Search Results (188)

This research examined the impact of dietary supplementation with Phlogacanthus pulcherrimus extract (PPE) on the growth, disease resistance, and expression of immune-, growth-, and antioxidant-related genes in Labeo chrysophekadion. Over 150 days, 90 fish from each group were fed diets with 0 (control), 0.25, 0.50, or 0.75 g/kg of PPE. Phytochemical analysis revealed phenolics (96.00 mg GAE/g), flavonoids (17.55 mg QE/g), anthraquinones, and triterpenoids, along with moderate antioxidant activity (IC₅₀ = 1314.08 μg/mL). One-way ANOVA of growth indices, including weight gain, specific growth rate, feed conversion ratio, and survival rate, revealed no significant differences (p > 0.05); however, PPE supplementation significantly enhanced immune and antioxidant gene expression. IL-1β was significantly (p < 0.05) upregulated at all doses, with the highest expression observed at 0.50 g/kg, showing a fivefold increase compared to the control. In addition, the highest relative expressions of IGF-1 and CAT were found at 0.75 g/kg, with 4.5-fold and 3.5-fold increases compared to the control, respectively. PPE at 0.75 g/kg decreased the cumulative mortality rate (CMR) by 20% compared to the control group, which had a CMR of 50% following exposure to Aeromonas hydrophila. PPE acted as an effective immunostimulant and antioxidant, supporting reduced antibiotic reliance in aquaculture. Full article

Lipopolysaccharide (LPS), the defining outer membrane component of Gram-negative bacteria, is a potent immunostimulant recognized by Toll-like receptor 4 (TLR4). While extensively studied for its roles in immune activation and barrier disruption, the potential function of LPS as a developmental cue remains largely unexplored. By leveraging Caenorhabditis elegans and its genetic and gnotobiotic advantages, we screened a panel of Escherichia coli LPS biosynthesis mutants. This screen revealed that the loss of outer core glycosylation in the ∆rfaG mutant causes significant developmental delay independent of bacterial metabolism. Animals exhibited developmental delay that was rescued by exogenous LPS or amino acid supplementation, implicating that LPS triggers nutrient-sensing signaling. Mechanistically, this developmental arrest was mediated by the host FOXO transcription factor DAF-16, which is the key effector of insulin/IGF-1 signaling (IIS). Our findings uncover an unprecedented role for microbial LPS as a critical regulator of host development, mediated through conserved host IIS pathways, fundamentally expanding our understanding of host–microbe crosstalk. Full article

Background/objectives: Propolis, known for its medicinal properties, faces challenges in pharmaceutical applications due to its low aqueous solubility, attributed to its resinous and hydrophobic nature. This limits oral administration, reducing its bioavailability and pharmacological activities. To overcome these barriers, cyclodextrins (CDs), cyclic oligosaccharides, are widely studied as carrier systems that enhance the solubility and bioavailability of propolis and other nonpolar compounds. This study aimed to review patents that developed innovative therapeutic approaches to improve the physicochemical and biological properties of propolis through complexation with CDs. Methods: Active and application patents registered over the last 17 years were searched across multiple databases, resulting in the selection of eight inventions for detailed analysis. Results: These patents highlight therapeutic applications of propolis–CD systems for conditions such as diabetes and skin and gastrointestinal cancers, as well as antimicrobial, immunostimulant, and antioxidant effects. Additionally, novel extraction processes free of organic solvents, including nanometric-scale powder extracts, are described. Conclusions: Findings from scientific articles support the patent data, demonstrating that CD complexation significantly enhances the solubility and therapeutic efficacy of propolis. Thus, these patents present an innovative and promising strategy for developing propolis-based pharmaceutical products. Full article

Lactic acid bacteria are components of the gastrointestinal tract microbiota in both humans and animals and are widely used as probiotics. Lactobacillus is the most closely related genus to probiotic activity. It is capable of releasing membrane microvesicles (MVs), whose primary functions include carrying and transmitting antigens to host tissues and modulating host defense responses. In the present study, MVs were isolated from Lactobacillus acidophilus resident in the ileum of free-living rats, and their immunostimulant effect was evaluated in two biological models. MVs were characterized using SDS-PAGE electrophoresis, electron microscopy, and nanoparticle tracking analysis. In the first model, the immunostimulatory effect of MVs was evaluated on ovine abomasal explants, which had been previously stimulated with MVs and then challenged with third-stage larvae of Haemonchus contortus. This resulted in a decrease in the percentage of larval association and favored the migration of inflammatory cells to the infection site. In the second model, the macrophage cell line RAW 264.7 was stimulated with MVs to evaluate the expression of transcripts encoding IL-1β and TNF-α. MVs isolated from L. acidophilus demonstrate immunostimulatory and probiotic effects in the two biological models assessed. This suggested that the MVs possess similar immunostimulatory effects as those reported for the parent bacteria. Full article

