Immune Organs Research Articles

Histopathological characteristics of PRRS and expression profiles of viral receptors in the piglet immune system

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious viral disease that causes significant economic losses to the swine industry worldwide. PRRS virus (PRRSV) infection is a receptor-mediated endocytosis and replication process. The purpose of this study was to determine the localization and expression of four important PRRSV receptors in immunological organs of piglets. After piglets were infected with PRRSV, Hematoxylin and Eosin staining, immunofluorescence, and Western blot were used to perform histopathological examination and receptors distribution analysis. The results showed that PRRSV caused severe damage to the piglets’ immune organs, including atrophy of the thymus and swelling of lymph node. Histopathological lesions were mainly observed in the lung and lymph node and were characterized by interstitial pneumonia, collapsed follicles, exhaustion of germinal centers, and extensive hemorrhage. Immunofluorescence staining and Western blot results showed that the receptors of CD163 and NMHCII-A were mainly distributed in the thymus, hilar lymph nodes, and mesenteric lymph nodes. However, Sn and vimentin receptors were expressed at low levels in the immune organs of piglets. The distribution of the four receptors in the immune organs was more concentrated in the cortex but was more scattered in the medulla. Compared to the control group, the relative expression of the four receptors increased significantly in most immune organs after viral infection. In conclusion, our study examined the distribution and expression of four PRRSV receptors in immunological organs. We observed a significant increase in the expression of Sn, CD163, and vimentin following viral infection. These findings may provide potential targets for future antiviral reagent design or vaccine development.

Vitamin D for very preterm infants-determining the how, when, and why.

A recent survey study found that 400 IU/day vitamin D is the most common dose in United States neonatal intensive care units. Results of clinical trials are inconsistent, and, therefore, have not determined the optimal vitamin D dose for efficacy and safety in the neonatal intensive care unit. Future studies must consider the unique attributes of perinatal vitamin D metabolism and the potential role of vitamin D in immune function and organ development. IMPACT: Preterm infant vitamin D metabolism is a complex yet important area of research.

Amelioration of Systemic Amyloidosis by Blocking IL-17A and Not by IL-17F, and Arteriosclerosis by Blocking Both IL-17A and IL-17F in an Inflammatory Skin Mouse Model

There are comorbidities and complications in atopic dermatitis and psoriasis that often occur after the appearance of skin inflammation. Statistically, data show that patients with psoriasis and atopic dermatitis have a shorter life expectancy than patients without psoriatic dermatitis, due to the occurrence of arteriosclerosis, myocardial infarction, and cerebral infarction. Many types of skin inflammation are treated with various antibody preparations, and marked improvement in patients’ quality of life can be achieved. The next theme is to understand the pathogenesis of arteriosclerosis, myocardial infarction, stroke, and other complications associated with dermatitis and to find treatments and drugs to reduce their occurrence. The skin, a crucial immune organ, generates large amounts of inflammatory cytokines in response to various stimuli, leading to systemic inflammation and potential damage to internal organs. The link between inflammatory skin conditions like psoriasis and atopic dermatitis with serious health complications such as vascular disorders and systemic amyloidosis has been increasingly recognized. In psoriasis, biological treatments targeting Interleukin (IL)-17A, a key cytokine, have shown promise in reducing cardiovascular risks. Recent developments include treatments that target both IL-17A and IL-17F in the psoriasis field, though each cytokine’s impact on internal organ damage is still under debate. Among visceral complications secondary to dermatitis, systemic amyloidosis and atherosclerosis have been reported to be controlled by suppressing IL-17 in the early stages of dermatitis. Still, it remains unclear whether suppressing IL-17 prevents organ damage in the late stages of persistent severe dermatitis. A study using a long-lasting dermatitis mouse model that overexpressed human caspase-1 in keratinocytes (Kcasp1Tg) investigated the effects of deleting IL-17A and IL-17F on visceral complications. Cross-mating Kcasp1Tg with IL-17A-, IL-17F-, and IL-17AF-deficient mice assessed the skin and visceral organs histologically, and RT-PCR analysis of aortic sclerosis markers was performed. Despite less improvement in dermatitis, deletion of IL-17A in Kcasp1Tg mice showed promising results in reducing multiple organ amyloidosis. On the other hand, the effect was observed in both IL-17A and IL-17F deleted mice for aortic sclerosis. The inhibition of IL-17A and IL-17F was suggested to reduce the risk of developing comorbidities in internal organs. IL-17A and IL-17F were found to act similarly or produce very different results, depending on the organ.

