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Introduction Cancer-associated fibroblasts (CAFs) promote tumor progression; thus, drugs that can modify CAFs need to be identified. Methods To test the effect of cinnamaldehyde on prostate CAFs, the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-2H-tetrazolium bromide assay was used to determine their survival. When spleen cells were treated with CAF supernatant, the proliferation of T cells was inhibited as determined by flow cytometry. After cinnamaldehyde treatment, this immunosuppressive function of CAFs was partially reversed. To explore the molecular mechanism, Western blotting and the quantitative real-time polymerase chain reaction were applied, and TLR4-dependent signaling pathway-related protein and mRNA levels were quantified. Results Cinnamaldehyde acted on the TLR4-dependent signaling pathway, altering the function of CAFs such that its supernatant no longer inhibited the proliferation of T cells. Conclusion These data indicate that cinnamaldehyde can modify the functions of CAFs, which may be helpful for treating tumors. Cinnamaldehyde can suppress CAF T-cell inhibition.

Polysaccharide from Gynostemma pentaphyllum Makino (GPP) could prevent H22 tumour growth and have immunostimulatory in mice, but the mechanism is largely unknown. In this study, we further investigated whether GPP prevents tumour growth by inducing cytotoxicity to the tumour cells or enhancing immunity in H22 ascites tumour-bearing mice. The results showed that GPP prevented the H22 ascites tumour growth in vivo, but showed little effect on cell viability and cycles to H22 cells in vitro. GPP improved the proportion and mitochondrial level of T cells, and promoted the secretion of IL-2 and IFN-γ in the ascites of the mice. Furthermore, GPP in vitro enhanced the cell viability and promoted activation (in particular T cells), proliferation, and the secretion of IL-2 and IFN-γ of lymphocyte. Taken together, our results demonstrated that GPP prevents H22 ascites tumour growth by enhancing immunity rather than cytotoxicity in mice.

In order to use the latitude and longitude coordinates for received signal strength difference (RSSD) localization, the errors of several spherical distance calculation methods and the error of arc length relative to string length were compared. The distance-calculation RSSD localization equations were established, including spherical accurate calculation RSSD, spherical approximate calculation RSSD, and normal cylindrical projection RSSD. And then, the optimization RSSD localization models based on geodetic coordinates and corresponding to the above equations were established, and the models were verified using the point by point search method with good convergence. The numerical results show there are a lot of weak localization areas for the RSSD localization networks lack of central stations with 4,5,6 stations. Among networks with central stations, there are only a small number of weak-localization areas for the concave 4 stations network, while there are no weak-localization areas for the networks composed of more stations. When the measurement errors and the additional losses of radio wave propagation are not considered, the localization errors of the spherical accurate model, the spherical approximate model and the equianglular projection model are very small, among which the second model has the shortest localization time. The localization errors of equidistance projection model and equal-area projection model are large, neither of which is suitable for the middle latitude and high latitude areas.

The received signal strength difference (RSSD) localization is a kind of method to locate emission sources by measuring the differences of received signal strength level between the monitoring stations and is essentially the truth value ratios of measured signal strength. In the existing literatures, only the rule of RSSD localization circle of two monitoring stations and the geometric relation of RSSD localization circle of five monitoring stations were analyzed, but the number and the station layout of the minimum RSSD localization network have not been investigated. In the present work, first, based on the existing RSSD localization equation, the constants of the commonly used wave propagation models are provided. Then, the minimum RSSD localization network is proved through algebraic analysis, which is that four monitoring stations not distributed on a straight line can locate the signal source at one point. The relationship between the localization accuracy and the signal strength error of the RSSD location network with different scales is studied further and formulated as a nonlinear programming optimization problem. It is found that the localization stability of the network with four stations is poor, and there is a serious localization deviation outlier phenomenon. Therefore, the network with four stations is not available for radio monitoring networks with a signal strength error of ± 5 to ± 10 dB. The RSSD network with five stations is basically the minimum available size, and the RSSD network with nine stations can approach the localization accuracy of the angle of arrival (AOA) network with three stations.

