Immune Organ Index Research Articles

Improving dexamethasone drug loading and efficacy in treating rheumatoid arthritis via liposome: Focusing on inflammation and molecular mechanisms.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects approximately 0.46% of the global population. Conventional therapeutics for RA, including disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs), and corticosteroids, frequently result in unintended adverse effects. Dexamethasone (DEX) is a potent glucocorticoid used to treat RA due to its anti-inflammatory and immunosuppressive properties. Liposomal delivery of DEX, particularly when liposomes are surface-modified with targeting ligands like peptides or sialic acid, can improve drug efficacy by enhancing its distribution to inflamed joints and minimizing toxicity. This study investigates the potential of liposomal drug delivery systems to enhance the efficacy and targeting of DEX in the treatment of RA. Results from various studies demonstrate that liposomal DEX significantly inhibits arthritis progression in animal models, reduces joint inflammation and damage, and alleviates cartilage destruction compared to free DEX. The liposomal formulation also shows better hemocompatibility, fewer adverse effects on body weight and immune organ index, and a longer circulation time with higher bioavailability. The anti-inflammatory mechanism is associated with the downregulation of pro-inflammatory cytokines like tumor necrosis factor-α (TNF-α) and B-cell-activating factor (BAFF), which are key players in the pathogenesis of RA. Additionally, liposomal DEX can induce the expression of anti-inflammatory cytokines like interleukin-10 (IL-10), which has significant anti-inflammatory and immunoregulatory properties. The findings suggest that liposomal DEX represents a promising candidate for effective and safe RA therapy, with the potential to improve the management of this debilitating disease by providing targeted delivery and sustained release of the drug.

Immunostimulatory activity of sea buckthorn polysaccharides via TLR2/4-mediated MAPK and NF-κB signaling pathways in vitro and in vivo

SP0.1–1, derived from Sea buckthorn (Hippophae rhamnoides L.), has been discovered to exhibit unique antioxidant activity. In this study, we investigated the immunomodulatory activity and mechanisms of SP0.1–1 on macrophage RAW 264.7 cells in vitro and immunosuppressive mice induced by cyclophosphamide in vivo. The results indicated SP0.1–1 strengthened the immune functions via promoting the proliferation of RAW264.7 cells and phagocytic activity, along with stimulating the release of NO, ROS and cytokines including TNF-α, IL-6, IL-1β and IFN-γ. Western blot and molecular docking analysis demonstrated that SP0.1–1 attached to the prime receptors TLR2 and TLR4 in RAW264.7 cells, and triggered the activation of MyD88-mediated MAPK and NF-κB signaling pathways, thereby exerting the immune response in RAW264.7 cells. However, the intervention of specific inhibitors against TLR2, TLR4, JNK, ERK, p38 and NF-κB blocked the TLR-mediated MAPK and NF-κB signaling pathways and downregulated the levels of NO and the aforementioned cytokines, thus suppressing the activation of macrophages. Therefore, it can be speculated that SP0.1–1 activated the macrophages principally via the TLR2/4-MyD88-mediated MAPK and NF-κB signaling pathways. Additionally, SP0.1–1 could protect against the cyclophosphamide-induced immunosuppression in mice, manifested by the improvement of body weight, immune organ indices, phagocytic index, and the relievement of spleen damage, along with the enhancement of cytokines TNF-α, IL-6, IFN-γ and immunoglobulin IgG and IgM. These findings will shed light on the molecular mechanism of SP0.1–1 on the immunoregulatory effect, and lay the foundation for exploiting a potential immunostimulatory agent of SP0.1–1.

Lacticaseibacillus rhamnosus LRa05 alleviates cyclophosphamide-induced immunosuppression and intestinal microbiota disorder in mice.

