The immunomodulatory effect of koumine on B cells under dependent and independent responses by T cells.

Dysregulated activation of polyclonal B cells and production of pathogenic antibodies are involved in the development of rheumatoid arthritis (RA). Therefore, targeted B cell therapy is effective against RA. Gelsemium elegans (Gardn. & Champ.) Benth., a toxic plant widely distributed in Southeast Asia, has been used for treating rheumatoid pain, neuropathic pain, spasticity, skin ulcers, and cancers for many years in traditional Chinese medicine. Koumine, an alkaloid monomer from Gelsemium elegans Benth., exerts therapeutic effects against RA. However, whether koumine affects B cells remains unknown. In this study, the effect of koumine on B cells under T cell-independent (TI) and T cell-dependent (TD) immune responses is investigated in vitro and in vivo. Mouse primary B cells were obtained by immunomagnetic bead sorting, and immunomodulatory effects of koumine on the activation, proliferation, and differentiation of B cells were determined in TI and TD models induced by lipopolysaccharide (LPS) and anti-CD40 antibodies in vitro, respectively. The humoral immune responses of TI and TD were established using NP-AECM-FICOLL and NP-CGG in C57BL/6J mice, respectively. We found that koumine inhibited B cell differentiation in the TI model and inhibited B cell activation and proliferation in the TD model in vitro. Koumine also inhibited antibody secretion in TI immune response, TD initial immune response, and in TD secondary immune response. Our results reveal that koumine has a direct and indirect immune regulatory effect on B cells, showing that it can directly inhibit the differentiation and secretion of autoantibodies after abnormal activation of B cells, and indirectly inhibit the activation and proliferation of TD B cells to reduce the secretion of antibodies. It may be an important mechanism for its anti-RA effect in mice, providing a rationale and laboratory data support for the application of koumine in anti-human RA therapy.

Polysaccharides derived from Chinese medicinal herbs: A promising choice of vaccine adjuvants.

Adjuvants have been used in vaccines for a long time to promote the body's immune response, reducing vaccine dosage and production costs. Although many vaccine adjuvants are developed, the use in human vaccines is limited because of either limited action or side effects. Therefore, the development of new vaccine adjuvants is required. Many studies have found that natural polysaccharides derived from Traditional Chinese medicine (TCM) possess good immune promoting effects and simultaneously improve humoral, cellular and mucosal immunity. Recently polysaccharide adjuvants have attracted much attention in vaccine preparation because of their intrinsic characteristics: immunomodulation, biocompatibility, biodegradability, low toxicity and safety. This review article systematically analysed the literature on polysaccharides possessing vaccine adjuvant activity from TCM plants, such as Astragalus polysaccharide (APS), Rehmannia glutinosa polysaccharide (RGP), Isatis indigotica root polysaccharides (IRPS), etc. and their derivatives. We believe that polysaccharide adjuvants can be used to prepare the vaccines for clinical use provided their mechanisms of action are studied in detail.

Liquiritigenin enhances cyclic adenosine monophosphate production to mitigate inflammation in dendritic cells.

OBJECTIVE: This study aims to dissect the mechanism of traditional Chinese medicinal herbs against asthma; we chose to first focus on the main chemical components of licorice to investigate their contribution to asthmatic inflammation inhibition. METHODS: Production of cellular nucleotide molecules such as cAMP, cGMP, and cGAMP was examined by using enzyme-linked immunosorbent assay (ELISA). Enzyme-encoding genes were tested in vitro using quantitative real-time PCR and protein level was detected by Western blotting analysis. In addition, co-culturing of murine dendritic cells together with T cells was conducted to examine the expression of cytokine genes and host immune response. RESULTS: We found that one of the components within licorice, named liquiritigenin (LR), could efficiently enhance cAMP production in different cell lines. The augmentation of such molecules was linked to the high expression of cAMP synthesis genes and repressed expression of cAMP breaking down genes. In addition, the downstream immune response was also alleviated by the increase in cAMP levels by LR, suggesting the great potential of this molecule against inflammation. Subsequent immunological tests showed that LR could efficiently inhibit the expression of several cytokines and alter the NF-κB pathway and T cell polarization. CONCLUSION: Altogether, we have identified a promising antiasthmatic agent LR that could exhibit immunosuppressive function by elevating the cAMP level.

