Search Results (2,499)

Introduction: Schistosomiasis, a tropical disease affecting humans and animals, affected 251.4 million people in 2021. Schistosoma mansoni, S. haematobium, S. intercalatum, and S. japonicum are primary human schistosomes, causing tissue damage, granulomas, ulceration, hemorrhage, and opportunistic pathogen entry. The gut and urinary tract microbiota significantly impact a host’s susceptibility to schistosomiasis, disrupting microbial balance; however, this relationship is not well understood. This systematic review and meta-analysis explores the intricate relationship between schistosomiasis and the host’s microbiota, providing crucial insights into disease pathogenesis and management. Methods: This systematic review used PRISMA guidelines to identify peer-reviewed articles on schistosomiasis and its interactions with the host microbiome, using multiple databases and Google Scholar, providing a robust dataset for analysis. The study utilized Meta-Mar v3.5.1; descriptive tests, random-effects models, and subgroups were analyzed for the interaction between Schistosomiasis and the microbiome. Forest plots, Cochran’s Q test, and Higgins’ inconsistency statistic (I²) were used to assess heterogeneity. Results: The human Schistosoma species were observed to be associated with various bacterial species isolated from blood, stool, urine, sputum, skin, and vaginal or cervical samples. A meta-analysis of the interaction between schistosomiasis and the host microbiome, based on 31 studies, showed 29,784 observations and 5871 events. The pooled estimates indicated a significant association between schistosomiasis and changes in the microbiome of infected individuals. There was considerable heterogeneity with variance effect sizes (p < 0.0001). Subgroup analysis of Schistosoma species demonstrated that S. haematobium was the most significant contributor to the overall heterogeneity, accounting for 62.1% (p < 0.01). S. mansoni contributed 13.0% (p = 0.02), and the coinfection of S. haematobium and S. mansoni accounted for 16.8% of the heterogeneity (p < 0.01), contributing to the variability seen in the pooled analysis. Similarly, praziquantel treatment (RR = 1.68, 95% CI: 1.07–2.64) showed high heterogeneity (Chi² = 71.42, df = 11, p < 0.01) and also indicated that Schistosoma infections in males (RR = 1.46, 95% CI: 0.00 to 551.30) and females (RR = 2.09, 95% CI: 0.24 to 18.31) have a higher risk of altering the host microbiome. Conclusions: Schistosomiasis significantly disrupts the host microbiota across various bodily sites, leading to increased susceptibility to different bacterial taxa such as E. coli, Klebsiella, Proteus, Pseudomonas, Salmonella, Staphylococcus, Streptococcus, and Mycobacterium species (M. tuberculosis and M. leprae). This disruption enables these bacteria to produce toxic metabolites, which in turn cause inflammation and facilitate the progression of disease. The impact of schistosomiasis on the vaginal microbiome underscores the necessity for gender-specific approaches to treatment and prevention. Effective management of female genital schistosomiasis (FGS) requires addressing both the parasitic infection and the resulting microbiome imbalances. Additionally, praziquantel-treated individuals have different microbiome compositions compared to individuals with no praziquantel treatment. This suggests that combining praziquantel treatment with probiotics could potentially decrease the disease severity caused by an altered microbiome. Full article

Among the most popular chemotherapeutic agents, irinotecan, regarded as a prodrug belonging to the camptothecin family that inhibits topoisomerase I, is widely used to treat metastatic colorectal cancer (CRC). Although immunotherapy is promising for several cancer types, only microsatellite-instable (~7%) and not microsatellite-stable CRCs are responsive to it. Therefore, it is important to investigate the mechanism of irinotecan function to identify cellular proteins and/or pathways that could be targeted for combination therapy. Here, we have determined the effect of irinotecan treatment on the expression/activation of tumor suppressor genes (including p15^Ink4b, p21^Cip1, p27^Kip1, and p53) and oncogenes (including OPN, IL8, PD-L1, NF-κB, ISG15, Cyclin D1, and c-Myc) using qRT-PCR, Western blotting, immunofluorescence (IF), and RNA sequencing of tumor specimens. We employed stable knockdown, neutralizing antibodies (Abs), and inhibitors of OPN, p53, and NF-κB to establish downstream signaling and sensitivity/resistance to the cytotoxic activities of irinotecan. Suppression of secretory OPN and NF-κB sensitized colon cancer cells to irinotecan. p53 inhibition or knockdown was not sufficient to block or potentiate SN38-regulated signaling, suggesting p53-independent effects. Irinotecan treatment inhibited tumor growth in syngeneic mice. Analyses of allograft tumors from irinotecan-treated mice validated the cell culture results. RNA-seq data suggested that irinotecan-mediated activation of NF-κB signaling modulated immune and inflammatory genes in mice, which may compromise drug efficacy and promote resistance. In sum, these results suggest that, for CRCs, targeting OPN, NF-κB, PD-L1, and/or ISG15 signaling may provide a potential strategy to overcome resistance to irinotecan-based chemotherapy. Full article