Ovotransferrin (OVT) is one of the major proteins of egg white and is known to bind and transport irons in animals. OVT exerts bacteriostatic and bactericidal activities due to its iron-binding capacity. OVT effectively controls the growth of various pathogenic microorganisms, including Pseudomonas, E. coli, Staphylococcus, Proteus, and Klebsiella species, as well as inhibiting the replication of viruses. OVT also has antioxidant, anti-inflammatory, anti-hypertensive, anticancer, and immuno-stimulating properties. For instances, OVT quenches free radicals, induces antioxidant enzymes, suppresses pro-inflammatory cytokines, increases immune cells, reduces angiotensin-converting enzymes, and inhibits the proliferation of cancer cells. In this review, the beneficial effects of OVT in both in vitro and in vivo, particularly livestock, are described. Because of its antimicrobial properties, OVT supplementation in livestock feed would be an excellent alternative to antibiotics, which reducing the development of antibiotic-resistant pathogenic microorganisms. Thus, OVT could be a game-changing protein for the growth, performance, and healthy life of animals. Full article

Measles, hepatitis C, and COVID-19 are significant human diseases caused by RNA viruses. While vaccines exist to prevent infections, there are a small number of currently available therapeutic agents that can effectively treat these diseases after infection occurs. This study explores a new therapeutic strategy using a small molecule designated polyprenyl immunostimulant (PI) to increase innate immune responses and combat viral infections. Using a multi-disciplinary approach, this study quantifies the effects of PI in mice and THP-1 cells using flow cytometry to identify immune phenotypic markers and mass spectroscopy to monitor the metabolomic profiles of immune cells perturbed by PI treatment. The metabolomic studies identified that sphinganine and ceramide, which are precursors of sphingosine-1-phosphate (S1P), were the common metabolites upregulated in THP-1 and mice blood. Sphingosine-1-phosphate can mediate the trafficking of T cells, whereas ceramide can signal the activation and proliferation of T cells, thereby modulating the mammalian host’s immunity. To demonstrate proof-of-principle, a case study was conducted to examine the benefit of administering PI to improve the outcomes of a feline co-infected with two distinct RNA viruses—feline leukemia virus and feline infectious peritonitis virus. Both viruses produce deadly symptoms that closely resemble RNA viruses that infect humans. The results identify quantifiable cellular and metabolic markers arising from PI treatment that can be used to establish a platform measuring the efficacy of PI in modulating the innate immune system. Full article

This study was designed to investigate the immunostimulatory and anticancer efficacies of pectic polysaccharides from ginseng leaves treated using the high-pressure extraction method (HPEM). The isolation of polysaccharides using HPEM resulted in 1.35-fold higher polysaccharide yields than those obtained using the commonly used hot water extraction method. In addition, component sugar analysis of ginseng-leaf-derived polysaccharides (GLHP) showed the presence of nine different types of monosaccharides, including galacturonic acid, galactose, rhamnose, and arabinose, which are characteristic of pectic polysaccharides. In addition, GLHP effectively induced activation of the complement system, and macrophages stimulated with GLHP showed enhanced production of cytokines such as IL-6, IL-12, and TNF-α. Intravenous (i.v.) and oral administration (p.o.) of GLHP significantly increased the cancer-cell-killing ability of spleen-derived NK cells. In a lung-cancer-bearing mouse model using Colon26-M3.1 carcinoma, prophylactic i.v. and p.o. GLHP potently inhibited 95.2% and 33.5% of lung cancer, respectively. Furthermore, GLHP showed significant anticancer effects, even in mice with NK cell dysfunction, via the anti-asialo GM1 antibody. These effects may be related to the cancer-cell-killing effects of cytotoxic T lymphocytes (CTL). Therefore, GLHP, a polysaccharide isolated from ginseng leaves using HPEM, has a potent anticancer effect, and these effects are closely related to the stimulation of various immune factors. Full article