Effect of methanolic extract of Citrus limetta peel on cellular and humoral immune response in mice.

Citrus limetta is well known for its anti-inflammatory, antimicrobial, antifungal, antidiabetic and antioxidant properties. Methanolic extract of Citrus limetta (MECL) was used to assess cellular and humoral immune responses in mice by carrying out cyclophosphamide-induced neutropenia, delayed-type hypersensitivity (DTH), carbon clearance assay, haemagglutination assay (HA) and mice lethality assay. Methanolic extract of Citrus limetta peel was administered orally to mice in two doses 200mg/kg and 400mg/kg.The extract treated groups showed improvement in neutropenia induced by cyclophosphamide and improvement in the WBC profile. Skin thickness was significantly (P<0.05) higher in 200mg/kg and 400mg/kg groups in comparison to control in DTH. The phagocytic index was significantly (P<0.05) more in 400mg/kg group in carbon clearance assay. Mice were vaccinated with hemorrhagic septicemia vaccine before challenge with Pasteurella multocida for mice lethality test. Percentage mortality was decreased in 400mg/kg treated group in comparison to negative control Antibody titre response to sheep red blood cells was significantly (P<0.05) higher with dose 400mg/kg in HA. Results suggested the effectiveness of the methanolic extract of Citrus limetta as an immunostimulating agent.

Development of a compound oral liquid containing herbal extracts and its effect on immunity and gastric mucosa.

Nowadays, consumers have an increasing demand for health products. In this study, an oral liquid was developed using a compound extract consisting of three herbal extracts (Dendrobium nobile Lindl., Lycium barbarum, and Puerariae lobatae Radix) because the compound extract (a combination of all three extracts) was superior to every single extract in promoting the phagocytic capacity of RAW264.7 macrophages and the proliferation ability of GES-1 cells. In this oral liquid, the dosage of the stabilizer and the sweetener was selected using a stability test and sensory quality evaluation. When 0.30% (m/v) xanthan gum and 0.20% (m/v) mogroside were added, the oral liquid had not only a good stability but also the highest sensory score for overall acceptability. The chemical composition analysis showed that the oral liquid had various functional ingredients including polysaccharides, phenols, alkaloids, and so forth. The immune-enhancing efficacy of the oral liquid was evaluated in BALB/c mice by measuring the levels of different immune indicators. The results indicated that the oral liquid obviously enhanced nonspecific and specific immunity. A rat model with ethanol-induced gastric ulcer was used to examine the protective effect of the oral liquid on the gastric mucosa and to explore the related mechanisms. The oral administration of the oral liquid for days significantly prevented the formation of gastric ulcer. This study provided an effective oral liquid that could enhance immunity and protect gastric mucosa.

Evaluation of Th1 and Th2 mediated cellular and humoral immunity in patients with COVID-19 following the use of melatonin as an adjunctive treatment.

Coronavirus (SARS-CoV-2) is spreading rapidly in the world and is still taking a heavy toll. Studies show that cytokine storms and imbalances in T-helper (Th)1/Th2 play a significant role in most acute cases of the disease. A number of medications have been suggested to treat or control the disease but have been discontinued due to their side effects. Melatonin, as an intrinsic molecule, possesses pharmacological anti-inflammatory and antioxidant properties that decreases in concentration with age; as a result, older people are more prone to various diseases. In this study, patients who were hospitalized with a diagnosis of coronavirus disease 2019 (COVID-19) were given a melatonin adjuvant (9 mg daily, orally) for fourteen days. In order to measure markers of Th1 and Th2 inflammatory cytokines (such as interleukin (IL)-2, IL-4, and interferon (IFN)-γ) as well as the expression of Th1 and Th2 regulatory genes (signal transducer and activator of transcription (STAT)4, STAT6, GATA binding protein 3 (GATA3), and T-box expressed in T cell (T-bet)), blood samples were taken from patients at the beginning and end of the treatment. Adjuvant therapy with melatonin controlled and reduced inflammatory cytokines in patients with COVID-19. Melatonin also controlled and modulated the dysregulated genes that regulate the humoral and cellular immune systems mediated by Th1 and Th2. In this study, it was shown for the first time that melatonin can be used as a medicinal adjuvant with anti-inflammatory mechanism to reduce and control inflammatory cytokines by regulating the expression of Th1 and Th2 regulatory genes in patients with COVID-19.

