytokines production and cytotoxicity of γδT cells were all remarkably improved in tumor-bearing mice treated with APS. In addition, the levels of TNF-α and IFN-γ were significantly increased, whereas the levels of IL-10 and TGF-β were significantly decreased in tumor-bearing mice treated with APS. In conclusion, this study demonstrated that APS could improve proliferation and function of intestinal intraepithelial γδT cells, which might an important pathway for immunomodulation of APS in cancer therapy.
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A series of novel gemini surfactants with morpholinium headgroup, 4, 4′-(alkane-4, n-4′)bis(4-decyl, dodecyl or tetradecyl morpholinium)bromide (Mm-n-Mm, m=10, 12, 14, n=3, 4), were ...synthesized and characterized using 1H NMR. The surfactants were investigated for their adsorption and micellization in aqueous solutions through surface tension and conductivity methods It was found that the physicochemical properties, such as surface activity and thermodynamic property of the aqueous surfactant system, were dependent on the lengths of both hydrophobic tail chain and spacer. With the increase of the hydrophobic chain length or the decrease of spacer length, the cmc value of the surfactant decreases and the ability to reduce the surface tension is stronger. The calculation result of thermodynamic parameters indicated that the surfactants we synthesized are more inclined to aggregate in solution as compared with traditional m-s-m type gemini surfactants, and the micellization of Mm-n-Mm was an entropy-driven process.
Rheumatoid arthritis (RA) is a chronic autoimmune disease accompanied with joint destruction that often leads to disability. Wang-Bi capsule (WB), a traditional Chinese medicine-based herbs formula, ...has exhibited inhibition effect on joint destruction of collagen-induced arthritis (CIA) animal model in our previous study. But its molecular mechanisms are still obscure.
CIA rats were treated intragastrical with WB for eight weeks, and the effect of joints protection were evaluated by hematoxylin and eosin (H&E) staining, safranin O fast green staining, tartrate-resistant acid phosphatase (TRAP) staining and micro‑CT scanning analysis. The transcriptomic of tarsal joints were used to investigate how WB alleviated joint destruction.
The histological examination of ankle joints showed WB alleviated both cartilage damage and bone destruction of CIA rats. This protective effect on joints were further evidenced by micro-CT analysis. The transcriptomic analysis showed that WB prominently changed 12 KEGG signaling pathways ("calcium signaling pathway", "cAMP signaling pathway", "cell adhesion molecules", "chemokine signaling pathway", "complement and coagulation cascades", "MAPK signaling pathway", "NF-kappa B signaling pathway", "osteoclast differentiation", "PI3K-Akt signaling pathway", "focal adhesion", "Gap junction" and "Rap1 signaling pathway") associated with bone or cartilage. Several genes (including Il6, Tnfsf11, Ffar2, Plg, Tnfrsf11b, Fgf4, Fpr1, Siglec1, Vegfd, Cldn1, Cxcl13, Chad, Arrb2, Fgf9, Egfr) regulating bone resorption, bone formation and cartilage development were identified by further analysis. Meanwhile, these differentially expressed genes were validated by real-time quantitative PCR.
Overall, the protective effect of WB treatment on joint were confirmed in CIA rats, and its basic molecular mechanisms may be associated with regulating some genes (including Il6, Tnfsf11, Ffar2 and Plg etc.) involved in bone resorption, bone formation and cartilage development.
Natural autoantibodies have been implicated to play a key role in the pathogenesis of coronary heart disease (CHD) because they augment autoimmune activation. The aim of this study was to identify ...novel specific autoantibodies of CHD, and analyze the relationship between their levels and CHD risk indicators.
First, clinical data and sera from CHD patients were collected. Then, one protein microarray containing 37 proteins that represent candidate autoantigens was developed. The arrays were used to profile autoantibodies in randomly selected sera from 35 samples (20 CHD patients, and 15 healthy controls). After that, microarray data were analyzed and autoantibodies for CHD were screened out. Then, ELISA detection was conducted to validate the differentiable autoantibodies using larger numbers of serum samples (131 CHD patients, and 131 healthy controls). Finally, the associations of antibodies with CHD risk indicator parameters were assessed. Inter-group comparison by microarray indicated that three CHD novel autoantibodies, including glucose-6-phosphate isomerase (G6PI), alpha-tropomyosin (TPM1), and heterogeneous nuclear ribonucleoprotein D-like (HnRNPDL), were significantly (
< 0.05) increased when compared with the healthy controls. Moreover, a significant increase of IgG autoantibodies for these three autoantigens was confirmed in CHD patients by ELISA (
< 0.0001). The correction analysis revealed a negative correlation of anti-TPM1 antibody levels and total cholesterol (
= 0.0034), and low-density lipoprotein cholesterol (
= 0.0086), respectively.