Probiotics play a crucial role in regulating the gut microbiota and enhancing immune response. Oral administration of probiotics modulates intestinal microbiota composition and immune homeostasis. In this study, we investigated the immunoregulatory effect of Lacticaseibacillus rhamnosus LRa05 on cyclophosphamide (CTX)-induced immunosuppressive mice. The results showed that oral administration of LRa05 reduced weight loss, restored immune organ indices, and maintained the structural integrity of the intestinal tissue in CTX-treated mice. Moreover, oral administration of LRa05 exhibited immune-modulating properties by promoting the secretion of cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-10, and secretory immunoglobulin A) in serum. Moreover, the analysis of 16S rRNA amplicon sequencing revealed that LRa05 increased gut microbiota diversity and regulated its composition. In detail, LRa05 intervention restored the Firmicutes/Bacteroidota ratio and significantly increased the relative abundance of Lachnospiraceae_NK4A136_group, Oscillibacter, Alloprevotella, Parasutterella, and Roseburia in immunocompromised mice. Conversely, the abundances of Helicobacter, Bacteroides, and unclassified_Desulfovibrionaceae were significantly decreased after administration of LRa05. Based on these findings, orally administered LRa05 could effectively maintain intestinal microbiota homeostasis and regulate immunity, suggesting the potential of L. rhamnosus LRa05 as a candidate probiotic strain in the application of dietary supplement. PRACTICAL APPLICATION: Supplement with L. rhamnosus LRa05 can improve immunity, regulate gut microbiota and promote body health.

Extraction and Identification of Polysaccharide from Lentinus edodes and Its Effect on Immunosuppression and Intestinal Barrier Injury Induced by Cyclophosphamide.

Lentinus edodes serves as a significant source of both medicine and food, with its key component, lentinan (LNT), recognized as an effective immunomodulator. However, the mechanisms by which it regulates immune and intestinal functions under conditions of immunosuppression remain unclear. This study aims to investigate the components of lentinan and examine its potential effects on countering cyclophosphamide (CP)-induced immunosuppression, intestinal barrier damage, and dysregulation of gut microbiota. In this study, the effects of LNT were evaluated by serological indicators, histopathological changes in ileum, tight-junction-related protein expression, cytokine expression levels, and gut microbiota 16S rRNA gene sequencing. We found that LNT was effective in mitigating the abnormalities in body weight, immune organ index, and serum levels of IL-6, IL-2, IFN-γ, and IgG in mice induced by CP (p < 0.05). Furthermore, LNT demonstrated the ability to alleviate intestinal barrier damage induced by CP by increasing the mRNA levels of TNF-α, IL-1β, IFN-γ, Occludin, and ZO-1 (p < 0.05). Additionally, 16S rRNA gene sequencing revealed that LNT also normalized the disrupted abundance of Firmicutes, Proteobacteria, and Bacteroidets caused by CP. This restoration brought the gut microbiota back to normal levels and increased the abundance of certain tumor-inhibiting bacteria, such as Alistipes. Overall, lentinan demonstrated the ability to reverse the immunosuppressive effects induced by cyclophosphamide and modulate gut microbiota to restore a healthy microbial balance.

Immunomodulation of exopolysaccharide produced by Lacticaseibacillus rhamnosus ZFM216 in cyclophosphamide-induced immunosuppressed mice by modulating gut microbiota

This study investigated the immunoregulatory activity of exopolysaccharides (EPS) produced by Lacticaseibacillus rhamnosus ZFM216 in immunosuppressed mice induced by cyclophosphamide (CTX). The results showed that EPS treatment effectively improved the body weight, immune organ index and splenic lymphocyte proliferation. EPS also mitigated the damage of immune organs, restored intestinal morphology, and regulated the levels of serum hemolysin and cytokines (e.g. TNF-α, INF-γ and IL-10). EPS promoted the release of NO, TNF-α, IL-1β, and IL-6 in RAW 264.7 cells, however, such effect was inhibited in the presence of inhibitors of TLR4 and MAPKs signaling pathways-related proteins, confirming that EPS achieved the immunomodulation by activating these two signaling pathways. Additionally, EPS, as a prebiotic, effectively improved the diversity of microbial communities, regulated the relative abundance of dominant microbial communities, restored CTX-induced gut microbiota dysbiosis, and promoted the production of short chain fatty acids (SCFAs) in the gut of mice. Thus, immunoregulatory effect of EPS could be attributed to its good ability to modulate the gut microbiota. EPS produced by L. rhamnosus ZFM216 has promising application as an ingredient of functional foods due to its potent probiotic effect.