Cordyceps Polysaccharides: A Review of Their Immunomodulatory Effects

Cordyceps primarily consists of ascomycetes, a parasitic fungus that infects insects and arthropods. Recently, Cordyceps has been shown to manifest a diverse range of pharmacological activities, rendering it applicable for the treatment and mitigation of various diseases, such as diabetes, acute liver injury, and colitis. Many active constituents have been identified from Cordyceps sinensis, including cordycepin, adenosine, sterols, and polysaccharides. Polysaccharides constitute a primary active component of Cordyceps, exhibiting immunomodulatory effects. We searched the Web of Science database with the keywords of cordyceps, polysaccharide, and immune modulation; collected related studies from 2004 to 2024; and eliminated articles with low influence and workload. A review of the research advancements regarding the immunomodulatory effects of Cordyceps polysaccharides was conducted with the aim of furnishing valuable reference information. Research indicates that polysaccharides exhibiting immunomodulatory activity are predominantly sourced from Cordyceps sinensis and Cordyceps militaris. Immunological experimental results demonstrate that Cordyceps polysaccharides can augment the activities of macrophages, lymphocytes, and dendritic cells while fostering the expression of immune-active substances such as cytokines and chemokines. Furthermore, animal experiments have substantiated the immunomodulatory effects of Cordyceps polysaccharides. These effects encompass ameliorating immune suppression induced by drugs or radiation, enhancing immune organ indices, elevating the expression of immunoreactive substances, and mitigating immune evasion prompted by tumors. In conclusion, Cordyceps polysaccharides exhibit significant immunomodulatory activity and merit further investigation.

Effects of chronic heat stress on spleen structure, apoptosis and immune response in Siberian Sturgeon (Acipenser baerii)

Chronic heat stress induced by global warming has important implications for fish survival, and the response of important immune organs, such as the spleen, to chronic heat stress remains to be investigated. In this study, one control group (20 ℃) and two heat stress groups (24 ℃ and 28 ℃) were set up to investigate the effects of heat stress on the spleen of Siberian Sturgeon (Acipenser baerii). As per the histological section analysis, heat stress caused vacuolization, reticulocyte hyperplasia, and macrophage infiltration in the spleen, with hyperplasia being more pronounced in the 28 ℃ group. The flow cytometry results showed that the spleen’s apoptosis level significantly increased at 28 ℃ (p < 0.05). Hematological studies revealed a significant increase in the number of red blood cells in the 28 ℃ group (p < 0.05). Meanwhile, the mRNA expression of immune-related factors (tgf-β, il-1β, and il-8) was significantly higher in the 28 ℃ heat stress group compared with the control group. This study reveals the effects of heat stress on the A. baerii spleen and contributes to the understanding of coping strategies of cold-water fish to chronic heat stress.

Targeting immunosenescence for improved tumor immunotherapy

AbstractTumor immunotherapy has significantly transformed the field of oncology over the past decade. An optimal tumor immunotherapy would ideally elicit robust innate and adaptive immune responses within tumor immune microenvironment (TIME). Unfortunately, immune system experiences functional decline with chronological age, a process termed “immunosenescence,” which contributes to impaired immune responses against pathogens, suboptimal vaccination outcomes, and heightened vulnerability to various diseases, including cancer. In this context, we will elucidate hallmarks and molecular mechanisms underlying immunosenescence, detailing alterations in immunosenescence at molecular, cellular, organ, and disease levels. The role of immunosenescence in tumorigenesis and senescence‐related extracellular matrix (ECM) has also been addressed. Recognizing that immunosenescence is a dynamic process influenced by various factors, we will evaluate treatment strategies targeting hallmarks and molecular mechanisms, as well as methods for immune cell, organ restoration, and present emerging approaches in immunosenescence for tumor immunotherapy. The overarching goal of immunosenescence research is to prevent tumor development, recurrence, and metastasis, ultimately improving patient prognosis. Our review aims to reveal latest advancements and prospective directions in the field of immunosenescence research, offering a theoretical basis for development of practical anti‐immunosenescence and anti‐tumor strategies.

Intra-specific variations in Schistosoma mansoni and their possible contribution to inconsistent virulence and diverse clinical outcomes.

