Immunological Enhancement Research Articles

A Review On The Potential Of Spirulina And Its Application In Nutraceuticals And Pharmaceuticals

Microalgae and lactic acid bacteria have become an innovative and promising resource of nutritional supplements as they are commercially cultivated to produce valuable compounds, including protein, pigments, lipids, essential amino acids, monounsaturated and polyunsaturated fatty acids, carotenoids, steroids and vitamins. The pharmacological actions, such as nutraceutical improvements, lowering LDL cholesterol levels, anti-inflammation, antioxidation, antitumor, immunological enhancement, and hepatorenal protection from Spirulina spp and Lactic acid Bacillus have been reported recently. Based on the therapeutic potential of spriulina fermentation based lactic acid bacteria, different application studies such as, determining the effect of Spirulina fermentation with Lactic acid bacteria (FSL) on enhancing the Nutraceutical properties of Spirulina species, investigating the effect of Spirulina fermentation with Lactic acid bacteria (FSL) on lowering the LDL cholesterol and increasing HDL cholesterol, and evaluating the cytotoxic effect and influence of FSL on human cancer cell line was reviewed in the current article.

Macrophage immunomodulatory activity of Acanthopanax senticousus polysaccharide nanoemulsion via activation of P65/JNK/ikkαsignaling pathway and regulation of Th1/Th2 Cytokines.

Nanoemulsions (NE) are used widely in pharmaceutical drug formulations and vaccine preparation, and Acanthopanax senticousus polysaccharide (ASPS) is a natural bioactive compound with immunostimulatory activity. Therefore, NE-loaded ASPS is expected to provide immunological enhancement for effective treatment. In the present study, Acanthopanax senticousus polysaccharide (ASPS was encapsulated into nanoemulsions, the resultant ASPS–NE were coated with a negative charge, and the immune enhancement mechanism of these ASPS-NE formulations was analyzed. The immunosuppressive animal models (70 ICR mice, male) for the study were established using cyclophosphamide. In addition, the activation of splenocyte proliferation, phagocytosis of the macrophages, the ratio of CD4+ to CD8+, the concentrations of the cytokines in serum, Western blot analysis was used for the analysis of the P65/JNK/ikk α signaling pathway in the peritoneal macrophage s. The results revealed that the ASPS-NE could stimulated the proliferation of splenocytes and enhance immunity. The ASPS-NE induced the expression of different cytokines (TNF-α, IFN-γ, IL-2, and IL-6), could activate the expressions of P65, JNK, and ikkα, and regulated the Th1/Th2 cytokines. These findings demonstrated the potential of ASPS-NE formulations for drug delivery and to induce potent and sustained immune responses.

Creation of a Single Cell RNASeq Meta-Atlas to Define Human Liver Immune Homeostasis.

The liver is unique in both its ability to maintain immune homeostasis and in its potential for immune tolerance following solid organ transplantation. Single-cell RNA sequencing (scRNA seq) is a powerful approach to generate highly dimensional transcriptome data to understand cellular phenotypes. However, when scRNA data is produced by different groups, with different data models, different standards, and samples processed in different ways, it can be challenging to draw meaningful conclusions from the aggregated data. The goal of this study was to establish a method to combine ‘human liver’ scRNA seq datasets by 1) characterizing the heterogeneity between studies and 2) using the meta-atlas to define the dominant phenotypes across immune cell subpopulations in healthy human liver. Publicly available scRNA seq data generated from liver samples obtained from a combined total of 17 patients and ~32,000 cells were analyzed. Liver-specific immune cells (CD45+) were extracted from each dataset, and immune cell subpopulations (myeloid cells, NK and T cells, plasma cells, and B cells) were examined using dimensionality reduction (UMAP), differential gene expression, and ingenuity pathway analysis. All datasets co-clustered, but cell proportions differed between studies. Gene expression correlation demonstrated similarity across all studies, and canonical pathways that differed between datasets were related to cell stress and oxidative phosphorylation rather than immune-related function. Next, a meta-atlas was generated via data integration and compared against PBMC data to define gene signatures for each hepatic immune subpopulation. This analysis defined key features of hepatic immune homeostasis, with decreased expression across immunologic pathways and enhancement of pathways involved with cell death. This method for meta-analysis of scRNA seq data provides a novel approach to broadly define the features of human liver immune homeostasis. Specific pathways and cellular phenotypes described in this human liver immune meta-atlas provide a critical reference point for further study of immune mediated disease processes within the liver.

