Search Results (2,748)

Intestinal diseases in nursery pigs harm health and performance and drive antimicrobial resistance. This study evaluated whether early probiotic inoculation helps piglets to cope with weaning-related gut challenges. The probiotic, containing Lacticaseibacillus rhamnosus, Enterococcus lactis, Bifidobacterium longum subsp. infantis, and Bifidobacterium breve, was given orally to newborn piglets daily until day 4 and then every other day until weaning at day 28 (at 4 × 10⁹ CFU/dose). The control piglets received a placebo. The results showed that the probiotic pigs had reduced fecal alpha-diversity on day 7 but greater Shannon diversity on day 28 (feces) and day 23 (intestinal contents) compared to those of the control pigs. Beta-diversity analysis showed microbial differences between the groups on day 35. Most zOTUs (zero-radius operational taxonomic units) found to significantly differentiate the two treatment groups were found pre weaning. Bifidobacterium breve, Ligilactobacillus salivarius, as well as Clostridium ramosum were significantly more abundant in the feces of the probiotic pigs more than once. The probiotic pigs had higher expression levels of mucin 2 (MUC2); solute carrier family 5, member 8 (SLC5A8); and interleukin 8 (IL-8) post weaning. In the early post-weaning period, the probiotic pigs had less diarrhea as well as lower cadaverine levels in digesta than the control pigs. In conclusion, early probiotic inoculation may induce lasting immunomodulation via microbial antigen changes, enhancing resilience during challenges, like weaning. Notably, the effects persisted beyond weaning and probiotic cessation. Full article

Lidocaine, a widely used local anaesthetic, has been shown to possess anti-inflammatory and immunomodulatory properties with applications in surgery. During a surgical procedure, inflammation is a natural response of the body, triggered by the release of inflammatory mediators and the activation of the immune system. However, an excessive response can lead to serious postoperative complications. Lidocaine modulates inflammation through mechanisms beyond its anaesthetic action. It reduces the activation of neutrophils and macrophages, decreases the release of pro-inflammatory cytokines and prostaglandins, and preserves endothelial integrity, helping to control excessive inflammatory responses. Additionally, its perioperative use has shown benefits such as reduced postoperative pain, lower opioid consumption, and faster intestinal recovery. Furthermore, studies have suggested that lidocaine may have an anti-metastatic effect by inhibiting the migration of tumour cells and the activation of inflammatory pathways related to cancer spread. Although its use in surgery is promising, further research is needed to determine optimal dosages and its long-term clinical impact. Full article

Background:Tumour-associated neutrophils play an important role in tumour progression and immunomodulation. However, the prognostic significance and immunological implications of neutrophil-associated genes (NAGS) in cervical cancer remain poorly defined. Methods: We analyzed neutrophil infiltration and its correlation with gene expression in TCGA cervical cancer data using immune deconvolution. NAGS were identified via correlation and enrichment analysis. A prognostic model was constructed using Cox and LASSO regression and validated in the GSE30759 cohort. Kaplan–Meier analysis, ROC curves, and multivariate Cox regression were used to assess prognostic performance. The model’s association with the tumor immune microenvironment and immunotherapy response was further analyzed. The expression pattern of SEMA6B was explored using cell lines, clinical subgroups, and human protein profiles, and its immunological relevance was evaluated using multiple immune infiltration algorithms. Results: Twelve genes were identified as significantly correlated with neutrophil infiltration and enriched in immune-related pathways such as chemotaxis, neutrophil degranulation, and PI3K-AKT signaling. Further NAGS models were developed based on key genes. High-risk patients exhibited an immunosuppressive tumor microenvironment, elevated TIDE scores, and lower predicted responsiveness to immunotherapy. SEMA6B was significantly downregulated in the tumour group but may be reactivated during metastasis. High expression of SEMA6B was associated with poorer prognostic features and immune evasion. Conclusions: We developed a NAGS signature that may inform prognosis and immune microenvironment status in cervical cancer. These findings suggest the potential clinical utility of NAGs-based models in guiding immunotherapy strategies. Moreover, SEMA6B may serve as a promising immunological and prognostic biomarker, pending further mechanistic validation. Full article

The current standard of care for inoperable stage III non-small cell lung cancer (NSCLC) is concurrent chemotherapy and radiation therapy with consolidation durvalumab. Despite this approach, about 50% of patients will experience disease recurrence, with about half of recurrence events occurring at distant metastatic sites. In this review, the authors performed a structured analysis of the available clinical trial data and literature related to the treatment of this disease. The authors discuss the detriments and merits of several of these trials and explore clinical and preclinical data that contribute to the growing body of literature supporting a future with new approaches, including new techniques in radiation therapy, sequencing, and agents. Upcoming trials may illuminate a path towards better outcomes for patients in this setting. Full article