Proteomic Insights into the Effects of Jianweixiaoshi Tablets on Functional Dyspepsia with Spleen Deficiency in Rats.

Jianweixiaoshi tablets (JWXS) is widely used in traditional Chinese medicine for treating functional dyspepsia with spleen deficiency (SD-FD) in China. However, the molecular mechanisms underlying the therapeutic effects of JWXS remain incompletely understood. Functional dyspepsia was induced in rats with spleen deficiency by iodoacetamide in combination with the modified multiple platform method. The SD-FD rats were administered JWXS at both low and high doses, as well as domperidone. We conducted a comprehensive evaluation of the treatment effects of JWXS, including body weight, gastrointestinal motility, immune organ index, biochemical analysis, gastrointestinal hormones, and hematological studies. Quantitative proteomic analysis based on data-independent acquisition (DIA) was used to determine the changes in protein profiles of gastric and duodenal tissues in SD-FD rats and JWXS intervention rats. The results showed that JWXS effectively alleviated gastrointestinal motility disorders in SD-FD rats, as indicated by accelerated gastric emptying and intestinal propulsion, increased levels of gastrin, motilin, and ghrelin, and reduced levels of cholecystokinin-octapeptide, vasoactive intestinal peptide, and somatostatin. Additionally, JWXS increased the spleen and thymus index, increased %lymphocyte in blood, reduced white blood cell count and %neutrophil, and improved immune function. Through quantitative proteomic analysis of gastric tissues, we identified 333 differentially expressed proteins in the JWXS treatment group and the model group. Notably, the mechanism by which JWXS accelerated gastric emptying may be related to PLC-γ and SERCA2 in the calcium signaling pathway. Furthermore, JWXS treatment altered the expression of 732 proteins in rat duodenal samples. The differentially expressed proteins were enriched in immune-related functions and pathways, including antigen processing and presentation, as well as the intestinal immune network for IgA production. In conclusion, JWXS exhibits a multi-faceted impact on various pathways, demonstrating its efficacy in treating SD-FD. These findings provide a foundation for the clinical application of JWXS in managing SD-FD.

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 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.

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.

Atractylodes macrocephala polysaccharides shield a D-galactose-induced aging model via gut microbiota modulation

This study explored the effect of a heteropolysaccharide (RAMP) on aging model mice and the importance of changes in the gut microbiota mediated by RAMP for the first time. The findings revealed that RAMP exerted protective effects on cognitive decline and oxidative stress in mice subjected to D-gal-induced aging, potentially by regulating the intestinal flora, according to the results of the Morris water maze test; brain and immune organ indices; hematoxylin and eosin-stained cerebral cortex images; transmission electron microscopy analysis of cortical neurons; and biochemical index measurements. In addition, 16S rRNA sequencing revealed notable changes in the abundance of Acidobacteriota, Anaerovoracaceae, and GCA-900066575 in the mouse model, all of which were abrogated by RAMP. These findings confirm that RAMP regulates the composition of mouse intestinal microorganisms. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) functional analyses linked these changes to 27 metabolic pathways, including those of the nervous system. Furthermore, metabolomics analysis revealed four RAMP-regulated metabolites related to lipid metabolism (2-dodecylbenzenesulfonic acid, N-undecylbenzenesulfonic acid, aspartyl-isoleucine, and 1-palmitoyl-2-(5-oxo-valeroyl)-sn-glycero-3-phosphate), suggesting that the mechanism potentially associated with lipid metabolism regulation. This study provides novel insights into the antiaging mechanisms of RAMP, suggesting its potential use in antiaging treatments.