Structural elucidation and immunomodulatory evaluation of a polysaccharide from Stevia rebaudiana leaves

Stevia rebaudiana, a sweetener with medicinal functions, has attracted extensive attention due to its application in food and pharmaceutical fields. However, a few studies were performed to explore polysaccharides in this plant. Herein, SRP70-1 was derived from S. rebaudiana. Structural analysis (monosaccharide composition analysis, high-performance liquid chromatography-multi-angle light scattering detection, gas chromatography-mass spectrometry, and nuclear magnetic resonance spectroscopy) revealed that SRP70-1 was composed of mannose, glucose, galactose, and arabinose at the molar ratio of 1.35:1.00:3.23:3.47, with an absolute molecular weight of 7698 Da. SRP70-1 was found to contain → 5)-α-l-Araf-(1→, →2,3,5)-α-l-Araf-(1→, →4)-β-l-Arap-(1→, →4)-β-d-Galp-(1→, →6)-β-d-Galp-(1→, →4)-β-d-Manp-(1→, →6)-β-d-Manp-(1→, and terminal α-l-Araf, β-d-Galp, and β-d-Glcp residues. Cell experiments showed that SRP70-1 could significantly promote phagocytosis and increase the release of nitric oxide and cytokines including IL-1β, IL-6, and TNF-α. Further zebrafish experiments confirmed the immunological enhancement effects of SRP70-1. This study revealed that SRP70-1 may be useful for the development of functional foods.

Camrelizumab plus apatinib combined with TACE and cryoablation in the first-line treatment of advanced hepatocellular carcinoma.

TPS4160 Background: Hepatocellular carcinoma (HCC) is a common cancer in the world, a leading cause of cancer-related death, and especially in China. Most of the HCC patients are diagnosed at an advanced stage and require a multidisciplinary approach. The IMbrave 50 trial has reported the successful efficacy of atezolizumab and bevacizumab combination therapy in advanced hepatocellular carcinoma, which indicate the potential efficacy of combination of immunotherapy and antiangiogenesis therapy in HCC patients. In some studies, the combinatorial approaches with immunotherapy and liver directed therapies such as transarterial chemoembolization (TACE), radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation are explored. Most combined interventional therapies reveal their enormous advantages as compared with any single therapeutic regimen alone, which may result from the immunologic enhancement effect of the multimodel therapy. In this study, we evaluated the efficacy and safety of combined therapy with camrelizumab plus apatinib mesylate and TACE plus cryoablation in patients with advanced HCC. Methods: This study was an open-label, single-arm, single centre, phase 2 trial in patients who were diagnosed with advanced HCC. Patients who meet the following criterias will be enrolled: (1) 18 - 75 years old; (2) Child-Pugh classification A or B(≤7);(3) Barcelona Clinic Liver Cancer stage B or C, or China liver cancer staging (CNLC) stage IIb̃IIIa; (4) Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0–1; (5) no history of previous systematic treatment; (6) expected life expectancy of more than 12 weeks; (7) adequate organs function. The key exclusion criteria were history of active autoimmune disease, or concurrent medical use of immunosuppressive medications or immunosuppressive doses of systemic corticosteroids. Eligible patients received camrelizumab 200 mg intravenously every 2 weeks and apatinib 250 mg orally once per day continuously in a treatment cycle of 4 weeks, treatment continued until 1 year or development of unacceptable toxicity or progression of disease. TACE was administrated at the first treatment cycles on day 1or 2, the chemotherapy regimens included 100-150mg oxaliplatin, 750-1000mg fluorouracil, or 30-50 mg lobaplatin, raltitrexed 2-4mg, and epirubicin 40-80 mg. Two or three weeks after the TACE, percutaneous cryoablation was performed under CT guidance. TACE and cryoablation was given as combination therapy and the periods were assessed by the investigator. The primary endpoint is objective response rate (complete or partial response according to mRECIST) and Progression-Free-Survival (Time ranges from random to the first occurrence of disease progression or death from any cause). This trial is registered with Chinese Clinical Trials Registry, ChiCTR2100043044, and is ongoing. Clinical trial information: ChiCTR2100043044.

