Search Results (372)

Background/Objectives: Cytokine release during organ transplantation contributes to primary graft dysfunction and requires careful immunomodulation. CytoSorb, a hemoadsorption device developed to reduce circulating cytokine levels, is increasingly used in critically ill patients. However, its impact on concurrent immunosuppressive therapy remains unclear. Methods: In this ex vivo study, we investigated the adsorption of five immunosuppressants—cyclosporine A, tacrolimus, methylprednisolone, mycophenolic acid, and 6-mercaptopurine—using a scaled-down CytoSorb hemoadsorption circuit and compared results to chronic and acute dialysis. Additionally, a whole blood model was used to assess the functional impact of CytoSorb treatment on leukocyte activation, using LPS and anti-CD3 stimulation and subsequent cytokine measurement (TNF-α, IL-1β, IL-6, IL-8). Results: CytoSorb significantly reduced serum levels of methylprednisolone (92 ± 3%), mycophenolate (80 ± 2%), 6-mercaptopurine (65 ± 32%), and cyclosporine A (61 ± 16%), but had no significant effect on tacrolimus. Dialysis effectively removed methylprednisolone and 6-mercaptopurine, while strongly protein-bound drugs such as cyclosporine A and tacrolimus remained largely unaffected. In the whole blood model, CytoSorb treatment did not significantly alter cytokine release after immunostimulation, suggesting preserved immunosuppressive efficacy. Conclusions: CytoSorb treatment reduces the plasma concentration of selected immunosuppressants. However, short-term treatment appears to have minimal impact on immunosuppressive function. These findings support the cautious use of CytoSorb in transplant settings but highlight the need for in vivo confirmation. Full article

Background: The potential of injectable hydrogels as drug depots lies in their ability to achieve local and sustained co-delivery of chemotherapeutic drugs and immunostimulants for combined tumor therapy. Method: In this study, we devised a localized chemo-immunotherapeutic strategy by co-loading the chemotherapeutic drug, oxaliplatin (OXA), and the immune-checkpoint blockade (ICB) antibody, anti-programmed cell death protein ligand 1 (anti-PD-L1), into a matrix metalloproteinase (MMP)-responsive injectable poly(L-glutamic acid) hydrogel (MMP-gel). Results: The in situ gelation of hydrogels enables local retention of OXA and model antibody IgG, as well as MMP-triggered sustained release. Meanwhile, the OXA-loaded MMP-gel caused the immunogenic cell death (ICD) of tumor cells. When administered intratumorally in mice carrying B16F10 melanoma, the MMP-gel co-loaded with OXA and anti-PD-L1 (OXA&anti-PD-L1@MMP-gel) demonstrated superior tumor suppression efficacy and prolonged the survival time of the animals with low systemic toxicity. Meanwhile, the OXA&anti-PD-L1@MMP-gel induced an increase in CD8⁺ T cells and M1 macrophages within tumors, and a decrease in Treg cells and M2 macrophages, demonstrating that the drug-loaded system enhanced the antitumor immune response. Moreover, the OXA&anti-PD-L1@MMP-gel effectively inhibited the growth of distal tumors in a bilateral-tumor experiment. Conclusions: Consequently, the responsive hydrogel-based chemo-immunotherapy holds potential in tumor treatment. Full article

White Spot Syndrome Virus (WSSV) is one of the most devastating viral pathogens affecting shrimp, causing severe economic losses to the global farmed shrimp trade. The globalization of live shrimp trade and waterborne transmission have facilitated the rapid spread of WSSV across major shrimp-producing countries since its initial emergence. The present review gives an updated account of WSSV biology, pathology, transmission dynamics, and recent developments in control measures. The virus, a double-stranded DNA virus of the Nimaviridae family, utilizes advanced immune evasion strategies, resulting in severe mortality. Shrimp lack adaptive immunity and hence rely predominantly on innate immunity, which is insufficient to mount an effective response against severe infections. Traditional disease control measures such as augmented biosecurity, selective breeding, and immunostimulants have, despite extensive research, achieved only limited success. New biotechnological tools such as RNA interference, CRISPR-Cas gene editing, and nanotechnology offer tremendous potential for disease mitigation. In parallel, the development of DNA and RNA vaccines targeting WSSV structural proteins, such as VP28, holds significant promise for stimulating the shrimp immune system. This review highlights the urgent need for a convergent approach to sustainable disease management in global shrimp aquaculture, with interdisciplinarity playing a pivotal role in shaping the future of WSSV control. Full article

