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Cyclophosphamide (CTX), used in cancer chemotherapy, a high dose of which would cause immunosuppressive effect and intestinal mucosa damage. American ginseng ( Panax quinquefolius L.) has a long history of functional food use for immunological disorder, colitis, cancer, and so on. This study aimed to illustrate the underlying mechanism of American ginseng’s immunomodulatory effect in CTX-induced mice. In this study, all groups of American ginseng (American ginseng polysaccharide [AGP], American ginseng ginsenoside [AGG], co-treated with American ginseng polysaccharide and ginsenoside [AGP_AGG]) have relieve the immune disorder by reversing the lymphocyte subsets ratio in spleen and peripheral blood, as well as stimulating CD4 + T cells and IgA-secreting cells in small intestine. These three treatment groups, especially AGP_AGG co-treated group recovered the intestine morphology that up-regulated villus height (VH)/crypt depth (CD) ratio, areas of mucins expression, quantity of goblet cells, and expression of tight junction proteins (ZO-1, occludin). Importantly, the microbiome-metabolomics analysis was applied in this study to illustrate the possible immuno-modulating mechanism. The synergistic effect of polysaccharides and ginsenosides (AGP_AGG group) restored the gut microbiota composition and increased various beneficial mucosa-associated bacterial taxa Clostridiales, Bifidobacterium, and Lachnospiraceae, while decreased harmful bacteria Escherichia-Shigella and Peptococcaceae. Also, AGP_AGG group altered various fecal metabolites such as uric acid, xanthurenic acid, acylcarnitine, 9,10-DHOME, 13-HDoHE, LysoPE15:0, LysoPC 16:0, LysoPI 18:0, and so on, that associated with immunometabolism or protective effect of gut barrier. These results suggest AG, particularly co-treated of polysaccharide and ginsenoside may be used as immunostimulants targeting microbiome-metabolomics axis to prevent CTX-induced side effects in cancer patients.

Purpose Lentinan is a polysaccharide extracted from Shiitake mushrooms that have been used to improve general health for thousands of years in Asia. Lentinan injection is a clinically approved drug in several countries in Asia. The purpose of this study is to review the structure, preclinical and clinical studies, and molecular mechanisms of lentinan. Most importantly, the clinical effectiveness of lentinan as an adjuvant therapeutic drug in treating patients with lung cancer in China during the past 12 years is analyzed statistically. Methods We carried out literature search of randomized controlled trials (RCTs) published from 2004 to 2016 based on CNKI (China National Knowledge Infrastructure), VIP (Chongqing VIP Chinese Scientific Journals Database) and Wanfang database, and 38 eligible RCTs of lentinan-associated lung cancer treatment were identified, containing 3,117 patients. Results The structure and function relationship and underlying molecular mechanism of lentinan as an immunostimulant has been summarized. The mean value of overall response rate in treating lung cancer was increased from 43.3% of chemotherapy alone to 56.9% of lentinan plus chemotherapy [ p  < 0.001, 95% confidence interval (CI) 0.102–0.170]. Compared with chemotherapy alone, lentinan plus chemotherapy showed more efficacy in treating lung cancer (pooled RR 0.79, 95% CI 0.74–0.85) and no statistical heterogeneity was found among studies ( I 2  = 11%). Conclusion Clinical data presented in the past 12 years shows that lentinan is effective not only in improving quality of life, but also in promoting the efficacy of chemotherapy during lung cancer treatment.

Aquaculture-based foods have enriched nutritional and medicinal value to meet the needs of the global population. Recently, improper maintenance of aquatic organisms in aquaculture sector led to the outbreak of infectious diseases by pathogens. Treatment of disease by conventional methods (chemical) causes adverse effects to culturing organisms, the environment, and even to consumers. As an alternative to conventional methods, a variety of medicinal plant compounds like curcumin, quercetin, silymarin, Ajoene, and caffeic acid were used for disease control since they enhance the non-specific immunity. Phytotherapy-based techniques/compounds were preferred by aqua industry to develop resistance against a variety of aquatic pathogens in culture organisms since they are inexpensive and eco-friendly. Recent advances in nanotechnology pave the way to incorporate various medicinal plant-based nanoformulations to control aquatic microbial pathogens. Therefore, this review expresses in detail the versatile uses of phytotherapies and their based nanoformulation as a promising tool for disease management in aquaculture.Highlights• Aquaculture and their food was highly nutritive, market value. During culture practices easily affected by pathogens leads to loss of social—economic value.• Using of chemicals causes adverse effects in culturing organisms, consumer producer and environment.• In this review explains about using of herbs and their consequences in aquaculture industry and their beneficial effects such as increase production rate, stress relief agent, Aphrodisiac activity, Anti- pathogenic activity and also act as immunostimulants.• Using of herbal based medicine in aquaculture industry safe to environment, farmer, consumer level. Hence to farming “ORGANIC AQUACULTURE”