Schistosoma mansoni was introduced from Africa to the Americas during the transatlantic slave trade and remains a major public health problem in parts of South America and the Caribbean. This study presents a comprehensive comparative analysis of three S. mansoni strains with different geographical origins-from Liberia, Belo Horizonte and Puerto Rico. We demonstrated significant variation in virulence and host-parasite interactions. We investigated the phenotypic characteristics of the parasite and its eggs, as well as the immunopathologic effects on laboratory mouse organ systems. Our results show significant differences in worm morphology, worm burden, egg size, and pathologic organ changes between these strains. The Puerto Rican strain showed the highest virulence, as evidenced by marked liver and spleen changes and advanced liver fibrosis indicated by increased collagen content. In contrast, the strains from Liberia and Belo Horizonte had a less pathogenic profile with less liver fibrosis. We found further variations in granuloma formation, cytokine expression and T-cell dynamics, indicating different immune responses. Our study emphasizes the importance of considering intra-specific variations of S. mansoni for the development of targeted therapies and public health strategies. The different virulence patterns, host immune responses and organ pathologies observed in these strains provide important insights for future research and could inform region-specific interventions for schistosomiasis control.

Wire injury induced moderate aortic valve stenosis in mice is accompanied by a chronic systemic inflammatory reaction

Abstract Background Patients with aortic valve stenosis (AS) have elevated serum levels of inflammation markers, and blood cytokine levels correlate with ventricular recovery after transcatheter aortic valve replacement. While presence of inflammatory processes in stenotic aortic valves is acknowledged, no systematic characterization of the systemic immune reaction upon AS has been performed, yet. Purpose Hypothesis of this study was that AS induces a systemic inflammatory reaction linked with local processes in the heart. Methods AS was induced by wire injury (WI) or sham surgery was performed in 3-4 months old male C57Bl/6J mice. AS severity, left ventricular (LV) function and hypertrophy indices were assessed with echocardiography (echo). After four weeks, explanted organs were weighted, and flow cytometry identified total leukocyte numbers in blood, heart, and peripheral immune organs (spleen, liver, lymph nodes) and uptake of Cy5-labelled perfluorocarbon nanoemulsions by whole blood leukocytes. Costimulatory molecules (flow cytometry, RT-qPCR) and cytokines (RT-qPCR, Multiplex Immunoassay) were analysed in heart, peripheral immune organs and blood. Results R-values were positive for spleen weight correlation with AS severity, cardiac function and mass suggesting cardiac hypertrophy to preserve heart function. Myocardial myeloid and T cell r-values were positive or negative, respectively, for correlation with spleen and liver weight, hinting at T cell recruitment from peripheral stores. Immune cell numbers in peripheral lymph nodes and spleen showed negative r-values for correlation with heart hypertrophy indices; number of liver myeloid cells correlated negatively with LV wall thickness (monocytes=-0.8571, p=0.0238) suggesting immune cell recruitment to hypertrophic hearts. Cytokine mRNA levels trended mainly towards increase in heart and regional lymph nodes and reduction in spleen and liver after WI. Correlation with echo was more homogeneous after WI, with r-values mainly positive, except of T cell activation markers, for aortic valves, but negative for myocardium, hinting at mechanisms preserving heart function. Correlating unchanged cytokine protein levels in myocardium and plasma with echo, r-values were mostly positive for myocardium, and were more positive than in sham for plasma. Echo and costimulatory molecule correlation showed a more homogeneous pattern in WI, with mostly positive r-values in myocardium and periphery, while most r-values were negative in sham. Together with reduced PFC-uptake by lymphatic cells, this hints at systemic immune cell activation in AS. Conclusion The results suggest that number and activation state of leukocytes in peripheral organs are directly linked to cardiac processes in AS. Considering the pathological value of inflammation, it is crucial to in future studies find out if modulation of the systemic inflammatory reaction relieves severity of AS and prevents development of heart failure.

Effect of coated calcium feeding on growth performance, carcass traits, immunity, blood biochemistry and tibial bone morphometry in commercial broiler chicken.