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

Improved efficacy of probiotics can be achieved by using different strategies, including the optimization of production parameters. The impact of fermentation parameters on bacterial physiology is a frequently investigated topic, but what happens during the formulation, i.e., the step where the lyoprotectants are added prior to freeze-drying, is less studied. In addition to this, the focus of process optimization has often been yield and stability, while effects on bioactivity have received less attention. In this work, we investigated different metabolic activities of the probiotic strain Limosilactobacillus reuteri DSM 17938 during formulation with the freeze-drying protectant sucrose. We discovered that the strain consumed large quantities of the added sucrose and produced an exopolysaccharide (EPS). Using NMR, we discovered that the produced EPS was a glucan with α-1,4 and α-1,6 glycosidic bonds, but also that other metabolites were produced. The conversion of the lyoprotectant is hereafter designated lyoconversion. By also analyzing the samples with GCMS, additional potential bioactive compounds could be detected. Among these were tryptamine, a ligand for the aryl hydrocarbon receptor, and glycerol, a precursor for the antimicrobial compound reuterin (3-hydroxypropionaldehyde). To exemplify the bioactivity potential of lyoconversion, lyoconverted samples as well as purified EPS were tested in a model for immunomodulation. Both lyoconverted samples and purified EPS induced higher expression levels of IL-10 (2 times) and IL-6 (4–6 times) in peripheral blood mononuclear cells than non-converted control samples. We further found that the initial cultivation of DSM 17938 with sucrose as a sugar substrate, instead of glucose, improved the ability to convert sucrose in the lyoprotectant into EPS and other metabolites. Lyoconversion did not affect the viability of the bacteria but was detrimental to freeze-drying survival, an issue that needs to be addressed in the future. In conclusion, we show that the metabolic activities of the bacteria during the formulation step can be used as a tool to alter the activity of the bacteria and thereby potentially improve probiotic efficacy. Full article

Cryptococcus neoformans is an environmental pathogen that causes life-threatening disease in immunocompromised persons. The majority of immunological studies have centered on CD4⁺ T-cell dysfunction and associated cytokine signaling pathways, optimization of phagocytic cell function against fungal cells, and identification of robust antigens for vaccine development. However, a growing body of literature exists regarding cytotoxic cells, specifically CD8⁺ T-cells, Natural Killer cells, gamma/delta T-cells, NK T-cells, and Cytotoxic CD4⁺ T-cells, and their role in the innate and adaptive immune response during C. neoformans and C. deneoformans infection. In this review, we (1) provide a comprehensive report of data gathered from mouse and human studies on cytotoxic cell function and phenotype, (2) discuss harmonious and conflicting results on cellular responses in mice models and human infection, (3) identify gaps of knowledge in the field ripe for exploration, and (4) highlight how innovative immunological tools could enhance the study of cytotoxic cells and their potential immunomodulation during cryptococcosis. Full article