Aquaculture is expanding rapidly worldwide, but its sustainability is threatened by intensive production practices, environmental stressors and recurrent disease outbreaks. Natural feed additives are increasingly studied as alternatives to antibiotics and synthetic compounds. Among them, bee-derived products—pollen, bee bread, propolis, royal jelly, honey and fermented derivatives—represent a promising resource due to their richness in proteins, amino acids, fatty acids, vitamins, flavonoids and phenolic compounds with demonstrated antioxidant, antimicrobial and immunostimulant properties. Evidence from studies on species such as Nile tilapia, rainbow trout, European sea bass, meagre and African catfish indicates that dietary supplementation with bee products can improve growth performance, immune and antioxidant responses, stress tolerance and resistance to bacterial infections while, in some cases, enhancing the nutritional value and shelf-life of fish products. Prominent examples include ~45% higher growth in African catfish with 10–30 g kg⁻¹ bee pollen, up to 93% protection in Nile tilapia fed 25 g kg⁻¹ pollen against Aeromonas hydrophila, and increased trout fillet carotenoids with pollen-derived pigments (with overall growth unchanged and pigmentation lower than synthetic astaxanthin). Conversely, meagre fed 20–40 g kg⁻¹ raw pollen showed reduced growth and digestibility with elevated intestinal stress markers, underscoring species- and dose-specific responses. Nevertheless, the available data remain fragmented and heterogeneous, reflecting differences in product type, origin, dosage and experimental design. This review critically analyses the current knowledge on bee products in aquaculture nutrition, identifies the main gaps and limitations, and outlines future research directions. By linking fish physiology, nutritional strategies and product quality, bee-derived products emerge as innovative tools for promoting fish health and resilience in sustainable aquaculture. Full article

This study systematically investigated lipophilic and polar metabolites of Atraphaxis virgata (Polygonaceae) and assessed its immunomodulatory activity in vivo. Supercritical CO₂ extraction of the aerial parts yielded a lipophilic fraction analyzed by means of gas chromatography–mass spectrometry (GC–MS), which identified 42 compounds, including fatty acid esters, sterols, hydrocarbons, and terpenoids. The residual plant meal was subjected to ultrasound-assisted extraction with 70% aqueous ethanol at 30–35 °C, using a solid-to-solvent ratio of 1:8 for 120 min. This polar extract was evaluated for amino acids, proteins, and carbohydrates, while solvent–solvent partitioning with chloroform, ethyl acetate, and water enabled isolation of phenolic- and flavonoid-enriched fractions. Six phenolic constituents, including four flavonol glycosides and two phenolic acids, were structurally confirmed. The extracts were rich in unsaturated fatty acids and water-soluble antioxidants, supporting their nutritional and pharmacological relevance. In vivo evaluation using a cyclophosphamide-induced myelosuppression model in Wistar rats demonstrated stimulation of erythropoiesis and leukopoiesis, confirming immunomodulatory potential. Collectively, this work provides the first comprehensive chemical and biological characterization of A. virgata and establishes a foundation for mechanistic studies and pharmacological validation. Full article

Amphioxus belongs to the subphylum Cephalochordata and occupies a transitional position in evolution between invertebrates and vertebrates. Due to the lack of viruses suitable for immunostimulation in amphioxus, this study for the first time explored the pathogenicity and waterborne transmission of Grass Carp Reovirus (GCRV), a double-stranded RNA virus, during its infection of amphioxus. Soaking amphioxus in GCRV suspension can cause obvious damage to gill tissues and severely disrupt the structure of gill filaments. The virus survived in seawater for no more than 48 h. Infection kinetics studies showed that the expression of VP5 (a viral capsid protein) mRNA in gill tissues peaked at 14 h. After co-culturing GCRV-infected amphioxus with healthy amphioxus for 72 h, the gills of healthy amphioxus showed obvious pathological damage. Additionally, the presence of the virus was verified by RT-PCR amplification of VP5 expression, indicating that GCRV can be transmitted via water. Transcriptome sequencing analysis showed that the Mitogen-Activated Protein Kinase (MAPK), calcium signaling pathway, and chitin metabolic pathway were significantly activated in amphioxus after GCRV stimulation. This study confirmed that GCRV can infect cephalochordates, revealing its gill-tropism and water-borne transmission ability, providing a new perspective for studying the cross-species infection mechanism of aquatic viruses and the prevention and control of aquatic diseases. Full article