Dietary supplementation of distiller's grains yeast cultures improves performance and immunity by altering the intestinal flora of broilers.

Distiller's grains are a by-product of liquor production with a higher yield than liquor. Developing and utilizing distiller's grains well could alleviate the problem of scarce feed resources. Our present experiment was conducted with 6000 yellow-feathered broilers to study the effects of adding distiller's grains yeast cultures (DGYC) to the diet on growth performance and immunity of broilers. The broilers were divided into five groups, receiving different DGYC concentrations during two stages. Growth performance, intestinal microorganisms and immune organ development were measured. The results showed that groups B and D, supplemented with medium and high concentrations of DGYC, respectively, had significantly improved growth performance compared to the control group (P < 0.05). Group D also showed higher immune organ index (P < 0.01), increased serum total protein, high-density lipoprotein and immunoglobulin levels (P < 0.05) and lower levels of low-density lipoprotein, triglycerides, interleukin 1β and tumor necrosis factor α (P < 0.05). Hematoxylin and eosin staining confirmed improved immune organ development in group D (P < 0.05). Furthermore, in high-concentration group D, levels of short-chain fatty acids (SCFA; acetic, propionic and butyric acids) in cecal chyme were significantly increased (P < 0.05). The richness (Chao1) and diversity (Faith-pd) index of cecal microbiota were significantly higher in group D compared to the control group (P < 0.05). The microbial composition in group D differed from the control and medium-concentration group B. Seven bacteria (Clostridia-UCG-014, UCG-009, DTU089, UCG-010, Campylobacter, Harryflintia, Shuttleworthia) showed significant differences (P < 0.05). After DGYC feeding, DTU089 decreased, while other SCFA-producing bacteria increased (P < 0.05). Subsequently, KEGG function and corresponding signal pathway predictions were performed on bacteria with significant differences. Group D exhibited a higher enrichment of immune function pathways (P < 0.01) and showed significant changes in four immune signaling pathways according to the signal pathway heatmap. Our data suggest that high concentrations of DGYC can be applied as a feed additive for broilers that promotes growth, improves intestinal health and enhances certain immunity. © 2024 Society of Chemical Industry.

Anti-colorectal cancer activity of mannatide from spent brewer's yeast by regulating immune cells and immune function in the tumor microenvironment

Chemotherapy and radiotherapy are generally accompanied by adverse effects, which reduce tolerance to cancer therapies. Immunonutrition improves the clinical outcomes of cancer patients. Hence, natural immunomodulator is therefore considered as a favorable alternative. This study aimed to elucidate the anti-colorectal cancer (CRC) effect of mannatide (MTE) from the immunostimulatory perspective. MTE (concentrations≥1200 μg/mL) significantly inhibited HT-29 cells viabilities compared with the 5-fluorouracil (5-FU) group and all predetermined concentrations of MTE promoted the proliferation of RAW264.7 (p < 0.01). Moreover, MTE treatment suppressed tumor growth, decreased leukocyte and platelet count, and regulated immune organ indexes compared with the model group. In comparison of Model and 5-FU groups, MTE treatment reshaped tumor-associated macrophages (TAMs) from alternatively activated macrophages (M2)-like into classical activated macrophages (M1)-like phenotype. Also, it increased the proportion of CD8+ and CD4+ T cells accompanied by secreting pro-inflammatory cytokines (interferon (IFN)-γ and tumor necrosis factor (TNF)-α) and decreasing pro-inflammatory cytokines (interleukin (IL)-4, interleukin (IL)-6, arginine (Arg)-1, and cyclooxygenase (COX)-2) to reduce immunosuppression. Moreover, MTE-administrated alleviated intestinal mucositis and improved the prognostic indexes compared with the 5-FU group. Notably, the ability of low-dose MTE to regulate immune cells and the function of the tumor microenvironment was higher than that of high-dose. Generally, MTE as an immunomodulator presents great potential to strengthen anti-CRC activity.