The bone abnormalities pose great concern in heavy, rapidly growing broilers, resulting in significant economic loss, and health issues in birds. To address these problems and prevent unnecessary mineral excretion into environment, it is crucial to optimise the inclusion level of dietary calcium in broiler's diet. The calcium utilisation by the bird is also affected by its source, particle size, bioavailability etc. Hence this study aimed to study the effect of partially replacing conventional dietary calcium source with coated calcium on growth performance, immune response, carcass traits, blood calcium and phosphorus, and mineral retention in broilers. About 416 broiler chicks were randomly distributed into four treatments, each with eight replicates of 13 birds and fed with iso-calcium, isocaloric, and isonitrogenous diet for 42 days. The T0 (control) was a basal diet while the T1, T2, and T3, were treatment diets in which conventional calcium source (limestone) was partially replaced with coated calcium by 10, 20, and 30% respectively. The birds of T3 group showed higher (P < 0.05) body weight gain, better feed conversion ratio and higher carcass yields compared to T0, T1, and T2 diet fed birds. Further the treatment groups exhibited higher (P < 0.05) cell-mediated and humoral immune responses and immune organ weights compared to control. The tibial bone weight, length and average diameter was highest (P < 0.05) in T3. Moreover, the T3 diet fed group also showed higher (P < 0.05) calcium and phosphorus content in serum and bone and lowest content of these minerals in the excreta followed by T2, T1 and control. These findings suggest that a 30% conventional calcium source with coated calcium may be used as a high-grade mineral source for broiler chicken feed.

Gonadotropin-releasing hormone and organs of the immune system

As a result of a literature search, the physiological aspects of the gonadotropin-releasing hormone (GnRH) influence on immune organs, such as red bone marrow, thymus, spleen and lymph nodes, were considered. The use of GnRH drugs leads to the replacement of red bone marrow with yellow one with an increase in the content of lymphoid and myeloid progenitor cells. In parallel, processes of osteoporosis occur due to increased bone resorption with corresponding changes in calcium metabolism and a decrease in the density of various bone tissues. At the same time, there are papers reporting no effect of GnRH on bone density and changes in calcium metabolism. GnRH acts on the thymus during embryonic development, and in postnatal ontogenesis, and during inflammation and age-related involution processes. Not only GnRH causes changes in the thymus; the thymus may also influence on the GnRH system. A direct effect of GnRH on spleen cells had not been detected, but the weight of the organ changed as a result of active immunization against GnRH in experiment. Unfortunately, very few articles demonstrate the physiological mechanisms of immunomodulation in such conditions. In any case, the obvious insufficiency and contradictory of publications on each aspect of GnRH effects indicates that they have been poorly studied, and it’s advisabile of further continuing not only applied research, but also fundamental investigations, due to its possible high prospects for creating immune control systems.

Alterations in tissue content of iron and zinc in mice bearing hepatoma 22a and their correction by zinc sulphate supplementation

It is known that many tumors induce iron and zinc deficiency in the organism. We studied the content of these metals, as well as the specific activity of two antioxidant metal-dependent enzymes – catalase and superoxide dismutase of three distal organs (thymus, liver and spleen) in animals bearing transplantable hepatoma 22a. These alterations were compared to weight changes of organs. On day 21 of tumor growth, as compared to control group, nonheme iron content in all three organs was decreased, and zinc content – only in the thymus. The specific activities of catalase and superoxide dismutase were both increased in the thymus, while in the liver activity of superoxide dismutase decreased. At the same time point thymic involution and splenomegaly were developed. In order to normalize metal content mice bearing hepatoma 22a were supplemented with 22 mkg of zinc sulphate per ml of drinking water during 3 weeks. Zinc sulphate supplementation partly compensated zinc deficiency in the thymus, increased zinc content in the liver and restored iron content in three organs. It also normalized superoxide dismutase activity in the liver and had no influence on enzymes in other organs. Zinc supplementation did not influence the weight of spleen and liver, but prevented the development of thymic involution. Moreover, metal deficiency in the thymus was restored while the activity of antioxidant enzymes remained unchanged. Based on this we can conclude that thymus involution in hepatoma 22a mice was associated with iron and zinc deficiency in this organ and was not linked with antioxidant enzyme activity, while splenomegaly had no relation to both types of parameters in the spleen. Thus, zinc sulphate positively influences metabolism of two vital trace elements – zinc and iron in animals bearing hepatoma 22a, what contributes to maintaining of the central immune organ – the thymus, and along with this it improves antioxidant system of the liver.

Coated oregano essential oil and cinnamaldehyde compounds supplementation improves growth performance, enhances immune responses and inhibits cecal Escherichia coli proliferation of broilers.

