Promote Lymphocyte Proliferation Research Articles

Adenosine 2A receptor antagonists promote lymphocyte proliferation in sepsis by inhibiting Treg expression of PD-L1 in spleen.

The spleen is essential for lymphocyte proliferation, which is associated to sepsis prognosis. Adenosine 2A receptor (A2AR) blocking promotes lymphocyte proliferation in sepsis, however the mechanism is uncertain. Our sepsis cecum ligation perforation model showed that blocking A2AR increased survival and CD4+ cell numbers in a spleen-dependent mechanism. The sequencing of the transcriptome of the spleen indicated alterations in the expression of genes involved in the control of lymphocyte proliferation by inhibiting A2AR, including a reduction in the expression of PD-L1. Flow cytometry analysis of PD-L1 expression intensity in splenic cell subpopulations revealed that the Treg cell subpopulation was the strongest PD-L1-expressing cell population, and Treg PD-L1 expression decreased after blocking A2AR. In vitro activation of A2AR was able to upregulate PD-L1 expression of Treg and boost Treg capacity to limit lymphocyte proliferation, while blockage of PD-L1 partly reduced A2AR-activated Treg's ability to inhibit lymphocyte proliferation. In addition, blocking CREB phosphorylation significantly inhibited A2AR-induced PD-L1 expression. According to the findings of our research, inhibiting A2AR improves the prognosis of sepsis by lowering the level of PD-L1 expression by Treg in the spleen and reducing the inhibition of lymphocyte proliferation.

The state of astragaloside IV research: A bibliometric and visualized analysis.

Astragaloside IV has emerged as a pharmaceutical monomer with great medical applications and potential. Astragaloside IV has many effects such as improving myocardial ischemia, cerebral ischemia-reperfusion injury, anti-inflammatory, analgesic, antiviral, promoting lymphocyte proliferation, and antitumor effects. However, there are few bibliometric studies on astragaloside IV. We aim to visualize the hotspots and trends in astragaloside IV research through bibliometric analysis to further understand the future development of basic and clinical research. Methods The articles and reviews on astragaloside IV were screened from the Web of Science Core Collection, and knowledge maps were generated using CiteSpace software. Bibliometric analysis was performed on 971 articles published from 1998 to 2022. The number of articles on astragaloside IV increased yearly. These publications came from 42 countries/regions, with China being the largest. The primary research institutions were Shanghai University of Traditional Chinese Medicine and Guangzhou University of Traditional Chinese Medicine. Journal of Ethnopharmacology was the most studied journal and co-cited journal. A total of 473 authors were included, among which Hongxin Wang had the highest number of publications and Zhang Wd had the highest total citation frequency. After analysis, the most common keywords are astragaloside IV, expression, and oxidative stress. Cardiovascular disease, cerebral ischemia, cancer, and kidney disease are current and developing research fields. This study used bibliometrics and visualization methods to analyze the research hotspots and trends of astragaloside IV. Astragaloside IV on ischemia-reperfusion injury, cancer, and tumor may become the focus of future research.

An immune-enhanced multivalent DNA nanovaccine to prevent H7 and H9 avian influenza virus in mice

H7 avian influenza virus has caused multiple human infections and poses a severe public health threat. In response to the highly variable nature of AIVs, a novel, easily regenerated DNA vaccine has great potential in treating or preventing avian influenza pandemics. Nevertheless, DNA vaccines have many disadvantages, such as weak immunogenicity and poor in vivo delivery. To further characterize and solve these issues and develop a novel H7 AIV DNA vaccine with enhanced stability and immunogenicity, we constructed nine AIV DNA plasmids, and the immunogenicity screened showed that mice immunized with pβH7N2SH9 elicited stronger hemagglutination-inhibiting (HI) antibodies than other eight plasmid DNAs. Then, to address the susceptibility to degradation and low transfection rate of DNA vaccine in vivo, we developed pβH7N2SH9/DGL NPs by encapsulating the pβH7N2SH9 within the dendrigraft poly-l-lysines nanoparticles. As expected, these NPs exhibited excellent physical and chemical properties, were capable of promote lymphocyte proliferation, and induce stronger humoral and cellular responses than the naked pβH7N2SH9, including higher levels of HI antibodies than naked pβH7N2SH9, as well as the production of cytokines, namely, IL-2, IFN-α. Taken together, our results suggest that the construction of an immune-enhanced H7-AIV DNA nanovaccine may be a promising strategy against most influenza viruses.

