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Bordetella infection can be efficiently prevented through vaccination. The current study investigated the effects of an extract of Cochinchina momordica seed (ECMS) combined with oil on the immune responses to the inactivated Bordetella vaccine in mice. Serum IgG and IgG1 level was significantly increased in ECMS-oil group compared to any other group ( P < 0.05 ) 2 weeks after immunization, while groups ECMS200 μg/400 μg-oil had a markedly higher level of serum IgG2b and IgG3 than any other groups ( P < 0.05 ). Moreover, lipopolysaccharide/ConA-stimulated proliferation of splenocytes was significantly enhanced in ECMS 400 μg-oil immunized mice in comparison with mice in any other group ( P < 0.05 ). RT-PCR assay revealed that while ECMS800 μg-oil group had significantly higher levels of serum IL-4, IL-10, Toll-like receptor (TLR)2, and IL-1 beta than any other group ( P < 0.05 ), the levels of serum IL-2, IL-4, and IL-10 were markedly increased in ECMS 400 μg-oil group as compared to any other groups ( P < 0.05 ). Blood analysis showed that ECMS800 μg-oil and oil groups had a significantly higher number of immunocytes than any other groups ( P < 0.05 ). There were significant differences in the number of IgG+, IgG2b+, and IgA+ cells in the lung between ECMS800 μg-oil group and any other groups ( P < 0.05 ). Western blot analysis demonstrated that stimulation with ECMS 25 μg/mL or 50 ng/mL led to a significant increase in the expression of TLR2, MyD88, and NF-κB in Raw264.7 cells ( P < 0.05 ). Compared with any other group, the expression of MyD88 was markedly increased in the cells stimulated with ECMS 50 ng/mL, as indicated by the RT-PCR analysis ( P < 0.05 ). Overall, we observed that ECMS-oil efficiently enhanced the humoral or cellular immune responses against Bordetella and suggested that the mechanism of adjuvant activity of ECMS-oil might involve TLR2/MyD88/NF-κB signaling pathway.

Money has been portrayed by major theorists as an agent of individualism, an instrument of freedom, a currency that removes personal values attached to things, and a generator of avarice. Regardless, the impact of money varies greatly with the cultural turf of the recipient societies. For traditional subsistence economies based on gifting and sharing, surplus perishable resources foraged from the environment carry low costs to the giver compared with the benefits to the receiver. With cash, costs to the giver are usually the same as benefits to the receiver, making sharing expensive and introducing new choices. Using quantitative data on possessions and expenditures collected over a 44-y period from 1974 to 2018 among the Ju/’hoansi (!Kung) in southern Africa, former hunter-gatherers, we look at how individuals spend monetary income, how a partial monetary economy alters traditional norms and institutions (egalitarianism, gifting, and sharing), and how institutions from the past steer change. Results show that gifting declines as cash is spent to increase the well-being of individual families and that gifting and sharing decrease and networks narrow. The sharing of meals and casual gifting hold fast. Substantial material inequalities develop, even between neighbors, but social, gender, and political equalities persist. A strong tradition for individual autonomy combined with monetary income allows individuals to spend their money as they choose, adapt to modern conditions, and pursue new options. However, new challenges are emerging to develop greater community cooperation and build substantial and sustainable economies in the face of such centrifugal forces.

Yee Huang, Li Nan, Chenwen Xiao, Jie Dong, Ke Li, Jvfen Cheng, Quanan Ji, Qiang Wei, Guolian Bao, Yan Liu Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Science, Hangzhou, 310021, People’s Republic of ChinaCorrespondence: Guolian Bao; Yan Liu, Institute of Animal Husbandry and Veterinary Medicine, Zhejiang Academy of Agricultural Science, Hangzhou, 310021, People’s Republic of China, Email baoguolian@163.com; 35792191@qq.comPurpose: Outer membrane vesicles (OMVs) are spherical nano-sized proteolipids secreted by numerous pathogenic Gram-negative bacteria. Due to the immunostimulatory properties and protective efficacy, OMVs have received increasing attention as a candidate for the vaccine to prevent and treat bacterial infections. However, the immune response remains elusive due to the low structural stability and poor size homogeneity of the vesicles. In this study, OMVs were used to coat self-assembled glycyrrhizic acid nanoparticles (GANs) and obtain a stable OMV vaccine. The immunoprotective effects and anti-infection efficacy were evaluated in vivo and in vitro.Methods: The OMVs were prepared by ultrafiltration method and fused with GAN through mechanical extrusion. The characteristics, including morphology, hydrodynamic size, zeta potential, and stability were evaluated. The in vitro immunological function of GAN-OMV on the macrophages and in vivo immune efficacy and anti-infection effect were examined and compared.Results: The results showed that the GAN-OMV were homogenous with a size of 130 nm and a stable core-shell structure. Micropinocytosis-dependent and clathrin-mediated endocytotic pathways effectively internalized the GAN-OMV into the macrophages and promoted cell proliferation, cytokine secretion, and M1 polarization. Furthermore, subcutaneous GAN-OMV vaccination contributed to significantly higher Borderella bronchiseptica (Bb)-specific antibody production and lymphocyte proliferation. The splenic lymphocytes of mice immunized with GAN-OMVs displayed a higher ratio of CD4+/CD8+ T cells and CD19+ B cells and produced significantly higher levels of Th1/Th2/Th17 cytokines. GAN-OMV also effectively prevented Bb reinfection.Conclusion: In this study, GAN-OMV was developed successfully to stimulate Th1/Th2/Th17 immune responses against Bb and provide a promising strategy for novel vaccine development against the microbial pathogen.Keywords: outer membrane vesicles, glycyrrhizic acid nanoparticle, macrophage, protective immune response, anti-bacterial infection

Background Rehmannia glutinosa polysaccharide is the main reason that contributes to the immunological function of R. glutinosa. Due to its disadvantages in clinical use, here we designed the PEGylation nano-RGP (pRL) to improve the drug-targeting effect and the immunological function. Our present work aims to establish the optimum condition of preparing the pRL and to investigate its immunological function on macrophages. Methods pRL was prepared by thin film hydration method combined with ultra-sonication technique. And its preparation conditions were optimized with response surface methodology. Also, the lyophilization method was optimized. The characteristics of the pRL were evaluated, including particle size, drug loading, encapsulation efficiency and morphology. The immunological function of pRL on macrophage was investigated through CCK-8 test, ELISA and flow cytometry. Results The lipid-to-cholesterol molar ratio of 8:1, the addition of DSPE-PEG2000 of 9% and the lipid-to-drug ratio of 5.4:1 were the optimum preparation technology for pRL. The encapsulation efficiency (EE) of pRL under this preparation technology was 95.81±1.58%, with a particle size of 31.98 ± 2.6 nm. The lactose-to-lipid ratio (2:1) was the optimal lyophilization method. pRL promoted macrophage proliferation, which is significantly better than that of nano-RGP without PEGylation (RL). pRL-stimulated RAW264.7 cells showed a high secretion of pro-inflammatory cytokines, which is the characteristic indicator of M1 polarization. Enhanced cellular uptake through macropinocytosis-dependent and caveolae-mediated endocytosis was observed in pRL-treated RAW264.7 cells. Conclusion Our study concluded that PEGylation effectively overcame the poor targeting effect of Rehmannia glutinosa polysaccharide (RGP) and significantly improved the immunological profile of its nano-formulation, which suggested that pRL could serve as an immune adjuvant in clinical application.