The present study aimed to identify a safe and novel approach using zinc oxide/copper oxide nanocomposites (AZ) to enhance growth parameters, immunity, and fight Sarcoptic mange in vitro and in vivo in rabbits. In vitro: the acaricidal activity of AZ was assessed at concentrations of AZ-25: 2.5% w/w AZ/molasses, AZ-125: 12.5% w/w AZ/molasses, and controls (normal saline, molasses, and Ivermectin) every hour for seven hours under a stereoscopic microscope. In vivo: involved 40 rabbits (10 replicates/group). G1 served as the control negative group (normal un-infected rabbits), G2 served as the control negative group (infected rabbits), the animals in the G3 group were given a combination of AZ (40 mg/kg body weight (BW)) and molasses (5 mg/mL), and G4 served as the control to the vehicle; receiving molasses 8 mL/kg BW twice weekly for 6 weeks. Blood, serum, and tissue samples were collected at the middle and the end of the trial. AZ was made using the sonication sol–gel method. X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) were performed to confirm the crystal structure, purity, particle size, and oxidation states. AZ showed immunostimulant, acaricidal, and antioxidant effects with normal tissue histological structure and low tissue residual levels. Additionally, there were improvements in blood interferon-gamma, immunoglobulin (Ig) M, IgG, phagocytic activity, phagocytic index, globulin, and total protein in the AZ group. The XRD patterns of AZ were coordinated by XRD reference codes Crystallography Open Database (COD): 9016326 for Tenorite (CuO) and by XRD reference COD: 9004179 for Zincite (ZnO). The CuO and ZnO crystal sizes were 21.87 Å and 24.89 Å, respectively. The XPS spectra indicated the presence of Cu as Cu (II) and Zn as ZnO.OH and ZnO. In conclusion, AZ exhibited antioxidant, acaricidal, and immunostimulant effects, with mild residues in the brain, liver, and kidney tissues, while maintaining a normal histological structure of tissues. Full article

The rising prevalence of infectious diseases and immune-related disorders underscores the need for effective and accessible therapeutic solutions. Herbal immunostimulants derived from medicinal plants offer promising alternatives, enhancing immune responses with lower toxicity and fewer side effects than synthetic drugs. This review explores the immunostimulatory potential of Morinda citrifolia, Echinacea purpurea, and Phyllanthus niruri, focusing on their bioactive compounds, mechanisms of action, and therapeutic relevance. These plants modulate innate and adaptive immune responses by activating macrophages, dendritic cells, and lymphocytes while regulating cytokine production to maintain immune homeostasis. Their immunomodulatory effects are linked to key signaling pathways, including NF-κB, MAPK, and JAK/STAT. In vitro and in vivo studies highlight their potential to strengthen immune responses and control inflammation, making them promising candidates for managing infectious and immune-related diseases. However, further research is needed to standardize formulations, determine optimal dosages, and validate safety and efficacy in clinical settings. Addressing these gaps will support the integration of herbal immunostimulants into evidence-based healthcare as sustainable and accessible immune-enhancing strategies. Full article