Cedrol from Ginger Ameliorates Rheumatoid Arthritis via Reducing Inflammation and Selectively Inhibiting JAK3 Phosphorylation.

Ginger, as a food spice, is widely applied due to its extensive effects. Cedrol (CE) found in ginger is a sesquiterpene with anti-inflammatory activity. The objective of this research is to discuss the efficacy of CE on ameliorating rheumatoid arthritis (RA). CE inhibited chronic inflammation and pain in a dose-dependent manner accompanied by rapid onset and long duration. Besides, CE treatment effectively ameliorated the paw edema volume and arthritis score with no significant effect on body weight. Organ index, T-cell and B-cell proliferation, histopathology, and immunohistochemistry demonstrated that CE had immunological enhancement and attenuated RA effects. Remarkably, inhibition of phosphorylated-JAK3 protein, thereby abating the secretion of pro-inflammatory cytokines and inflammation-related mediators, was involved in the potential mechanism of CE efficiency through forming a hydrogen bond with ARG953 and ILE955 in the JAK3 active pocket. At the same time, the pharmacokinetic results showed that the absolute bioavailability of CE at 20, 40, and 80 mg/kg was 30.30, 23.68, and 16.11%, respectively. The current results offered clues for mastering the ameliorated RA of CE and further perfected the effective substance basis on the anti-inflammatory effect of ginger, which was beneficial for further applications.

Recent Progress on Biomaterials Fighting against Viruses.

Viruses not only pose severe threats to public health, but also influence the development of society. Over the past decade, rapid advances have been seen in the application of nanomaterials to virus research. As an interdisciplinary field, nanotechnology offers powerful functions because the structures of nanomaterials are unique, with remarkable physicochemical properties and excellent biocompatibility. Nanomaterials have been developed for virus detection and tracking and for antiviral strategies, to better understand viruses and reduce viral infections, implying a bright future for this field. Herein, the recent advances are systematically summarized regarding the nanomaterials used in viral studies. Representative applications of nanomaterials to viral detection and tracking are described. The antiviral effects achieved with nanomaterials based on different mechanisms are also described, including entry inhibition, inhibition of viral replication, and immunological enhancement. The current challenges and future opportunities in this promising field are also discussed.

The Role of Interaction between Mitochondria and the Extracellular Matrix in the Development of Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a condition which affects mainly older adults, that suggests mitochondrial dysfunction and oxidative stress, which follow cells senescence, and might contribute to the disease onset. We have assumed pathogenesis associated with crosstalk between the extracellular matrix (ECM) and mitochondria, mainly based on mitochondrial equilibrium impairment consisting of (1) tyrosine kinases and serine-threonine kinase (TKs and ST-Ks) activation via cytokines, (2) mitochondrial electron transport chain dysfunction and in consequence electrons leak with lower ATP synthesis, (3) the activation of latent TGF-β via αVβ6 integrin, (4) tensions transduction via α2β1 integrin, (5) inefficient mitophagy, and (6) stress inhibited biogenesis. Mitochondria dysfunction influences ECM composition and vice versa. Damaged mitochondria release mitochondrial reactive oxygen species (mtROS) and the mitochondrial DNA (mtDNA) to the microenvironment. Therefore, airway epithelial cells (AECs) undergo transition and secrete cytokines. Described factors initiate an inflammatory process with immunological enhancement. In consequence, local fibroblasts exposed to harmful conditions transform into myofibroblasts, produce ECM, and induce progression of fibrosis. In our review, we summarize numerous aspects of mitochondrial pathobiology, which seem to be involved in the pathogenesis of lung fibrosis. In addition, an increasing body of evidence suggests considering crosstalk between the ECM and mitochondria in this context. Moreover, mitochondria and ECM seem to be important players in the antifibrotic treatment of IPF.

Structural elucidation of an immunological arabinan from the rhizomes of Ligusticum chuanxiong, a traditional Chinese medicine

In the present study, an immunological arabinan, LCP70-2A, was isolated from Ligusticum chuanxiong for the first time. The absolute molecular weight of LCP70-2A was determined to be 6.46 × 104 g/mol using the HPSEC-MALLS-RID method. The absolute configuration of arabinose in LCP70-2A was determined to be L-configuration. Physicochemical characterization revealed that LCP70-2A was a homogeneous polysaccharide and had a backbone of (1 → 5)-linked α-L-Araf with terminal α-L-arabinose residues at position O-2 and O-3. Molecular conformation analysis showed that LCP70-2A was a branching polysaccharide with a compact coil chain conformation in 0.1 M NaCl solution. In addition, in vitro cell assays showed that LCP70-2A can activate macrophages by enhancing the phagocytosis and potentiating the secretion of immunoregulatory factors including NO, TNF-α, IL-6, and IL-1β. Furthermore, LCP70-2A was proved to promote the production of ROS and NO using the zebrafish model, suggesting that LCP70-2A can be further developed as a candidate supplement for immunological enhancement.