Graphene oxide quantum dots (GOQDs) have attracted substantial attention in numerous fields due to their unique physicochemical properties. However, their nanotoxicity and potential for use in biomedicine still require further study. In this work, the effects of GOQD and trans- 10-hydroxy-2-decenoic acid (10-HDA) cotreatment on the immune function of macrophages (RAW264.7 cells) were investigated. In particular, LC/MS-based metabolomics was performed to evaluate the effects of GOQDs on the metabolism of LPS-stimulated macrophages. Herein, we fabricated GOQDs with good dispersibility and a uniform size distribution of approximately 7 nm using a polyimide-pyrolyzed carbon film as the working electrode, a high-voltage graphite electrode as the cathode, and H

Outer membrane vesicles (OMVs) are spherical nano-sized proteolipids secreted by numerous pathogenic Gram-negative bacteria. Due to the immunostimulatory properties and protective efficacy, OMVs have received increasing attention as a candidate for the vaccine to prevent and treat bacterial infections. However, the immune response remains elusive due to the low structural stability and poor size homogeneity of the vesicles. In this study, OMVs were used to coat self-assembled glycyrrhizic acid nanoparticles (GANs) and obtain a stable OMV vaccine. The immunoprotective effects and anti-infection efficacy were evaluated in vivo and in vitro.The OMVs were prepared by ultrafiltration method and fused with GAN through mechanical extrusion. The characteristics, including morphology, hydrodynamic size, zeta potential, and stability were evaluated. The in vitro immunological function of GAN-OMV on the macrophages and in vivo immune efficacy and anti-infection effect were examined and compared.The results showed that the GAN-OMV were homogenous with a size of 130 nm and a stable core-shell structure. Micropinocytosis-dependent and clathrin-mediated endocytotic pathways effectively internalized the GAN-OMV into the macrophages and promoted cell proliferation, cytokine secretion, and M1 polarization. Furthermore, subcutaneous GAN-OMV vaccination contributed to significantly higherIn this study, GAN-OMV was developed successfully to stimulate Th1/Th2/Th17 immune responses against Bb and provide a promising strategy for novel vaccine development against the microbial pathogen.

The objective of this study was to assess the effects of dietary supplementation with Clostridium butyricum (CB) and a bacteriophage cocktail (BP) on growth performance, serum biochemical parameters, intestinal digestive and oxidase enzymes, intestinal morphology, immune responses, and the cecum microbiota in rabbits. In total, 108 New Zealand rabbits (5 weeks old) were randomly and equally allotted into three dietary treatment groups (four replicates per treatment, n = 36/treatment): (1) the control (CN) group—rabbits fed the basal diet; (2) CB group—rabbits fed the basal diet supplemented with 100 mg/kg diet Clostridium butyricum; and (3) BP group—rabbits fed the basal diet supplemented with 200 mg/kg diet BP cocktail, respectively, for 6 weeks. Compared with the CN diet, dietary CB and BP inclusion increased the average daily gain (ADG) and average daily feed intake (ADFI) and decreased the feed/gain (F/G) ratio of rabbits. Furthermore, CB increased the digestive enzyme activity (α-amylase and trypsin in the ileum); the chymotrypsin activity was also significantly increased in the duodenum and jejunum. Supplementation with CB significantly enhanced antioxidant capacity (SOD and GSH-Px) in the jejunum and ileum and reduced MDA levels. Additionally, rabbits fed CB had significantly elevated villus height (V) and (V/C) ratios but reduced crypt depth (C). Moreover, dietary CB supplementation markedly increased the ileal expression of tight junction proteins (occludin, ZO-1, and claudin-1) and increased secretory immunoglobulin A (sIgA) production. High-throughput sequencing indicated that the microbiota in the rabbit intestine was altered by CB and BP. Venn diagrams and heatmap plots revealed that the gut microbial community composition varied obviously among rabbits fed different diets. Specifically, CB increased the relative abundance of beneficial bacteria to maintain intestinal barrier homeostasis, whereas BP decreased the relative abundance of Gammaproteobacteria, which included a plenty of pathogenic bacteria.

Vaccines, in many cases, stimulate only too weak immunogenicity to prevent infection. Therefore, adjuvants are required during their preparation to boost the immune response. We herein developed a PEGylated nano-adjuvant based on Rehmannia glutinosa polysaccharide (RGP). The addition of PEG layer exhibits enhanced immune performance of the nano-RGP. Stimulation of dendritic cells (DCs) with PEGylated nano-RGP (pRL) led to increased proliferation and cytokine production (IL-6, IL-12, IL-1β and TNF-α). The pRL was internalized into DCs via a rapid and efficient method. The mice immunized with pRL exhibited enhanced antigen-specific serum IgG and Th1-(IFN-γ), Th2-(IL-4), and Th17-(IL-17, IL-6) cytokine production, contributing to a good anti-infection performance. Furthermore, the pRL could effectively deliver the antigen to the lymph nodes (LNs), activate DC in the LN and produce enhanced CD4+and CD8+ T-cells-derived memory (CD44high CD62Lhigh), and effector (CD44high CD62Llow) as well as functional phenotypes. Our results revealed that pRL can act as a promising adjuvant with targeted delivery of antigen due to its effective activation and robust adaptive immunity induction of DCs.

