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Lycium barbarum is an edible fruit widely used in herbal medicines and as a functional food. Polysaccharide is one of the most important active ingredients. Only L. barbarum grown in the Ningxia region of China are officially recognised as suitable for use in traditional Chinese medicine, but the systematic comparison of L. barbarum polysaccharide between Ningxia and the other growing regions of China has been rarely reported.To compare the difference of L. barbarum polysaccharide from different grown regions of China.A chemical fingerprint of L. barbarum polysaccharide hydrolysates was established based on controlled acidolysis combined with hydrophilic interaction liquid chromatography-evaporative light scattering detection-electrospray ionisation-time-of-flight-mass spectrometry (HILIC-ELSD-ESI-TOF-MS). Then, it was employed for the comparison of L. barbarum samples from different geographical origins of China combined with chemometrics analysis.Six monosaccharides [rhamnose (Rha), xylose (Xyl), arabinose (Ara), mannose (Man), glucose (Glu), galactose (Gal)] were qualitatively and quantitatively determined and four glycoconjugates were preliminarily identified from the hydrolysates. Content determination for the polysaccharide and monosaccharide indicated obvious geographical features. The HILIC-ELSD fingerprint combined with partial least squares-discriminant analysis (PLS-DA) was able to differentiate L. barbarum samples from Ningxia, Xinjiang, Gansu and Qinghai regions with 89.19% classification accuracy. Orthogonal projection to latent structure discriminant analysis (OPLS-DA) was able to differentiate between samples from Ningxia and those from the other three growing regions, polysaccharide and Ara were the potential chemical markers.These findings form the basis of a reliable method to trace the region of origin of L. barbarum sample and thereby, improve the quality control of L. barbarum therapeutic polysaccharides.

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.

Biological functions of chondroitin sulfate, including anti-oxidation and anti-inflammation, are associated with its molecular weight. This study aimed to evaluate the correlation between antioxidant activity and molecular weights of chondroitin sulfate derived from bovine nasal cartilage (BCS). BCS extracted by compound enzymatic method was further purified via DEAE-cellulose column separation to obtain BCS-II (129.4 kDa), which was further degraded by H2O2-Vc to obtain four subfractions: BCS-II-1 (92.7 kDa), BCS-II-2 (54.1 kDa), BCS-II-3 (26.3 kDa), and BCS-II-4 (19.7 kDa). Changes in the physicochemical properties of BCS-II before and after degradation were compared via FT-IR, NMR and monosaccharide composition analysis. Finally, antioxidant activities of BCS-II and its subfractions BCS-II-1–4 were compared. Our results showed that the H2O2-Vc system did not disrupt the primary functional group of BCS-II, with no significant change in sulfate content between BCS-II and its degraded fractions; however, uronic acid levels increased in degraded fractions when compared with BCS-II. In vitro, BCS-II-4 displayed the lowest molecular weight and had the strongest antioxidant activity. Therefore, the antioxidant activity of chondroitin sulfate in vitro is robustly associated with its molecular weight, and low-molecular-weight chondroitin sulfate can be used as an antioxidant in the food and pharmaceutical industries and other sectors.

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.

Dietary intervention during early life has a significant impact on colonization of the gut microbiota. In addition, some polysaccharides have the potential to selectively stimulate the growth and metabolic activity of intestinal bacteria associated with health and well-being. However, less is known about the effect of polysaccharides on the development of gut microbiota in younger individuals. This study was conducted to investigate the health effects of supplementation with dietary compound polysaccharides (Lycium barbarum polysaccharides (LBP), Poria cocos polysaccharides (PCPs) and Lentinan, 1 : 1 : 1) on the intestinal microecosystem and metabolism of young rats. Male 21-day-old Sprague-Dawley rats received daily intragastric administration of either compound polysaccharides (three dosages, 6 g kg-1, 12 g kg-1 or 24 g kg-1) or saline for 28 consecutive days. 1H-NMR spectroscopy integrated with multi-variate pattern recognition analysis was applied to reveal the metabolism of the host and microflora, while 16S rRNA gene sequencing was used to monitor the dynamic changes in the gut microbiota. The relative concentrations of 35 urinary metabolites and 24 faecal metabolites were significantly changed compared with the control group. 16S rRNA analysis showed that the relative abundances of 4 bacterial genera (Bifidobacterium, Lactobacillus, Allobaculum and Oligella) significantly increased, whereas the relative abundance of 1 bacterial genus (Enterococcus) significantly declined in the compound polysaccharide-treated groups compared with the control group. Meanwhile, dietary compound polysaccharide treatment promoted the functional maturation of the gut bacterial community, characterised by increased basic metabolism (amino acid metabolism and energy metabolism), short chain fatty acid (SCFA)-related metabolism and nucleotide metabolism. These findings suggest that compound polysaccharides may help to promote the colonisation and functional maturation of infant intestinal microbiota and maintain the health of the intestinal microecosystem.