The clinical efficacy and adverse effects of Entecavir plus Thymosin alpha-1 combination therapy versus Entecavir Monotherapy in HBV-related cirrhosis: a systematic review and meta-analysis

BackgroundPrevious studies have demonstrated the benefits of thymosin alpha-1 (Tα1) in anti-virus, immunological enhancement and anti-inflammation. However, it is controversial about the efficacy and safety of entecavir (ETV) plus Tα1 combination therapy versus ETV monotherapy in cirrhotic patients with hepatitis B virus (HBV) infection.MethodsThe systematic review and meta-analysis of randomized clinical trials (RCTs) were performed to evaluate the efficacy and safety of ETV plus Tα1 combination therapy versus ETV monotherapy in HBV-related patients with cirrhosis. We performed a systematic literature search via PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journals Database (VIP), and Chinese Biological Medicine database (CBM). Relative risk (RR) and standardized mean difference (SMD) with a fixed- or random- effect model were calculated. Heterogeneity was assessed through a Cochrane Q-test and I2 values.ResultsSeven RCTs involving 1144 subjects were included in the systematic review and meta-analysis. Compared with ETV monotherapy, ETV plus Tα1 combination therapy led to a higher complete response (RR = 1.18; 95% CI, 1.07–1.30). In post treatment for 24 weeks, the HBV DNA undetectable rate and HBeAg loss rate were higher in ETV plus Tα1 group than in ETV alone group (RR = 1.91; 95% CI, 1.56–2.35; RR = 2.05; 95% CI, 1.62–2.60). However, after 48 and 52 weeks of treatment, there was no significant difference between the combination therapy and ETV monotherapy (RR = 1.07; 95% CI, 0.96–1.18; RR = 1.17; 95% CI, 0.89–1.55). At week 52 of treatment, the HBsAg loss rate of ETV plus Tα1 group was no significance with that of ETV alone group (RR = 1.03; 95% CI, 0.15–7.26). In comparison with ETV alone, the some biochemical parameters and liver fibrosis were obviously improved by ETV plus Tα1, and there was significant heterogeneity. In addition, the number of adverse events was significantly reduced by ETV plus Tα1, compared to ETV alone (RR = 0.48; 95% CI, 0.24–0.95).ConclusionsETV plus Tα1 might lead to a higher clinical response and a lower comprehensive adverse reaction rate in HBV-related patients with cirrhosis, compared to ETV alone. However, the whole patients included in this meta-analysis were from Chinese mainland, so that more worldwide RCTs with a larger sample size are needed to verify the current findings.

Carboxylated nanodiamond-mediated NH2-PLGA nanoparticle-encapsulated fig polysaccharides for strongly enhanced immune responses in vitro and in vivo

Nanodiamonds (NDs), which are safe carbon nanomaterials, have been used for the transmission of DNA, proteins and drugs. The feasibility of utilizing NDs to deliver NH2-PLGA nanoparticle-encapsulated fig polysaccharides for strongly enhanced immune responses has not been clearly studied. In this study, we aimed to use NDs as carriers to deliver NH2-PLGA nanoparticle-encapsulated fig polysaccharides for strongly enhanced immune responses. ND particles with a diameter of 5 nm were functionalized by surface carboxylation and covalently conjugated with NH2-PLGA nanoparticle-encapsulated fig polysaccharides. NDs-PLGA-FP/OVA could promote antigen uptake and lymphocyte proliferation, increase the expression levels of MHC II, CD80 and CD86, and upregulate the ratio of Th1/Th2 cells in immunized mice. NDs-PLGA-FP/OVA could also upregulate the IL-17 signalling pathway for further immunological enhancement. NDs-PLGA-FP/OVA induced increased TNF-α, IFN-γ, IL-4, and IL-6 cytokine secretion and the levels of OVA-specific antibodies (IgG). These findings demonstrate that NDs-PLGA-FP/OVA have the potential to serve as an effective vaccine delivery and adjuvant system to induce vigorous and long-term immune responses.