Honey and other bee products, including propolis, royal jelly, and bee pollen, are widely recognized for their medicinal properties. Among their numerous biological activities, their anti-inflammatory and immunomodulatory effects have gained significant attention in recent years. Immune and inflammatory disorders contribute significantly to the development of chronic conditions, including cancer and diabetes. Bee-derived products, along with their bioactive compounds such as polyphenols, have shown promising therapeutic effects in modulating inflammatory mediators. Studies indicate that these products help regulate tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), and interleukin-7 (IL-7) levels while reducing reactive oxygen species (ROS) production. Additionally, both in vitro and in vivo research, along with clinical studies, highlight their role in enhancing immune responses by activating B and T lymphocytes. This review explores the molecular mechanisms underlying these properties, emphasizing the role of bioactive compounds such as flavonoids, phenolic acids, and proteins in modulating immune responses and reducing inflammation. Evidence from in vitro, in vivo, and clinical studies suggests that honey and bee products influence cytokine production, regulate immune cell activity, and mitigate oxidative stress, making them potential therapeutic agents for inflammatory and immune-related disorders. To gather relevant information, databases such as Google Scholar, PubMed, and ScienceDirect were searched using various keyword combinations, including immunomodulatory, anti-inflammatory, bee products, honey, propolis, royal jelly, bee venom, and bee pollen. Given their anti-inflammatory, immune-protective, antioxidant, anti-apoptotic, and antimicrobial properties, bee products remain a subject of interest for further clinical evaluation. Full article

Red blood cells (RBCs) have traditionally been excluded from orthobiologic formulations due to inflammation, oxidative stress, and hemolysis concerns. However, emerging evidence suggests that RBCs may play an active role in regenerative medicine, contributing to immune modulation, vascular support, and oxidative balance. Their interactions with macrophages, involvement in nitric oxide signaling, and release of extracellular vesicles suggest they may influence tissue repair more than previously assumed. Despite these potential benefits, RBC retention in orthobiologic preparations like platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) remains controversial, with most protocols favoring their removal in the absence of robust translational clinical data. This review explores the biological functions of RBCs in regenerative medicine, their potential contributions to PRP and BMAC, and the challenges associated with their inclusion. While concerns about hemolysis and inflammation persist, controlled studies are needed to determine whether selective RBC retention could enhance musculoskeletal healing in some scenarios. Future research should focus on optimizing RBC processing techniques and evaluating their impact on clinical applications. Addressing these gaps will clarify whether RBCs represent an overlooked but valuable component in regenerative therapies or their exclusion remains justified. Full article

Deep-seated tumors present significant diagnostic challenges and pose substantial mortality risks due to their occult anatomical localization. Current diagnostic paradigms predominantly depend on conventional imaging modalities; nevertheless, inherent technical constraints persistently compromise diagnostic precision and therapeutic efficacy. In contrast to traditional methodologies, near-infrared (NIR; 700–1700 nm) fluorescence imaging (FLI) demonstrates superior sensitivity and spatiotemporal resolution, facilitating real-time intraoperative visualization and precision-guided surgical interventions. This paper explores fluorescence materials with tailored structures for tumors at different depths. We critically analyze optimization strategies for NIR fluorescence materials while evaluating their comparative advantages in stratified tissue imaging. This study presents a systematic evaluation of NIR fluorescence molecular tomography (FMT) systems and image reconstruction methodologies. These insights provide feasible ideas for detecting and treating tumors at varying depths in clinical practice. Furthermore, the application of NIR fluorescent materials in tumor diagnosis, navigation-guided surgery, and phototherapy (including photothermal, photodynamic, and immunomodulation therapies) is discussed. Finally, the prospects and challenges of clinical transformation are summarized. Full article

Schistosomes are intravascular parasitic worms that cause the debilitating tropical disease schistosomiasis, affecting >200 million people worldwide. How the worms survive within the body of immunocompetent hosts for many years is unclear. Here, using chromatography and mass spectrometry, we report on the ex vivo ability of adult Schistosoma mansoni worms to modulate the levels of 27 small molecule (often immunomodulatory) metabokines in murine plasma. Schistosomes significantly alter the relative amounts of most (16) of these molecules. Three (inosine, genistein, and glucose) are significantly decreased in the presence of the parasites. While levels of several immunomodulatory metabolites from the kynurenine pathway (kynurenine, kynurenic acid, and xanthurenic acid) remain unchanged, levels of anthranilate (an endogenous regulator of innate immunity) are significantly increased. Of particular interest are increases in levels of metabolites that are known to skew immune responses in a manner that is seen following natural schistosome infection, such as by promoting Th2 immunity (succinate), Treg generation (lactate) and M2 macrophage polarization (lactate and succinate). In addition, significant increases are also observed for 2-hydroxyglutarate, adenine, hypoxanthine, xanthine, myoinositol, betaine and N-acetylglucosamine. Each of these compounds can have immunosuppressive effects that could impact host immunological status and contribute to schistosome survival. Full article