Sulbactam, a class A β-lactamase inhibitor, added to cefoperazone either at a fixed 8 mg/L level of sulbactam or at a level of fixed cefoperazone: sulbactam ratio (2:1) would constitute a combination form of cefoperazone/sulbactam, which has better activities against Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii than cefoperazone alone. Cefoperazone/sulbactam (1:1 or 1:2) has greater in-vitro activity against most multidrug-resistant organisms (ESBL- and AmpC-producing Enterobacteriaceae and carbapenem-resistant A. baumannii except for carbapenem-resistant P. aeruginosa) than a 2:1 ratio. However, increased sulbactam concentration may induce AmpC production. Besides, sulbactam concentration might not be readily achievable in serum if the susceptibility rates were defined by the breakpoints of higher sulbactam composites, such as ≤16/16 (1:1) or 16/32 (1:2) mg/L. Carbapenemases (KPC-, OXA-type enzymes and metallo-β-lactamases) can't be inhibited by sulbactam. Some in-vitro studies showed that increasing sulbactam composites of cefoperazone/sulbactam had no effect on carbapenem-resistant P. aeruginosa, suggesting the presence of carbapenemases or AmpC overproduction that could not be overcome by increasing sulbactam levels to recover cefoperazone activity. Sulbactam alone has good intrinsic activity against carbapenem-resistant Acinetobacter strains sometimes even in the presence of carbapenemase genes, suggesting unsteady levels of carbapenemases. In conclusion, appropriate composites of cefoperazone and β-lactamase inhibitor sulbactam may expand the clinical use if the pharmacokinetic optimization could be achieved in the human serum.

Lentinan (LNT), a β-1,3-linked-d-glucan with β-1,6 glucose branches, is the main bioactive component extracted from Lentinus edodes. As a carbohydrate polymer, it has attracted increasingly attention because of immune enhancement effect. Pickering emulsion has been widely used in biomedicine due to its great stability, high loading capacity, and appreciable biocompatibility. The aim of this study is to construct an adjuvant delivery system (LNTPP/OVA) (Lentinan PLGA-stabilized Pickering emulsion loading OVA antigen) which can enhance the immune activity of LNT and can together deliver model protein antigen ovalbumin (OVA) into the organism. The characterization of the LNTPP/OVA was demonstrated that the size of LNTPP/OVA was around 1050.68 nm and was stable to store at least 28 days. Pickering emulsion was spherical shape like the raspberry with the high antigen load rate at around 82.53%. Moreover, the adjuvant effect of LNTPP/OVA formulation was detected. Compared with LNT/OVA formulation, our experimental results showed that LNTPP/OVA could promote the uptake of the OVA-antigen by macrophages in vitro. In vivo experiments, LNTPP/OVA facilitated the activation of dendritic cells (DCs) and induced strong humoral and cellular immune responses carrying a Th1 and Th2 immune responses. Therefore, LNTPP/OVA formulation have the latent capacity as a vaccine transmission system.

Compared to conventional carrier-assistant drug delivery systems (DDSs), drug self-delivery systems (DSDSs) have advantages of unprecedented drug loading capacity, minimized carrier-related toxicity and ease of preparation. However, the colloidal stability and blood circulation time of DSDSs still need to be improved. Here we report on the development of a novel biomimicry drug self-delivery system by the integration of a top-down cell membrane complexing technique into our self-delivery multifunctional nano-platform made from the bottom-up approach that contains 100% active pharmaceutical ingredients (API) pheophorbide A and irinotecan conjugates (named PI). Compared to conventional cell membrane-coated nanoparticles with a polymer framework as the core and a relatively low drug loading capacity, this system consisting of red blood cell membrane vesicle complexed PI (RBC-PI) is polymer-free with up to 50% API loading. RBC-PI exhibited 10 times higher area under curve in a pharmacokinetic study and a much lower macrophage uptake compared with the parent PI nanoparticles. RBC-PI retained the excellent chemophototherapeutic effects of the PI nanoparticles, but possessed superior anti-cancer efficacy with prolonged blood circulation, improved tumor delivery, and enhanced photothermal effects in animal models. This system represents a novel example of using a cell membrane complexing technique for the effective surface modification of DSDSs. This is also an innovative study to form a polymer-free cell membrane nanoparticle complexing with positive surface-charged materials. This biomimicry DSDS takes advantage of the best features from both systems to make up for each other's shortcomings and provides all the critical features for an ideal drug delivery system.

The objective of this study was to assess the effects of dietary supplementation with Clostridium butyricum (CB) and a bacteriophage cocktail (BP) on growth performance, serum biochemical parameters, intestinal digestive and oxidase enzymes, intestinal morphology, immune responses, and the cecum microbiota in rabbits. In total, 108 New Zealand rabbits (5 weeks old) were randomly and equally allotted into three dietary treatment groups (four replicates per treatment, n = 36/treatment): (1) the control (CN) group—rabbits fed the basal diet, (2) CB group—rabbits fed the basal diet supplemented with 100 mg/kg diet Clostridium butyricum, and (3) BP group—rabbits fed the basal diet supplemented with 200 mg/kg diet BP cocktail, respectively, for 6 weeks. Compared with the CN diet, dietary CB and BP inclusion increased the average daily gain (ADG) and average daily feed intake (ADFI) and decreased the feed/gain (F/G) ratio of rabbits. Furthermore, CB increased the digestive enzyme activity (α-amylase and trypsin in the ileum), the chymotrypsin activity was also significantly increased in the duodenum and jejunum. Supplementation with CB significantly enhanced antioxidant capacity (SOD and GSH-Px) in the jejunum and ileum and reduced MDA levels. Additionally, rabbits fed CB had significantly elevated villus height (V) and (V/C) ratios but reduced crypt depth (C). Moreover, dietary CB supplementation markedly increased the ileal expression of tight junction proteins (occludin, ZO-1, and claudin-1) and increased secretory immunoglobulin A (sIgA) production. High-throughput sequencing indicated that the microbiota in the rabbit intestine was altered by CB and BP. Venn diagrams and heatmap plots revealed that the gut microbial community composition varied obviously among rabbits fed different diets. Specifically, CB increased the relative abundance of beneficial bacteria to maintain intestinal barrier homeostasis, whereas BP decreased the relative abundance of Gammaproteobacteria, which included a plenty of pathogenic bacteria.

Aspergillus-associated infection might comprise up to 23–29% of severe influenza patients from the community throughout stay in an intensive care unit (ICU). In Taiwan, cases of severe influenza with aspergillosis are increasingly reported. Therefore, we describe the relative risk of mortality among severe influenza patients with aspergillosis and other coinfections compared to severe influenza patients without Aspergillus coinfections. Methods: We retrospectively reviewed 124 adult patients with severe influenza in a tertiary medical center in southern Taiwan from January 2015 through March 2016. The definition of probable aspergillosis required abnormal radiological findings and positive Aspergillus galactomannan (GM) antigen and/or Aspergillus isolation. Results: Probable aspergillosis (detected throughout the whole course) and other coinfections (only community-acquired) were diagnosed in 21 (17%) and 38 (31%) of all patients respectively. Klebsiella pneumoniae (36.8%), Pseudomonas aeruginosa (31.6%) and Staphylococcus aureus (31.6%) were the most frequent isolates of other coinfections. In-ICU mortality of Aspergillus group (66.7%) was significantly higher than other coinfections (23.7%, p = 0.001) or control group without coinfections (15.4%, p