Litopenaeus vannamei, a highly adaptable shrimp species known for its growth, thrives in environmental conditions with proper water quality. However, salinity stress poses a significant challenge, compromising shrimp survival and growth. To optimize shrimp feed, the inclusion of alginate and Spirulina sp. offers benefits such as enhanced growth and resistance to environmental stress. This research aims to assess the impact of adding Spirulina sp., alginate, and their combination on the survival rate, resistance to the salinity shock test, and growth of L. vannamei. In this study, a completely randomized design (CRD) method with nine different feed doses was used. The treatments included control, supplementation of Alg 1 (alginate 1 g/kg feed), Alg 3 (alginate 3 g/kg feed), Alg 5 (alginate 5 g/kg feed), Sp 3 (spirulina 3 mg/kg feed), Sp 6 (spirulina 6 mg/kg feed), Sp 9 (spirulina 9 mg/kg feed), AS 1+1 (alginate 1 g/kg feed + spirulina 1 mg/kg feed), AS 2+3 (alginate 2 g/kg feed + spirulina 3 mg/kg feed), and AS 3+5 (alginate 3 g/kg feed + spirulina 5 mg/kg feed). The supplementation of feed was given during the fourteen-day rearing period. The results of the study show that the supplementation of Sp 9 (spirulina 9 mg/kg feed) led to a significant growth (α = 0.05). All treatments supplemented with alginate and/or Spirulina sp. water extract had a significant effect (α = 0.05) on the resistance to the salinity shock test. The different treatments in L. vannamei feed supplementation significantly influenced (α = 0.05) shrimp survival. Polysaccharides and antioxidant properties in alginate and Spirulina sp. have an important role in increasing the growth and resistance to salinity shock of L. vannamei.

Immunostimulants and vaccines are important for controlling infectious diseases in fish aquaculture. In this study we assess the potential of flagellin to be used for such purposes in rainbow trout ( ). A recombinant flagellin from the salmonid pathogen (YRF) has been produced previously by us and shown to be a potent activator of inflammatory cytokines, acute phase proteins and antimicrobial peptides . Here we show that YRF is the most potent inflammatory activator of three bacterial PAMPs (LPS, peptidoglycan and flagellin) tested. The host response to flagellin was next studied . The YRF modulated gene expression was examined in two systemic (spleen and liver) and two mucosa-associated (gills and skin) tissues. YRF injection initiated a transient systemic inflammatory response with key pro-inflammatory cytokines (IL-1β, TNFα, IL-6, and IL-11 etc.) and chemokines (CXCL_F4 and CXCL-8) induced rapidly (by 6 h) but subsiding quickly (by 24 h) in multiple tissues. Consequently, a variety of anti-microbial pathways were activated systemically with heightened expression of acute phase proteins, antimicrobial peptides and complement genes in multiple tissues, which was sustained to 24 h in the liver and mucosal tissues. The Th17 cytokine IL-17A/F1 was also induced in the spleen and liver, and Th2 cytokine IL-4/13 was induced in the liver. However, the anti-inflammatory IL-10 and the Th1 cytokine IFNγ were refractory. A secreted form of TLR5 (TLR5s) was induced by flagellin in all tissues examined whilst the membrane form was refractory, suggesting that TLR5s may function as a negative feedback regulator. Trout liver appeared to be an important organ responding to flagellin stimulation, with marked induction of IL-11, IL-23P19, IL-17C1, SAA, and cathelicidin-2. YRF induced a strong antibody response. These antibodies reacted against the middle domain of YRF and were able to decrease YRF bioactivity. Intact YRF was necessary for its bioactivity, as deletion of the N-terminal, C terminal or middle domain of YRF led to functional loss. This study suggests that flagellin could be a potent immunostimulant and vaccine adjuvant for fish aquaculture.

The major hindrance in the development and sustainability of aquaculture industry is the occurrence of various diseases in the farming systems. Today, preventive and management measures are central concern to overcome such outbreak of diseases. Immunostimulants are considered as an effective tool for enhancing immune status of cultured organisms. Among different immunostimulants used in aquaculture practices, β-glucan is one of the promising immunostimulant, which is a homopolysaccharide of glucose molecule linked by the glycoside bond. It forms the major constituents of cell wall of some plants, fungi, bacteria, mushroom, yeast, and seaweeds. Major attention on β-glucan was captivated with the gain in knowledge on its receptors and the mechanism of action. The receptor present inside the animal body recognizes and binds to β-glucan, which in turn renders the animal with high resistance and enhanced immune response. This review highlights β-glucan as an immunostimulant, its effective dosages, and route of administration and furthermore provides an outline on role of β-glucan in enhancing growth, survival, and protection against infectious pathogens pertaining to fishes and shellfishes. Study also summarizes the effect of β-glucan on its receptors, recognition of proteins, immune-related enzymes, immune-related gene expression and their mechanisms of action.