Midazolam nanocrystal facilitates submandibular lymphatic metabolism via cAMP signal transduction pathway

Midazolam is a short-acting benzodiazepine for sedation, but its application is limited by its poor solubility. This study explored the impact of midazolam nanocrystals on Cyclic adenosine monophosphate (cAMP0 signal transduction. A rat model of hypercalcemia was established and divided into model group, control group, midazolam nanocrystal group, midazolam group, inhibitor group and agonist group. After treatment, the contents of cAMP and cGMP were detected by radioimmunoassay, and transformation rate, proliferation and apoptosis of lymphocytes were analyzed. Additionally, we observed microcirculation of lymphocytes and calculated contraction activity, overall lymphatic contractile activity and lymph dynamic index. The structure of the prepared nanocrystals was uniform and stable. Higher cGMP concentration and lymph viscosity of rats in the midazolam nanocrystal, midazolam and inhibitor groups were lower, while cGMP was raised in the agonist group. Besides, modeled rats exhibited decreased cAMP concentration, T lymphocyte conversion rate, lymphatic vessel contraction frequency, contraction activity index, total contraction activity index, lymph dynamic index/flow and lymphocyte output (p < 0.05), which were all increased in the midazolam nanocrystal group, midazolam group and agonist group but decreased in the inhibitor group (p < 0.05). Moreover, Midazolam nanocrystals improved lymphocyte proliferation and decreased apoptosis (<0.05). Midazolam nanocrystals can increase the concentration of cAMP and conversion rate of T lymphocytes, thereby reducing the concentration of cGMP, promoting lymphocyte proliferation, inhibiting apoptosis, and effectively improving the contraction frequency and contraction activity of lymphatic vessels. The cGMP can elevate total contractile activity index and lymph dynamics index, and enhance lymphatic transport function, while reducing lymph viscosity.

Assignment of IVL-Methyl side chain of the ligand-free monomeric human MALT1 paracaspase-IgL3 domain in solution

Mucosa-associated lymphoid tissue protein 1 (MALT1) plays a key role in adaptive immune responses by modulating specific intracellular signalling pathways that control the development and proliferation of both T and B cells. Dysfunction of these pathways is coupled to the progress of highly aggressive lymphoma as well as to potential development of an array of different immune disorders. In contrast to other signalling mediators, MALT1 is not only activated through the formation of the CBM complex together with the proteins CARMA1 and Bcl10, but also by acting as a protease that cleaves multiple substrates to promote lymphocyte proliferation and survival via the NF-κB signalling pathway. Herein, we present the partial 1H, 13C Ile/Val/Leu-Methyl resonance assignment of the monomeric apo form of the paracaspase-IgL3 domain of human MALT1. Our results provide a solid ground for future elucidation of both the three-dimensional structure and the dynamics of MALT1, key for adequate development of inhibitors, and a thorough molecular understanding of its function(s).

Activated T cells are the cellular source of IL-22 that enhances proliferation and survival of lymphocytes in Nile tilapia

As a pleiotropic cytokine mainly secreted by CD4+ T cells, interleukin (IL)-22 plays an important role in immune regulation and infection elimination. Despite IL-22 homologues have been identified in non-mammal, whether and how IL-22 participates in the adaptive immune response of early vertebrates have not been fully addressed. In this study, we identified an evolutionarily conserved IL-22 from Nile tilapia Oreochromis niloticus (defined as OnIL-22), proved by its properties regarding sequence, gene structure, functional domain, tertiary structure and phylogeny. IL-22 was broadly expressed in lymphoid-related tissues of tilapia, and with relatively higher levels in skin, gill, intestine and liver. The expression of OnIL-22 in spleen lymphocytes was markedly induced at the adaptive immune stage after Streptococcus agalactiae infection. Moreover, once lymphocytes were activated by PMA plus ionomycin or T-cell specific mitogen PHA in vitro, OnIL-22 expression was obviously up-regulated at both mRNA and protein levels. These results thus suggest that activated T cells produce IL-22 to take part in the adaptive immune response of tilapia. Furthermore, treatment of lymphocytes with recombinant OnIL-22 increased the expression of genes related to proliferation and survival, and further promoted the proliferation and reduced the apoptosis of lymphocytes during bacterial infection or T-cell activation. These cellular effects of IL-22 seem to be associated with JAK1/STAT3 axis downstream of IL-22, because IL-22 application not only elevated the mRNA expression of JAK1 and STAT3, but also enhanced their phosphorylation in lymphocytes. Altogether, we suggest that activated T cells produce IL-22 to promote lymphocyte proliferation and survival probability via JAK1/STAT3 signaling pathway, thus participating in adaptive immune response of Nile tilapia. Our study therefore provides helpful perspective for understanding the function and mechanism of adaptive immune system in teleost.