Plant essential oils are unstable due to high volatility and easy oxidation, while microencapsulation provides a potentially effective strategy for increasing the stability of natural essential oils and preserving their function. This study examined the effects of feeding coated oregano essential oil and cinnamaldehyde (COEC) compounds on growth, immune organ development, intestinal morphology, mucosal immune function, and the cecal microbiota populations of broilers. Three hundred one-day-old male Arbor Acres broiler chicks were organized into five groups: (1) negative control fed basal diet alone (NC), (2) positive control receiving basal diet plus 50mg/kg of chlortetracycline (CTC), (3) basal diet plus 150mg/kg COEC (COEC150), (4) plus 300mg/kg COEC (COEC300), and (5) plus 450mg/kg COEC (COEC450). The supplement trial was continued for 42 days. The results showed that CTC, COEC300 and COEC450 treatments decreased the feed conversion ratio of broilers both in the starter and whole experiment phases, increased the height of jejunal villi at 21 d and the number of goblet cells and IgA-producing cells at 21 or 42 d compared with NC group (P < 0.05). Members of the COEC300 treatment group had a higher thymus weight index and jejunum length index than birds of NC or CTC groups at 21 d (P < 0.05). CTC and all COEC treatments decreased malondialdehyde content in jejunal mucosa at 42 d (P < 0.05). The population of Escherichia coli in the cecal digesta at 21 d was lower in the CTC, COEC300 and COEC450 treatment groups compared with the NC group (P < 0.05). In contrast to the CTC group, COEC supplementation dose-dependently accelerated body weight gain, improved jejunal morphology, decreased malondialdehyde content in jejunal mucosa, increased numbers of jejunal goblet cells and IgA-producing cells, and decreased the Escherichia coli population in cecal digesta at 21 or 42 d (P < 0.05). Thus, we concluded that feeding broiler chickens with 300 or 450mg/kg in antibiotic-free diets can improve growth performance, enhance immune responses and inhibit the proliferation of cecal pathogenic bacteria.

Anti irradiation nanoparticles shelter immune organ from radio-damage via preventing the IKK/IκB/NF-κB activation

BackgroundNormal tissue and immune organ protection are critical parts of the tumor radiation therapy process. Radiation-induced immune organ damage (RIOD) causes several side reactions by increasing oxidative stress and inflammatory responses, resulting in unsatisfactory curability in tumor radiation therapy. The aim of this study was to develop a novel and efficient anti irradiation nanoparticle and explore its mechanism of protecting splenic tissue from radiation in mice.MethodsNanoparticles of triphenylphosphine cation NIT radicals (NPs-TPP-NIT) were prepared and used to protect the spleens of mice irradiated with X-rays. Splenic tissue histopathology and hematological parameters were investigated to evaluate the protective effect of NPs-TPP-NIT against X-ray radiation. Proteomics was used to identify differentially expressed proteins related to inflammatory factor regulation. In addition, in vitro and in vivo experiments were performed to assess the impact of NPs-TPP-NIT on radiation therapy.ResultsNPs-TPP-NIT increased superoxide dismutase, catalase, and glutathione peroxidase activity and decreased malondialdehyde levels and reactive oxygen species generation in the spleens of mice after exposure to 6.0 Gy X-ray radiation. Moreover, NPs-TPP-NIT inhibited cell apoptosis, blocked the activation of cleaved cysteine aspartic acid–specific protease/proteinase, upregulated the expression of Bcl-2, and downregulated that of Bax. We confirmed that NPs-TPP-NIT prevented the IKK/IκB/NF-κB activation induced by ionizing radiation, thereby alleviating radiation-induced splenic inflammatory damage. In addition, when used during radiotherapy for tumors in mice, NPs-TPP-NIT exhibited no significant toxicity and conferred no significant tumor protective effects.ConclusionsNPs-TPP-NIT prevented activation of IKK/IκB/NF-κB signaling, reduced secretion of pro-inflammatory factors, and promoted production of anti-inflammatory factors in the spleen, which exhibited radiation-induced damage repair capability without diminishing the therapeutic effect of radiation therapy. It suggests that NPs-TPP-NIT serve as a potential radioprotective drug to shelter immune organs from radiation-induced damage.

Comparative and experimental pathology of passaged Newcastle disease virus isolates in ducks.