Rotavirus (RV) is one of the main etiologic agents associated with diarrheal diseases (DDs), being responsible for approximately 200 thousand deaths annually. Currently, there are still many aspects regarding the virus biology, cell cycle, and pathophysiology of RV that need further elucidation. Therefore, the present work aimed to investigate whether the triggering receptor expressed on myeloid cells 1 (TREM-1) might be associated with RV infection. This immune receptor has been observed as an amplifier of inflammatory responses in different infectious and non-infectious diseases, including inflammatory bowel disease and celiac disease. Initially, we searched for public transcriptomic data regarding RV infection and the expression of TREM-1 and its associated genes, which were significantly upregulated in infected mice and children. Then, we infected monocytes with the virus, with or without a TREM-1 inhibitor. The inhibition of the receptor’s activity resulted in a significant decrease in IL-1β production. We also observed a reduction in cytopathic effects when MA104 cells were treated with TREM-1 inhibitors and then infected with simian RV. To further elucidate the interactions between the virus and TREM-1, in silico tools were used to simulate interactions between the receptor and RV proteins. These simulations suggested the occurrence of interactions between TREM-1 and VP5*, a protein involved in viral attachment to target cells, and also between the receptor and NSP4, a viral enterotoxin with immunostimulant properties. Hence, our results indicate that TREM-1 is involved in RV infection, both as a mediator of inflammatory responses and as a player in the host–virus relationship. Full article

The green alga Haematococcus pluvialis, rich in natural astaxanthin, is a key feed additive for salmonid pigmentation. This study evaluated dietary micro-algal astaxanthin effects on structure, antioxidative and immune response, as well as microbiota in different gut segments of rainbow trout Oncorhynchus mykiss (initial average weight: 0.67 ± 0.02 kg). Three diets contained 0 (Diet 1, control), 18.57 (Diet 2) and 31.25 mg/kg (Diet 3) micro-algal astaxanthin. After a 4-month feeding trial, dietary astaxanthin promoted the goblet cell proliferation of pyloric caeca and increased hindgut tunica muscularis thickness (p < 0.05). It also improved antioxidant capacity, characterized by the upregulation of gpx and cat expression in the midgut, accompanied by a significant decrease in MDA content (p < 0.05). Furthermore, dietary astaxanthin could upregulate tgf-β, tor1 and pcna levels in midgut and igm in hindgut, while il1β, il6, il8 and tnfα in hindgut were significantly downregulated in Diet 2 (p < 0.05). Additionally, dietary astaxanthin also enhanced the α-diversity of hindgut and altered the core microbiota (reduced Proteobacteria, increased Actinobacteria). Diet 2 increased microbic abundance associated with reducing gut inflammation and promoting nutrient absorption while decreasing that of pathogenic bacteria. Overall, dietary 18.57 mg/kg astaxanthin supplementation could promote gut structure, antioxidant and immune capacity, reduce inflammation and modulate microbiota. These findings indicate that natural astaxanthin from H. pluvialis has potential as an immunostimulant to promote gut health in salmonids. Full article

Aquaculture has rapidly become a vital sector for ensuring global food security by meeting the growing demand for animal protein. Bangladesh, one of the world’s leading aquaculture producers, recorded a production of 4.91 million MT in 2022–2023, largely driven by inland farming systems. Despite this remarkable growth, the sector is highly vulnerable to disease outbreaks, which are aggravated by different factors. Pathogens such as bacteria, viruses, fungi, and parasites cause significant losses, while conventional disease diagnosis in Bangladesh still depends mainly on visual assessment and basic laboratory techniques, limiting early detection. This narrative review highlights recent advances in diagnostics as molecular tools, immunodiagnostics, nanodiagnostics, machine learning, and next-generation sequencing (NGS) that are widely applied globally but remain limited in Bangladesh due to infrastructure gaps, lack of skilled manpower, and resource constraints. Current treatment strategies largely rely on antibiotics and aquaculture medicinal products (AMPs), often misused without proper diagnosis, contributing to antimicrobial resistance (AMR). Promising alternatives, including probiotics, immunostimulants, vaccines, and enhanced biosecurity, require greater adoption and farmer awareness. The near-term priorities for Bangladesh include standardized disease and AMR surveillance, prudent antibiotic stewardship, phased adoption of validated rapid diagnostics, and investment in diagnostic and human capacity. Policy-level actions, including a national aquatic animal health strategy, stricter antimicrobial regulation, strengthening diagnostic infrastructure in institution, are crucial to achieve sustainable disease management and ensure long-term resilience of aquaculture in Bangladesh. Full article