Mucosal immunity of mannose-modified chitosan microspheres loaded with the nontyepable Haemophilus influenzae outer membrane protein P6 in BALB/c mice.

Nontypeable Haemophilus influenzae (NTHi) is a common opportunistic pathogen that colonizes the nasopharynx. NTHi infections result in enormous global morbidity in two clinical settings: otitis media in children and acute exacerbation of chronic obstructive pulmonary disease (COPD) in adults. Thus, there is an urgent need to design and develop effective vaccines to prevent morbidity and reduce antibiotic use. The NTHi outer membrane protein P6, a potential vaccine candidate, is highly conserved and effectively induces protective immunity. Here, to enhance mucosal immune responses, P6-loaded mannose-modified chitosan (MC) microspheres (P6-MCMs) were developed for mucosal delivery. MC (18.75%) was synthesized by the reductive amination reaction method using sodium cyanoborohydride (NaBH3CN), and P6-MCMs with an average size of 590.4±16.2 nm were successfully prepared via the tripolyphosphate (TPP) ionotropic gelation process. After intranasal immunization with P6-MCMs, evaluation of humoral immune responses indicated that P6-MCMs enhance both systemic and mucosal immune responses. Evaluation of cellular immune responses indicated that P6-MCMs enhance cellular immunity and trigger a mixed Th1/Th2-type immune response. Importantly, P6-MCMs also trigger a Th17-type immune response. They are effective in promoting lymphocyte proliferation and differentiation without toxicity in vitro. The results also demonstrate that P6-MCMs can effectively induce MHC class I- and II-restricted cross-presentation, promoting CD4+-mediated Th immune responses and CD8+-mediated cytotoxic T lymphocyte (CTL) immune responses. Evaluation of protective immunity indicated that immunization with P6-MCMs can reduce inflammation in the nasal mucosa and the lung and prevent NTHi infection. In conclusion, MCMs are a promising adjuvant-delivery system for vaccines against NTHi.

Intranasal immunization with O-2\u2032-Hydroxypropyl trimethyl ammonium chloride chitosan nanoparticles loaded with Newcastle disease virus DNA vaccine enhances mucosal immune response in chickens

BackgroundThere has been a great interest in developing strategies for enhancing antigen delivery to the mucosal immune system as well as identifying mucosal active immunostimulating agents. To elevate the potential of O-2ʹ-Hydroxypropyl trimethyl ammonium chloride chitosan (O-2ʹ-HACC) as an adjuvant and mucosal immune delivery carrier for DNA vaccine, we prepared the O-2ʹ-HACC loaded with Newcastle disease virus (NDV) F gene plasmid DNA and C3d6 molecular adjuvant (O-2ʹ-HACC/pFDNA microparticles).ResultsThe O-2ʹ-HACC/pFDNA exhibited a regular spherical morphology with a particle size of 202.3 ± 0.52 nm, a zeta potential of 50.8 ± 8.21 mV, encapsulation efficiency of 90.74 ± 1.10%, and a loading capacity of 49.84 ± 1.20%. The plasmid DNA could be sustainably released from the O-2ʹ-HACC/pFDNA after an initial burst release. Intranasal vaccination of chickens immunized with O-2ʹ-HACC/pFDNA not only induced higher anti-NDV IgG and sIgA antibody titers but also significantly promoted lymphocyte proliferation and produced higher levels of IL-2, IL-4, IFN-γ, CD4+, and CD8 + T lymphocytes compared with the NDV commercial live attenuated vaccine. Intranasal delivery of the O-2ʹ-HACC/pFDNA enhanced humoral, cellular, and mucosal immune responses and protected chickens from the infection of highly virulent NDV compared with the intramuscular delivery.ConclusionsCollectively, our findings indicated that the O-2ʹ-HACC could be used as a vaccine adjuvant and delivery system for mucosal immunity and have an immense application promise.Graphic