Although waterfowl are less susceptible to Newcastle disease (ND) virus (NDV) infection compared with chickens and turkeys, lethal ND in waterfowl has been sporadically reported. Factors underlying the high pathogenicity of certain NDV strains in waterfowl remain unclear. In ducks, the NDV 9a5b isolate shows low pathogenicity while the d5a20b isolate shows high pathogenicity. This study aimed to identify the definitive lesions that led to the lethal virulence of d5a20b by comparing the histopathology of 9a5b- or d5a20b-inoculated ducks in order to elucidate lesions related to the enhanced pathogenicity of certain NDV strains in ducks. Herein, 7-day-old ducks were intranasally inoculated with either 9a5b or d5a20b NDV strains. The neurological signs were more severe in the d5a20b-inoculated group than in the 9a5b-inoculated group. Ducks in the d5a20b-inoculated group exhibited more severe lymphoid depletion in immune organs than those in the 9a5b-inoculated group, which may have caused an immunosuppressive state in the d5a20b-inoculated ducks. Ducks in the d5a20b-inoculated group had more severe nonsuppurative encephalitis with increased NDV nucleoprotein than those in the 9a5b-inoculated group. Additionally, pancreatic necrosis, with intralesional NDV nucleoprotein, was more severe in the d5a20b-inoculated group than in the 9a5b-inoculated group. Our results showed that the immune organs, brain, and pancreas were significant targets of the NDV d5a20b infection in ducks.

Escherichia coli heat-labile enterotoxin B subunit as an adjuvant of mucosal immune combined with GCRV-II VP6 triggers innate immunity and enhances adaptive immune responses following oral vaccination of grass carp (Ctenopharyngodon idella)

The grass carp reovirus (GCRV) is the most major pathogen that has threatened the grass carp (Ctenopharyngodon idella) industry of China for years. Though the oral vaccine has many advantages, the current vaccines still do not provide complete protection. Therefor the exploration of new preventive strategies is urgently needed. In this study, heat-labile enterotoxin B subunit of Escherichia coli (LTB) was combined with VP6 from GCRV type II (GCRV-II) via Lactococcus lactis expression system to form a potent oral vaccine and determines if fusion of LTB to the protective vaccine antigen can enhance protection in the fish. The expression of recombinant protein was confirmed by Western-blotting and enzyme-linked immunosorbent assay. The rare minnow was set as the model for the evaluation of the experiment administrated orally. The immune response including the antibody titer and the immune-related gene expression, and the protective efficacy which included the virus loaded and the relative protection, were thoroughly investigated after the trial. The results indicated that LTB can significantly elicit a higher neutralizing antibody responses and enhanced T-cell priming, activities and proliferation in mononuclear cells from intestine, spleen and kidney tissues when compared to the VP6 vaccine alone. Moreover, the combined adjuvant can significantly up-regulate type I interferon signaling in different immune organs, especially the mucosa associated lymphoidtissue which could not be induced by VP6 along, result in the contribution of the improvement in adaptive immune responses of the fish. In addition, challenge study showed that LTB combined VP6 could greatly improve the relative percent survival of the fish during the virus infection. These results highlight that LTB has the potential value to be a mucosal adjuvant of the fish, approaching for improving the efficacy of vaccination against GCRV-II, which does elicit both non-specific and specific immune responses.

Effects of Lagenaria siceraria (Molina) Standl polysaccharides on growth performance, immune function, cecum microorganisms and short-chain fatty acids in broilers.

In this study, Lagenaria siceraria (Molina) Standl polysaccharides (LSP) was prepared using the water-alcohol precipitation method to evaluate its effects on growth performance, slaughter performance, cytokines, immune organ indices, cecal short-chain fatty acids (SCFAs), and microbial community structure in broiler chickens when added to the basal diet. Seventy-five broiler chickens were selected and randomly divided into five groups, with 15 chickens per group. All groups were fed a basal diet for 7 days. From 7 days of age, the control group continued to receive the basal diet, while the positive drug group was fed a diet supplemented with Astragalus polysaccharides (APS, 100 g/kg) in addition to the basal diet. The experimental groups were fed diets containing different concentrations of LSP (50, 100, and 200 g/kg) in addition to the basal diet, and the supplementation continued for 42 days. The findings indicated that the incorporation of LSP into the feed significantly enhanced average daily weight gain (ADWG), average daily feed intake (ADFI), feed to gain ratio (F/G), dressing percentage, percentage of breast muscle, percentage of leg muscle, and percentage of abdominal fat while concurrently reducing drip loss rate and cooking loss rate (p < 0.01) in comparison to the control group. Additionally, it significantly augmented the levels of interleukin-4 (IL-4) and interleukin-12 (IL-12) in cytokines, secreted immunoglobulin A (SIgA) and immunoglobulin G (IgG) in immunoglobulins, as well as immune organ indicators (p < 0.05). Furthermore, LSP also modulated the intestinal microbiome composition by increasing the abundance of Bacteroides species and significantly changing concentrations of specific short-chain fatty acids (SCFAs) such as propionic acid, isobutyric acid, acetic acid, and isovaleric acid (p < 0.01). These results suggest that dietary supplementation with LSP can effectively regulate intestinal microbiome composition while promoting short-chain fatty acid production. The alterations in microbial characteristics ultimately contribute to improved intestinal immunity and immune organ development as well as enhanced production performance and immune function in broilers.