Nanomedicine, the medical application of nanotechnology, promises a seemingly limitless range of applications from drug delivery to adjuvants and therapeutics. Our current research is focused on natural polymer-based liposome adjuvants. With the aim of inducing protective and long-lasting immunity, the immunological adjuvant activity of Rehmannia glutinosa polysaccharide liposome (RGPL) was investigated. In vivo, the splenic lymphocyte proliferation ratios and ovalbumin-specific immunoglobulin G titers of ovalbumin-RGPL-vaccinated mice were significantly upregulated. In draining lymph nodes, the expression of MHC II+CD11c+ and CD86+CD11c+ was increased by RGPL; in addition, the percentages of central memory cells (TCM) and effector memory cells (TEM) were also elevated. RGPL could effectively provide adequate antigen exposure in lymph nodes. In vitro, RGPL could promote dendritic cell maturation and enhance dendritic cell functions, such as the mixed lymphocyte reaction and antigen presentation. Overall, the results demonstrated that RGPL has the potential to act as an effective controlled release vaccine adjuvant.

The plasmid-mediated extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases in Enterobacter spp. have increasingly been reported. In this study, we investigated the prevalence of the plasmid-mediated β-lactamases in Enterobacter cloacae from bloodstream isolates at a medical center in southern Taiwan. ESBL and ampC genes were detected by PCRs and DNA sequencing. Conjugation experiments were conducted to confirm the transferability of the genetic resistance trait. Among 41 non-repetitive blood isolates of cefuroxime-resistant E. cloacae, eight isolates exhibited ESBL phenotype confirmed by double-disk synergistic tests. Nearly all the strains were susceptible to carbapenems. The prevalence rate of the plasmid-mediated blaampC genes was 73% (30/41), including one blaDHA-1, one blaMIR-6, two novel blaCMH-1 genes and other blaACT-like genes. Coexistence of plasmid-mediated blaACT and ESBL genes (10 with blaSHV-12 and one with blaCTX-M-3) was observed. Successful transmissions of the blaACT and blaCMH-1 were demonstrated in some transconjugants. The inducible or derepressed CMH-1 had expanded activity of isolates versus ceftazidime. Enterobacterial repetitive intergenic consensus (ERIC)-PCR analysis and pulsotype showed distinct patterns suggesting non-clonal relationship. In conclusion, plasmid-mediated blaACT-like ampC genes in E. cloacae isolates have been highly prevalent in southern Taiwan and may continue genetic evolution, contributing to the complexities in antibiotic-resistant mechanisms.

Liposome-based vaccine delivery systems are known to enhance immune responses. Ganoderma lucidum polysaccharides (GLP) have been widely studied as immunomodulator and it could be as inducers of strong immune responses. In the research, GLP and ovalbumin (OVA) were encapsulated into liposome as vaccine and inoculated to mice. The magnitude and kinetics of the humoral and cellular immune responses were investigated. The results showed that GLP-OVA-loaded liposomes (GLPL/OVA) could induce more powerful antigen-specific immune responses than each single-component formulation. Mice immunized with GLPL/OVA displayed higher antigen-specific IgG antibodies, better splenocytes proliferation, higher cytokine secretion by splenocytes and significant activation of CD3+CD4+ and CD3+CD8+ T cells. Thus the GLPL/OVA formulation produced a heightened humoral and cellular immune response, with an overall Th1 bias. Enhanced immune responses elicited by the GLPL/OVA formulation might be attributed to effective activation and mature of DC in draining lymph nodes. Overall, these findings indicate that GLPL have the potential to enhance immune responses as vaccine delivery systems.

One acidic polysaccharide named EPS-1 was isolated from the aqueous extract of the leaves of Epimedium acuminatum Franch. It may be composed of 1,4-linked α-d-GalpA, 1,3,4-linked α-d-GalpA, 1,6-linked β-d-Galp and terminal α-l-Rhap residues in a molar ratio of 11.0:1.0:1.0:1.0 by chemical and spectroscopic analysis. EPS-1 possessed immune modulation effects on peripheral T lymphocyte and immature chBM-DCs such as promoting the proliferation and cytokine secretion of these cells and increasing the phagocytosis ability of immature chBM-DCs.

The activation of murine peritoneal macrophages by Ganoderma lucidum polysaccharides liposomes (GLPL) was investigated in vitro. After treatment with GLPL, the changes of the nitric oxide (NO) secretion and iNOS (inducible nitric oxide synthase) activity were evaluated. The results showed that NO production and iNOS activity of macrophages were enhanced compared to GLP and BL group. In addition, both the phagocytic activity and levels of cytokines IL-1β, TNF-α and IFN-γ were enhanced in the peritoneal macrophages of mice by stimulation of GLPL. The expression of the major histocompatibility complex class II molecule (MHC II) on the surface of peritoneal macrophages significantly increased. These indicated that GLPL could enhance the activation of peritoneal macrophages and their potential for use as a delivery system of GLP.

Photodynamic therapy (PDT) is a promising non-invasive therapeutic modality that has been proposed for treating prostate cancer, but the procedure is associated with limited efficacy, tumor recurrence and photo-toxicity. In the present study, we proposed to develop a novel multifunctional nano-platform for targeted delivery of heat, reactive oxygen species (ROS) and heat shock protein 90 (Hsp90) inhibitor simultaneously for combination therapy against prostate cancer. This new nano-platform combines two newly developed entities: 1) a unique organic and biocompatible nanoporphyrin-based drug delivery system that can generate efficient heat and ROS simultaneously with light activation at the tumor sites for dual-modal photothermal- and photodynamic- therapy (PTT/PDT), and 2) new nano-formulations of Hsp90 inhibitors that can decrease the levels of pro-survival and angiogenic signaling molecules induced by phototherapy, therefore, further sensitizing cancer cells to phototherapy. Furthermore, the nanoparticles have activatable near infrared (NIR) fluorescence for optical imaging to conveniently monitor the real-time drug delivery in both subcutaneous and orthotopic mouse models bearing prostate cancer xenograft. This novel multifunctional nano-platform has great potential to improve the care of prostate cancer patients through targeted combination therapy.

The widespread multidrug-resistant Enterobacteriaceae pose a serious therapeutic challenge. Colistin and tigecycline are potential antimicrobial agents for treating infections caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae . We evaluated the in-vitro activity of colistin sulfate against 253 ESBL producers isolated from patients admitted to a medical center in southern Taiwan ( Escherichia coli , n = 82; Klebsiella pneumoniae , n = 102; Enterobacter cloacae , n = 34; and Serratia marcescens , n = 35). Colistin showed promising in-vitro activity against E. coli, K. pneumoniae, and E. cloacae, but not S. marcescens. One ESBL-producing K. pneumoniae strain with resistance to carbapenems (ertapenem, imipenem, and meropenem) was selected for time-killing studies. A combination of colistin and tigecycline showed synergism, but there was an inoculum effect. In conclusion, colistin was active against most ESBL-producing Enterobacteriaceae , and a combination of colistin with tigecycline was synergistic against some highly resistant strains, even those with carbapenem resistance.