Immunological studies of Morinda officinalis How polysaccharides as an adjuvant

Morinda officinalis polysaccharides (MOPS) were investigated for their physicochemical properties, monosaccharide composition, and immune-modulating effects in vitro and in vivo. In vitro, MOPS significantly promoted lymphocyte proliferation and increased IFN-γ and IL-4 secretion. In vivo, MOPS acted as adjuvant, which significantly up-regulated HBsAg-specific IgG and IgG isotype levels, promoted antigen-specific T cell proliferation and cytokine (IL-2 and IL-5) production, and induced CTL and NK cytotoxicity. Moreover, MOPS increased DC maturation. Overall, MOPS can serve as an adjuvant to promote humoral and cellular immune responses via promoting DC maturation, suggesting that MOPS may have potentials as a natural immune-enhancing agent.

Pectin-like polysaccharide extracted from the leaves of Conocarpus erectus Linnaeus promotes antioxidant, immunomodulatory and prebiotic effects

Pectins are complex heteropolysaccharides made up of a linear main chain of repeated units of galacturonic acid that can promote different biological activities. This work aimed to isolate and elucidate the chemical structure of a polysaccharide similar to pectin, obtained from C. erectus leaves. Furthermore, we evaluate the antioxidant and immunomodulatory potential promoted by this macromolecule. The physical-chemical analyzes showed that the pectin obtained showed low degree of esterification and low molecular weight. In addition, it presented in its structure galacturonic acid, glucose, xylose, rhamnose and arabinose. In antioxidant assays in vitro the pectin expressed high activity for the DPPH and ABTS methods. In addition, the pectin obtained was able to promote the growth of probiotic microorganisms in vitro. Immunological tests have shown that pectin was able to stimulate immune cells through the oxidative stress mechanism, promoting lymphocyte proliferation and activation TCD4+ and inhibit lymphocyte activation TCD8+ and stimulate its effector mechanisms through the production of cytokines and nitric oxide, mainly producing a pro-inflammatory immune response, without causing damage to cells. These results highlight the potential use of pectin extracted from C. erectus leaves as an antioxidant, prebiotic and immunomodulatory agent.

Immunoregulatory activities of the selenylated polysaccharides of Lilium davidii var. unicolor Salisb in vitro and in vivo

Studies have demonstrated that the modification of selenylation can improve the activity of polysaccharides. Lilium davidii var. unicolor Salisb (known as “lily bulb”) is the dried succulent bulb of the genus Lilium in the family Liliaceae. We wished to investigate the immunoregulatory activities of the selenized polysaccharides of lily bulb (sLP). We undertook experiments in vitro and in vivo taking the unmodified polysaccharides of lily bulb (LP) as controls. The results of in vitro studies showed that sLP could promote the phagocytosis of RAW 264.7 cells significantly, increase the content of interleukin (IL)-1β and IL-2, enhance the activity of acid phosphatase, and increase the surface molecular expression of CD86 and CD80. The results of in vivo studies showed that sLP could improve the index of immune organs, increase the contents of interferon-γ, IL-6, immunoglobulin (Ig)G and IgM in serum, and promote lymphocyte proliferation. The immunoregulatory activities of sLP were significantly more robust than those of LP in vitro and in vivo. These results indicated that selenylation could enhance the immune-enhancement activity of LP significantly.

Myeloid and plasmacytoid dendritic cell combined vaccines loaded with heat-treated tumor cell lysates enhance antitumor activity in murine lung cancer.