It is essential to comprehend the humoral immune response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its vaccines to maximize the effectiveness of anti-SARSCoV-2 community immunization efforts. The aim of this cross-sectional study was to determine the seroprevalence of anti-SARS-CoV-2 IgM/IgG among newcomer students at Kafr Elsheikh University in Egypt, whether they had been vaccinated or not. Blood samples from 400 healthy newcomer students (200 non-vaccinated and 200 vaccinated) were evaluated for the presence of anti-SARS-CoV-2 IgM/IgG using colloidal gold immunochromatography lateral flow immunoassay cards, and then the results were confirmed by using specific ELISA tests. The prevalence of anti-SARS-CoV-2 antibodies among the participants (n = 400) was 56.3% for IgG and 13.3% for IgM. Regarding the non-vaccinated participants, 55.0% were females, the mean age was 18.2 years, and the mean BMI was 25.35. Regarding the vaccinated participants, 58.5% were females, the mean age was 18.1 years, and the mean BMI was 25.3. There were statistically non-significant correlations (p ˃ 0.05) between gender, BMI, and each of IgM- or IgG-positivity in both vaccinated and non-vaccinated groups. In total, 41.5% and 48.5% of the anti-SARS-CoV-2 IgM-positive and anti-SARS-CoV-2 IgG-positive participants were non-vaccinated, respectively. Furthermore, 58.5% and 51.5% of the anti-SARS-CoV-2 IgM-positive and anti-SARS-CoV-2 IgG-positive participants were vaccinated, respectively. No statistically significant association (p ˃ 0.05) in immunoglobulins positivity between the anti-SARS-CoV-2 non-vaccinated, and vaccinated groups. The anti-SARS-CoV-2 immunological response of nonsmokers, people who exercise regularly, and those who take vitamin supplements, eat a balanced diet, and use certain herbs is noteworthy. Among the vaccinated subjects, 96.6%, 25.0%, 31.9%, 45.7%, and 7.8% of the IgG-positive group, versus 97.2%, 60.6%, 64.2%, 52.3%, and 6.4% of the IgG-positive non-vaccinated group, were nonsmokers, exercisers, and those taking vitamin supplements, eating a balanced diet, and using herbs, respectively. Furthermore, 93.5%, 32.3%, 35.5%, 48.4%, and 6.5% of the IgM-positive vaccinated group, versus 100.0%, 63.6%, 81.8%, 45.5%, and 4.5% of the IgM-positive non-vaccinated participants, were nonsmokers, physical exercisers, vitamin supplement users, balanced eaters, and herbalists, respectively. Persons who are free from comorbidities, young, non-obese, non-smokers, engage in physical exercise, take vitamins, eat a balanced diet, and use certain immunostimulant herbal supplements, all have a strong anti-SARS-CoV-2 humoral immune response, even if they were not vaccinated. During pandemics, vaccination of this group should not be a priority to preserve vaccine doses for high-risk vulnerable people. Even if there is a lockdown during an anticipated future epidemic or pandemic, we should prioritize healthy eating and lifestyle choices, along with increasing physical activity. Full article

This study analyzed the performance, antioxidant status, hepatopancreatic lipoperoxidation, and proximate composition of Macrobrachium rosenbergii juveniles fed diets supplemented with clove basil (Ocimum gratissimum) essential oil (EO-OG). A total of 360 M. rosenbergii (initial weight 0.028 g ± 0.004) were randomly divided into four experimental groups with six replications each (n = 6). The prawns were fed diets with different EO-OG inclusion levels: 0.0, 1.0, 2.0, and 3.0 g kg⁻¹ EO-OG. After a 42-day feeding trial, dietary EO-OG showed no significant effect on prawn performance or carcass proximate composition, except on final antenna length. Prawns fed 3.0 g kg⁻¹ EO-OG displayed a 1.2- to 1.3-fold longer final antenna length than prawns from all other experimental groups. Likewise, prawns fed 3.0 g kg⁻¹ EO-OG presented a 2.6- to 3.2-fold higher catalase activity than prawns from all other experimental groups. Prawns fed EO-OG, regardless of the inclusion level, showed a 1.6- to 1.7-fold decreased hepatopancreatic lipoperoxidation compared to the control group. Therefore, EO-OG has been demonstrated to be a potential management tool as a non-nutritional dietary immunostimulant and animal welfare promoter for freshwater prawn farming, without affecting animal performance. This study recommends the dietary inclusion level of 3.0 g kg⁻¹ EO-OG for M. rosenbergii juveniles. Full article

Background: As the population ages, enhancing immune function is crucial to mitigating age-related physiological decline. Since immunostimulant drugs are known to have potential side effects, medicinal plants emerge as promising candidates offering a safer alternative. To leverage the advantages of medicinal plants with fewer side effects and develop a potent immune-enhancing agent, we investigated the efficacy of a novel immunomodulatory candidate derived from the combination of Angelica gigas and Pueraria lobata (CHL). Methods: In vitro, CHL was treated in RAW 264.7 macrophages at various time points, and the experiments conducted in the study were performed using ELISA, Western blot, and RT-qPCR analysis. In vivo, C57BL/6 mice were administrated CHL for 16 days (p.o.) and CTX on the three days (i.p.), and experiments were conducted with ELISA, western blot, RT-qPCR analysis, H&E staining, flow cytometry, gut microbiome, and correlation analysis. Results: In vitro, CHL has upregulated NO and cytokines expression, substantially enhancing the NF-κB and MAPK activation. Furthermore, CHL promoted the TAK1, TRAF6, and MyD88 via TLR2/6 signaling. In vivo, the CHL improved the reduced body weight and immune organs’ indices and recovered various cytokines expression, NK cell cytotoxicity activity, and immune cell population. CHL also improved the histological structure and tight junction markers, mucin-2, and TLR2/6 in the intestines of CTX-induced mice. Conclusions: Overall, CHL demonstrated immunostimulatory potential by enhancing immune responses and restoring immune function, suggesting its promise as a safe and effective immune-enhancing agent. Full article