Efficacy of Qi-Gen powder for immunity enhancement and investigation of its therapeutic mechanisms through gene expression profiling

Infection with different viruses threatens the health of animals in the livestock and poultry industry. Immunopotentiators can increase natural immunity and vaccination efficacy; however, most are expensive chemical and biological compounds with questionable safety. Traditional Chinese medicines (TCMs) such as Yupingfeng (YPF), a well-known immunomodulatory remedy, provide healthy alternatives to such agents. The aim of this study was to examine the therapeutic properties of Qi-Gen powder (QG) and compare them with those of YPF. The immune organ index, cytokine levels, and other indicators were utilized to evaluate the effects of QG in an immunosuppression mouse model. QG was further assessed for its ability to enhance vaccine effectiveness in chickens immunized for Newcastle disease virus (NDV). Potential therapeutic mechanisms and targets of QG were examined in the breast cancer cell line MCF-7 using microarray technology combined with the TCM systems pharmacology database of known targets. Compared with model controls, QG improved immunological function, outperforming YPF in mice. QG also enhanced the immunological response to NDV vaccine in immune organs and increased feed intake of chickens. Further research is needed to validate the link between the PI3K/Akt/GSK-3 pathway and the immune-boosting effects of QG.

Effect of Phage Spray on Hatchability and Chick Quality of Eggs Contaminated with Salmonella Typhimurium.

Salmonella Typhimurium (S. Typhimurium) contamination poses a significant challenge to breeder egg hatchability and chick health, necessitating the exploration of alternative disinfection methods. This study investigates the potential of phage vB_SPuM_SP02 (SP02) as a novel disinfectant for breeder eggs contaminated with S. Typhimurium SM022. Phage SP02 was isolated from poultry farm effluent and characterized for morphology, biological properties, and genome properties. Experimental groups of specific pathogen-free (SPF) eggs were treated with Salmonella and phage SP02, and efficacy was assessed through hatching rates, chick survival, weight, Salmonella load, immune organ indices, and intestinal flora. Phage treatment effectively eradicated Salmonella contamination on eggshells within 12 h, resulting in increased hatching and survival rates compared to controls. Furthermore, phage treatment mitigated weight loss and tissue Salmonella load in chicks without causing immune organ damage while reducing Salmonella spp. abundance in the intestinal tract. This study demonstrates the potential of phage SP02 as an eco-friendly and efficient disinfectant for S. Typhimurium-contaminated breeder eggs, offering promising prospects for practical application in poultry production.

Mesua assamica (King & Prain) kosterm. bark ethanolic extract attenuates rheumatoid arthritis via down-regulating TLR4/NF-κB/COX-2/iNOS and activation of Nrf2/HO-1 pathways: A comprehensive study on in-vitro and in-vivo models