Background: Acute infections in children are prevalent and often lead to antibiotic overuse due to the lack of evidence-based alternative approaches. Phytotherapeutic, homeopathic treatments and bee products are frequently sought as alternative or adjunctive therapies. This scoping review aims to map the existing evidence on the efficacy and safety of these interventions in managing acute pediatric infections. Methods: A comprehensive literature search was conducted across multiple databases to identify studies assessing the use of phytotherapeutic, homeopathic remedies and bee products in children with acute infections. Gastrointestinal infections were not considered since the use of non-antibiotic treatments (probiotics) in these conditions has been widely addressed. Effectiveness: Phytotherapeutic agents and bee products demonstrated promising results in reducing symptom severity and duration in respiratory infections, whereas homeopathic data were limited and inconsistent. Regarding safety, both interventions were generally well-tolerated, with few adverse events reported. No studies or very limited evidence were available for other acute infections such as urinary, dermatological, osteoarticular and nervous system infections. Conclusions: Phytotherapeutic interventions and bee products, particularly in acute upper respiratory tract and acute bronchitis, show encouraging signals of efficacy and safety in pediatric populations. However, evidence for their use in other frequent childhood infections, such as otitis media, or gastrointestinal infections, is almost entirely lacking. In addition, the available literature on homeopathic remedies is scarce and methodologically inconsistent, preventing any firm conclusions. Well-designed, large-scale clinical trials focusing on these underexplored conditions are needed to clarify the potential role of phytotherapeutics and homeopathy in pediatric infectious diseases. Full article

Plant-derived immunostimulants stimulate the fish immune system, prevent diseases, and reduce economic losses for farmers. This study fed tilapia (Oreochromis mossambicus) either water (WSF) or hexane soluble fraction (HSF) of Solanum trilobatum leaves for 1, 2, or 3 weeks to assess their effects on nonspecific immune responses, antibody response, and disease resistance to bacterial challenge after each feeding period. Both WSF and HSF increased serum globulin levels after 3 weeks and significantly elevated lysozyme and antiprotease activity. WSF increased ROS production after 3 weeks, while HSF had a significant effect after 2 weeks. MPO content increased after 1 week for WSF and after 1, 2, and 3 weeks for HSF. The antibody response was significantly higher in the HSF-fed group across most time points. Challenge with Aeromonas hydrophila showed reduced mortality in fish fed with HSF for 1, 2, and 3 weeks, while WSF only reduced mortality at certain doses after 1 or 3 weeks. GC-MS analysis revealed that HSF contained about 40% aromatic compounds and 11% steroids, mainly phytosterols. In contrast, WSF contained several low-molecular-weight alcohols and carbonyls, each in proportions of less than 10%. Due to their hydrophobic nature, the aromatic compounds and steroids in HSF are likely more bioavailable, which may explain its superior immunostimulating and disease resistance properties. Full article

Hyaluronan (HA), a high-molecular-weight polysaccharide naturally found in vertebrate tissues such as skin, joints, and the vitreous body, plays a critical role in various biological processes. Its functionality is highly dependent on molecular weight, with high-molecular-weight HA exhibiting anti-inflammatory and immunosuppressive effects, while low-molecular-weight HA promotes inflammation, immunostimulation, and angiogenesis. Due to its biocompatibility, biodegradability, and tunable properties, HA has gained increasing attention in biomedical applications. This review summarizes recent advances in the encapsulation of HA with other polymers and therapeutic agents in nanosystems, particularly hydrogels and nanoparticles. HA-based formulations demonstrate improved therapeutic outcomes, including drug release sustained up to 7 days, wound closure rates exceeding 90% in animal models, particle size in the range of 50–300 nm, and enhanced bioavailability of encapsulated drugs by 2–3 fold compared with free drugs. Such properties have shown promise in enhancing therapeutic efficacy and targeted drug delivery in the treatment of skin wound healing, diabetes, osteoarthritis, rheumatoid arthritis, and ophthalmic diseases. The review emphasizes how HA’s modifications and composite systems optimize drug release profiles and biological interactions, thereby contributing to the development of next-generation biomedical therapies. Full article