G6PI, TPM1, and HnRNPDL were CHD natural autoantigens, and serum anti-TPM1 antibody could be used as a potential marker to predict the risk for CHD patients.
Kidney-Yang Deficiency syndrome (KYDS) is a diagnostic pattern in traditional Chinese medicine (TCM) and clinical data showed that the unbalance in adrenal cortical hormone is the key issue in KYDS ...patients. The processed Ranunculaceae Aconitum carmichaeli debx (Bai-Fu-Pian in Chinese, BFP) is one of the most commonly used Chinese herbs for treating KYDS. The present study was conducted to explore the therapeutic biomarkers of the BFP in treating hydrocortisone administration induced KYDS rats.
Thirty male Sprague-Dawley rats were randomly divided into five groups with six in each group. KYDS in rats was induced by i.p. injection of hydrocortisone at the dose of 10mg/kg per day for 15 days as described previously. The rats with KYDS were administered orally, starting from the day of hydrocortisone administration stopped, with BFP extract at the dose of 0.32g/kg, 0.64g/kg and 1.28g/kg per day respectively for 15 days. The blood samples were collected for the liquid chromatography quadruple time-of-flight mass spectrometry (LC-Q-TOF-MS) test, as well as radioimmunoassay to determine the concentrations of cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP) and adrenocorticotrophic hormone (ACTH). The metabolic responses to BFP administration were investigated by using the principal components analysis (PCA) and orthogonal partial least squares analysis (OPLS). Bioinformatics analyses were performed by using the Ingenuity Pathway Analysis (IPA). Variance analysis and linear regression analysis were used in this study.
The signs and concentrations of cAMP, cGMP and ACTH in the model rats were similar to those previously described about KYDS rats and BFP treatment can reverse the changes. Seventeen significantly changed metabolites among different groups were identified. Thirteen metabolites were identified in the KYDS rats comparing to healthy rats with nine up-regulated and four down-regulated. After BFP treatment at three dosages, five up-regulated metabolites including phosphate, betaine, (4-hydroxyphenyl) acetaldehyde, 5-hydroxyindol-3-acetic acid and 5'-phosphoribosyl-N-formylglycinamide were dose-dependently reversed. The network analysis with IPA showed that four canonical pathways including superpathway of methionine degradation, purine nucleotides De Novo biosynthesis II, tyrosine synthesis and serotonin receptor signaling involved the therapeutic mechanism of BFP in treating the KYDS rats.
Five therapeutic biomarkers (phosphate, betaine, (4-hydroxyphenyl) acetaldehyde, 5-hydroxyindol-3-acetic acid and 5'-phosphoribosyl-N-formylglycinamide) and two corresponding canonical pathways (amino acid metabolism and purine nucleotide metabolism) were identified to be involved in the therapeutic mechanism of BFP treating the KYDS.
The therapeutic biomarkers of BFP in treating hydrocortisone administration induced KYDS rats included phosphate, betaine, (4-hydroxyphenyl) acetaldehyde, 5-hydroxyindol-3-acetic acid and 5'-Phosphoribosyl-N-formylglycinamide. Two canonical pathways related to the therapeutic biomarkers, amino acid metabolism and purine nucleotide metabolism, were identified to be involved in the therapeutic mechanism of BFP treating the KYDS rats. Display omitted
Radix Glycyrrhizae polysaccharide (GP) possesses multiple pharmacological activities. However, the effect of GP on CD4+CD25+ regulatory T (Treg) cells has not been elucidated. This study aimed to ...investigate the effects of GP on Treg cells and Th1/Th2 cytokines in H22 hepatocarcinoma tumor-bearing mice. The results demonstrated that GP inhibits tumor progression. In the lymph nodes of the tumor microenvironment and spleen, the proportion of Treg cells was significantly higher in the tumor-bearing mice. GP administration down-regulated the population of Treg cells (P < 0.01) and decreased lymph node Foxp3 and IL-10 mRNA expression (P < 0.01). In addition, GP treatment decreased IL-10 and TGF-β level (P < 0.01) and increased IL-2 and IL-12p70 level in serum (P < 0.01). In conclusion, GP reduced the proportion of Treg cells and Foxp3 lowered expression in Treg cells, and up-regulated Th1/Th2 cytokine ratio in serum in the tumor bearing mice, which might partially cause the inhibition of tumor growth.