Carotenoids are part of a diverse group of isoprenoid compounds. Due to the many properties they possess, they may become an alternative to synthetic additives in various industrial sectors. The increase in consumer demand and awareness determines research into extracting them from plants, algae and microorganisms. The extraction of carotenoids from plants is an inefficient method and generates additional production costs. On the other hand, the carotenoid potential of microorganisms, especially among yeasts, has not been fully exploited. The diversity of yeast species and strains influences the extraction of many fractions of carotenoids, including the less known ones such as thorulene and tholuradine. The developed adaptability of yeast enables the optimisation of their culture, which facilitates the understanding of their metabolic pathways. At the same time, the coordination of carotenoid and lipid synthesis may prevent their degradation or the loss of their bioactive properties. Application research has been conducted mainly in the feed industry, where their colouring and antimicrobial or immunomodulating properties are used. In the medical and pharmaceutical fields, there is not much research due to safety restrictions and the necessity of the high purity of the fractions. This review also highlights the overlooked aspect of carotenoids’ biodegradability, which is required to exploit the bioactive properties of microbial carotenoids. Full article

Lactoperoxidase (LPO) (E.C. 1.11.1.7) is a member of the superfamily of mammalian heme peroxidases that is isolated from milk, and it is the first enzyme announced to be found in milk. In addition to milk, LPO is also found in saliva, tears, and airways (airway goblet cells and submucosal glands). It contributes significantly to the self-defense of the mammal body. It catalyzes the oxidation of certain molecules such as thiocyanate (SCN⁻), I⁻, and Br⁻ in the presence of hydrogen peroxide (H₂O₂). This reaction leads to the formation of antimicrobial products that have a great antimicrobial spectrum, including antibacterial, antiviral, and antifungal activity, especially hypothiocyanite (OSCN⁻) and hypoiodite (OI⁻), which are coming into prominence via their high antimicrobial activity. The lactoperoxidase system (LPOS) is the system consisting of LPO, H₂O₂, and SCN⁻. LPO has a great potential to be used in various areas such as preservation and shelf-life elongation of milk; milk products; meat; meat products; plants, including fruits and vegetables; and oral care, diagnosis, immunomodulation, and treatment of nephrotoxicity. The LPO gene, along with LPO itself, is important for animals. In the absence of the LPO gene, there is an increase in the frequency of diverse diseases, including inflammation, tumor formation, and obesity. In this review, we mentioned general information about the enzyme LPO and its potential. Chemical properties and other features of other components of the LPOS, H₂O₂, and SCN⁻ were also touched on the review. To offer readers a comprehensive understanding of the enzyme’s biological significance and research progress over time, both recent and older studies have been used together. Lastly, we discussed potential applications of LPO in different areas and left future remarks in the light of recent studies. Full article

Peripheral nerve injuries (PNIs) commonly result from trauma, compression, or iatrogenic causes, leading to functional deficits. Despite the peripheral nervous system’s regenerative capacity, current treatments yield inconsistent outcomes. Basic science and translational research supporting nerve repair remain underdeveloped, partly due to the absence of standardized protocols, limiting reproducibility. Animal models are essential for studying injury mechanisms, repair strategies, and therapeutic development. This review examines commonly used animal models in PNI research, from non-mammalian species to rodents and large mammals. We discuss the relevance of injury types, experimental variables (i.e., age, sex, nerve type), and study design elements (i.e., nerve gap size, injury induction methods). Assessing these models’ strengths and limitations, this review aims to guide researchers in selecting appropriate models that enhance preclinical relevance. It also addresses the need for standardized protocols and future directions for improving PNI research and patient outcomes. Various PNI treatments—including microsurgery, nerve grafts, scaffolds, stem cells, immunomodulators, nerve augmentation strategies, and polyethylene glycol-mediated fusion—have been developed using animal models. These models are essential for driving innovation and translating emerging therapies to improve outcomes across a broad range of peripheral nerve injuries. Full article

