Search Results (353)

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

Studies on plant extracts as growth promoters and immunostimulants have shown promising results. However, their effects on fish health and growth remain unclear. This study evaluated the in vitro and in vivo effects of Eucalyptus globulus pyroligneous extract (PE) on Nile tilapia. In vitro, minimal inhibitory and bactericidal concentration (MIC and MBC) and antibiogram analyses showed that PE could eliminate key bacterial strains affecting fish and human health, but only if its volatile components were preserved. In vivo, Oreochromis niloticus juveniles were fed diets containing 0.5% and 1% PE. We assessed fish hematology, phagocytosis, survival against Streptococcus agalactiae, and growth parameters. Fish fed 1% PE had lower erythrocyte and lymphocyte counts but higher neutrophil levels than controls. Their phagocytic capacity was significantly enhanced compared to both the control and 0.5% groups. However, the 0.5% PE group had a higher phagocytic index than both the control and 1% groups. No protection against S. agalactiae or significant effects on growth were observed. In conclusion, distilled E. globulus PE shows potential as an immunostimulant for fish. However, further studies are needed to preserve its volatile compounds and optimize its use in aquaculture. Full article

Tumor necrosis factor alpha (TNFα) is a central pro-inflammatory cytokine that mediates host immune responses during infection. In this study, we identified and characterized the TNFα gene in the starry flounder (Platichthys stellatus) through transcriptomic analysis. The deduced protein contained a conserved TNF domain and transmembrane region, and phylogenetic analysis confirmed its homology with other teleost TNFα proteins. Tissue-specific expression profiling revealed high baseline expression in immune-related peripheral organs and a distinct temporal modulation in response to Streptococcus parauberis infection. Recombinant TNFα (rTNFα), produced using a cell-free expression system, significantly enhanced phagocytic activity in peripheral and kidney-derived leukocytes in a dose-dependent manner. Peak activity was observed at 150–200 μg/mL, while a decline at higher concentrations suggested a threshold for immune stimulation. Importantly, hemolysis assays confirmed the safety of rTNFα even at the highest tested concentrations. These results demonstrate the immunomodulatory potential of TNFα as a molecular adjuvant in aquaculture vaccines and underscore its potential utility in immune-enhancing strategies for sustainable aquaculture. 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

Seahorse (Hippocampus spp.) is popular in the markets of traditional Chinese medicine, aquarium, and curio. In order to protect wild stocks and still meet the market demand, China attempted the large-scale cultivation of seahorses in the early 21st century and achieved it in the 2010s. However, in recent years, two new issues have gradually emerged in Chinese seahorse cultivation. One is that the juveniles are prone to disease during diet conversion, and the other is that the reproductive performance of broodstocks is significantly reduced. With the aim to provide some measures that can alleviate these issues, in the present study, we used lined seahorse (Hippocampus erectus, a species widely cultured in China) as the experimental subject and Astragalus polysaccharides (APSs) as the immunostimulant to test whether APSs could improve the immune-health status and reproductive performance of seahorses. The measured indices for reproductive performance included ovarian lipid content, assessment time required before mating for paired male and female seahorses, mating success rate, brood size, and newborn body height. The results showed that for juveniles during diet conversion, their body weight, survival rate, plasma immunocytokine contents (interleukin-2, interferon-α, and immunoglobulin M), and alpha diversity indices (Simpson and Pielou’s-e) of the intestinal microbiota were significantly higher than those of the control group after dietary APSs. For broodstocks, compared with the control group, the expression of lipid substances in the ovary was significantly upregulated, the assessment time was significantly shortened, and the body height of their newborns was significantly increased in the APS group. These results demonstrate that APSs could indeed improve the immune-health status and reproductive performance of seahorses, providing guidance for addressing existing issues in seahorse cultivation. Full article

Sjögren’s disease (SjD) is an autoimmune disease of exocrine tissues. Prior research has shown that ETS proto-oncogene 1 (ETS1), STAT1, and IL33 may contribute to the disease’s pathology. However, the regulatory mechanisms of these genes remain poorly characterized. Our objective was to explore the mechanisms of SjD pathology and to identify dysfunctional regulators of these genes by immunostimulation of SjD and sicca relevant cell lines. We used immortalized salivary gland epithelial cell lines (iSGECs) from Sjögren’s disease (pSS1) and sicca (nSS2) patients, previously developed in our lab, and control cell line A253 to dose with immunostimulants IFN-γ or poly(I:C) (0 to 1000 ng/mL and 0 to 1000 µg/mL, respectively) over a 72 h time course. Gene expression was determined using qRT-PCR delta-delta-CT method based on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) for mRNA and U6 small nuclear RNA 1 (U6) for miRNA, using normalized relative fold changes 48 h post-immunostimulation. Protein expression was quantified 72 h post-stimulation by Western blotting. Reference-based RNA-seq of immunostimulated pSS1 and nSS2 cells was performed to characterize the reactome of genes conserved across all used doses. The expression of ETS1 and STAT1 protein was upregulated (p < 0.05) in IFN-γ-treated pSS1 and nSS2, as compared to A253 cells. IFN-γ-treated nSS2 cell showed significant IL33 upregulation. Also, IL33 had a correlated (p < 0.01) U-shaped response for low-mid-range doses for IFN-γ- and poly(I:C)-treated pSS1 cells. RNA-seq showed 175 conserved differentially expressed (DE) genes between nSS2 and pSS1 immunostimulated cells. Of these, 44 were shown to interact and 39 were more abundant (p < 0.05) in pSS1 cells. Western blotting demonstrated nSS2 cells expressing ETS1 uniformly across treatments compared to pSS1 cells, despite similar mRNA abundance. miR-145b and miR-193b were significantly under-expressed in IFN-γ-treated nSS2 cells compared to pSS1 cells (p < 0.01). ETS1 and IL33 showed disproportionate mRNA and protein abundances between immunostimulated Sjögren’s disease-derived (pSS1), and sicca-derived (nSS2) cell lines. Such differences could be explained by higher levels of miR-145b and miR-193b present in pSS1 cells. Also, RNA-seq results suggested an increased sensitivity of pSS1 cells to immunostimulation. These results reflect current pathobiology aspects, confirming the relevance of immortalized salivary gland epithelial cell lines. Full article