Ewing sarcoma family tumors (ESFTs) are a group of aggressive and highly metastatic tumors lacking efficient therapies. Insulin-like growth factor 1 receptor (IGF1R) blockade is one of the most efficient targeting therapy for ESFTs. However, the appliance is obstructed by drug resistance and disease recurrence due to the activation of insulin receptor (IR) signaling induced by IGF1R blockade. Herein β-elemene, a compound derived from natural plants, exhibited a remarkable proliferation repression on ESFT cells, which was weakened by a caspase inhibitor Z-VAD. β-elemene in combination with IGF1R inhibitors enhanced markedly the repression on cellular proliferation and mTOR activation by IGF1R inhibitors and suppressed the PI3K phosphorylation induced by IGF1R inhibitors. To investigate the mechanisms, we focused on the effects of β-elemene on IR signaling pathway. β-elemene significantly suppressed the insulin-driven cell growth and the activation of mTOR and PI3K in tumor cells, while the toxicity to normal hepatocytes was much lower. Further, the phosphorylation of IR was found to be suppressed notably by β-elemene specifically in tumor cells other than normal hepatocytes. In addition, β-elemene inhibited the growth of ESFT xenografts in vivo, and the phosphorylation of IR and S6 ribosomal protein was significantly repressed in the β-elemene-treated xenografts. These data suggest that β-elemene targets IR phosphorylation to inhibit the proliferation of tumor cells specifically and enhance the effects of IGF1R inhibitors. Thus, this study provides evidence for novel approaches by β-elemene alone or in combination with IGF1R blockades in ESFTs and IR signaling hyperactivated tumors.

Glossy privet fruit and Ecliptae herba (GE) as formula was used as traditional Chinese medicine for liver diseases. However, systematic research of GE in liver injury has been explored rarely. Here, we comprehensively investigate the hepato-protective effects of the mixture of GE on different models. Our data indicated that GE administration decreased the levels of ALT and AST in serum compared with the model group. The histopathological changes were markedly alleviated in the GE treated groups. In addition, expression of cytokines including TNF-α, IL-6 and TGF-β in liver tissue associated with liver injury was elevated in the model groups, but significantly decreased after GE treatment. Furthermore, we explored that activation of Kupffer cells in liver tissue were suppressed after treatment with GE. Therefore, the major mechanism of the liver protective effects of GE may be attributed to the inhibition of Kupffer cell activation.

To investigate the effect of Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 (1:1) on microbiota composition and function, metabolism as well as microbiota-metabolite relationships of weaned rats, four groups of male Sprague-Dawley rats were orally supplemented with either probiotics (2.5 × 1010 cfu/kg, 5.0 × 1010 cfu/kg, 1.0 × 1011 cfu/kg) or vehicle (water) for 28 days. Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 treatment increased levels of glutamate, short chain fatty acids and ketone bodies, and decreased levels of choline, creatine and lactate. Levels of Rothia, Bifidobacterium, Jeotgalicoccus, Lactobacillus, Acinetobacter and Oligella were significantly increased, whereas Parabacteroides, Enterococcus and Candidatus Arthromitus were reduced. The PICRUSt analysis indicated Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 could promote the functional maturation of gut bacterial community. Strong correlations were observed between metabolites and Parabacteroides, Enterococcus, Candidatus Arthomitus, Bifidobacterium, Jeotgalicoccus, Lactobacillus and Acinetobacter. Collectively, supplementation of Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 helps promote the structure and functional maturation of intestinal microbiome in weaned rats.

Introduction Cancer-associated fibroblasts (CAFs) promote tumor progression; thus, drugs that can modify CAFs need to be identified. Methods To test the effect of cinnamaldehyde on prostate CAFs, the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-2H-tetrazolium bromide assay was used to determine their survival. When spleen cells were treated with CAF supernatant, the proliferation of T cells was inhibited as determined by flow cytometry. After cinnamaldehyde treatment, this immunosuppressive function of CAFs was partially reversed. To explore the molecular mechanism, Western blotting and the quantitative real-time polymerase chain reaction were applied, and TLR4-dependent signaling pathway-related protein and mRNA levels were quantified. Results Cinnamaldehyde acted on the TLR4-dependent signaling pathway, altering the function of CAFs such that its supernatant no longer inhibited the proliferation of T cells. Conclusion These data indicate that cinnamaldehyde can modify the functions of CAFs, which may be helpful for treating tumors. Cinnamaldehyde can suppress CAF T-cell inhibition.