Signaling pathways associated with macrophage-activating polysaccharide isolated from the fermentation liquor of Rhizopus nigricans

Our previous reports showed that the structural features and immunologic enhancement of polysaccharide (EPS1-1) from Rhizopus nigricans. However, the molecular mechanism in cellular immunomodulatory of EPS1-1 remains unclear. Here the experiments for the molecular mechanisms of EPS1-1 on the peritoneal macrophages were performed. The results demonstrated that the expression of TLR4 was significantly improved by EPS1-1. Subsequently, the phosphorylation of p38MAPK, ERK1/2, JNK and IKKα/β were promoted. Moreover, EPS1-1 enhanced the expressions of IL-2, TNF-α and iNOS in EPS1-1-induced macrophages which were pretreated with MAPK signaling pathway inhibitors, and reduced the blocking effects of the inhibitors to the expressions of p-p38MAPK, p-ERK1/2 and p-IKKα/β. Therefore, these results illustrated that EPS1-1 could improve the immune functions of peritoneal macrophages by promoting the gene expressions of IL-2, TNF-α and iNOS via the MAPK and NF-κB signaling pathways.

Itraconazole Promotes Macrophage M1 Polarization and Phagocytic Capacity of Macrophage to Candida Albicans

Abstract Objective: The present study was designed to evaluate whether and how itraconazole affects the macrophage polarization and its reactivity to Candida albicans. Methods: Cell toxicity of itraconazole was measured using cell counting kit-8 assay in RAW264.7 cells. The cell models were induced by lipopolysaccharide (LPS), interleukin (IL)-4, or Candida albicans. Levels of cytokines secreted by RAW246.7 treated with itraconazole were detected by Luminex or Cytometric Bead Array compared to the controls without itraconazole treatment, and the expressions of inducible nitric oxide synthase and arginase (Arg) were determined by Western blot. Phagocytosis ability was measured by both flow cytometry and fluorescence microscope. The Student's t test and one-way analysis of variance were used to calculate the differences between groups. Results: In comparison to the control, itraconazole inhibited the growth of the cells in both a time- and a dose-dependent manner. Increased secretion of IL-6 (0.25 μmol/L ITZ [538.03 ± 60.23 pg/mL, P < 0.05], 0.5 μmol/L [550.32 ± 47.87 pg/mL, P < 0.05] and 1 μmol/L [626.95 ± 75.24 pg/mL, P < 0.01] vs. control [370.43 ± 33.98 pg/mL]) and tumor necrosis factor-alpha (TNF-α) (1 μmol/L ITZ vs. control: 2521.51 ± 444.06 pg/mL vs. 1617.85 ± 94.57 pg/mL, P < 0.05) were detected in the LPS-induced cell model with itraconazole treatment. In the cells induced by IL-4, itraconazole increased the secretion of IL-6 (1 μmol/L ITZ vs. control: 528.33 ± 11.60 pg/mL vs. 466.99 ± 28.32 pg/mL, P < 0.05), TNF-α (1 μmol/L ITZ vs. control: 4.85 ± 0.32 pg/mL vs. 4.30 ± 0.19 pg/mL, P < 0.05), and IL-1β (0.25 μmol/L [325.95 ± 13.97 pg/mL, P < 0.05], 0.5 μmol/L [332.38 ± 11.97 pg/mL, P < 0.05] and 1 μmol/L [334.35 ± 16.23 pg/mL, P < 0.05] vs. control [291.62 ± 17.03 pg/mL]), and reduced the secretion of IL-10 (1 μmol/L ITZ vs. control: 7.21 ± 0.68 pg/mL vs. 9.11 ± 0.14 pg/mL, P < 0.05). The secretion of IL-6 (1 μmol/L ITZ vs. control: 38.34 ± 1.36 pg/mL vs. 32.32 ± 0.84 pg/mL, P < 0.05) and TNF-α (1 μmol/L ITZ vs. control: 1060.17 ± 80.16 pg/mL vs. 890.84 ± 52.82 pg/mL, P < 0.01) was improved in Candida albicans-stimulated RAW264.7 cells under the treatment of itraconazole, while the secretion of IL-4 (0.5 μmol/L [2.86 ± 0.20 pg/mL, P < 0.05] and 1 μmol/L [2.24 ± 0.33 pg/mL, P < 0.001] vs. control [3.91 ± 0.23 pg/mL]) and IL-10 (1 μmol/L ITZ vs. control: 19.46 ± 2.05 pg/mL vs. 25.67 ± 1.95pg/mL, P < 0.05) decreased. In all three activated patterns, itraconazole enhanced the expression of inducible nitric oxide synthase (P < 0.01) and slightly inhibited the Arg-1 expression (P < 0.05). Phagocytosis ability of RAW264.7 cells at 1 μmol/L ITZ treatment was increased by 7.53% ± 2.21% (P < 0.01) and 9.73% ± 2.03% (P < 0.01) at the ratio of cells: yeast of 1:4 and 1:8, respectively, in comparison to the control group. Conclusion: Itraconazole improved M1 polarization of RAW264.7 cells and enhanced the phagocytic capacity of RAW264.7 to Candida albicans, indicating a significant immunological enhancement. The study improves the understanding of undergoing mechanisms related to the anti-tumor and anti-infection effects of itraconazole.