Schisandra chinensis is a medicinal and edible plant that contains various bioactive compounds. Among these, lignans are the major functional compounds. Nevertheless, detailed information about lignans in Schisandra chinensis oil remains scarce. A powerful UPLC-Q/TOF-MS method was established for the rapid identification of the lignan constituents of Schisandra chinensis oils. The results showed that 21 lignans have been unambiguously identified, and four lignans have been tentatively identified in the Schisandra chinensis oils. In addition, semi-quantitative analysis indicated that the total lignan content in the Schisandra chinensis oils was distributed from 67.73 ± 0.06 to 87.61 ± 1.83 mg/g. Schisandrin and schisandrin B were the most abundant lignans in the Schisandra chinensis oils, their content ranging from 15.85 ± 0.09 to 20.57 ± 0.38 mg/g. Additionally, this study provided a systematic characterization of lignans in Schisandra chinensis oil and indicated that the oil might be used as lignan-related functional foods.

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.

The bioactivity of onion, particularly its oil, has gained increasing research attention. Preparation of onion oil is challenging due to its low oil content and abundance of water. In this study, pilot-scale drying combined with laboratory extraction was conducted for sample preparation. GC/MS and solid phase microextraction (SPME) analyses were performed to evaluate the correlation between onion oil and drying. Results showed that drying significantly influenced the sulfocompounds composition of onion oils. Dipropyl disulfide and dispropyl trisulfide were the most abundant compounds in fresh onions (accounting for 68.41% to 93.13% of the total volatile sulfocompounds). The total contents of sulfocompounds in vacuum freeze dried and hot air dried onion powder were 4.96% and 39.79%, respectively, which account for 24.59% to 48.89% of the total content. Dimethyl sulfides and thiophenes were the main compounds in the onion oils. The highest content of sulfocompounds was obtained in the oil of hot air...

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.

Despite decades of research, malignant tumors are extremely difficult to eliminate with conventional methods. Although surgical resection potentially eradicates the problem, only a few cases are suitable for operation, and other approaches often involve harmful consequences. Revolutionary methods are desperately needed to improve patient outcomes and diminish harmful side effects. Myeloid-derived suppressor cells (MDSCs), downregulators of the innate and adaptive immune systems, have been widely studied over the past 2 decades. MDSCs inhibit the antitumor immune response by suppressing T cell proliferation, cytokine production, and tumor cell killing. With MDSCs becoming novel targets in cancer therapy, our research has focused on the anti-MDSC function of Asparagus polysaccharide (AP), extracted from asparagus, a traditional Chinese herb. In this study, we have used MDSCs isolated from the spleen of mice with colon cancer as an in vitro model to assess the efficacy of AP. Treatment of MDSCs with AP significantly decreased cell proliferation and induced apoptotic cell death through a toll-like receptor 4 dependent way. Subsequent studies showed that the AP treatment enhanced the expression of Bax and Caspase-9 and inhibited the expression of Bcl-2, suggesting that AP induced apoptosis in the MDSCs via the intrinsic pathway. Altogether, the results showed that AP exhibited a significant anti-MDSC activity and attenuated suppression of the antitumor immune response, thereby indicating its potential use in cancer therapy.