Bordetella bronchiseptica (B. bronchiseptica) causes a respiratory disease in rabbits. To determine the proteins of B. bronchiseptica in rabbits related to the disease, differentially accumulated proteins in B. bronchiseptica-infected cells are identified by comparative proteomic analysis. Comparative proteomic analysis detects 5814 proteins and quantifies 4854 of these. Fifty eight upregulated and 38 downregulated proteins are identified in spleen tissue after B. bronchiseptica infection of rabbits (both p < 0.05). The significantly enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways are ribosome, biosynthesis of amino acids, biosynthesis of amino acids, protein export, and carbon metabolism etc. (all p < 0.01). Significantly enriched KEGG pathways include 'ocu03010 ribosome' (a); 'ocu00260 glycine, serine threonine metabolism'. Analyses of control and infected spleen cells detect responses to B. bronchiseptica infection. Many differentially affected proteins are evident, and reflect different biological changes and diverse subcellular localizations between control and infected spleen cells. Infection markedly alters the expressions of proteins linked to the serine protease system, with the 'phagosome,' 'biosynthesis of amino acids,' 'glycine, serine threonine metabolism,' 'intestinal immune network for IgA production', and 'amino sugar and nucleotide sugar metabolism' associated with B. bronchiseptica infection. The result will inform studies of responses to B. bronchiseptica infections in rabbits.

Monitoring of in vivo drug release from nan by non-invasive approaches Remains very challenging. Herein we report on novel redox-responsive polymeric magnetosomes (PolyMags) with tunable magnetic resonance imaging (MRI) properties for in vivo drug release monitoring and effective dual-modal cancer therapy. The encapsulation of doxorubicin (DOX) significantly decreased PolyMags’ T(2) contrast enhancement and transverse relaxation rate R(2), depending on the drug loading level. The T(2) enhancement and R(2) could be recovered once the drug was released upon PolyMags’ disassembly. T(2) & T(2)* MRI and diffusion-weighted imaging (DWI) were utilized to quantitatively study the correlation between MRI signal changes and drug release, and discover the MR tuning mechanisms. We visualized the in vivo drug release pattern based on such tunable MRI capability via monitoring the changes in T(2)-weighted images, T(2) & T(2)* maps and R(2) & R(2)* values. Interestingly, the PolyMags possessed excellent photothermal effect, which could be further enhanced upon DOX loading. The PolyMags were highly efficacious to treat breast tumors on xenograft model with tumor-targeted photothermal-and chemo-therapy, achieving a complete cure rate of 66.7%. The concept reported here is generally applicable to other micellar and liposomal systems for image-guided drug delivery & release applications toward precision cancer therapy.

This study demonstrated that the use of a ITO/AgNW/ITO stacked structure could considerably enhance the mechanical flexibility of a transparent conducting oxide while minimizing AgNWs caused rough surface morphology. The bending test showed the electrical resistance variation of the stacked film could reach 1% much lower than that of the initial ITO of 32%. The top ITO also improve the adhesion of AgNWs on ITO. Optimization on the thickness of AgNWs and top ITO layer is necessary for better optical and surface morphological characteristics.

Photodynamic therapy is a promising and effective non-invasive therapeutic approach for the treatment of bladder cancers. Therapies targeting HSP90 have the advantage of tumor cell selectivity and have shown great preclinical efficacy. In this study, we evaluated a novel multifunctional nanoporphyrin platform loaded with an HSP90 inhibitor 17AAG (NP-AAG) for use as a multi-modality therapy against bladder cancer. NP-AAG was efficiently accumulated and retained at bladder cancer patient-derived xenograft (PDX) over 7 days. PDX tumors could be synergistically eradicated with a single intravenous injection of NP-AAG followed by multiple light treatments within 7 days. NP-AAG mediated treatment could not only specifically deliver 17AAG and produce heat and reactive oxygen species, but also more effectively inhibit essential bladder cancer essential signaling molecules like Akt, Src, and Erk, as well as HIF-1α induced by photo-therapy. This multifunctional nanoplatform has high clinical relevance and could dramatically improve management for bladder cancers with minimal toxicity.

Conventional drug delivery systems contain substantial amounts of excipients such as polymers and lipids, typically with low drug loading capacity and lack of intrinsic traceability and multifunctionality . Here, we report fully active pharmaceutical ingredient nanoparticles (FAPIN) which were self-assembled by minimal materials, but seamlessly orchestrated versatile theranostic functionalities including: i) self-delivery: no additional carriers were required, all components in the formulation are active pharmaceutical ingredients; ii) self-indicating: no additional imaging tags were needed. The nanoparticle itself was composed of 100% imaging agents , so that the stability, drug release, subcellular dispositions, biodistribution and therapeutic efficacy of FAPINs can be readily visualized by ample imaging capacities, including energy transfer relay dominated, dual-color fluorogenic property, near-infrared fluorescence imaging and magnetic resonance imaging; and iii) highly effective trimodality cancer therapy, encompassing photodynamic-, photothermal- and chemo-therapies . FAPINs were fabricated with very simple material (a photosensitizer-drug conjugate), unusually achieved ∼10 times better in vitro antitumor activity than their free counterparts, and were remarkably efficacious in patient-derived xenograft (PDX) glioblastoma multiforme animal models. Only two doses of FAPINs enabled complete ablation of highly-malignant PDX tumors in 50% of the mice.

The purpose of this study was to optimize the preparation conditions of Lycium barbarum polysaccharides liposome (LBPL) by response surface methodology (RSM) and to investigate the effect of LBPL activating function of peritoneal macrophages. LBPL was prepared using the reverse-phase evaporation method. The optimal preparation conditions of LBPL by RSM were as follows: the ratio of lipid to drug (w/w) of 25:1, the ultrasound time of 14 min and the ratio of soybean phospholipids to cholesterol (w/w) of 2.4:1. Under these conditions, the experimental encapsulation efficiency of LBPL was 86.37±0.63%, which was close to the predicted value. These indicated that LBPL with high entrapping efficiency and small particle size could be prepared by the reverse-phase evaporation method, which is applied easily. Furthermore, macrophages are the key players in the innate immune system. LBPL could effectively enhance peritoneal macrophages phagocytosis and resulted in inducing NO (nitric oxide) production in mouse peritoneal macrophages.