Introduction: As the COVID-19 pandemic becomes an endemic state, still many questions remain regarding the risks and impact of SARS-CoV-2 infection and vaccination in patients with immune-mediated inflammatory diseases (IMIDs) who were excluded from the phase 3 COVID-19 vaccination trials. Methods: The BELCOMID study collected patient data and serological samples from a large, multicentric IMID patient cohort that was prospectively followed during sequential stages of the pandemic. Patients were stratified according to vaccination status into five groups across three sampling periods. Interactions between SARS-CoV-2 infection, COVID-19 vaccination status, IMID-treatment modalities and IMID course were explored. Results: In total, 2165 patients with IBD, a dermatological or rheumatological IMID participated. SARS-CoV-2 infection rates increased over the course of the pandemic and were highest in IMID patients that had refused every vaccine. After baseline COVID-19 vaccination, serologic spike (S)-antibody responses were attenuated by particular types of immune-modulating treatment: anti-TNF, rituximab, JAKi, systemic steroids, combined biologic/immunomodulator treatment. Nonetheless, S-antibody concentration increased progressively in patients who received a booster vaccination, reaching 100% seroconversion rate in patients who had received two booster vaccines. Previous SARS-CoV-2 infection was found as a predictor of higher S-antibody response. Patients who had refused every vaccine showed the lowest rates of S-seroconversion (53.8%). Multiple logistic regression did not identify previous SARS-CoV-2 infection as a risk factor for IMID flare-up. Furthermore, no increased risk of IMID flare-up was found with booster vaccination. Conclusions: Altogether, the BELCOMID study provides evidence for the efficacy and safety of COVID-19 vaccination and confirms the importance of repeated booster vaccination in IMID patients. Full article

Background: Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have been proposed as an alternative to live-cell administration for Acute Respiratory Distress Syndrome (ARDS). MSC-EVs can be chiefly influenced by the environment to which the MSCs are exposed. Here, lipopolysaccharide (LPS) priming of MSCs was used as a strategy to boost the natural therapeutic potential of the EVs in acute lung injury (ALI). Methods: The regenerative and immunemodulatory effect of LPS-primed MSC-EVs (LPS-EVs) and non-primed MSC-EVs (C-EVs) were evaluated in vitro on alveolar epithelial cells and macrophage-like THP-1 cells. In vivo, ALI was induced in adult male rats by the intrapulmonary instillation of HCl and LPS. Rats (n = 8 to 22/group) were randomized to receive a single bolus (1 × 10⁸ particles) of LPS-EVs, C-EVs, or saline. Lung injury severity was assessed at 72 h in lung tissue and bronchoalveolar lavage. Results: In vitro, LPS-EVs improved wound regeneration and attenuated the inflammatory response triggered by the P. aeruginosa infection, enhancing the M2 macrophage phenotype. In in vivo studies, LPS-EVs, but not C-EVs, significantly decreased the neutrophilic infiltration and myeloperoxidase (MPO) activity in lung tissue. Alveolar macrophages from LPS-EVs-treated animals exhibited a reduced expression of CXCL-1, a key neutrophil chemoattractant. However, both C-EVs and LPS-EVs reduced alveolar epithelial and endothelial permeability, mitigating lung damage. Conclusions: EVs from LPS-primed MSCs resulted in a better resolution of ALI, achieving a greater balance in neutrophil infiltration and activation, while avoiding the complete disruption of the alveolar barrier. This opens new avenues, paving the way for the clinical implementation of cell-based therapies. Full article

EBV infects more than 90% of people globally, causing lifelong infection. The phases of the EBV life cycle encompass primary infection, latency, and subsequent reactivation or lytic phase. The primary infection usually happens without noticeable symptoms, commonly in early life stages. If it manifests after childhood, it could culminate in infectious mononucleosis. Regarding potential late consequences, EBV is associated with multiple sclerosis, rheumatoid arthritis, chronic active EBV infection, lymphomas, and carcinomas. Previous reports that the lytic phase plays a negligible or merely secondary role in the oncogenesis of EBV-related tumors are steadily losing credibility. The right mechanisms through which the lytic cycle contributes to carcinogenesis are still unclear, but it is now recognized that lytic genes are expressed to some degree in different cancer-type cells, implicating their role here. The lytic infection is a persistent aspect of virus activity, continuously stimulating the immune system. EBV shows different strategies to modulate and avoid the immune system, which is thought to be a key factor in its ability to cause cancer. So, the principal goal of our review is to explore the EBV’s lytic phase contribution to oncogenesis. Full article