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...

Glaucoma is an ophthalmic disease that is characterized by elevated intraocular pressure (IOP). Eye drops are the preferred choice to reduce IOP for the treatment of glaucoma. However, the bioavailability of eye drops is low (

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.

Epimedium has been traditionally used to treat a variety of medical conditions, including neurological disorders. In this study, an acidic polysaccharide EbPS-A1 is isolated from Epimedium brevicornum and found to contain mainly galacturonic acid, galactose, and rhamnose but also arabinose and glucuronic acid. Using Caenorhabditis elegans models, we show that EbPS-A1 is capable of inhibiting behavioral dysfunction mediated by polyglutamine (polyQ), which is implicated in several neurodegenerative disorders such as Huntington's disease. Interestingly, EbPS-A1 does not inhibit polyQ aggregation or extend lifespan in the nematodes; it does, however, improve the survival under increased oxidative stress of both polyQ and wild-type nematodes intoxicated by paraquat. Further studies reveal that EbPS-A1 is capable of not only scavenging free radicals in vitro but also reducing reactive oxygen species levels, enhancing antioxidant enzyme activities, and decreasing lipid peroxidation product in C. elegans models. Together, these results suggest that the protective effect of Epimedium polysaccharide against polyQ-mediated neurotoxicity is likely due to its antioxidant function.

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 fruits of Lycium barbarum are considered medicinal foods with high nutritional value and bioactivity. In this study, we aimed to evaluate the effect of a crude L. barbarum polysaccharide (LBP) and two derived fractions, LBP-1 and LBP-2, on the lifespan of Drosophila melanogaster (fruit fly). The average lifespan of fruit flies was extended by supplementing their diet with either of the three LBP preparations. In vivo analysis of antioxidant activities detected increased superoxide dismutase (SOD) and catalase (CAT) activities and decreased malondialdehyde (MDA) levels. Dietary LBP supplements significantly reduced the mortality rate of fruit flies induced by paraquat and hydrogen peroxide. Importantly, the strongest anti-aging activity was exhibited by the LBP-2 fraction, containing arabinogalactan with a molecular weight of 9 × 104 Da. Further studies showed that the anti-aging activity of LBP was, at least in part, mediated by an age-related signaling pathway (MAPK, TOR, S6K) and the expression of longevity genes (Hep, MTH, and Rpn11).

The purpose of this work was to study the effects and underlying molecular mechanisms of ligustilide on cancer-associated fibroblasts (CAFs). The effects of ligustilide on the growth of CAFs and splenocytes were detected by MTT assay, and flow cytometry was used to detect effects on T-cell proliferation. Western blotting was used to detect the expression levels of CAF-related proteins after ligustilide treatment. This study found that ligustilide had no effect on the growth of splenocytes but that it could change the immunosuppressive function of CAFs through the TLR4-NF-κB pathway and restore T-cell proliferation previously inhibited by the CAF supernatant. Thus, ligustilide is expected to be a candidate for new antitumor drugs.

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.

Tumor-associated macrophages (TAMs) with an M2-like phenotype have been linked to immunosuppression and resistance to chemotherapies of cancer, thus targeting TAMs has been an attractive therapeutic strategy to cancer immunotherapy. We have reported that the β-D-(1→6) glucan (AAMP-A70) isolated from Amillariella Mellea could promote macrophage activation. The present study showed that the β-1,6-glucan could promote the transformation of M2-like macrophages to M1-like phenotype and inhibit the viability of colon cancer cells in vitro and in vivo. On a cellular mechanistic level, the β-1,6-glucan reset tumor-promoting M2-like macrophages to tumor-inhibiting M1-like phenotype via increasing the phosphorylation of Akt/NF-κB and MAPK. Further, TLR2 was identified as the receptor of β-1,6-glucan in the transformation effect. In addition, a very similar β-1,6-glucan with side chains of β-Glc or α-Galρ which was purified from Lentinus edodes showed same activities with those from Amillariella Mellea. Our findings shed light on the action mode of β-1,6-glucan in cancer immunotherapy.