The efficacy of polysaccharides is widespread, especially in immune regulation. However, the genetic basis of the changes in polysaccharides regulating immunity is unclear. To obtain genome-wide insights into transcriptome changes and regulatory networks, we designed a polysaccharide formula, comprising lentinan, pachymaran and tremelia, to increase the availability of their optimized active sites. In this case, we focused on a model of immunosuppression to investigate genes by digital gene expression (DGE) tag profiling in T and B cells. These genes were further validated by qRT-PCR and Western blot experiments. Consequently, polysaccharide formula treatment helped to recover the expression of immune-related genes, including CADM1, CCR2, IGLL1, LIGP1, and FCGR3, FCGR2 in B cells, as well as S100A8, S100A9, ChIL3, MMP8 and IFITM3 in T cells. These results suggest that treatment with polysaccharides improves the immunity of immunosuppressive mice by regulating genes associated with T and B cell functions.

To study the effect and underlying molecular mechanism of eugenol on CD11b+Gr1+ myeloid-derived suppressor cells (MDSCs). The effect of eugenol on the inhibition of immortalized MDSC cell line MSC-2 and murine peritoneal macrophages was detected by MTT. Flow cytometry was used to detect the pro-apoptosis effect of eugenol on MDSCs. The expression levels of apoptosis-related proteins were detected by western blot. Eugenol has a selective inhibitory effect on MDSCs in a dose-dependent manner, which activates an endogenous apoptosis pathway, leading to apoptosis. Eugenol promotes the apoptosis of MDSCs via the intrinsic pathway.

The present study aimed to use a chemometric study to compare the in-vitro antioxidant activities and bioactive compounds of flaxseed based on the variety and geographical origins, and further expl...

This study aimed to improve the industrial production of Bifidobacterium adolescentis strain Z25 by establishing a method that could rapidly evaluate proliferation efficiency in response to different carbon, and nitrogen sources, inorganic salts, trace elements. Notably, glucose, yeast extract, fish peptone, Mg were the optimum substrates for high-efficient proliferation of the strain. The inorganic salts were not required in a pH-controlled culture. Both batch culture and automatic feedback feeding culture methods were optimized and compared. The maximum proliferation efficiency was achieved when the carbon-nitrogen ratio was equivalent to the carbon-nitrogen consumption ratio at the point of growth rate inhibition and the osmotic pressure of the medium was lower than 550 mOsm kg−1. Within a certain concentration range, the maximum biomass was positively correlated with the concentration of Mg2+. The automatic feedback feeding method was more conducive for a high-density bifidobacterial culture. Finally, at the optimum pH of 5.5 and the initial medium osmotic pressure of 312 ± 6 mOsm kg−1, the viable bacterial count reached (1.6 ± 0.1) × 1010 CFU mL−1 after 15 h with a feed liquid containing 320 g L−1 glucose, a 20-fold increase compared to the yield obtained with the original culture method and MRS medium.

We have previously reported that a novel polysaccharide, MPSSS, from Lentinus edodes can reverse the function of myeloid immune suppressor cell-mediated T cell inhibition and improve the efficacy of cancer therapy, but the mechanisms remained unknown. Here, an immortalized myeloid immune suppressor cell line (MSC2) was used to determine the molecular mechanisms of MPSSS-treatment. The results showed that MPSSS eliminated the immortalized myeloid suppressor cell line (MSC2)-mediated T cell inhibition through downregulating the activation of arginase and decreasing the cell-membrane receptor TNFR2. A p38 inhibitor almost completely prevented the MPSSS-impaired MSC2-mediated T cell inhibition by increasing arginase activity and TNFR2. MPSSS-treated MSC2 cells exhibited increased mRNA levels of TNFα and NOS2 and decreased mRNA levels of TGFβ1, c/EBPβ and HO1. The levels of TNFα were significantly increased after MPSSS stimulation of the MSC2 cells compared with the p38 inhibitor pretreatment group or the control group by ELISA analysis, while TGFβ1 induced the opposite effect under the same treatment condition. Together, these results suggest that MPSSS may reverse the function of the MSC2 cells through p38 activation and ERK suppression and provide a novel anti-cancer strategy by targeting myeloid immune suppressor cells.