Aquaculture currently supplies over half of the world’s fish and relies heavily on feed additives to enhance growth, improve feed efficiency, and increase disease resistance. This review consolidates peer-reviewed studies identified through targeted searches of Web of Science, Scopus, and Google Scholar, focusing on aquaculture feed additives. It emphasizes the principal classes of additives employed in finfish and shrimp cultivation, such as natural immunostimulants (including beta-glucans and nucleotides), probiotics, prebiotics, synbiotics, phytogenics, enzymes, and synthetic nutrients. For each, it summarizes their mechanisms of action, commonly reported inclusion rates, production outcomes, environmental risks, and regulatory statuses. Evidence indicates that immunostimulants enhance innate defences (including phagocyte activity and cytokine responses). Probiotics and prebiotics, on the other hand, regulate gut microbiota and barrier function. Phytogenics offer antimicrobial and antioxidant effects, and synthetic additives provide targeted nutrients or functional compounds that support growth and product quality. Where data are available, typical application ranges include probiotics in the order of 10⁴–10⁹ CFU per gram, prebiotics at approximately 2–10 g per kilogram, and pigments or antioxidants (such as astaxanthin) at 50–100 mg per kilogram. Significant gaps exist, notably the absence of species-specific dose–response data for tropical and subtropical aquaculture species, as well as limited experimental evidence regarding additive–additive interactions under commercial rearing conditions. Additional gaps include long-term ecological fate, regional regulatory discrepancies, and species-specific dose–response relationships. It is recommended that mechanistic studies employing omics approaches, standardised dose–response trials, and harmonized risk assessments be conducted to promote the sustainable and evidence-based application of feed additives. Full article

Chagas disease, caused by Trypanosoma cruzi, remains a major health concern in Latin America, particularly affecting low-income and rural communities. Among the many vaccine strategies explored, live attenuated parasites have shown the strongest ability to trigger protective immune responses. In this study, we investigated whether adding saponin-based adjuvants—Immunostimulant Particle Adjuvant (ISPA) and Quil-A—could improve the effectiveness and safety of a live parasite attenuated T. cruzi vaccine. Mice were vaccinated with a T. cruzi attenuated strain (TCC) alone or in combination with each adjuvant, and immunoglobulin G (IgG) subtypes in the serum of vaccinated mice, and interferon gamma (IFN-γ) and interleukin-10 (IL-10) in the supernatants of stimulated cells were measured at two weeks and twelve months post-vaccination. While protection levels were similar across all groups, the adjuvants assist in modulating the immune response over time: ISPA and Quil-A initially shifted antibody production toward IgG1 but later favored a balanced T_H1/T_H2 profile. ISPA also promoted long-term regulation through increased IL-10. Both adjuvants reduced tissue inflammation and enhanced clearance of vaccine-derived parasites. These findings suggest that while adjuvants may not boost protection directly, they significantly improve vaccine safety and immune quality, reinforcing their value in developing better vaccines for Chagas disease. Full article

Liver malignancies are among the most prevalent cancers worldwide and can be managed using various therapeutic approaches. However, the available options for treating these malignancies are characterized by several limitations. Histotripsy, which was recently approved by the Food and Drug Administration (FDA), seems to be promising for overcoming these limitations. It is an emerging non-invasive, non-thermal ultrasound technology, which is based on the controllable initiation of cavitation from endogenous nanometer-scale gas pockets within tissues. Numerous preclinical studies as well as three clinical studies highlight this technique as feasible, safe, and effective. Among its advantages are the lack of thermal injury, its non-invasive nature, its immunopreserving and possibly immunostimulating ability, as well as the low number of complications that accompany it. Nonetheless, long-term clinical outcomes are still lacking, and further studies are needed to establish its definitive role in liver cancer treatment. In conclusion, histotripsy shows strong potential to become a transformative tool in liver oncology, but continued clinical evaluation is essential to validate its long-term efficacy and integration into standard care. Full article