Research progress on stability of polysaccharides in traditional Chinese medicine

Polysaccharides are natural polymer compounds composed of monosaccharides,which are widely found in traditional Chinese medicines( TCM) and work as one of the important active ingredients in TCM. Modern pharmacological studies reported that TCM polysaccharides had many functions such as anti-tumor,immunologic enhancement,intestinal microenvironment regulation and anti-oxidation. At present,TCM polysaccharide preparations such as Astragalus polysaccharide injection,Ginseng polysaccharide injection and Poria cocos polysaccharide oral liquid have been widely applied for clinical use. Besides,Glycyrrhiza polysaccharide,Achyranthes bidentata polysaccharide,Acanthopanax senticosus polysaccharide and some other TCM polysaccharides also have received widespread attention and research because of their good biological activities. Meanwhile,more and more attention has been paid to the TCM polysaccharides and their preparations,illumination of mechanisms,and development of corresponding preparations which meet clinical standards. However,due to the complex structure of TCM polysaccharides,their structure analysis is difficult,with only a few reports on the stability and quality control of polysaccharides and their preparations. As a result,it will impede the development of new polysaccharide drugs and reduce the application value of polysaccharides. In order to provide an effective basis for the formulation development and quality control of TCM polysaccharides,the research progress on the stability of TCM polysaccharides and their preparations were reviewed in this paper from the classification of TCM polysaccharides,the existing application and the analytical method of TCM polysaccharides.

A peptide-Fe(II) complex from Grifola frondosa protein hydrolysates and its immunomodulatory activity

Grifola frondosa protein was hydrolysed using Alcalase, and the resulting hydrolysates (CGFP) were filtered using 5 and 1 kDa nominal cut-off ultrafiltration membranes and separated using Sephadex gel chromatography. Two main fractions, named GFP-1 and GFP-2 were obtained. CGFP-Fe and GFP-Fe were synthesized using ferrous chelation. Results showed that the GFP-2 fraction with molecular weight of 963 Da had the highest Fe(II) chelating activity (2680 ± 40 μg/g). UV spectrum showed that the Fe(II) shifted the maximum absorption to shorter wavelengths. The peptides measured using FTIR showed that the GFP-Fe peptide and the un-chelated peptide had different C–O and C= O absorption peaks. The effects of CGFP, CGFP-Fe, GFP2-2 and GFP-Fe on splenocytes proliferation and cytokines secretion were studied in vitro . Both the GFP-2 and GFP-Fe had good immune-enhancing activity. Furthermore, GFP-Fe showed an ability to promote the proliferation of splenocytes and peritoneal macrophages. The iron-chelating peptide of Grifola frondosa still maintained its immune enhancing activity after in vitro gastrointestinal digestion. The results suggested that GFP-Fe might be beneficial as a new iron supplement and as an immunological enhancement.