Cow Placenta Extract Ameliorates Cyclophosphamide-Induced Intestinal Damage by Enhancing the Intestinal Barrier, Improving Immune Function, and Restoring Intestinal Microbiota

Immunosuppression undermines intestinal barrier integrity. Cow placenta extract (CPE) primarily consists of active peptides with immunomodulatory and antioxidant effects. This study aimed to examine the preventive effect of CPE against intestinal damage induced by cyclophosphamide (Cy) in immunosuppressed mice. Thirty-six mice were randomly allocated into three groups: control group (C), model group (M), and treatment group (CPE). The mice in the CPE group were provided with 1500 mg/kg/day of CPE via gavage. In the last 3 days, mice in the groups M and CPE received intraperitoneal injections of 80 mg/kg/day of Cy. The results showed that CPE improved intestinal barrier function by decreasing serum d-Lactate (D-LA) levels and diamine oxidase (DAO) activity, while elevating the relative expression of Occludin, zonula occludens-1 (ZO-1), and mucin-2 (MUC-2) mRNA. Additionally, CPE improved the immune organ index and elevated the levels of secretory immunoglobulin A (sIgA), superoxide dismutase (SOD), interleukin-1beta (IL-1β), interleukin-4 (IL-4), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) in the intestine, thereby enhancing intestinal mucosal immune function. Furthermore, CPE improved the diversity of intestinal microbiota and increased the abundance of Candidatus_Saccharimonas, Psychrobacter, and Enterorhabdus, which promoted the proper functioning of the intestines. These findings suggest that CPE effectively ameliorates Cy-induced intestinal damage by enhancing the intestinal barrier, improving immune function, and restoring intestinal microbiota.

Effects of Dietary Yeast β-1,3/1,6-D-Glucan on Immunomodulation in RAW 264.7 Cells and Methotrexate-Treated Rat Models.

A new subclass of nutraceuticals, called immunoceuticals, is dedicated to immunological regulation. Although yeast-derived β-1,3/1,6-D-glucan shows promise as an immunoceutical candidate, further studies are needed to define its precise immune-enhancing processes and to standardize its use. Following methotrexate (MTX)-induced immunosuppression in rats, we evaluated the immunomodulatory efficacy of a highly pure and standardized β-1,3/1,6-D-glucan sample (YBG) in RAW 264.7 macrophages. In in vitro and in vivo models, YBG demonstrated remarkable immunomodulatory effects, such as repair of immune organ damage, elevation of blood cytokine levels, and enhanced phagocytosis and nitric oxide production in RAW 264.7 cells. These results are consistent with the established immunostimulatory properties of β-glucan. It is noteworthy that this research indicates the potential of YBG as an immunomodulatory nutraceutical, as it is among the first to demonstrate immunological augmentation in an immunosuppression setting produced by MTX. Based on these observations, further investigation of YBG is warranted, particularly given its potential to emerge as a combination immunoceutical to mitigate immunosuppression and reduce the risk of infection in rheumatoid arthritis (RA) patients receiving long-term MTX therapy.

7662 Mass Spectrometry Imaging Reveals Region-, Age-, And Sex-Specific Effects Of Lipopolysaccharide Administration On Glucocorticoids In Mouse Lymphoid Organs