The polysaccharides MPSSS was extracted from Lentinus edodes and has been reported to effectively inhibit tumor growth and eliminate the function of myeloid-derived immune suppressor cell-mediated T cell inhibition, thus improving the efficacy of cancer therapy. The exploration of how MPSSS affects the functions of cancer-associated fibroblasts (CAFs) will provide a new perspective for understanding the antitumor effects of MPSSS. In the present study, prostate CAFs were selected as target cells to study whether MPSSS affected cell proliferation and function. The results showed that MPSSS did not directly inhibit the growth of prostate CAFs but interfered with CAF-mediated T cell inhibition and affected the immunosuppressive function of prostate CAFs. Mechanistic studies were further performed and showed that MPSSS activated key node proteins in the NF-κB pathway that were dependent on MyD88, and a TLR4 inhibitor blocked the changes in these proteins and the effect of MPSSS. We hypothesize that MPSSS can activate the MyD88-dependent TLR4-NF-κB signaling pathway to change the function of CAFs. In conclusion, these results demonstrate that MPSSS can not only effectively inhibit the growth of prostate cancer as we previously reported but also alter the function of prostate CAFs by activating the TLR4-NF-κB pathway, providing a new strategy for the comprehensive treatment of tumors.

Summary Polysaccharide compounds (PCs), which composed of different kinds of polysaccharides always isolated from different kinds of traditional Chinese medicine, are now attracting more and more attentions due to their strong immunomodulatory activities beyond the corresponding one-component polysaccharides. In this study, we demonstrated for the first time that PCs-1 and PCs-2 had strong immunomodulatory effects on macrophages both in in vitro and in vivo models by atomic force microscopy (AFM). By high resolution AFM imaging, PCs-1 and PCs-2 were found to inhibit LPS induced cell surface particle size and roughness increase in RAW264.7 macrophages, demonstrating the anti-inflammatory effects of PCs-1 and PCs-2 on macrophages. PCs-1 and PCs-2 were also proved to increase the particle size and roughness of resting RAW264.7 macrophages, which suggested that PCs could activate resting RAW264.7 macrophages. And additionally, PCs-1 and PCs-2 were also found to reverse the surface particle size and roughness decrease of peritoneal macrophages isolated from cyclophosphamide induced immunosuppressive mice, suggesting the activation effects of PCs-1 and PCs-2 on immunosuppressive macrophages. These results further enhanced our understanding of macrophage activations by direct imaging of cell surface ultrastructure and also highlighted AFM as a novel nanotool for macrophage detections. And most importantly, these results also indicated the outstanding immunomodulatory effects of PCs on macrophages, which therefore suggested that PCs could be served as a kind of novel immunomodulatory agents that would benefit human health. SCANNING 9999:1–10, 2016. © 2016 Wiley Periodicals, Inc.

The goal of this research was to study the selective pro-apoptotic effect of ligustilide on prostate-cancer-associated fibroblast in the tumor microenvironment and the related molecular mechanisms. The effects of ligustilide on cancer-associated fibroblasts (CAFs) and normal fibroblasts (NFs) isolated from the prostate were determined by MTT assay. Flow cytometry and cellular immunofluorescence were used to detect the effects of ligustilide on the cell cycle and apoptosis. Western blotting was used to detect the expression of apoptosis-related proteins after the action of ligustilide on CAFs. In the investigation, ligustilide had a selective pro-apoptotic effect on prostate-CAFs. After ligustilide treatment, the proportion of CAFs in the G2-M phase of the cell cycle increased, and the expression of apoptosis-related proteins (p-P53, Bcl-2, Caspase9 and Cytochrome C) changed. Ligustilide blocks the CAF cell cycle and induces the apoptosis of CAFs.