This literature review investigated the anti-inflammatory properties of brown algae, emphasizing their potential for dermatological applications. Due to the limitations and side effects associated with corticosteroids and immunomodulators, interest has been growing in harnessing therapeutic qualities from natural products as alternatives to traditional treatments for skin inflammation. This review explored the bioactive compounds in brown algae, specifically looking into two bioactive compounds, namely, fucoidans and phlorotannins, which are widely known to exhibit anti-inflammatory properties. This review synthesized the findings from various studies, highlighting how these compounds can mitigate inflammation by mechanisms such as reducing oxidative stress, inhibiting protein denaturation, modulating immune responses, and targeting inflammatory pathways, particularly in conditions like atopic dermatitis. The findings revealed species-specific variations influenced by the molecular weight and sulphate content. Challenges related to skin permeability were addressed, highlighting the potential of nanoformulations and penetration enhancers to improve delivery. While the in vivo results using animal models provided positive results, further clinical trials are necessary to confirm these outcomes in humans. This review concludes that brown algae hold substantial promise for developing new dermatological treatments and encourages further research to optimize extraction methods, understand the molecular mechanisms, and address practical challenges such as sustainability and regulatory compliance. This review contributes to the growing body of evidence supporting the integration of marine-derived compounds into therapeutic applications for inflammatory skin diseases. Full article

Background: Craniofacial clefts can form a significant defect within bone and cartilage, which can negatively affect tissue homeostasis and the remodeling process. Multiple proteins can affect supportive tissue growth, while also regulating local immune response and tissue protection. Some of these factors, like galectin-10 (Gal-10), nuclear factor kappa-light-chain-enhancer of activated B cells protein 65 (NF-κB p65), heat shock protein 60 (HSP60) and 70 (HSP70) and cathelicidin (LL-37), have not been well studied in cleft-affected supportive tissue, while more known tissue regeneration regulators like type I collagen (Col-I) and bone morphogenetic proteins 2 and 4 (BMP-2/4) have not been assessed jointly with immunomodulation and protective proteins. Information about the presence and interaction of these proteins in cleft-affected supportive tissue could be helpful in developing biomaterials and improving cleft treatment. Methods: Two control groups and two cleft patient groups for bone tissue and cartilage, respectively, were organized with five patients in each group. Immunohistochemistry with the semiquantitative counting method was implemented to determine Gal-10-, NF-κB p65-, HSP60-, HSP70-, LL-37-, Col-I- and BMP-2/4-positive cells within the tissue. Results: Factor-positive cells were identified in each study group. Multiple statistically significant correlations were identified. Conclusions: A significant increase in HSP70-positive chondrocytes in cleft patients could indicate that HSP70 might be reacting to stressors caused by the local tissue defect. A significant increase in Col-I-positive osteocytes in cleft patients might indicate increased bone remodeling and osteocyte activity due to the presence of a cleft. Correlations between factors indicate notable differences in molecular interactions within each group. Full article

The potential of chimeric antigen receptor (CAR)-based immunotherapy as a promising therapeutic approach is often hindered by the presence of highly immunosuppressive tumor microenvironments (TME). Combination therapies with either co-administration or built-in expression of additional TME-modulating therapeutic molecules to potentiate the functions of CAR-T cells can cause systemic toxicities due to the lack of control over the delivery of biologics. Here, we present a proof-of-concept engineered platform in human Jurkat T cells that combines CAR with a therapeutic gene circuit capable of sensing β-galactosidase (a reported cancer-associated signal) and subsequently activate the production of customized therapeutic gene products. We have demonstrated the integration of the chemically induced proximity (CIP) and associated signal sensing technologies with CAR in this study. A β-galactosidase-activatable prodrug was designed by conjugating a galactose moiety with a CIP inducer abscisic acid (ABA). We showed that Jurkat T cells engineered with CAR and the ABA-inducible genetic circuits can respond to recombinant β-galactosidase to drive the production and secretion of various immunotherapeutics including an anti-cancer agent, an immunomodulatory cytokine, and immune checkpoint inhibitors. Our design is highly modular and could be adapted to sense different cancer-related signals to locally produce antitumor therapeutics that can potentially boost CAR-T efficacy and persistence. Full article