The present study aimed to investigate the efficacy of a myeloid dendritic cell (mDCs) and plasmacytoid (p)DC combined vaccine loaded with heat-treated cancer cell lysates against lung cancer cells. The mDCs and pDCs were selected using magnetic bead sorting. Antigen loading was performed by adding heat-treated Lewis lung cancer cell lysates to mDC, pDC or mDC+pDC (1:1). Surface expression of CD80, CD86, CD40 and major histocompatibility complex (MHC)-II molecules were determined using flow cytometry, and the secretion of cytokines IL-12, IL-6 and TNF-α were assessed using ELISA assays. The effect of the mDC and pDC vaccine on cytotoxic T lymphocytes (CTLs) against tumor cells was investigated. Tumor-bearing nude mice were intravenously injected with the mDC and pDC combined vaccine. Tumor tissues were collected for hematoxylin and eosin and TUNEL staining. Loading with tumor cell lysate significantly upregulated the surface expression of costimulatory molecules MHC-II on DCs and enhanced secretions of IL-6, IL-12 and TNF-α by DCs. In addition, the tumor cell lysate-loaded mDC and pDC combined vaccine significantly promoted lymphocyte proliferation and enhanced CTL-mediated cytotoxicity against Lewis lung cancer cells compared with mDC or pDC treatment alone. Furthermore, intravenous injection of the mDC and pDC combined vaccine into tumor-bearing nude mice significantly inhibited subcutaneous tumor growth and induced necrosis and apoptosis within the tumor tissue. Overall, the pDC and mDC combination vaccine loaded with heat-treated Lewis lung cancer cell lysate had a synergistic effect on the induction of T lymphocyte proliferation and antitumor efficacy, which may be associated with the upregulation of co-stimulatory molecules and cytokine secretions.

Immunomodulatory effect of Acanthopanax senticosus polysaccharide on immunosuppressed chickens

The immunomodulatory effect of Acanthopanax senticosus polysaccharide (ASPS) on immunosuppressed chickens induced by cyclophosphamide (Cy) was observed in this study. Four hundred 7-day-old chickens were randomly divided into 4 groups: vaccinated control group (VC group), Cy-challenged control group (Cy group), Cy-challenged + low-dose ASPS group (ASPSL + Cy group), and Cy-challenged + high-dose ASPS group (ASPSH + Cy group). All groups except the VC group were injected with Cy at a dose of 80 mg/kg/day of BW for 3 successive days to induce immunosuppression. At the age of 10 d, the ASPSL + Cy group and ASPSH + Cy group were intramuscularly injected with 0.2 mL of ASPS at the dose of 100 and 200 mg/mL/day, respectively, once a day for 3 successive days. The Cy group was injected with saline solution in the same way as the 2 ASPS groups. At the age of 14 d, the chickens were vaccinated with Newcastle disease (ND) vaccine in all groups. On day 7, 14, 21, and 28 after the vaccination, BW, lymphocyte proliferation, the serum antibody titers of the ND vaccine, the proportion of CD4+ and CD8+ T lymphocytes, and the concentrations of interferon gamma and IL-2 were determined. The results showed that chickens were injected with Cy at a dose of 80 mg/kg of BW for 3 d displayed lower immune responses than the control group, indicating that the immunosuppressive model was successfully established. At most time points, both high and low doses of ASPS could significantly promote lymphocyte proliferation; enhance BW, antibody titers, and the proportion of CD4+ and CD8+ T lymphocytes; and raised the concentrations of interferon gamma and IL-2 in Cy-treated chickens compared with those in the Cy control group (P < 0.05). These results indicated that ASPS could resist immunosuppression induced by Cy and may be a new-type immune adjuvant to improve vaccination in normal and immunosuppressed chickens.

The structural characterization and immune modulation activitives comparison of Codonopsis pilosula polysaccharide (CPPS) and selenizing CPPS (sCPPS) on mouse in vitro and vivo

Codonopsis pilosula polysaccharide (CPPS) and selenizing CPPS (sCPPS) were prepared and identified by a combination of chemical and instrumental analysis. Their immune modulation activities were compared by lymphocyte proliferation and flowcytometry tests in vitro or serum antibody responses and cytokines with immunization against OVA mice in vivo. The results showed that the sCPPS was successfully modified in selenylation. In vitro, the sCPPS were more effective compared with CPPS in promoting lymphocyte proliferation synergistically with PHA or LPS and increasing the ratio of CD4+ to CD8 + T cells. In vivo, sCPPS could significantly raised IgG, IgM, IFN-γ, IL-2 and IL-4 contents in the serum of mouse against OVA in comparison with CPPS. These results indicate that selenylation modification can enhance the immune modulation activitives of CPPS. sCPPS would be as a component drug of new-type immunoenhancer.