Immunity due to immune balance contributes to disease prevention and treatment. Radix Codonopsis polysaccharide (RCP) is isolated from the root of the Chinese herb Codonopsis pilosula. Previous studies have indicated that RCP has immunomodulatory activities; however, the effects of RCP on immunity, especially immune balance, are still largely unknown. In the present study, we investigated the effects of RCP on T-cell balance in mice. The mice were pretreated intragastrically with or without RCP for 15 days and injected with hydrocortisone on days 10-15 to disturb the immune system. The spleen and thymus were weighed and used to calculate immune organ indexes. The percentages of CD4+ T cells, CD8+ T cells, Th1 cells, Th2 cells, regulatory T cells (Tregs) and Th17 cells in peripheral blood were assayed by flow cytometry. Pro-inflammatory and anti-inflammatory cytokines, TNF-α, IL-1β and IL-10, in serum were determined by enzyme-linked immunosorbent assay (ELISA) kits. The results showed that RCP pretreatment could maintain the homeostasis of CD8+ T cells, Tregs, Th17 cells, TNF-α, IL-1β and IL-10 in hydrocortisone-treated mice. Furthermore, RCP pretreatment maintained the immune balance of CD4+/CD8+ T cells, Th1/Th2 cells, Tregs/Th17 cells, IL-10/TNF-α and IL-10/IL-1β. Taken together, RCP pretreatment had beneficial effects on the maintenance of T-cell balance against hydrocortisone disturbance in mice and potential to be developed into novel functional food.

The aim of the present study was to investigate whether fraction from Lycium barbarum polysaccharide (LBP) could reduce immunotoxicity and enhance antitumor activity of doxorubicin (Dox) in mice. A water-soluble LBP fraction, designated LBP3, was isolated from edible Chinese herbal Lycium barbarum and used in this study. To investigate the effect of LBP3 on Dox-induced immunotoxicity, tumor-free mice were used and treated with either normal saline, Dox, or Dox plus LBP3. To investigate the effect of LBP3 on antitumor activity of Dox, H22 tumor-bearing mice were used and treated with either normal saline, Dox, LBP3, or Dox plus LBP3. The results showed that LBP3 did not protect against the body weight loss caused by Dox, but it promoted the recovery of body weight starting at day 5 after Dox treatment in tumor-free mice. LBP3 also improved peripheral blood lymphocyte counts, promoted cell cycle recovery in bone marrow cells, and restored the cytotoxicity of natural killer cells. Furthermore, in H22 tumor-bearing mice, LBP3 enhanced antitumor activity of Dox and improved peripheral blood lymphocyte counts and the cytotoxicity of splenocytes. In brief, our results demonstrated that LBP3 could reduce the immunotoxicity and enhance antitumor activity of Dox.

The present study aimed to use a chemometric study to compare the in-vitro antioxidant activities and bioactive compounds of flaxseed based on the variety and geographical origins, and further explore the specific components constructed the endogenous antioxidant system of flaxseed in China. The differential contents of α-linolenic acid (35.83–58.91%), lignans (11.37–33.31 mg/g), total phenolic acids (109.93–246.88 mg/100 g) and phytosterols (56.52–125.12 mg/g) of 32 flaxseed varieties were observed. Concomitantly, the in-vitro antioxidant activities varied from 32.56 to 46.22 mg TE/100 g, 0.58 to 1.08 mg TE/g, and 14.22 to 36.14 mmol TE/g as determined by the 2,2’-diphenyl-1-picrylhydrazyl radical (DPPH), ferric reducing antioxidant power (FRAP) and 2,2′-azinobis-(3-ethylbenzthiazoline 6-sulfonic acid) (ABTS) assays, respectively. Significant correlations were found between the antioxidant activities and contents of free syringic acid, p-coumaric acid glucoside and secoisolariciresinol diglucoside (SDG) (p in-vitro antioxidant activities and bioactive component contents, primarily in relation to variety specificity.