Groundwater is a critical component of the water supply for agriculture, urban areas, industry, and ecosystems, but managing it is a challenge because groundwater is difficult to map, quantify, and evaluate. Until recently, study and assessment of governance of this water resource has been largely neglected. A survey was developed to query state agency officials about the extent and scope of groundwater use, groundwater laws and regulations, and groundwater tools and strategies. Survey responses revealed key findings: states' legal frameworks for groundwater differ widely in recognizing the hydrologic connection between surface water and groundwater, the needs of groundwater-dependent ecosystems, and the protection of groundwater quality; states reported a range in capacity to enforce groundwater responsibilities; and states have also experienced substantial changes in groundwater governance in the past few decades. Overall, groundwater governance across the United States is fragmented. States nevertheless identified three common priorities for groundwater governance: water quality and contamination, conflicts between users, and declining groundwater levels. This survey represents an initial step in a broader, continuing effort to characterize groundwater governance practices in the United States.

Klebsiella pneumoniae (KP) resistance to broad-spectrum cephalosporin (BSC) in meningitis is important because of limited therapeutic options. To investigate the antibiotic resistance, virulence and epidemiology of KP in meningitis, we conducted a retrospective study for 33 non-metastatic isolates, including primary meningitis (n = 20) and post-craniotomy meningitis (n = 13) collected from 1999 to 2013. BSC resistance was found in 9 (27.3%) isolates, all from post-craniotomy meningitis, harboring blaSHV-5 (n = 6), blaCMY-2 (n = 2), blaDHA-1 (n = 2), and blaTEM-1B (n = 1). Positive virulence factors were hypermucoviscosity (n = 22), larger bacterial size (n = 24), virulent capsule serotypes (n = 24, K2, 11; K1, 5; K57, 3; K5, 2; K20, 2 and K54, 1), rmpA (n = 23), rmpA 2 (n = 20), aerobactin gene (n = 22) and high-grade serum resistance (n = 23, 69.7%). Higher mouse lethality (LD50 6) was found in 16 isolates (48.5%). Post-craniotomy isolates were significantly less virulent than primary meningitis isolates, except for similar serum resistance capability. The pulsotype and sequence typing (ST) results were diverse. A minor cluster with pulsotype C and ST23 (n = 5) was identified in primary meningitis isolates. In conclusion, virulence factors and BSC resistance corresponded to about 70% and 30% of KP meningitis isolates respectively. BSC remains appropriate for treating primary meningitis, whereas meropenem is indicated for post-craniotomy meningitis empirically.

The aim of this study was to investigate and assess the effects of propolis flavonoids liposome imposed on the immune system by comparing it to propolis flavonoids and blank liposome.In vitro, the effects of the above drugs on macrophages were assessed by measuring the phagocytic function and cytokine production.In vivo, the immunological adjuvant activity of propolis flavonoids liposome was compared with those of propolis flavonoids and blank liposome. The results showed thatin vitropropolis flavonoids liposome can significantly enhance the phagocytic function of macrophages and the release of IL-1β, IL-6, and IFN-γ. In addition, subcutaneous administration of propolis flavonoids liposome with ovalbumin to mice could effectively activate the cellular and humoral immune response, including inducing higher level concentrations of IgG, IL-4, and IFN-γin serum and the proliferation rates of splenic lymphocytes. These findings provided valuable information regarding the immune modulatory function of propolis flavonoids liposome and indicated the possibility of use of propolis flavonoids liposome as a potential adjuvant.

Groundwater is an increasingly important source of freshwater, especially where surface water resources are fully or over-allocated or becoming less reliable due to climate change. Groundwater reliance has created new challenges for sustainable management. This article examines how regional groundwater users coordinate and collaborate to manage shared groundwater resources, including attention to what drives collaboration. To identify and illustrate these facets, this article examines three geographically diverse cases of groundwater governance and management from the United States Sun Belt: Orange County Water District in southern California; Prescott Active Management Area in north-central Arizona; and the Central Florida Water Initiative in central Florida. These regions have different surface water laws, groundwater allocation and management laws and regulations, demographics, economics, topographies, and climate. These cases were selected because the Sun Belt faces similar pressures on groundwater due to historical and projected population growth and limited availability of usable surface water supplies. Collectively, they demonstrate groundwater governance trends in the United States, and illustrate distinctive features of regional groundwater management strategies. Our research shows how geophysical realities and state-level legislation have enabled and/or stimulated regions to develop groundwater management plans and strategies to address the specific issues associated with their groundwater resources. We find that litigation involvement and avoidance, along with the need to finance projects, are additional drivers of regional collaboration to manage groundwater. This case study underscores the importance of regionally coordinated and sustained efforts to address serious groundwater utilization challenges faced by the regions studied and around the world.

Salidroside, the important composition, of Rhodiola rosea L. has been reported to have various pharmacological properties. Liposome is known to be effective as drug carriers and immune adjuvant. Therefore, the aim of this study is to investigate immunological adjuvant activity of salidroside liposome. Here we reported the preparation, the effect on DCs in vitro and the immune response in vivo. The immunological adjuvant activity of salidroside liposome formulation was compared with that of salidroside and liposome. The result showed that salidroside liposome formulation not only could promote the maturation of DCs, the stimulation of DCs on MLR proliferation and the antigen presenting ability, but also induced the sustained cellular immune and humoral immune response. Overall, the results showed that salidroside liposome formulation had the potential to act as effective sustained release vaccine delivery systems.

The aim of this study is to investigate immunomodulatory effect of rehmannia glutinosa polysaccharide (RGP) on murine splenic lymphocyte and bone marrow derived dendritic cells (DCs). Splenic lymphocytes obtained from mice were co-cultured with RGP for 48 h and then harvested for analyzing with MTT method. The cytokine production of T lymphocytes was measured by ELISA. Effects of RGP treatment on DCs were investigated and assessed by MTT method. The results showed RGP significantly stimulated lymphocyte proliferation and the growth rate of T cell was more significant. The IL-2 and IFN-γ production of T lymphocyte were significantly upregulated after being stimulated with RGP. DCs stimulating on proliferation of T cells and the ability of antigen presenting of DCs have been enhanced under the stimulation of RGP. In conclusion, these findings provided valuable information that RGP possessed strong immunoenhancement activity, which provided the theoretical basis for the further experiment.