Abstract Disclosure: M. Salehzadeh: None. S. Khan: None. R. Andrew: None. K.K. Soma: None. Glucocorticoids (GCs) are steroids that are critical for immune function. Immune organs, such as the thymus and spleen, locally produce GCs (i.e., immunosteroids). However, GC concentrations in the thymus and spleen at the cellular level, and how these levels are affected by stress, remain largely unknown. We used state-of-the-art mass spectrometry imaging (MSI) to elucidate the spatial distribution of GCs in the neonatal and adult mouse thymus and spleen 1) at baseline and 2) after an acute stressor. We used MSI to measure 11-deoxycorticosterone (DOC), corticosterone, and 11-dehydrocorticosterone (DHC) in different regions of the thymus (medulla/cortex) and spleen (white/red pulp) after an immunological challenge. We administered lipopolysaccharide (LPS; i.p.) at low (50μg/kg) and high (400μg/kg) doses or saline (vehicle) to male and female C57BL/6J mice at post-natal day (PND) 5 (neonatal) and 90 (adult) (n=6/sex/group/age). 4hr after treatment, we collected thymus and spleen on liquid nitrogen. Cryosections (10μm) were subject to MSI following Girard-T reagent derivatization and α-cyano-4-hydroxycinnamic acid matrix application. Matrix assisted laser desorption/ionisation (MALDI) was used for sampling, coupled to Fourier-transform ion cyclotron mass spectrometry (100μm resolution; positive mode; Bruker 12T SolariX). Adjacent sections were taken to determine histological zones by H&amp;E staining. Preliminary results indicate that LPS increased DOC, corticosterone, and DHC levels by 2- to 9-fold in lymphoid organs at both ages. There was a dose-dependent increase in thymus and spleen GC levels at PND5, but not PND90. At PND5, GC levels were similarly distributed across each tissue in both sexes. In contrast, at PND90, thymic corticosterone levels were greater in males than females in the medulla and cortex. Interestingly, in PND90 thymus, the medulla had greater DHC levels than the cortex only after LPS treatments. In PND90 spleen, GC levels significantly increased after LPS, yet there was no significant difference in GC distribution between sexes or red and white pulp. These results suggest that GC production is uniform across neonatal lymphoid organs. However, in adulthood, the thymus exhibits region-specific GC metabolism. Our results expand knowledge of steroid intracrinology in thymus and spleen and potential effects of environmental stressors (e.g., infectious diseases, toxins) on immune GC responses. Further, our novel MSI method for GC detection in murine lymphoid organs can help inform future techniques in pharmacokinetics for localized thymic and splenic targeting of steroids and steroid modulators. Presentation: 6/3/2024

Chromone components of Saposhnikovia divaricate attenuate rheumatoid arthritis development by inhibiting the inflammatory response

Ethnopharmacological relevanceSaposhnikovia divaricata (Turcz.) Schisck., a traditional Chinese medicine (TCM), has historically been utilized in the clinical treatment of RA. It was initially documented in the 'Shennong Ben Cao Jing' as a superior quality, with the text stating: 'The herb is widely renowned for its efficacy in alleviating whole-body discomfort, bone pain, malaise, and promoting long-lasting vitality. Chromones (CHR) were identified as the primary active components in Saposhnikovia divaricata. However, the specific molecular mechanisms by which CHR impacts RA remain incompletely understood. Aim of the studyTo explore the therapeutic efficacy of CHR, a class of compound derived from Saposhnikovia divaricata, in alleviating arthropathy and immune hyperactivity in a collagen-induced arthritis (CIA) mouse model. Material and methodsSurface plasmon resonance (SPR) molecular fishing and UHPLC-QTOF/MS technology were used to identify CHR in Saposhnikovia divaricata as an active ingredient for treating RA. A CIA mouse model was used to verify the anti-RA effect of CHR in vivo. The anti-RA efficacy of CHR in vivo was evaluated by body weight change, joint swelling, arthritis index, immune organ index, ankle joint disease, and immunoglobulin G (IgG) content. The mechanism of improving RA was further analyzed by a protein chip assay and verified by Western blotting. ResultsCHR treatment reduced swelling, arthritis index, and IgG, IgG1, IgG2a, and IgG2b levels in CIA mice. Protein microarray indicated that CHR mitigated CIA-induced joint inflammation by inhibiting immune cell activation, reducing the expression of inflammatory factors and chemokines, potentially by modulating the rheumatoid arthritis pathway involving tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), and chemokines. This hypothesis was supported by the upregulation of bone morphogenetic proteins 3 (BMP3) and phospho-Smad2 (p-Smad2) proteins, coupled with the downregulation of interleukin-6 (IL-6), interleukin-1β (IL-1β), TNF-α, and IL-17A proteins in the joints of CHR-treated mice. ConclusionCHR shows promise as a potential therapeutic agent for RA, exerting its effects through anti-inflammatory mechanisms.