Background/Objectives: Severe acute respiratory syndrome (SARS-CoV-2) has had a profound global impact and continues to represent a health challenge worldwide. The durability of SARS-CoV-2 vaccine responses in pediatric inflammatory bowel disease (PIBD) patients receiving biologic therapies is unknown. This study aimed to quantify SARS-CoV-2 antibody responses post vaccination in these immunosuppressed patients over 12 months. Methods: Prospective study comparing antibody responses against SARS-CoV-2 spike protein at 1, 3, 6, and 12 months in PIBD patients aged 5–18 years treated with anti-tumor necrosis factor alpha (anti-TNF) therapies with or without an immunomodulator (IM) versus vedolizumab. Results: Between 1 May 2021 and 1 May 2022, 194 participants on anti-TNF monotherapy (n = 78), anti-TNF with IM (n = 83), vedolizumab (n = 15), and steroids (n = 18) were recruited. Anti-SARS-CoV-2 spike levels increased after the first vaccine and were further boosted 1 month after the second dose. Linear mixed-effects modelling showed antibody waning over time (effect difference −2509 IgG AU/mL per week [95%CI: −4998–−20, p = 0.048]), counterbalanced by booster doses (effect difference 184,138 IgG AU/mL per additional vaccine dose [95%CI: 138,342–229,934, p < 0.001]). Receiving anti-TNF therapy contributed to reduced antibody responses compared to vedolizumab (anti-TNF monotherapy effect difference: −212,640 [95%CI: −336,928–−88,351] p = 0.001; anti-TNF with IM: −151,880 [95%CI: −277,309–−26,451] p = 0.018). Seroconversion and breakthrough infection rates were similar between groups, and all infections were mild, without hospitalizations. Conclusions: Although SARS-CoV-2 antibody responses were attenuated in PIBD patients receiving anti-TNF therapy compared with vedolizumab, this did not impact protection, as seroconversion and breakthrough infection rates were similar, with no hospitalizations. These data reinforce the importance of updating vaccines and, in particular, SARS-CoV-2 vaccines in immunosuppressed PIBD patients on advanced therapies. 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

Probiotics play a pivotal role in animal production by promoting growth, enhancing gut health, and modulating immune responses. Bacillus subtilis, a widely utilized probiotic, forms robust spores that exhibit exceptional resistance, making it ideal for feed applications. While B. subtilis spores have been shown to stimulate innate immune signaling, the specific contributions of spore coat proteins to immune modulation remain poorly characterized. In this study, we investigated the immunostimulatory effects of spores deficient in six key coat proteins: SpoIVA, SafA, CotE, CotX, CotZ, and CgeA. These proteins are essential for the assembly and structural integrity of the spore’s multi-layered coat, and are involved in recruiting other coat components. Deletion of these genes result in defects in spore coat architecture, potentially altering spore–host interactions. Using porcine alveolar macrophages (MΦ3D4/2), we assessed cytokine responses to each mutant strain. Our findings demonstrate that the absence of specific structural proteins significantly impacts immune activation, particularly through Toll-like receptor pathways. This work provides novel insights into the immunomodulatory functions of spore coat proteins and lays the foundation for the rational design of next-generation B. subtilis-based probiotics with enhanced immunological properties for agricultural applications. Full article

Deficiencies in immune function increase susceptibility to infections and chronic diseases by impairing immune surveillance and tolerance mechanisms, especially in children with immature immune systems. Chronic inflammation associated with immune dysfunction can impair childhood by suppressing the GH–IGF-1. HT042 is composed of Astragalus mongholicus, Eleutherococcus senticosus, and Phlomis umbrosa, which are medicinal herbs that are traditionally utilized in East Asia to promote growth and enhance immune function; thus, HT042 itself holds potential as an immunomodulator. We evaluated the immunomodulatory effects of HT042 in a cyclophosphamide (CYP)-induced immunosuppressed mouse model, as well as in ex vivo primary splenocytes and RAW 264.7 macrophages. HT042 demonstrated remarkable immune-enhancing effects, including the restoration of weight loss and hematological parameters, as well as enhancing NK cell activity. Primary splenocytes treated with HT042 showed increased expression of CD3, CD4, and CD8, along with Th subset transcription factors (T-bet, GATA3, RORγt, Foxp3) and corresponding cytokines (IFN-γ, IL-4, IL-17, IL-10). In RAW 264.7 macrophages, HT042 increased nitric oxide production and upregulated NOS2, COX-2, and inflammatory cytokines (IL-6, IL-1β, TNF-α). It is noteworthy that HT042 enhances both innate and adaptive immune pathways, particularly via T cell modulation and macrophage activation, as this study is among the first to demonstrate such effects in the context of CYP-induced immunosuppression. Full article