Ethnopharmacological relevanceRheumatoid arthritis (RA) is a multifactorial, polygenic inflammatory disease. Mesua assamica (King & Prain) Kosterm. (MA) is an endangered medicinal plant indigenous to South Asia, primarily to Assam in India. The tree bark is claimed to possess anti-inflammatory, anti-diabetic, anti-cancer, and anti-malarial properties; nevertheless, its role in RA has not been elucidated. Hence, this study aims to investigate the in-vitro and in-vivo anti-arthritic effects of Mesua assamica bark ethanolic extract (MAE). Aim of the studyThis study aims to investigate the anti-rheumatic potential of MAE in-vitro on RAW 264.7 cells for its anti-oxidant and anti-inflammatory activities and in-vivo on the CFA-induced adjuvant arthritis in the rat model. Materials and methodsWe investigated the possible therapeutic effects of MAE in-vitro using RAW 264.7 cells triggered by LPS. Meanwhile, adult Wistar rats were injected intradermally with 100 μl of CFA to induce arthritis, and they were given MAE orally at doses of 100 and 200 mg/kg for up to 28 days. Paw volume analysis, X-ray radiography, anti-oxidant levels analysis, gene and protein expression studies, and histological analysis were carried out to assess the effects of MAE in-vivo. ResultsMAE significantly mitigated the inflammation by reducing ROS levels and dropped the nitrite, PGE2, and COX-2 levels enhanced by LPS in-vitro. At the same time, MAE treatment reduced the paw and joint inflammation and increased the immune organ index in the CFA rats. Histopathology data revealed that MAE mitigated the CFA-induced lesions of the ankle joints and synovial tissues. Similarly, MAE significantly abated the secretion of pro-inflammatory cytokines, inhibited the protein expression of TLR4, NF-кB, COX-2, and iNOS, as well as improved the Nrf2 and HO-1 levels in-vitro and in-vivo. ConclusionAll the results highlighted the anti-rheumatic potential of MAE in RA in-vitro and in-vivo by inhibiting the TLR4/NF-кB/COX-2/iNOS and promoting the Nrf2/HO-1 signaling axis.

Immune mechanism of Daphnes Cortex and its processed products on CIA rats based on B7/CD28/CTLA-4 pathway

This study investigates the effects of Daphnes Cortex and its processed products on the differentiation of Th17/Treg cells in SD rats with type Ⅱ collagen-induced arthritis(CIA).Sixty-four SD rats were randomly divided into the normal group(normal),model group(model),fried Daphne giraldii Nitsche low-dose and high-dose groups(FDGN-L group, FDGN-H group),raw D. giraldii Nitsche low-dose and high-dose groups(RDGN-L group, RDGN-H group),daphnetin group(DAPH group),and tripterygium glycosides group(GTW group).Except for the normal group, the CIA model was immunized on the seventh day after the first immunization, and was gavaged for 28 days after the second immunization.After sampling, the inflammation of articular synovial membrane in CIA rats was observed by hematoxylin-eosin(HE)staining; the levels of transforming growth factor-β(TGF-β),interferon-γ(IFN-γ),interleukin(IL)-2,IL-4,and IL-10 in serum were detected by enzyme-linked immunosorbent assay(ELISA); real-time reverse transcription-PCR(qRT-PCR)and Western blot were used to detect the mRNA and protein expressions of cluster of differentiation(CD) 80(B7-1),CD 86(B7-2),CD28,and cytotoxic T lymphocyte-associated antigen 4(CTLA-4)in the synovial membrane of rats; flow cytometry was used to detect the proportion of Th17 and Treg cells in the synovial membrane of rats.The results showed that compared with the normal group, the joint synovial inflammation of rats in the model group was significantly aggravated, the arthritis index was significantly increased, and the immune organ index was increased(P&lt;0.01).Compared with the model group, each drug administration group could improve the joint inflammation of rats to varying degrees, reduce the arthritis index, inhibit synovial hyperplasia, and reduce the immune organ index; compared with the model group, the serum levels of IL-2 and IFN-γ in each drug administration group were significantly decreased(P&lt;0.01),TGF-β,IL-4,and IL-10 were significantly increased(P&lt;0.01),the mRNA and protein expressions of B7-1 and CTLA-4 in the synovial membrane were significantly increased(P&lt;0.01),and the proportion of Th17 cells and Treg cells in the joint tissue was significantly decreased(P&lt;0.01).In conclusion, Daphnes Cortex inhibits the expression of Th17 cells in CIA rats and promotes the expression of Treg cells by regulating the B7/CD28/CTLA-4 pathway and the balance of Th17/Treg, thereby treating rheumatoid arthritis.