Atractylenolide I enhances responsiveness to immune checkpoint blockade therapy by activating tumor antigen presentation.

One of the primary mechanisms of tumor cell immune evasion is the loss of antigenicity, which arises due to lack of immunogenic tumor antigens as well as dysregulation of the antigen processing machinery. In a screen for small-molecule compounds from herbal medicine that potentiate T cell-mediated cytotoxicity, we identified atractylenolide I (ATT-I), which substantially promotes tumor antigen presentation of both human and mouse colorectal cancer (CRC) cells and thereby enhances the cytotoxic response of CD8+ T cells. Cellular thermal shift assay (CETSA) with multiplexed quantitative mass spectrometry identified the proteasome 26S subunit non-ATPase 4 (PSMD4), an essential component of the immunoproteasome complex, as a primary target protein of ATT-I. Binding of ATT-I with PSMD4 augments the antigen-processing activity of immunoproteasome, leading to enhanced MHC-I-mediated antigen presentation on cancer cells. In syngeneic mouse CRC models and human patient-derived CRC organoid models, ATT-I treatment promotes the cytotoxicity of CD8+ T cells and thus profoundly enhances the efficacy of immune checkpoint blockade therapy. Collectively, we show here that targeting the function of immunoproteasome with ATT-I promotes tumor antigen presentation and empowers T cell cytotoxicity, thus elevating the tumor response to immunotherapy.

A purified acidic polysaccharide from Sarcandra glabra as vaccine adjuvant to enhance anti-tumor effect of cancer vaccine.

Immunological adjuvants are an important part of tumor vaccines and are critical for stimulating anti-tumor immune responses. However, the clinical needs of strong adjuvants have not been met. In this work, we found that the purified acidic polysaccharide from Sarcandra glabra, named p-SGP, is an ideal adjuvant for tumor vaccines. Cancer vaccines could induce stronger humoral and cellular immune responses when they are adjuvanted with p-SGP. Compared with CpG, a well-studied adjuvant, p-SGP significantly augmented the anti-tumor immunity of various cancer vaccines, which is leading to noticeable inhibition of tumor growth and metastasis in tumor-bearing mice. Moreover, p-SGP promoted dendritic cells (DCs) maturation and Th1-polarized immune response. Toll-like receptor 4 (TLR4) inhibitor TAK-242 could significantly inhibit the expression of mature molecules on the surface of DCs stimulated by p-SGP, suggesting that p-SGP could play the role of activating DCs through the TLR4 receptor. Results of RNA-seq showed that the Delta-like ligand 4 (DLL4) gene in the pathway Th1 and Th2 cell differentiation was significantly up-regulated in the DCs treated with p-SGP, suggesting that p-SGP has a unique mechanism of enhancing anti-tumor immunity.

Advancements in Adjuvanticity of Bioactive Inorganic and Organic Compounds.

BACKGROUND: Regardless of the enormous success of vaccines over decades, the formulation of biocompatible and highly effective vaccines is still insufficient for combating new pathogens. DISCUSSION: The degree of effectiveness of any vaccine largely depends on the choice of appropriate adjuvant. Along with the optimum biocompatibility, an ideal adjuvant must be biodegradable, economical and easy to manufacture. To date, various organic and inorganic substances have been used as an adjuvant to augment the effectiveness of the vaccine. Immunological adjuvants are essential for strong and long-term effects against various pathogens. However, a very limited number of licensed adjuvants are available for the formulation of a successful vaccine. This leads to a challenging situation in medical science. CONCLUSION: The present review concisely summarizes the mechanism of action of various bioactive organic and inorganic immunological adjuvants, their limitations and future perspectives for their appropriate modification. Current trends of anticancer therapies using immunological adjuvants have also been highlighted in this review.