Abnormalities in the integral components of bone, including bone matrix, bone mineral and bone cells, give rise to complex disturbances of skeletal development, growth and homeostasis. Non-specific ...drug delivery using high-dose systemic administration may decrease therapeutic efficacy of drugs and increase the risk of toxic effects in non-skeletal tissues, which remain clinical challenges in the treatment of skeletal disorders. Thus, targeted delivery systems are urgently needed to achieve higher drug delivery efficiency, improve therapeutic efficacy in the targeted cells/tissues, and minimize toxicities in non-targeted cells/tissues. In this review, we summarize recent progress in the application of different targeting moieties and nanoparticles for targeted drug delivery in skeletal disorders, and also discuss the advantages, challenges and perspectives in their clinical translation.
This study aims to examine the causal and long-term effects of domestic finance, political risks, and global risk on domestic economic risk in QISMUT countries, namely Qatar, Indonesia, Saudi Arabia, ...Malaysia, UAE, and Turkey, covering the period of 1997Q1 to 2015Q2. The study used the threshold cointegration test, which involves Gregory and Hansen Cointegration and Hatemi-J Cointegration tests. The tests endogenously combined possible regime shifts in the long-run relationship of the underlying variables. Our results reveal (i) the presence of cointegration among the time series variables with endogenous structural breaks. The linear Toda-Yamamoto causality and nonlinear—Diks and Panchenko and Hatemi-J—causality test shows (ii) changes in domestic financial risk significantly lead to changes in economic risk in the QISMUT countries; (iii) domestic political risk causes economic risk in Indonesia, Qatar, Saudi Arabia, UAE; (iv) global risk affects significantly on economic risk in Saudi Arabia, Turkey, and UAE. Critical policy intervention could include governors in the QISMUT countries should control financial stability indicators such as domestic and foreign debts, exchange rate, and liquidity problems to control macroeconomic dynamics in their respective markets.
Puerarin is a major active ingredient extracted from the root of
P.
lobata, a traditional Chinese herb, and possesses anti-oxidative and anti-inflammatory activities. However, the low oral ...bioavailability of puerarin limits its further application. Therefore, we synthesized tetraacetyl puerarin (4AC) through acetylation to improve its liposolubility and bioavailability. In the present investigations, we tested the anti-oxidative and TNF-α suppressive activity of 4AC in lipopolysaccharide (LPS)-induced RAW264.7 macrophages and bovine type II collagen-induced arthritic (CIA) rats. The results showed that 4AC retained the bioactivity of puerarin. And 4AC significantly increased the activity of SOD and reduced the level of MDA both in vitro and in vivo. It also improved the level of GSH-PX and the total antioxidant capacity in vivo. Furthermore, it dramatically decreased TNF-α level in the cultured supernatant of RAW264.7 cells treated with LPS and in the serum of CIA rats. These initial results indicated that 4AC had a potential therapeutic effect on CIA rats through an anti-oxidative and TNF-α suppressive activity. In addition, the molecular mechanism of anti-oxidation of 4AC was explored by testing the MAPKs/NF-κB signaling pathway. The results showed that 4AC significantly inhibited NF-κB expression and down-regulated the levels of p-ERK and p-JNK in LPS-activated RAW264.7 cells. These results indicated that 4AC had bioactive anti-oxidative effects and suggest the potential value of 4AC for the treatment of rheumatoid arthritis.
► The liposolubility of puerarin derivative (4AC) was improved through acetylation. ► 4AC retained anti-oxidative and TNF-α suppressive activity both in vitro and in vivo. ► The anti-oxidative roles of 4AC were based on MAPK/NF-κ b signaling pathway. ► In these regards, 4AC has a potential value for the treatment of rheumatoid arthritis.
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