The present research aimed to assess the anti-cancer effects of the polysaccharide fraction (SJP) isolated from Saccharina japonica. The release of immune-activating cytokines, including IL-6, IL-12, and TNF-α, was markedly stimulated by the SJP in a concentration-dependent manner within the range of 1 to 100 µg/mL. Furthermore, the prophylactic intravenous (p.i.v.) and per os (p.p.o.) injection of SJP boosted the cytolytic activity mediated by NK cells and CTLs against tumor cells. In a study involving Colon26-M3.1 carcinoma as a lung cancer model, both p.i.v. and p.p.o. exhibited significant anti-lung-cancer effects. Notably, p.i.v. and p.p.o. administration of SJP at a dose of 50 mg/kg reduced tumor colonies by 84% and 40%, respectively, compared to the control. Moreover, the anti-lung-cancer effects of SJP remained substantial, even when NK cell function was inhibited using anti-asialo-GM1. Fractionation with CaCl₂ suggested that SJP is a mixture of alginate and fucoidan. The fucoidan fraction stimulated the immune response of macrophages more strongly than the alginate fraction. Consequently, this finding suggested that SJP from S. japonica possesses remarkable anti-cancer effects through the activation of various immunocytes. In addition, this finding indicates that the potent biological activity of SJP may be attributed to fucoidan. Full article

Background/Objectives: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) greatly complicates the treatment of skin and soft tissue infections (SSTI). It was previously found that subcutaneous (SQ) treatment with the mononuclear phagocyte (MP)-selective activator complement peptide-derived immunostimulant-02 (CPDI-02; formerly EP67) increases prophylaxis of outbred CD-1 mice against SQ infection with CA-MRSA. Here, we determined if treatment with CPDI-02 also increases curative protection. Methods: Female CD-1 mice were challenged SQ with CA-MRSA USA300 LAC, then CPDI-02 or inactive scCPDI-02 was administered by a topical, SQ, IM, or IV route at 6 or 24 h post-challenge. Abscess sizes were compared over 10 days and CA-MRSA burden, neutrophils, MP, and pro-inflammatory cytokines were compared in subcutaneous abscesses. CPDI-02 PK and distribution in female CD-1 mice were compared after IM or IV dosing and CPDI-02 toxicity in male and female CD-1 mice was determined by IM dose escalation and repeat IM dosing. Results: Repeat IM treatment starting at 6 h post-challenge decreased maximum abscess surface area, CA-MRSA burden, and time to resolution, whereas repeat treatment by a topical, SQ, or IV route had no effect. Repeat treatment starting at 24 h post-challenge was ineffective by the current routes. Single IM treatment starting at 6 h post-challenge was as effective as repeat IM treatment, increased systemic exposure to CPDI-02, and, in subcutaneous abscesses, initially decreased IL-1β and increased MP. CPDI-02 was tolerated between 130 and 170 mg/kg after IM dose escalation and between 65 and 130 mg/kg after repeat IM dosing with males being more tolerant. Conclusions: Single early-stage IM treatment with CPDI-02 may increase curative protection against SSTI caused by CA-MRSA and/or other pathogens controlled by activated MP. Full article

The natural compounds PSK and PSP have antitumor and immunostimulant properties. These pharmacological benefits have been documented in vitro and in vivo, although there is no information in silico which describes the action mechanisms at the molecular level. In this study, the inverse docking method was used to identify the interactions of PSK and PSP with two local databases: BPAT with 66 antitumor proteins, and BPSIC with 138 surfaces and intracellular proteins. This led to the identification interactions and similarities of PSK and the AB680 inhibitor in the active site of CD73. It was also found that PSK binds to CD59, interacting with the amino acids APS22 and PHE23, which coincide with the rlLYd4 internalization inhibitor. With the isoform of the K-RAS protein, PSK bonded to the TYR32 amino acid at switch 1, while with BAK it bonded to the region of the α1 helix, while PSP bonded to the activation site and the C-terminal and N-terminal ends of that helix. In Bcl-2, PSK interacted at the binding site of the Venetoclax inhibitor, showing similarities with the amino acids ASP111, VAL133, LEU137, MET115, PHE112, and TYR108, while PSP had similarities with THR132, VAL133, LEU137, GLN118, MET115, APS111, PHE112, and PHE104. Full article