Toward improved human health: efficacy of dietary selenium on immunity at the cellular level.

Selenium, an essential trace element in the body, participates in various biological processes in the form of selenoproteins. In humans, a suitable concentration of selenium is essential for maintaining normal cellular function. Decreased levels of selenoproteins can lead to obstruction of the normal physiological functions of tissues and cells and even death. In addition, the level of selenium in the body affects cellular immunity, humoral immunity, and the balance between type 2 and type 1 helper T cells. Selenium can affect the immune function of the body through the reactive oxygen species (ROS), NF-κB, ferroptosis and NRF2 pathways. This paper reviews the immune effect of selenium on the body and the process of signal transduction and aims to serve as a reference for follow-up studies of immune function and research on the development of new selenium compounds and active targets.

San Wu Huangqin decoction regulates inflammation and immune dysfunction induced by influenza virus by regulating the NF-κB signaling pathway in H1N1-infected mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The San Wu Huangqin Decoction (SWHD), which is made from the dried root of Sophora flavescens Aiton (Kushen in Chinese), the dried root of Scutellaria baicalensis Georgi (Huangqin in Chinese), and the dried root tuber of Rehmannia glutinosa (Gaertn.) DC. (Dihuang in Chinese), is a traditional Chinese formula used to treat prolonged fever and inflammatory diseases in clinics and proven to inhibit influenza virus effectively in our previous study. AIM OF THE STUDY: This work was performed to study the regulation of SWHD on inflammation and immune dysfunction induced by the influenza virus and the underlying mechanism in the treatment of SWHD. METHODS: In this study, the influenza virus A/PR/8/34 (H1N1)-infected mouse model was used to investigate the regulation of SWHD on inflammation and immune dysfunction induced by H1N1. The pathological changes, the capacity of proliferation of T and B lymphocytes, the cytotoxicity of natural killer (NK) cells, and the levels of IL-6, TNF-α, IL-1ß, IL-4, and IFN-γ in the serum, bronchoalveolar lavage fluid (BALF), and lung were analyzed. The effects of type 1 T helper cell (Th1) and type 2 T helper cell (Th2) immune responses were discussed indirectly. In addition, the expression levels of p-p65, p65, IKKα/ß, p-IκBα, and IκBα in relation to the NF-κB pathway were measured using Western blot analysis, or immunohistochemical assay. RESULTS: SWHD decreased the pathological changes in lung tissues, promoted the proliferation of T and B lymphocytes, enhanced NK cell activity, and accelerated the phagocytic function of macrophages in H1N1-infected mice. At the same time, SWHD decreased the levels of IL-6, TNF-α, IL-1ß, IFN-γ, and increased the level of IL-4 in the serum, BALF, and lung of model mice. Moreover, the p-p65, p65, and IκBα protein expression levels were inhibited, whereas the p-IκBα protein expression levels were improved in the lungs of H1N1-infected mice. CONCLUSIONS: SWHD can inhibit the replication of the H1N1 virus and reduced the excessive inflammation and immune dysfunction induced by the H1N1 virus in the body. This work provides rich experimental basis for further anti-inflammation research of SWHD and sets the foundation for the development of a viral inflammation drug of traditional Chinese medicine.

A natural oil increases specific anti-OVA IgG levels and induces a cellular immune response combined with aluminum hydroxide.

The efficacy of certain vaccines is improved by the use of adjuvants. Nowadays, the development of new, effective, and safe adjuvants that stimulate the innate immune response is researched. In this context, medicinal plants appear as a suitable alternative. Minthostachys verticillata essential oil (EO) has demonstrated the ability to modulate mechanisms of the innate immune response. Thus, the present work aimed to evaluate the EO adjuvant effect on humoral and cellular immunity, coadministered with OVA as antigen. The chemical analysis of EO by gas chromatography-mass spectrometry revealed a predominant pulegone-menthone chemotype. EO (1.25, 2.5, or 5.0 mg/ml) did not alter the viability of murine fibroblasts (3T3 cell line) neither showed signs of toxicity in Balb/c mice inoculated subcutaneously. The serum of mice immunized with OVA + EO showed increased levels of anti-OVA-specific antibodies of IgG1 subclass compared with the mice immunized with OVA alone revealing an adjuvant effect of EO. The delayed type hypersensitivity showed that the combination OVA + Al(OH)3  + EO was the best to induce a cellular immune response that extended until 48 h postinjection of OVA. M. verticillata EO appears as a new, safe, and effective adjuvant, which should continue to be studied for their possible future incorporation into vaccine formulations.