Lycium barbarum polysaccharide (LBP) is isolated from the fruit of Chinese herbal Lycium barbarum. Previous studies had demonstrated that LBP could inhibit tumor growth and enhance the immunity in mice. However, the effect of LBP on systemic and local immune responses in vivo, especially on phenotypic and functional changes of T cells, is still largely unknown. In the present study, we investigated the effects of LBP on systemic and local T cell-dependent antitumor immune responses in H22 tumor-bearing mice. The results showed that LBP could inhibit the solid tumor growth in mice, but showed little effect on the body weight or spleen index. Furthermore, LBP could maintain high levels of T cells in peripheral blood (PB), tumor draining lymph node (TDLN), and tumor tissue, prevent the increase of Tregs while promote infiltration of CD8+ T cells in tumor tissue, inhibit the production of TGF-β1 and IL-10 in serum, decrease the exhaustion phenotype of T cells, and maintain cytotoxicity of lymphocytes. Taken together, our results demonstrated that LBP simultaneously induced systemic and local immune responses in H22 tumor-bearing mice by alleviating immunosuppression and maintaining antitumor immune responses in mice.

Background Polysaccharides can alleviate obesity in mammals; however, studies on mechanism of this alleviation are limited. A few studies have indicated that polysaccharides improve obesity by regulating the metabolism of the body. Therefore, a metabolomics approach, consisting of high resolution nuclear magnetic resonance (NMR) spectroscopy and a multivariate statistical technique, was applied to explore the mechanism of the protective effects of lentinan and Flos Lonicera polysaccharides (LF) on high-fat diet (HFD) induced obesity. Methods In this study, rats were randomly divided into three groups: control diet (CD), HFD, and HFD supplemented with a mixture of lentinan and Flos Lonicera polysaccharide. Histopathological and clinical biochemical assessments were also conducted. A combination of a NMR metabolomics study and a multivariable statistical analysis method to distinguish urinary and fecal metabolites was applied. Results Significant obesity symptoms appeared in HFD rats (for example, significant weight gain, epididymal adipose accumulation and lipid deposition in hepatocytes), which was attenuated in the LF group. Additionally, the HFD induced a reduction of choline, citrate, pyruvate and glycerol and increased the levels of trimethylamine oxide (TMAO) and taurine. Of note, these metabolic disorders were reversed by LF intervention mainly through pathways of energy metabolism, choline metabolism and gut microbiota metabolism. Conclusions LF supplementation had a re-balancing effect on the disturbed metabolic pathways in the obese body. The results of this study validate the therapeutic effect of the compound polysaccharide--LF in obesity and described the biochemical and metabolic mechanisms involved. Electronic supplementary material The online version of this article (10.1186/s12986-018-0246-2) contains supplementary material, which is available to authorized users.

Figure S1. Effects of LF on body weight gain, liver weight, epididymal adipose weight and mean energy take in HFD-fed rats. (A) Body weight gain in 12 weeks; (B) liver weight; (C) epididymal adipose weight; (D) mean energy intake. Values are expressed as means ± standard error. Graph bars with different letters on top represent statistically significant results (p

Malignant tumors are among the most life-threatening diseases in the world. Although many different types of antitumor agents are available, severe side effects and toxicity limit their applications. Myeloid-derived suppressor cells (MDSCs) inhibit the antitumor immune response by suppressing the proliferation of T cells, the production of cytokines and the killing of tumor cells. As MDSCs have become novel targets in cancer therapy, this research focused on the anti-MDSC function of cinnamaldehyde (CA), which is extracted from cinnamon, a traditional Chinese spice. In the present study, MDSCs isolated from the spleens of mice with colon cancer were used as an in vitro model to assess the efficacy of CA. Treatment of MDSCs with CA significantly decreased cell proliferation and induced apoptotic cell death. Subsequent experiments demonstrated that CA treatment enhanced the expression of Bax and caspase-9 and inhibited the expression of Bcl-2, suggesting that CA induced apoptosis in the MDSCs via the intrinsic pathway. Taken together, the results demonstrated that CA exhibited significant anti-MDSC activity and attenuated the suppression of the antitumor immune response, indicating a potential use for CA in cancer therapy.