Quorum quenching intervened in vivo attenuation and immunological clearance enhancement by Solanum torvum root extract against Pseudomonas aeruginosa instigated pneumonia in Sprague Dawley rats

BackgroundPseudomonas aeruginosa have been delineated for its disreputable charisma in nosocomial infections leading to pulmonary pneumonia. The recent developments in multi-drug resistance accelerate the need of alternative antibacterial strategies. In this study we analysed the efficacy of quorum quenching mediated bacterial silencing in effective immunological clearance upon pulmonary infected rat models.ResultsQuorum sensing inhibitor was extracted from Solanum torvum which is a native plant in Kerala, India. The in vitro pilot studies upon Pseudomonas aeruginosa strain jb07 revealed the ability of Solanum torvum root extract (STRE) to successfully inhibit quorum sensing controlled virulent factors such as chromogenesis and biofilm formation; though the bacterial growth was unaffected. In vivo analysis upon Sprague Dawley rats shown the potential of STRE in aiding successful bacterial clearance where in cent percentage of survival was evident that compared with untreated group. Subjects treated with STRE possessed natural immunological response with inflammation, MNC infiltration and BALT (bronchus associated lymphoid tissue) hyperplasia unlike the Ciprofloxacin treated comparative group.ConclusionsThe observations of this study suggests that STRE is not having any bactericidal activity rather its silencing the infectant in a system which in turn disables the virulence of bacteria and remain attenuated; therefore immune system get adequate time for successful countermeasures.

Evaluation of The Immunological and Growth Enhancing Effect of Probiotic Used in Poultry Ration

A total of 60 one day old broiler chicks (Cobb 500) were used, the chicks were first weighted and randomly assigned into three experimental groups (20 chicks per each), the first group (G1) was negative control and received basal diet, the second one (G2) was a positive control and received basal diet and challenged orally with mixed culture of Salmonella Pullorum and Salmonella Gallinarum (1x108/ml) at 25 days of age, the third one(G3) received the probiotic mix from 1 day of age this mix contained: Bacillus subtilis MORI 91 [2×108colony forming unit (cfu)/g], Clostridium butyricum M7 (2.06×108cfu/g), Lactobacillus plantarumK34 (2×108cfu/g),and challenged orally with mixed culture of S.Pullorum and S.Gallinarumat 25 days of age. The results of the cytokines and inflammatory markers were detected as follows: the first group gave (105, 89.5, and 68.1), the second group gave (160,135, and 115), and the third group gave (85, 65.3, and 56.3) for IFN- γ, IL12, and IL4 respectively. The results of body weights and feed conversion ratios were: the first group gave (1550 and1.91), the second group gave (1300 and 1.8), and the third group gave (1800 and 2.01) respectively. Furthermore, the results of mortalities, and PM lesions were: the first group showed 4/20 (20%) dead chicks with enteritis, while the second group showed7/20 (35%) dead chicks with enteritis and enlargement with necrosis of the liver, spleen and kidneys, and the third group showed 2/20 (10%) dead chicks with enlargement of the liver, spleen and kidney. For the hematological parameters the first group gave (30.65 ± 0.85, 2.82 ± 0.31, and 9.25 ± 0.16), the second group gave (28.26± 0.76, 2.62 ± 0.23, and 8.75± 0.26), and the third group expressed (34.85± 1, 3.66 ± 0.25, and 10.5.13 ± 0.37) for PCV, mean RBCs (106 µl-1), and hemoglobin, respectively. There was a significant difference in the results of cytokines, body weight, feed conversion ratios, mortality rate, PM lesions, and hematological parameters between the probiotic treated and the control groups with P < 0.05. It was concluded that the probiotic mix enhanced the growth and hematological parameters, also it lowered the inflammatory markers and the mortalities.

Research progress on Chinese herbal medicine fermentation and profile of active substances derived

Chinese herbal medicines( CHMs) are a class of preparations made from natural plants that pose health beneficial properties as well as illness prevention functions. Thanks to a panel of salutary features,such as comprehensive immunological enhancement and inhibition of pathogenic bacteria,negligible side-effects,inappreciable drug-resistance,CHMs have been taken as one of the costeffective candidates for antibiotics substitutions. Through probiotics fermentation,the enzymatic hydrolysis of matrixes of CHMs enables easier release of the active ingredient as well as endows less toxicity of the preparations derived. During fermentation,the macromolecule or polymers forms of the active ingredient can be cut down to smaller molecule,which favors the transmembrane transport and improve adsorption of the active ingredients by the tissues. Other than the enzymatic benefits,probiotics can produce metabolites that inhibit pathogenic bacteria propagation,which may function synergically with the inhibitory effects of the CHMs preparations to fight the target pathogens. In addition,the oligosaccharide like components of CHMs can promote the growth of probiotics in intestinal environment which may largely facilitate the gut health. To summarize,the fermentation of CHMs using probiotics brings about the biochemical reactions and elevates the health beneficial effects by synergy of the microbial and herbal activities. It has been proved to be one of promising approaches as to antibiotic substitutions,particularly in livestock and poultry breeding industries. This review covered the recent progress of CHMs fermentation on the aspects of microbial strains,patterns of fermentation and active substances from fermentation of CHMs and their potency,respectively.