Adjuvants enhance immunogenicity and sustain long-term immune responses. As vital components of vaccines, efficient adjuvants are highly desirable. Recent evidence regarding the potential of carbon nanotubes (CNTs) to act as a support material has suggested that certain properties, such as their unique hollow structure, high specific surface area, and chemical stability, make CNTs desirable for a variety of antigen-delivery applications. Lentinan, a β-1,3-glucohexaose with β-1,6-branches that is extracted from the mushroom Lentinus edodes, is an effective immunostimulatory drug that has been clinically used in Japan and China, and recent studies have proved that specific beta-glucans can bind to various immune receptors. In this research, we covalently attached lentinan to multiwalled carbon nanotubes (MWCNTs) and tested their ability to enhance immune responses as a vaccine delivery system. In vitro study results showed that the nanotube constructs could rapidly enter dendritic cells and carry large amounts of antigen. Moreover, maturation markers were significantly upregulated versus the control. Thus, lentinan-modified multiwalled carbon nanotubes (L-MWCNTs) were regarded as an effective intracellular antigen depot and a catalyzer that could induce phenotypic and functional maturation of dendritic cells. Furthermore, compared with L-MWCNTs (35 μg/mL), a corresponding concentration of carboxylic carbon nanotubes (C-MWCNTs, 31.8 μg/mL) and an equivalent concentration of lentinan (3.2 μg/mL) did not remarkably influence the immune reaction in vitro or in vivo. Hence, we can hypothesize that the capability of L-MWCNTs was a consequence of the increased intracellular quantity of lentinan grafted onto the nanotubes. Overall, our studies demonstrated that L-MWCNTs significantly increased antigen accumulation in the cells and potentiated cellular and humoral immunity. In conclusion, L-MWCNTs constitute a potential vaccine delivery system to enhance immunogenicity for therapeutic purposes.

This paper first provides that Chinese yam polysaccharide (CYP) is encapsulated by PLGA using a double emulsion solvent evaporation method and aims to screen the optimal preparation of CYP-PLGA nanoparticles (CYPP) using response surface methodology (RSM). The volume ratio of the internal water phase to the organic phase (W1:O), the volume ratio of the primary emulsion to the external water phase (PE:W2) and the concentration of Poloxamer 188 (F68) are deemed key variables for the encapsulation efficiency of CYPP. The results demonstrated that the data were accurately fitted into the RSM model. According to the RSM, the optimal scheme was a volume ratio of W1:O of 1:9, a volume ratio of PE: W2 of 1:10 and a concentration of F68 (W/V) of 0.7%. TEM and SEM images demonstrated that the nanoparticles had a spherical shape and smooth surface. The CYP and CYPP in vitro release studies demonstrated that the CYPP showed a release rate 53.41% lower than the release rate of CYP after 48h. The result of pro-proliferation and flow cytometry emerged that the CYPP were more effective compared with the free CYP and blank PLGA nanoparticles in promoting lymphocyte proliferation and triggering the transformation of T lymphocytes into Th cells.

Purpose: To investigate the synergistic and bactericidal effects of antimicrobial combinations of any two of colistin, fosfomycin and tigecycline against the nine extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (KP) clinical isolates, including 4 carbapenem-susceptible strains and five imipenem and/or meropenem-resistant strains. Methods: In vitro synergism and bactericidal activity of combination of colistin, fosfomycin and tigecycline were evaluated by time-kill studies in standard inoculum of bacterial densities of a suspension containing 5 Ã 105 CFU/mL by using 1/2à MIC for each alone, and both 1/2à and 1/4à MIC for any two drugs. The settings of low MIC dosing were allowed to rapidly survey the most active drug combination. Results: The most active combination group was colistin plus tigecycline, showing synergy in 8 isolates and bactericidal activities in 6 isolates by using concentrations of 1/2à MIC and 1/4à MIC, respectively. The least active combination was tigecycline plus fosfomycin, which showed synergy in only 4 isolates and no bactericidal activities by using concentrations of 1/2à MIC and 1/4à MIC, respectively. Conclusions: The combination of tigecycline and colistin may be considered as a last-resort approach to the ESBL-producing KP infections, especially those isolates with carbapenem resistance. Keywords: Carbapenem resistance, Colistin, ESBL, Fosfomycin, Tigecycline

Liposomes, one kind of vaccine adjuvants, have been demonstrated as effective adjuvants and vaccine delivery system. Immunization against PCV-2 has been studied intensely and found to be the most effective strategy for protecting pigs against PCV-2 infection. Inactivated vaccines represent a complex mixture of viral antigens closely resembling the native virion. In the present study, PCV-2 attenuated antigen was encapsulated within Rehmannia glutinosa polysaccharide liposome, instead of oil adjuvant which is the mainstream adjuvant. Our results showed that RGPL could elicit a strong IgG response and significantly increased the production of Th1 and Th2 associated IgG subtypes and cytokines. R. glutinosa polysaccharide liposome showed excellent particle stability. In vitro, R. glutinosa polysaccharide liposome could also significantly promote phagocytic activity of macrophage and the levels of cytokines it produced. Overall, the results demonstrated that R. glutinosa polysaccharide liposome has the potential to be developed into a more effective and safer vaccine adjuvant.

The emergence of multidrug-resistant Salmonella isolates has created the need for new therapeutic agents. We evaluated the intracellular activity of four carbapenem compounds against clinical nontyphoid Salmonella (NTS) isolates in vitro and ex vivo . Subsequently, the efficacy of carbapenem treatment against selected Salmonella isolates in vivo was assessed using a murine peritonitis model. The MIC 50 and MIC 90 for doripenem, ertapenem, imipenem, and meropenem against 126 NTS isolates were found to be 0.062 and 0.062, 0.015 and 0.015, 0.5 and 1, and 0.031 and 0.031 μg/ml, respectively. The intracellular killing effect of ertapenem was sustained for 24 h and was superior to that of imipenem, meropenem, and doripenem; its effect was comparable to that of ceftriaxone. Ertapenem demonstrated an excellent pharmacokinetic profile with a percent time above the MIC of 75.5% and an area under the concentration-time curve/MIC ratio of 20,733. When peritoneal exudate cells were examined directly ex vivo from mice with Salmonella -induced peritonitis, cells from mice treated with ertapenem and ceftriaxone had intracellular and extracellular bacterial counts reduced 10 2 - to 10 4 -fold and exhibited killing effects similar to each other. The survival rates of mice inoculated with 1 × 10 5 and 10 6 CFU of a ceftriaxone-susceptible Salmonella isolate that were subsequently treated with ertapenem or ceftriaxone were 100% and 90%, respectively. When mice were inoculated with 5 × 10 4 and 10 5 CFU of a ceftriaxone-resistant and ciprofloxacin-resistant Salmonella isolate, mice treated with ertapenem had a higher survival rate than mice treated with ceftriaxone (70% versus 0% and 50% versus 0%, respectively; P < 0.001). Our results suggest that ertapenem is at least as effective as ceftriaxone in treating murine Salmonella infections and show that further clinical investigations on the potential use of ertapenem in treatment of human Salmonella infections are warranted.