Immunomodulatory activities of polysaccharides from Ganoderma on immune effector cells.

Polysaccharides are the most abundant bioactive compounds in Ganoderma and have been widely used as dietary supplements in traditional Chinese medicine for thousands of years. Polysaccharides from Ganoderma exhibit unique biological properties, including anti-tumor, anti-inflammatory, and immunomodulatory activities. Herein, the sources and structures of polysaccharides from Ganoderma were presented. This work also reviews the immunomodulatory activities and possible mechanisms of polysaccharides from Ganoderma on different immune effector cells, including lymphocytes and myeloid cells. As an available adjunctive remedy, polysaccharides from Ganoderma can potentially be applied for the modulation of the host immune system, namely the innate immunity, the cellular immunity, and the humoral immunity.

Stimulatory effect of dietary chasteberry (Vitex agnus-castus) extract on immunity, some immune-related gene expression, and resistance against Aeromonas hydrophila infection in goldfish (Carassius auratus).

Chasteberry is highly recommended as an herbal medicine across the globe for treating of many gynaecological disorders. In this study, chasteberry extract (CBE) was supplemented in goldfish diet to evaluate the immunity responses at the cellular and molecular levels. Moreover, after the feeding trial, the fish were challenged with Aeromonas hydrophila. The fish (300 individuals, 2.4 ± 0.12 g initial weight) were randomly distributed in 12 tanks and were fed with 0 (control), 5, 10, and 15 g CBE per kg of feed for 8 weeks. Based on the results, lysozyme activity, alkaline phosphatase, and total immunoglobulin (Ig) in the skin mucus samples were significantly enhanced in the fish fed with 15 g/kg CBE (P < 0.05). Moreover, dietary CBE positively affected lysozyme activity, complement components, and IgM content of the serum samples compared to the control group. Also, the number of monocytes and lymphocytes were increased significantly with increasing CBE in the diet (P < 0.05). The highest mRNA levels of tumor necrosis factors (TNF-α, TNF-2α) and Lysozyme were observed in 15 g/kg CBE treatment. After the challenge test, the highest relative percentage survival value (60%) was observed in the fish fed with 15 g/kg CBE. We concluded that dietary CBE especially at 15 g/kg has an immunomodulatory effect in goldfish by stimulating the innate immunity and some inflammatory cytokines as well as disease resistance against A. hydrophila.

Canola oilseed- and Escherichia coli- derived hepatitis C virus (HCV) core proteins adjuvanted with oil bodies, induced robust Th1-oriented immune responses in immunized mice.

Induction of broad Th1 cellular immune responses and cytokines is crucial characteristics for vaccines against intracellular infections such as hepatitis C virus (HCV). Plants (especially oilseed tissues) and plant-immunomodulators (like oil bodies) offer cost-effective and scalable possibilities for the production of immunologically relevant and safe vaccine antigens and adjuvants, respectively. Herein, we provide data of the murine immunization by transgenic canola oilseed-derived HCV core protein (HCVcp) soluble extract (TSE) and Escherichia coli- derived rHCVcp in combination with Canola oil bodies (oil) compared to that of the Freund's (FA) adjuvant. Mice immunized by TSE+ oil developed both strong humeral (IgG) and Th1-biased cellular responses, manifested by high levels of IFN-γ and lower IgG1/IgG2a ratio and IL-4 secretion. Results of the intracellular cytokine staining indicated that TSE+ oil immunization in mice triggered both CD4+ and CD8+ T cells to release IFN-γ, while CD4+ cells were mostly triggered when FA was used. Analyses by qRT-PCR indicated that a combination of rHCVcp/TSE with oil body induced high levels of IL-10 cytokines compared to that of the FA adjuvant. These characteristics are important properties for the design of an HCV vaccine candidate and indicate the potential of Canola-derived antigen and oil bodies in addressing these concerns.