Microalgae are often used as nutritional supplements for aquatic animals and are widely used in the aquaculture industry, providing direct or indirect nutrients for many aquatic animals. Microalgae are abundant in nature, of high nutritional value, and some of them are non-toxic and rich in antioxidants so that they can be explored as a medicinal carrier for human or animals. Natural wild-type microalgae can be adopted as an immunostimulant to enhance non-specific immune response and improve growth performance, among which Haematococcus pluvialis, Arthrospira (Spirulina) platensis, and Chlorella spp. are commonly used. At present, there have been some successful cases of using microalgae to develop oral vaccines in the aquaculture industry. Researchers usually develop recombinant vaccines based on Chlamydomonas reinhardtii, Dunaliella salina , and cyanobacteria. Among them, in the genetic modification of eukaryotic microalgae, many examples are expressing antigen genes in chloroplasts. They are all used for the prevention and control of single infectious diseases and most of them are resistant to shrimp virus infection. However, there is still no effective strategy targeting polymicrobial infections and few commercial vaccines are available. Although several species of microalgae are widely developed in the aquaculture industry, many of them have not yet established an effective and mature genetic manipulation system. This article systematically analyzes and discusses the above problems to provide ideas for the future development of highly effective microalgae recombinant oral vaccines.

Aquaculture makes a significant contribution in the production of protein-rich food for human consumption. Aquaculture practices encounter many challenges, and one of the most devastating problems is disease outbreaks caused by microbial pathogens. To control disease outbreaks, several chemotherapeutics and antibiotics were used indiscriminately, which in turn leads to residual problems in the surrounding environment affecting higher animals and also humans. Immunostimulants are considered as an alternative for antibiotics, which will boost the immune system of the cultured organism, thus effectively countering the assault of pathogens. The use of plant materials as immunostimulant will be an ecofriendly approach for the control of pathogens. The botanicals present in the plants have a key role in enhancing the fish immunity. This review focuses on the importance of plant material as immunostimulant in the control of diseases in aquaculture.

A successful vaccine depends on its capacity to elicit a protective immune response against the target pathogen. The adjuvant used plays an important role in enhancing and directing the immune response. Liposomes are vaccine adjuvants that allow the co-encapsulation of antigens and immunostimulants. Our aim was to evaluate the adjuvanticity of a cationic liposome (Lip) formulated with a novel gemini lipopeptide (AG2-C16) alone or in combination with CpG-ODN as immunostimulants. To achieve this, we used the recombinant clumping factor of Staphylococcus aureus (rClfA) as a model antigen, in a murine model. We characterized the formulations by DLS, Cryo-SEM, and TEM, and analyzed the humoral and cellular immune responses induced in BALB/c and C57BL/6J mice injected with free rClfA and three formulations: Lip + CpG-ODN + rClfA, Lip + AG2-C16 + rClfA and Lip + AG2-C16 + CpG-ODN + rClfA. The addition of immunostimulants to the liposomes did not change the membrane diameter but affected their hydrodynamic diameter, z-potential, and homogeneity. All liposomal formulations were able to stimulate a specific humoral response, with high serum IgG, IgG1 and IgG2a or IgG2c titers in BALB/c or C57BL/6J mice, respectively. In addition, increased vaginal IgG levels were detected after injection, with no specific IgA. The cellular immunity induced by Lip + AG2-C16 + CpG-ODN + rClfA was characterized by a predominant Th1 profile, with the co-induction of Th2 and Th17 cells, and IFN-γ+ cytotoxic T cells. Furthermore, we studied the capacity of the different formulations to stimulate murine keratinocytes and fibroblasts in vitro. While no formulation activated keratinocytes, Lip + AG2-C16 + CpG-ODN increased the expression of CXCL9 in fibroblasts. These results suggest Lip + AG2-C16 + CpG-ODN as a promising adjuvant candidate to be used in vaccines against pathogens that require Th1/Th2/Th17 combined profiles, like S. aureus. Additionally, based on the IFN-γ+ cytotoxic T cells stimulation and the CXCL9 production by fibroblasts, we propose the use of this adjuvant formulation for the stimulation of a Th1 profile.

Nanomedicine in combination with immunotherapy offers opportunities to treat cancer in a safe and effective manner; however, remote control of immune response with spatiotemporal precision remains challenging. We herein report a photothermally activatable polymeric pro-nanoagonist (APNA) that is specifically regulated by deep-tissue-penetrating second near-infrared (NIR-II) light for combinational photothermal immunotherapy. APNA is constructed from covalent conjugation of an immunostimulant onto a NIR-II semiconducting transducer through a labile thermo-responsive linker. Upon NIR-II photoirradiation, APNA mediates photothermal effect, which not only triggers tumor ablation and immunogenic cell death but also initiates the cleavage of thermolabile linker to liberate caged agonist for in-situ immune activation in deep solid tumor (8 mm). Such controlled immune regulation potentiates systemic antitumor immunity, leading to promoted cytotoxic T lymphocytes and helper T cell infiltration in distal tumor, lung and liver to inhibit cancer metastasis. Thereby, the present work illustrates a generic strategy to prepare pro-immunostimulants for spatiotemporal regulation of cancer nano-immunotherapy. Precise control of immune response remains challenging for cancer immunotherapy. Here, the authors report on photothermally activatable semiconducting polymeric pro-agonist in response to second near-infrared window light for regulated photothermal immunotherapy.