The ulvans are sulfated heteropolysaccharides that can stimulate the immune response in vitro. Using a human cell model, this study aimed to characterize and evaluate the immunostimulatory properties of crude ulvans extracted from Ulva spp., collected in Algarrobo, Chile. The crude ulvans, characterized by spectrophotometric methods, are composed of 47.6% total sugars, 14.3% uronic acids, and 8.9% sulfates, with an average molecular weight of 40.000 kDa. The FTIR spectrum showed bands related to uronic acids, rhamnose, and sulfate groups. GCMS analysis confirmed the presence of rhamnose, xylose, glucose, and galactose, with a predominance of the disaccharides U3s and B3s. HL60 cells differentiated into macrophages were cultured with three concentrations of crude ulvans (25, 50, and 100 μg/mL), with cell viability remaining above 90% at the lower concentrations. The crude ulvan activated CD86 co-stimulatory molecules and promoted the release of IL-6, IL-10, IL-4, and nitric oxide cytokines. The results suggest that ulvan is non-toxic and can activate inflammatory pathways, making it a potential candidate for studies as a vaccine adjuvant. 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

Ectoine is a substance produced by extremophiles and is naturally used by them as protection against adverse environmental conditions in which they live. Scientific contributions discuss its excellent effect through cosmotropic properties, prevention of secondary messenger release in cells, and transcription factors. The influence on the lipid layer of the cell membrane and its preventive effect as a UV filter were also demonstrated. What is more, its anti-oxidative effect was established. Ectoine works as an immunostimulant and also has anti-inflammatory and anti-cancer properties. These attributes are dominating factors in the use of ectoine’s properties in skin fractionation treatment with a C${\mathrm{O}}_2$ laser. In the following work, the influence of ectoine on skin parameters was described, focusing on redness, moisturization, and TEWL after the use of a C${\mathrm{O}}_2$ laser (Załęska 2019). The rheological properties of preparations with ectoine addition were also tested. The yield point was determined, the viscosity changes of cosmetic preparations were measured with increasing shear rates, and oscillation tests were performed. With increasing percentages of ectoine and frequency of application, the occurrence of redness after C${\mathrm{O}}_2$ therapy decreased. The highest moisture level values from 54.4 × 0.02 mg/c${\mathrm{m}}^2$ to 72.5 × 0.02 mg/c${\mathrm{m}}^2$ were obtained for preparation A applied twice a day; for the same preparation, a reduction in TEWL from 6.2 to 5.3 g/(${\mathrm{m}}^2$·h) was obtained. The results of the tests of cosmetic emulsions allowed us to conclude that the preparations in the analyzed shear rate range at all tested temperatures are non-Newtonian liquids that are shear-thinning and have a flow limit. The obtained results of the conducted research prove the positive effect of dermocosmetics with ectoine content in the process of skin healing. 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

A female domestic shorthair cat aged 2 years was referred with a 1-month history of subcutaneous nodules and multiple sites of draining tracts at the ventral abdomen. Initially, the cat was diagnosed with a fungal infection and treated with oral itraconazole, without improvement. Comprehensive diagnostics, including cytology, which indicated pyogranulomatous inflammation, fungal culture that was negative, and bacterial culture, confirmed the presence of Mycobacterium abscessus. This infection was treated with a combination of oral azithromycin and topical amikacin based on susceptibility testing; later, doxycycline and an immunostimulant supplemented were combined at day 36 of treatment due to mild improvement of the lesions. The cat showed gradual improvement, achieving complete resolution of the lesions after 14 weeks, with no relapse noted 24 weeks post-treatment. This case report demonstrates the diagnostic challenges and the necessity for tailored, multi-drug therapeutic approaches in managing mycobacterial infections in cats. The findings may guide future treatments and raise awareness of mycobacterial diseases in cats. Full article