Anticancer Melatplatin Prodrugs: High Effect and Low Toxicity, MT1-ER-Target and Immune Response In Vivo.

Multitargeted therapy could rectify various oncogenic pathways to block tumorigenesis and progression. The combination of endocrine-, immune-, and chemotherapy might exert a highly synergistic effect against certain tumors. Herein, a series of smart Pt(IV) prodrugs 3-6, named Melatplatin, were rationally designed not only to multitarget DNA, MT1, and estrogen receptor (ER) but also to activate immune response. Melatplatin, conjugating first-line chemotherapeutic Pt drugs with human endogenous melatonin (MT), significantly enhanced drug efficacy especially in ER high-expression (ER+) cells, among which 3 presented the most potent cytotoxicity toward ER+ MCF-7 with nanomolar IC50 values 100-fold lower than cisplatin. Melatplatin could bind well to melatonin receptor (MT1) according to molecular docking. Besides, 3 evidently increased intracellular accumulation and DNA damage, upregulated γH2AX and P53, and silenced NF-κB to induce massive apoptosis. Most strikingly, 3 effectively inhibited tumor growth and attenuated systemic toxicity compared to cisplatin in vivo, promoting lymphocyte proliferation in spleen to achieve immune modulation.

Adjuvant activities of CTAB-modified Polygonatum sibiricum polysaccharide cubosomes on immune responses to ovalbumin in mice

Recently, the cubosomes have been widely studied as drug carriers. It has been described that cubosomes could further stimulate the immune response after carrying the immune enhancer. Polygonatum sibiricum polysaccharide (PSP), one of the most important biologically active ingredients of Polygonatum sibiricum, has been reported as an immunostimulant to improve immune responses. This study was aimed to observe the immunomodulation effects of ovalbumin (OVA) absorbed cetyltrimethylammonium bromide-modified Polygonatum sibiricum polysaccharide cubosomes (CTAB-modified PSP-Cubs/OVA). Firstly, the antigen uptake of CTAB-modified PSP-Cubs/OVA by macrophages was determined in vitro. After that, mice were immunized with CTAB-modified PSP-Cubs/OVA. The activation of dendritic cells in lymph nodes, activation of lymphocyte, ratios of CD4+ to CD8+, the concentrations of OVA-specific IgG in serum and the cytokines concentrations were analyzed. As the results showed, CTAB-modified PSP-Cubs/OVA could promote the production of OVA-specific IgG in serum. The ratio of CD4+ to CD8+ in CTAB-modified PSP-Cubs/OVA group was significantly increased compared with other groups. CTAB-modified PSP-Cubs/OVA could significantly activate dendritic cells and promote lymphocyte proliferation. The results indicated that CTAB-modified PSP-Cubs/OVA could promote the secretion of related cytokines and the proliferation of lymphocytes, stimulate the cellular immune response and increase the level of humoral immunity. Above all, CTAB-modified PSP-Cubs had good adjuvant activity.

Immunomodulatory effect of thymopentin on lymphocytes from supramammary lymph nodes of dairy cows

Previous study showed that injection of thymopentin (TP 5) in the area of supramammary lymph nodes (SMLN) had therapeutic effect on the intramammary infection (IMI) in cows. This study was to explore the underlying mechanisms by investigating the immunomodulatory effect of TP 5 on SMLN lymphocytes. Lymphocyte proliferation, cell cycle distribution and cytokine mRNA expression were determined by MTT, FCM and RT-qPCR, respectively. Laser scanning confocal microscope (LSCM) was used to observe the binding between TP 5 and SMLN lymphocytes. Moreover, RNA-sequencing (RNA-seq) was performed to observe the difference between the lymphocytes with and without TP 5 treatment. The results showed that TP 5 significantly promoted lymphocyte proliferation, accelerated cell cycle progression, and enhanced mRNA expression of IL-17A and IL-17F. Laser scanning confocal microscopic analysis revealed the binding of TP 5 to the surface of SMLN lymphocytes. A total of 1094 genes were identified as differentially expressed genes (DEGs) using RNA-seq with 692 up- and 402 down-regulated genes. 48 significantly enriched GO terms were identified by RNA-seq. In KEGG analysis, 1/3 of DEGs were enriched in the immune system pathway, including IL-17 signaling pathway, cytokine-cytokine receptor interaction, Th1 and Th2 cell differentiation, T cell receptor signaling pathway, Th17 cell differentiation. Among them, IL-17 signaling pathway was the most prominent. This study suggested that the therapeutic benefit of TP 5 in the treatment of bovine mastitis might be attributed to its immunomodulatory activity in SMLN lymphocytes.