To study the effect and underlying molecular mechanism of eugenol on CD11b

The purpose of this study is to investigate the effects of probiotics combined with prebiotics (PP) supplementation on weaned rat metabolism. A metabonomic strategy employing 1H-NMR spectroscopy and multivariate data analysis was used to examine weaned rat biological responses to PP supplementation. Male Sprague-Dawley rats (post-natal day 21, PD 21) received probiotics (Lactobacillus acidophilus NCFM (L-NCFM) and Bifidobacterium lactis Bi-07 (B-LBi07), 1 : 1, 1.0 × 1011 cfu kg−1) and prebiotics (Lycium barbarum polysaccharides (LBP), Poria cocos polysaccharides (PCPs) and Lentinan, 1 : 1 : 1, 24 g kg−1) via intragastric administration for 28 consecutive days. Urine and feces were collected for analysis. Significant topographical metabolic variations were present in urine and feces. Urinary metabolites upregulated by PP treatment included alanine, N-acetylglycine, glutamine, dimethylamine, phosphorylcholine, ethylene glycol, mannitol, phenylacetylglycine and glycoate, which were related to alanine, aspartate and glutamate metabolism, and choline metabolism. Feces-derived metabolites, including caproate, valerate, butyrate, propionate, lactate, acetate, succinate, methanol, threonine and methionine, were significantly increased, which were related to short-chain fatty acid (SCFA) metabolism and TCA cycle metabolism. These results indicate that dietary PP supplementation can regulate common systemic metabolic processes, including energy metabolism, amino acid metabolism, lipid metabolism, nucleic acid metabolism, and gut microbiota-related metabolism. This study also illuminates the vital role of PP supplementation in regulating the metabolism of weaned rats.

Rice bran oil (RBO) is a great and important vegetable oil resource, but usually contain high content of free fatty acids (FFAs). Phytosterol esters are functional lipids possessing hypocholesterolemic activity. In this study, Candida rugosa lipase (CRL) was immobilized on the octyl-functionalized ordered mesoporous silica (C8-OMMs) to obtain immobilized CRL arrays (CRL@C8-OMMs). The resulting CRL@C8-OMMs arrays showed much better thermal stability and reusability in comparison to free CRL. The deacidification and simultaneous preparation of functional oil rich in phytosterol esters (PEs) was successfully achieved by enzymatic esterification of high-acid RBO with phytosterol. The contents of FFAs and PEs were below 2.3% and above 84.7%, respectively. Repeated reaction tests indicated that CRL@C8-OMSs arrays could be used 11 times with 80.7% of its original catalytic activity still retained. The strategy could not only take advantage of the high-acid oils resources, but also product PEs-enriched functional oils.

Inflammatory bowel disease (IBD) results from alterations in intestinal flora and the immune system. Sulfasalazine (SASP) is a sulfa antimicrobial used to treat IBD in clinic for years. However, how SASP affects gut microbes and its potential functions remains unclear. To investigate the relationships of SASP, IBD, and gut microbiome, we used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis in rats, and analyzed the microbiota in the fecal samples, which come from the control group (treated with ethanol + saline), the model group (treated with TNBS-ethanol + saline) and the SASP group (treated with TNBS-ethanol + SASP), with 16S gene sequencing and followed up a subset sample using shotgun sequencing. The study found that SASP treatment could not only restore the TNBS-induced gut dysbiosis, which was proved by the increasing amount of SCFAs-producing bacteria and lactic acid-producing bacteria as well as the decreasing amount of Proteobacteria, but also modulate the dysregulated function of the TNBS-induced colitis to resemble that of the control group, including an increased capacity for basic metabolism (carbohydrate metabolism, citrate cycle) and a decrease in the oxidative stress (riboflavin, sulfur, cysteine) as well as bacterial pathogenesis (cell motility and secretion, bacterial motility proteins, flagellar assembly). Moreover, a higher proportion of Mycoplasma was observed in the SASP group, which may associate with infertility. In all, the study provides insight into specific microbial clades and pathways linked with SASP treatment to elaborate the mechanism for treatment of IBD.

Polyglutamine (polyQ) aggregation plays a pivotal role in the pathological process of Huntington’s disease and other polyQ disorders. Therefore, strategies aiming at restoring dysfunction and reducing stresses mediated by polyQ toxicity are of therapeutic interest for proteotoxicity diseases. Salidroside, a glycoside from Rhodiola rosea, has been shown to have a variety of bioactivities, including antioxidant activity. Using transgenic Caenorhabditis elegans models, we show here that salidroside is able to reduce neuronal death and behavioral dysfunction mediated by polyQ expressed in ASH neurons, but the neuroprotective effect is not associated with prevention of polyQ aggregation per se. Further experiments reveal that the neuroprotective effect of salidroside in C. elegans models involves its antioxidant capabilities, including decrease of ROS levels and paraquat-induced mortality, increase of antioxidant enzyme activities and reduction of lipid peroxidation. These results demonstrate that salidroside exerts its neuroprotective function against polyQ toxicity via oxidative stress pathways.