Extraction and immunomodulatory effects of acid Lagenaria siceraria (Molina) Standl. Polysaccharide on chickens

Herbal polysaccharides are extensively studied as vaccine adjuvants due to their safety and potent immunoenhancing activity. This study aimed to analyze the structure of Lagenaria siceraria (Molina) Standl polysaccharide (LSP50) and investigate its adjuvant activity for the H9N2 vaccine in broiler chickens. Structural analysis revealed that LSP50 primarily consisted of rhamnose, arabinose, xylose, mannose, glucose, and galactose with molar ratios of 23.12: 12.28: 10.87: 8.26: 2.64: 22.82 respectively. The adjuvant activity of LSP50 was evaluated, which showing significant enhancements compared to the H9N2 group. Parameters including the immune organ index, H9N2 specific IgG level, cytokines contents (IFN-γ, IL-2, IL-4, and IL-5), and the proportion of CD3e+CD8aT+cells were significantly increased in the LSP50 group (P < 0.05). Additionally, sequencing results showed that LSP50 modulates the immune response by regulating PLA2G12B and PTGDS genes involved in the arachidonic acid pathway. These findings were further validated through qPCR analysis to affirm the reliability of the sequencing data. In conclusion, our results demonstrate that LSP50 exhibits potent adjuvant activity, enhancing both cellular and humoral immunity.

Effect of Wei Qi Booster on immune and anti-oxidative function in aged mice.

This research was conducted to examine the impact of Wei Qi Booster (WQB) on immune parameters and anti-oxidative function in aged mice. Fifty aged mice were randomly assigned to five different groups. Group A was designated as the control group. Mice in Group B were receiving Levamisole at 10 mg/kg body weight. Each mouse in groups C, D and E received 0.1, 1, and 2% WQB, respectively. Another ten young mice, designated as group F, were fed regularly. The mice were fed according to the above methods for 28 days. Results showed that relative to the control group, the body weight and immune organs indexes experienced a substantial rise in the group with 1% WQB. In addition, 1% WQB could improve the activity of SOD and reduce the MDA levels. Expressions of CD4 and sIgA increased while CD8 decreased in the jejunum of aged mice treated with WQB. IL2 and IFN-γ levels increased in the 1% WQB group, showing no notable difference compared to the young mice group. The results demonstrated that WQB can elevate immune levels and enhance anti-oxidative functions in aged mice.

Chemical compounds, anti-tumor and anti-neuropathic pain effect of hemp essential oil in vivo

Hemp (Cannabis sativa L.), an annual dioecious plant, has shown extensive application in the fields of fibers, food, oil, medicine, etc. Currently, most attention has been paid to the therapeutic properties of phytocannabinoids. However, the pharmaceutical research on essential oil from hemp is still lacking. In this study, hemp essential oil (HEO) was extracted from hemp flowers and leaves, and the components were analyzed by GC–MS. Quatitative analysis of three main compounds β-caryophyllene, β-caryophyllene oxide, α -humulene were determined by GC-FID. The anti-tumor and anti-neuropathic pain effects of HEO were evaluated. In the paclitaxel induced neuropathic mice model, HEO reduced the serum level of inflammatory cytokines TNF-α to achieve the analgesic effect, which was tested by evaluating mechanical and thermal hyperalgesia. Further investigation with cannabinoid receptor 2 (CB2 R) antagonist AM630 revealed the mechanism of reversing mechanical hyperalgesia may be related to CB2 R. In Lewis lung cancer grafted mice model, the tumor growth was significantly inhibited, the levels of tumor inflammatory cytokines TNF-α and IL-6 were downregulated, immune organ index was modified and immune-related CD4+, CD8+ T lymphocytes level, CD4+/CD8+ ratio were increased when administered with HEO. These results reveal that HEO plays a role not only in tumor chemotherapy induced peripheral neuropathy treatment, but also in anti-tumor treatment which offers key information for new strategies in cancer treatment and provides reference for the medicinal development of hemp.