In previous researches, the results showed that Lycium barbarum polysaccharides (LBP) encapsulated with liposome could enhance the immune activity of LBP. Therefore, the present study was designed to investigate the effects of LBPL on spleen lymphocytes and macrophages of mice in vitro and evaluate the immunological adjuvant activity of PCV2 vaccine in vivo. The results showed that LBPL could significantly promote splenocyte proliferation synergistically with PHA or LPS, increase the ratio of CD4(+) to CD8(+) T cells and promote the cytokine secretion of macrophages; enhance PCV2-specific IgG antibody responses, promote Th1 cytokines (IFN-γ and TNF-a) and Th2 cytokine (IL-4) secretion. The histomorphological observation of spleen demonstrated that LBPL as a vaccine adjuvant also has good improvement and stimulating effect on the immune organ.

Regardless of the efforts governments may take to mitigate the impacts of greenhouse gas emissions and other human activities on climate change, the need for society to adapt to climate change is unavoidable. Adapting to the myriad impacts of climate change will require actions at all levels of government. This article focuses on the anticipated impacts of climate change on the Puget Sound region in the northwestern United States as an example of the range of problems climate change will present and of the solutions available to governments and others interested in avoiding or minimizing the adverse impacts of climate change. As a guide for policy-makers, the article offers general principles for formulating climate change adaptation policies, suggestions for changes in decision-making processes that make them more suitable for addressing the unpredictable impacts of climate change, and strategies for adapting to three specific categories of climate change effects: impacts on the hydrologic cycle, sea-level rise, and altered meteorological conditions. The strategies and recommendations analysed in the article can provide a model for climate change adaptation policies, both in the Puget Sound region and more broadly, that are both environmentally protective and socially equitable.

Dengue is an important mosquitoes-borne viral disease which is endemic in tropics and subtropics region. Rapid spreading of disease to previously unaffected region was found in recent years. Atypical manifestations, such as myocarditis, were reported during large outbreak. There is a wide range of clinical manifestations of cardiac involvement in dengue, but rarely fatal. Here we reported a case of fulminant dengue myocarditis in fatal outcome despite cardiac mechanical support.

We investigated the synergism of colistin and imipenem against a multidrug-resistantK. pneumoniaeisolate which was recovered from a severe hip infection. PCR and DNA sequencing were used to characterize the outer membrane porin genes and the resistance genes mediating the commonβ-lactamases and carbapenemases. Synergism was evaluated by time-kill studies. TheblaSHV-31,blaCMY-2, andblaDHA-1were detected. Outer membrane porin genes analysis revealed loss ofompK36and frame-shift mutation ofompK35. The common carbapenemase genes were not found. Time-kill studies demonstrated that a combination of 1x MIC of colistin (2 mg/L) and 1x MIC of imipenem (8 mg/L) was synergistic and bactericidal but with inoculum effect. Bactericidal activity without inoculum effect was observed by concentration of 2x MIC of colistin alone or plus 2x MIC of imipenem. In conclusion, colistin plus imipenem could be an alternative option to treat carbapenem-resistantK. pneumoniaeinfections.

The aim of this study was to investigate the optimizing preparation conditions of Ganoderma lucidum polysaccharide liposome (GLPL) with response surface methodology (RSM) and the immunological enhancement activity of GLPL. The immunological enhancement activity of GLPL on splenocyte proliferation was measured. The optimum formulation of GLPL, in which the ratio of soybean phospholipid to cholesterol(w/w) of 11:1, the ratio of soybean phospholipid to tween-80 (w/w) of 10.5:1 and ultrasonic time(min) of 11, had higher entrapment efficiency (EE) of 71.43±0.49% with spherical shape and uniform sizes. In addition, GLPL could significantly promote splenocyte proliferation singly or synergistically with PHA and LPS. That indicated that the immunological enhancement of Ganoderma lucidum polysaccharide (GLP) was significantly enhanced after encapsulation with the liposome.

The aim of this study was to investigate the optimizing preparation conditions and immunological enhancement activity of Rehmannia glutinosa polysaccharide liposome (RGPL). RGPL was prepared using the reverse-phase evaporation method and optimized using the response surface methodology. The immunological enhancement activity of RGPL on splenocyte proliferation was measured. These results showed that the optimum preparation conditions were: a soybean phosphatide to cholesterol ratio of 8:1, a chloroform to methanol ratio of 3:5, a soybean phosphatide to tween 80 ratio of 10:1, a temperature (°C) of 66°C and an entrapment efficiency of 72.753 ± 0.318%. In a single stimulation of drugs, RGPL could significantly promote splenocyte proliferation, specifically at 200 μg mL(-1). Moreover, in a synergistic stimulation of drugs with LPS or PHA, a significant difference was obtained between the RGPL and RGP at 100-400 μg mL(-1), which indicated that the immunological enhancement of RGP was significantly improved after encapsulation with the liposome.

A previous study found that epimedium polysaccharide (EP)-propolis flavonoid (PF) injection (EPI) produced reliable immunoenhancement. In this study, we investigate the effects of EP-PF oral liquid (EFO) on mucosal immunity in the chicken small intestine while using EPI, EP and PF as controls. Groups of fourteen-day-old chickens were given EFO orally at one of the three doses when they were vaccinated with ND vaccine. On days 7, 21 and 35 after the first vaccination, six chickens were selected randomly from each group for measurements of the sIgA and IL-17 contents of the washing liquors of the duodenum and jejunum, counts of the lymphocytes in the duodenal endothelium and counts of the IgA(+) cells in the jejunal endothelium and cecum tonsil. The results indicated that EFO significantly promoted the secretion of sIgA and IL-17 and increased the numbers of lymphocyte and IgA(+) cells. Furthermore, EFO was more efficient than EPI at the high and medium doses. These findings indicate that EPO may enhance intestinal mucosal immunity and may be exploited as an oral immunopotentiator.

Optimization of preparation of gypenosides liposome (GPSL) was investigated with response surface methodology (RSM) and the effect of GPSL activating phagocytosis activity and cytokine secretion of macrophages was determined in the paper. The results showed that the optimal conditions of GPSL preparation were as follows: the ratio of lipid to drug (w/w) of 8:1, the ratio of soybean phospholipid to cholesterol (w/w) of 6:1, the temperature of incubation of drug in water bath of 55°C, the time of incubation of drug of 11 min. With the condition, the experimental encapsulation efficiency of GPSL was 90.17 ± 0.38%. In addition, GPSL could significantly enhance phagocytosis activity and the secretion of cytokines of the peritoneal macrophages of mice. These indicated that GPSL with high entrapping efficiency and small particle size could be prepared by ethanol injection combined with ammonium sulfate gradient method, which is applied easily, and GPSL could enhance the activity of peritoneal macrophages.