Effect of sulfated yeast beta-glucan on cyclophosphamide-induced immunosuppression in chickens

Immunosuppression is a condition that causes large economic losses in the poultry industry. To investigate the effect of sulfated yeast beta-glucan on immunosuppression, two hundred and fifty 11-day-old chickens were randomly assigned to five groups, and except for the normal control group, injected with cyclophosphamide once a day for 3 successive days. At 14 days of age, sulfated yeast beta-glucan from Saccharomyces cerevisiae(sGSC) was orally administered at three doses to the chickens in three experimental groups for 14 days. On days 7 and 14 after the first sGSC dose, serum cytokine concentrations and peripheral lymphocyte proliferation were measured. Gut microbiota, organ index, and histopathological changes in the bursa were investigated on day 14. The results demonstrated that at 4 mg/kg, sGSC could significantly enhance the bursa index and IFN-γ and IL-6 concentrations, decrease TGF-β1 concentration, and promote lymphocyte proliferation; it could effectively decrease histopathological changes in the bursa and improve gut Bifidobacterium and Lactobacillus populations in cecal digesta of chickens compared with the model control group. This indicated that sGSC could effectively alleviate immunosuppression and regulate the beneficial microbiota in the gut.

The enhanced immunological activity of Paulownia tomentosa flower polysaccharide on Newcastle disease vaccine in chicken.

The extracts of Paulownia tomentosa (P. tomentosa) exhibit multiple pharmacological activities. In the present study, P. tomentosa flower polysaccharides (PTFP) were extracted by water decoction and ethanol precipitation, and the immunologic modulations of PTFP against Newcastle disease (ND) vaccine was investigated in chickens. The results showed that in a certain range of concentrations, PTFP treatment can dose-dependently enhance lymphocyte proliferation. Then, 280 14-days-old chickens were randomly divided into seven groups, and vaccinated with ND vaccine except blank control (BC) group. At the first vaccination, chickens were orally administrated with PTFP at concentration ranging from 0 to 50 mg/kg once a day for 3 successive days, and the BC group was treated with physiological saline. The lymphocyte proliferation rate, serum antibody titer, and levels of interferon-γ (IFN-γ) were respectively measured on 7, 14, 21, and 28 days after the first vaccination. The results showed that PTFP at the suitable doses could significantly promote lymphocyte proliferation, enhance serum antibody titer, and improve serum IFN-γ concentrations. Taken together, these data indicated that PTFP could improve the immune efficacy against ND vaccine in chickens, and could be as the candidate of a new-type immune adjuvant.

The core structure characterization and of ginseng neutral polysaccharide with the immune-enhancing activity

The study aims to clarify the structural domain required for the immune enhancement of ginseng neutral polysaccharide (GPN). GPN was first obtained through water extraction and ion-exchange chromatography from Panax ginseng. GPN was hydrolyzed by α-amylase for 24 h and fractionated through gel permeation chromatography to give two final fragments GPNE-I and GPNE-II, with molecular weight of 8.03 × 104 Da for GPNE-I and 3.15 × 104 Da for respectively. FT-IR, methylation and 1D/2D NMR analysis demonstrated that GPNE-I was a heteropolysaccharide consisting mainly of a glucan domain and type I and II arabinogalactans (AG-I and AG-II). GPNE II was a glucan consisting of (1 → 4)-α-d-Glcp backbone with a substitution at O-6 on every two residues. (1 → 3)-α-d-Glcp and (1 → 6)-α-d-Glcp were located at the branches. In the two fractions, both α- and β-t-Glcp as reductive terminals and →4)-α-Glcp as a non-reducing end were detected. The branching degrees of GPNE-I and GPNE-II were 38.17% and 50.78%, respectively. Immunological experiments revealed that GPNE-I exhibited more effectively stimulated lymphocyte proliferation than GPN and GPNE-II, indicating the former showed potential for immunomodulators applications, indicating that GPNE-I might be the core active domain and necessary for GPN to promote lymphocyte proliferation.