Astragalus membranaceus is a medicinal plant traditionally used in China for a variety of conditions, including inflammatory and neural diseases. Astragalus polysaccharides are shown to reduce the adverse effect of levodopa which is used to treat Parkinson’s disease (PD). However, the neuroprotective effect of Astragalus polysaccharides per se in PD is lacking. Using Caenorhabditis elegans models, we investigated the protective effect of astragalan, an acidic polysaccharide isolated from A. membranaceus, against the neurotoxicity of 6-hydroxydopamine (6-OHDA), a neurotoxin that can induce parkinsonism. We show that 6-OHDA is able to degenerate dopaminergic neurons and lead to the deficiency of food-sensing behavior and a shorter lifespan in C. elegans. Interestingly, these degenerative symptoms can be attenuated by astragalan treatment. Astragalan is also shown to alleviate oxidative stress through reducing reactive oxygen species level and malondialdehyde content and increasing superoxide dismutase and glutathione peroxidase activities and reduce the expression of proapoptotic gene egl-1 in 6-OHDA-intoxicated nematodes. Further studies reveal that astragalan is capable of elevating the decreased acetylcholinesterase activity induced by 6-OHDA. Together, our results demonstrate that the protective effect of astragalan against 6-OHDA neurotoxicity is likely due to the alleviation of oxidative stress and regulation of apoptosis pathway and cholinergic system and thus provide an important insight into the therapeutic potential of Astragalus polysaccharide in neurodegeneration.

Anti-aging Chinese medicines have been used in traditional beverages to promote health and prevent diseases. Interestingly, these functional beverages may be used differently between men and women, reflecting the "yin-yang" philosophy of Chinese medicine. Modern studies have revealed that some dietary natural products can slow aging in model organisms, and functional beverages containing such products have recently emerged in Chinese market, challenging the dominance of traditional functional beverages. Here we summarize both traditional anti-aging herbs and modern natural dietary compounds currently used in functional beverages in China, and also briefly outline the underlying mechanisms of the beverages in slowing aging process.

Background: Micronutrients in oil reduce one or more risk factors of cardiovascular diseases, while the contents of micronutrients in oil are relatively poor, which is insufficient to reverse the metabolic disorders at different stages of progress. The aim of this study was to investigate the effects of endogenous micronutrients in optimized cold-pressed rapeseed oil and restoratively added or fortified micronutrients in traditional refined rapeseed oil (restoring micronutrients to be nearly equal to or significantly higher than levels in crude rapeseed oil) on the antioxidant status and lipid profile in high-fat fed rats. Methods: Male Wistar rats were fed high-fat diets containing different rapeseed oils for 4 weeks, including the standard refined rapeseed oil(SRO), optimized cold-pressed rapeseed oil(CRO) and the traditional refined rapeseed oil with restorative addition or fortification of micronutrients (LF, HF-SRO). Results: CRO exhibited significant increases in contents of tocopherols (+13%), phytosterols (+34%), polyphenols (+92%) and phospholipids (+725%) compared with SRO, as well as the total antioxidant capacities (+82-125%) (p < 0.05). While the HF-SRO revealed improved antioxidant properties in vitro than the CRO, which was comparable to LF-SRO. Significant improved plasma antioxidant capacities and lipid peroxidation evaluated by T-AOC, GSH, tocopherols and MDA were found in rats fed HF-SRO when compared with CRO and LF-SRO (p < 0.05). Furthermore, HF-SRO also decreased the plasma and hepatic TC levels compared to CRO and LF-SRO, accompanying higher fecal cholesterol excretion (p < 0.05). Conclusion: The standard refined rapeseed oil with fortification, not restorative addition of micronutrients was comparable to the optimized cold-pressed rapeseed oil in improving the antioxidant status and lipid profile of high-fat fed rats.