Tumor Microenvironment-Triggered Aggregated Magnetic Nanoparticles for Reinforced Image-Guided Immunogenic Chemotherapy.

Anticancer therapies, which can induce cell death and elevate antitumor immune response in the meantime, are considered as effective treatments for many types of cancers. Immunogenic cell death (ICD) induced by chemodrugs is a promising and typical strategy to achieve cell cytotoxicity and immunological enhancement together. However, due to the low level of ICD induction and less tumor‐targeting accumulation, application of traditional ICD inducers is limited. Here, tumor‐targeting core–shell magnetic nanoparticles (ETP‐PtFeNP:α‐enolase targeting peptide modified Pt‐prodrug loaded Fe3O4 nanoparticles) are developed to reinforce ICD induction of loaded‐oxaliplatin (IV) prodrug. After tumor‐targeting accumulation and endocytosis, platinum (IV) complexes are activated by intracellular reductive elimination to yield and release the Pt (II) congener, oxaliplatin, leading to DNA lesions and reactive oxygen species (ROS) generation. Simultaneously, in‐progress‐released ferric ions elicit highly toxic ROS (·OH or ·OOH) burst and interfere with the intracytoplasmic redox balance (like endoplasmic reticulum stress), leading to ICD‐associated immunogenicity enhancement and specific antitumor immune responses to kill the tumor cells synergistically. Meanwhile, the transverse relaxation rate R 2 of ETP‐PtFeNP is remarkably increased by more than three times while triggered by reductant, suggesting ETP‐PtFeNP a high‐sensitivity T 2 contrast agent for magnetic resonance imaging.

The immunopotentiator CVC1302 enhances immune efficacy and protective ability of foot-and-mouth disease virus vaccine in pigs

The immunological enhancement characteristics of the immunopotentiator CVC1302 were evaluated for foot-and-mouth disease virus (FMDV) inactivated vaccine in pigs. Eight-week-old piglets were vaccinated with the foot-and-mouth disease (FMD) vaccine alone (FMD-vaccine group) or with the addition of CVC1302 (FMD-CVC1302 group), and the serum liquid phase blocking ELISA (LPB-ELISA) antibody titers, IgG1 and IgG2 levels, and the levels of four cytokines secreted by peripheral blood lymphocytes were measured at 28 days post vaccination (dpv). In the FMD-CVC1302 group, the LPB-ELISA antibody titers, IgG1, and IgG2 titers, and IL-2, IL-4, IL-6, and IFN-γ levels at 28 dpv were significantly higher than those in the FMD-vaccine group. The FMD-CVC1302 group had long-lasting antibody titers (>7.8 log2), lasting for at least 6 months. In addition, piglets were vaccinated with or without addition of CVC1302 to the FMD vaccine at three different doses (1, 1/3, and 1/9 of the standard vaccine dose) and the serum LPB-ELISA antibody and serum neutralizing (SN) antibody titers were detected at 28 dpv. Then all pigs were challenged with virulent FMDV for PD50 value, and the levels of FMDV-specific RNA copies for the two full-dose groups at 3 and 10 days post challenge (dpc) were measured. The LPB-ELISA and SN antibody titers for the three doses in the FMD-CVC1302 groups were significantly higher than those in the FMD-vaccine groups at the same doses (p < 0.05). Post-virus challenge, the FMDV-specific RNA copy number in the FMD-CVC1302 group was lower than that in the FMD-vaccine group at 3 and 10 dpc. The PD50 value was 15.85 for the FMD-CVC1302 group, which was obviously higher than that for the FMD-vaccine group (10.96), and in the 1/9-dose of FMD-vaccine group only 3/5 pigs were protected. These results indicate that CVC1302 can enhance the immune efficacy and protective ability of the FMD vaccine in pigs.