Glaucoma is a progressive optic neuropathy that has become the most common cause of irreversible blindness worldwide. Studies have shown that the protein mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a central role in regulating numerous functions, such as growth, proliferation, cytoskeletal organization, metabolism, and autophagy. Clinical trials have shown that Rho-associated protein kinase (ROCK) inhibitors reduced intraocular pressure (IOP) in patients with glaucoma and ocular hypertension (OHT). In this study, we explored whether rapamycin (RAPA) eye drops can reduce IOP and protect retinal ganglion cells (RGCs). Our results indicated that in rats treated with RAPA, the drug was detected in the aqueous humor (AH), and the IOP was reduced. This may be related to the inhibition of RhoA protein activation by RAPA and regulation of the actin cytoskeleton in trabecular meshwork (TM) cells. In addition, the retinal thickness and the survival rate of RGCs were significantly reduced in the OHT group compared with the control group. These changes in the OHT group were significantly improved after treatment with RAPA. This may be because RAPA inhibited the activation of glial cells and the release of proinflammatory factors, thereby attenuating further damage to the retina and RGCs. Taken together, the results of this study demonstrated that RAPA not only reduced IOP but also protected RGCs, suggesting that RAPA is likely to be an effective strategy for the treatment of glaucoma.

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.

Host gut microbiota dysbiosis occurs for multiple reasons and is often accompanied by chronic inflammation induced by a high-fat-high-sucrose (HFHS) diet and related metabolic disorders. Intervention with probiotics is a novel strategy for amelioration of metabolic syndrome, which is believed to regulate the gut microbiota composition to some extent. We investigated the relationship amongst bifidobacteria treatment, HFHS diet-induced metabolic disorders and the gut microbiota composition. Seven strains of bifidobacteria from four species were individually administered to rats fed a HFHS diet for 12 weeks. Various bifidobacteria strains showed various effects on the recovery of metabolic disorders and gut microbiota dysbiosis, and these effects seemed to be inter- or intra-species specific. Bifidobacterium longum, B. adolescentis and B. bifidum seemed to affect the blood glucose balance, whilst two strains of B. breve showed extremely different effects in this area. However, only one strain of B. longum and the B. adolescentis displayed significant regulation of blood lipid levels. The protective effects of bifidobacteria on the pancreas were strongly correlated with those on blood glucose. Furthermore, the influence of bifidobacteria on gut microbiota dysbiosis also showed a potential relationship with symptoms of metabolic disorders. Of these seven strains, B. adolescentis Z25 displayed an outstanding ability to alleviate metabolic syndrome, including glucose and lipid metabolism disorders, tissue damage and gut microbiota dysbiosis. This strain, coupled with other prebiotics and probiotics, could be used as a potential treatment approach for metabolic syndrome induced by a HFHS diet.

Weaning is an essential and important event for infants and rodent animals, and the dietary supplementation plays a crucial role in regulating the composition and function of gut microbiota in the initial period after weaning. In this study, we investigated the potential effects of two probiotics along with three polysaccharides (PP) in weaned rats. Male SD rats, 21 days of age, were divided into two groups: one group was administered with PP for four weeks and the other was not. Body weight, food intake, gut epithelial barrier function, digestive enzyme activities, and the composition and function of gut microbiota were analyzed. The dietary PP increased the body weight and food intake, promoted gut epithelial barrier integrity, and elevated the activities of digestive enzymes. Moreover, the microbial community structure was different between the two groups. At the genus level, Bifidobacterium, Lactobacillus, and Allobaculum were significantly increased, whereas Anaerostipes, Enterococcus, and Parabacteroides were observably reduced. Furthermore, PP significantly increased amino acid metabolism, energy metabolism, and SCFA-related metabolism. This study shows that synbiotics containing probiotics (L. acidophilus NCFM and B. lactis Bi-07) in combination with polysaccharides (LBP, PCPs, and Lentinan) can modulate the composition of gut microbiota, stimulate the maturation of gut microbiota biological function, and promote the growth performance in weaned rats.

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.