[ISA 61 VG adjuvant enhances protective immune response of Listeria monocytogenes inactivated vaccine].

Listeria monocytogenes (Lm) is zoonotic pathogen that can cause listeriosis, and vaccine is one of the effective methods to prevent this pathogen infection. In this study, we developed a novel vaccine that is a mixture of inactivated bacteria and Montanide™ ISA 61 VG, a mineral oil adjuvant, and evaluated the safety and immune response characteristics of this vaccine. The mice immunized with the ISA 61 VG adjuvant had high safety, and it could induce significantly higher titer of anti-listeriolysin O (LLO) antibody and higher value of IgG2a/IgG1 ratio compared with the group without the adjuvant. In particular, it could provide 100% immune protection against lethal doses of Lm challenge in mice. In summary, ISA 61VG adjuvant significantly enhanced the ability of inactivated listeria vaccine to induce humoral and cellular immune responses, thereby enhanced the protective immune response in the host, and it is a potential vaccine candidate for the prevention of Lm infection in humans and animals.

Influence of Nigerian Jelly Ear Culinary-Medicinal Mushroom, Auricularia auricula-judae (Agaricomycetes), on Humoral and Cellular Immunity.

The fruiting body of Auricularia auricula-judae has received attention in folk medicine due to its possible medicinal values. Therefore, this study evaluated the immunomodulatory effects of the hot aqueous extract (AAAJ) and the ß-D-glucan-rich polysaccharide fraction of A. auricula-judae (BGPA) on specific and nonspecific humoral and cell mediated immune responses in immunocompetent and immunosuppressed mice. Oral supplementation with AAAJ or BGPA (100, 200, or 400 mg/kg) produced significantly high titers of total OVA specific or TT specific IgG1 and IgG2a compared with the levels in untreated control. Oral administration of AAAJ or BGPA (100, 200, or 400 mg/kg) evoked a significant increase in carbon clearance at all doses, indicating stimulation of the reticuloendothelial system, and potentiated the delayed-type hypersensitivity reaction induced by sheep red blood cells (SRBC) compared with the untreated mice. Total lymphocyte count, neutrophil count, and lymphocytes count increased significantly (P < 0.05) at all doses, following acute administration of AAAJ or BGPA (100, 200, or 400 mg/kg), showing increased protection toward cyclophosphamide induced myelosuppression compared with the untreated negative control group. In the hemolytic complement assay, AAAJ and BGPA at all doses significantly (P < 0.05) inhibited the hemolytic activity of the complement proteins on the sensitized SRBC. The present study reveals that the extract holds promise as an immunomodulatory agent and strengthens the rationale for its use in traditional medicine.

Micronutrients as immunomodulatory tools for COVID-19 management.

COVID-19 rapidly turned to a global pandemic posing lethal threats to overwhelming health care capabilities, despite its relatively low mortality rate. The clinical respiratory symptoms include dry cough, fever, anosmia, breathing difficulties, and subsequent respiratory failure. No known cure is available for COVID-19. Apart from the anti-viral strategy, the supports of immune effectors and modulation of immunosuppressive mechanisms is the rationale immunomodulation approach in COVID-19 management. Diet and nutrition are essential for healthy immunity. However, a group of micronutrients plays a dominant role in immunomodulation. The deficiency of most nutrients increases the individual susceptibility to virus infection with a tendency for severe clinical presentation. Despite a shred of evidence, the supplementation of a single nutrient is not promising in the general population. Individuals at high-risk for specific nutrient deficiencies likely benefit from supplementation. The individual dietary and nutritional status assessments are critical for determining the comprehensive actions in COVID-19.

Single or Combined Dietary Supply of Psidium guajava and Phyllanthus amarus Extracts Differentially Modulate Immune Responses and Liver Proteome in Striped Catfish (Pangasianodon hyphophthalmus).