Selenium (Se) is an essential nutrient that has gained attention for its impact on the human immune system. The purpose of this review is to explore Se’s immunomodulatory properties and to make up-to-date information available so novel therapeutic applications may emerge. People acquire Se through dietary ingestion, supplementation, or nanoparticle applications. These forms of Se can beneficially modulate the immune system by enhancing antioxidant activity, optimizing the innate immune response, improving the adaptive immune response, and promoting healthy gut microbiota. Because of these many actions, Se supplementation can help prevent and treat pathogenic diseases, autoimmune diseases, and cancers. This review will discuss Se as a key micronutrient with versatile applications that supports disease management due to its beneficial immunomodulatory effects. Further research is warranted to determine safe dosing guidelines to avoid toxicity and refine the application of Se in medical treatments. Full article

This study aimed to enhance the ultrasonic-assisted extraction (UAE) yield of seawater Arthrospira platensis polysaccharides (APPs) and investigate its structural characteristics and bioactivities. The optimization of UAE achieved a maximum crude polysaccharides yield of 14.78%. The optimal extraction conditions were a liquid–solid ratio of 30.00 mL/g, extraction temperature of 81 °C, ultrasonic power at 92 W and extraction time at 30 min. After purification through cellulose DEAE-52 and Sephadex G-100 columns, two polysaccharide elutions (APP-1 and APP-2) were obtained. APP-2 had stronger antioxidant and immunoregulatory activities than APP-1, thus the characterization of APP-2 was conducted. APP-2 was an acidic polysaccharide consisting of rhamnose, glucose, mannose and glucuronic acid at a ratio of 1.00:24.21:7.63:1.53. It possessed a molecular weight of 72.48 kDa. Additionally, APP-2 had linear and irregular spherical particles and amorphous structures, which contained pyranoid polysaccharides with alpha/beta glycosidic bonds. These findings offered the foundation for APP-2 as an antioxidant and immunomodulator applied in the food, pharmaceutical and cosmetic industries. Full article

The potential effects of Astragalus polysaccharides (APS) were evaluated in coral trout (Plectropomus leopardus). Five APS levels (0%, 0.05%, 0.10%, 0.15%, and 0.20%) were added to the diet of coral trout, and a 56-day growth trial (initial weight 18.62 ± 0.05 g) was conducted. Dietary APS enhanced growth performance, with the highest improvement observed in fish fed the 0.15% APS diet. This concentration also enhanced the antioxidant capacity and immunomodulation of the fish by regulating the expression of genes associated with antioxidant enzymes and immune responses. Intestinal microbiota analysis revealed that APS supplementation significantly increased the Chao1 index and relative abundance of beneficial bacteria (Firmicutes and Bacillus). A high level of APS (0.20%) did not provide additional benefits for growth and health compared to a moderate level (0.15%). These findings indicate that an optimal APS dose promotes growth, enhances antioxidant activity, supports immune function, and improves intestinal microbiota in coral trout. Based on a cubic regression analysis of the specific growth rate, the optimal APS level for the maximal growth of coral trout was determined to be 0.1455%. Full article

Haloarchaea are a group of moderate and extreme halophilic microorganisms, belonging to the Archaea domain, that constitute relevant microbial communities in salty environments like coastal and inland salted ponds, marshes, salty lagoons, etc. They can survive in stress conditions such as high salinity and, therefore, high ionic strength, high doses of ultraviolet radiation (UV), high temperature, and extreme pH values. Consequently, most of the species can be considered polyextremophiles owing to their ability to respond to the multiple extreme conditions characterizing their natural habitats. They cope with those stresses thanks to several molecular and metabolic adaptations. Thus, some of the molecules produced by haloarchaea show significantly different biological activities and physicochemical properties compared to their bacterial counterparts. Recent studies have revealed promising applications in biotechnology and medicine for these biomolecules. Among haloarchaeal biomolecules, rare natural pigments (C₅₀ carotenoids) and small peptides called halocins and microhalocins have attracted attention worldwide due to their effects on animal and human commercial tumoral cells, apart from the role as antibiotics described for halocins or the immunomodulatory activity reported from C₅₀ carotenoids like bacterioruberin. This review summarizes recent knowledge on these two types of biomolecules in connection with cancer to shed new light on the design of drugs and new therapies based on natural compounds. Full article