Guava Psidium guajava L (Pg) and bhumi amla Phyllanthus amarus Schum. et Thonn (Pa) are well-known plants in traditional medicine. However, the capacity of these plants for improving the immune system of aquatic species has received less attention so far. This study aimed to investigate the effects of single supply or mixture of Pg and Pa extracts on immune responses, disease resistance and liver proteome profiles in striped catfish Pangasianodon hypophthalmus. Fish were fed diets including basal diet 0% or one of three doses of each plant extract, either alone or in mixture, 0.08, 0.2, or 0.5% Pg, Pa or mixture (Pg:Pa, v/v) for 6 weeks. The immune parameters (respiratory burst activity (RBA); nitric oxide synthase (NOS), total immunoglobulin, lysozyme, and complement activities) were examined at W3, W6 post-feeding, and after challenge test. The growth parameters and the challenge test with Edwardsiella ictaluri were done at W6. The liver proteome profiles were analyzed in W6 at 0.08 and 0.5% of each extract. The results showed that extract-based diets significantly improved growth parameters in the Pg0.2 group compared to control. The cellular immune responses in spleen and the humoral immune responses in plasma were significantly improved in a dose and time-dependent manner. Diets supplemented with single Pg and Pa extracts, and to lesser extent to combined extracts, could significantly decrease the mortality of striped catfish following bacterial infection compared to control. The proteomic results indicated that some pathways related to immune responses, antioxidant and lipid metabolism were enriched in liver at W6. Several proteins (i.e., CD8B, HSP90AA1, HSP90AB1, PDIA3, CASP8, TUBA1C, CCKAR, GNAS, GRIN2D, PLCG1, PRKCA, SLC25A5, VDAC2, ACTN4, GNAI2, LCK, CARD9, NLRP12, and NLRP3) were synergistically upregulated in mixture of Pg and Pa-based diets compared to control and single dietary treatments. Taken together, the results revealed that single Pg and Pa extracts at 0.2 and 0.5% and their mixture at 0.08 and 0.5% have the potential to modulate the immune mechanisms and disease resistance of striped catfish. Moreover, the combination of Pg and Pa in diets suggested positive synergistic effects liver proteome profile related to immune system processes.

Research "recover from illness defense complex" helper T cell immune mechanisms based on the "Fuxie" theory clearing away heat evil thoroughly nourishing kidney treatment of recurrent blood-heat syndrome Psoriasis.

INTRODUCTION: Psoriasis vulgaris (PV) is a chronic, painful, disfiguring, and disabling dermatological disease, which affects the physical and mental health of patients and impacts their quality of life. Current conventional systemic therapies can be costly, present risks of side effects, have limited efficacy and commonly recur following treatment cessation. Some Chinese herbal medicine therapies have shown therapeutic benefits for psoriasis vulgaris, including relieving symptoms and improving quality of life, and a potential of reducing relapse rate. However, explicit evidence has not yet been obtained. METHODS AND ANALYSIS: This is a pilot randomized controlled trial with the objective of investigating the effect of Jia Wei Liang Xue Xiao Feng San granules on relapse rate of recurrent PV and the correlation between Psoriasis area severity index (PASI) and key psoriasis-related cytokine changes and the number of cells. A total of 102 participants were recruited for this study, including 72 patients with recurrent PV, 15 healthy volunteers and 15 patients with psoriasis vulgaris who have recovered for more than 1 year. A total of 72 patients, with recurrent PV, will be randomized (1:1) to receive the oral Chinese herbal medicine Jia Wei Liang Xue Xiao Feng San or the oral Acitretin Capsule treatments for a period of 8 weeks. After this period, participants whose PASI scores improvement reached more than 75%, will undergo a 52-week follow-up phase.The primary outcome measures are as follows:The secondary study outcomes will include:This trial may provide a novel regimen for recurrent PV patients if the granules decrease recurrence rate without further adverse effects. ETHICS AND DISSEMINATION: The ethics approval was provided by the Sichuan Traditional Chinese medicine regional ethics review committee. The ethics approval number is 2018KL-055. The design and the results of the study will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR1900022766).