Search Results (343)

The enteric nervous system (ENS) constitutes a highly organized and intricate neuronal network comprising two principal plexuses: myenteric and submucosal. These plexuses consist of neurons and enteric glial cells (EGCs). Neurons ensure innervation throughout the intestinal wall, whereas EGCs, distributed within the mucosa, contribute to epithelial barrier integrity and modulation of local inflammatory responses. The ENS orchestrates essential gastrointestinal functions, including motility, secretion, absorption, vascular regulation, and immune interactions with gut microbiota. Under physiological conditions, intestinal homeostasis involves moderate generation of reactive oxygen species (ROS) through endogenous processes such as mitochondrial oxidative phosphorylation. Cellular antioxidant systems maintain redox equilibrium; however, excessive ROS production induces oxidative stress, promoting EGCs activation toward a reactive phenotype characterized by pro-inflammatory cytokine release. This disrupts neuron–glia communication, predisposing to enteric neuroinflammation and neurodegeneration. Obesity, associated with hyperglycemia, hyperlipidemia, and micronutrient deficiencies, enhances ROS generation and inflammatory cascades, thereby impairing ENS integrity. Nevertheless, non-pharmacological strategies—including synthetic and natural antioxidants, bioactive dietary compounds, probiotics, and prebiotics—attenuate oxidative and inflammatory damage. This review summarizes preclinical and clinical evidence elucidating the interplay among the ENS, obesity-induced oxidative stress, inflammation, and the modulatory effects of antioxidant interventions. Full article

Background: Polysaccharides modulate host health by interacting with gut microbiota and reshaping the host–microbial metabolome, potentially facilitating immune regulation. Methods: This study evaluated the modulatory effect of Artocarpus heterophyllus Lam. (jackfruit) polysaccharide (JFP-Ps) against cyclophosphamide (Cy)-induced immunosuppression in mice, focusing on gut microbiota modulation and metabolite changes. Results: JFP-Ps effectively increased the beneficial bacteria ratio, such as Lactobacillus and Lachnospiraceae, while inhibiting some species like Akkermansia. Metabolomic analysis showed that JFP-Ps notably regulated gut microbe-associated metabolites, including short-chain fatty acids (SCFAs), amino acids, bile acids, indoles, and derivatives. These metabolites were involved in various metabolic pathways, including primary bile acid synthesis and biosynthesis of phenylalanine, tyrosine, and tryptophan, along with tryptophan catabolism, purine metabolic processes, and unsaturated fatty acid production. Additionally, significant correlations between microbial groups and functional metabolites were identified. Overall, JFP-Ps exerted an immuno-modulatory effect by reshaping gut microbiota and enhancing co-metabolism with the host. Conclusions: These results provided valuable insights into host–microbiota interactions and gut microbiota-targeted intervention strategies of tropical natural bioactive polysaccharides. Full article

Vitamin D is well established for its skeletal effects, being a cornerstone of several endocrine disorders. In recent years, it has come under investigation as a potential disease-modifying drug in several endocrine disorders through its immune modulatory and anti-tumorigenic action, particularly in thyroid disease, gynecologic disorders, and general fertility. Vitamin D supplementation is well established in the treatment of osteoporosis, osteomalacia, hypoparathyroidism, and primary hyperparathyroidism. In autoimmune thyroid disease, there is a negative correlation between 25(OH)D3 levels and prevalence. Currently available data are inconclusive on supplementation as a disease-modifying treatment. In Hashimoto’s thyroiditis, while some found improved thyroid function, a decline in progression, and antibody titers, these findings were not consistent, and some found no improvements. Painless postpartum thyroiditis severely lacks evidence. Interventional studies failed to demonstrate benefits in Graves’ disease. The literature consistently reports lower vitamin D levels in infertility, polycystic ovarian syndrome (PCOS), and endometriosis. In PCOS, data suggest that vitamin D supplementation is beneficial; however, results in exact benefits vary and there is no consensus on dosing. Current guidelines support supplementation as part of preconception nutritional care. In general, for female infertility and endometriosis, the results are conflicting, with a lack of high-quality evidence. The literature suggests there is a possible benefit regarding sperm motility, but not in testosterone levels for males. In conclusion, while in vitro studies and animal models are promising, the available evidence is often contradictory, with high heterogeneity in study designs and populations. Our paper highlights the need for further high-quality research to resolve current controversies. Full article

Background/Objectives: Burn wound infections caused by Staphylococcus aureus remain a major clinical challenge, leading to delayed healing and high mortality. Natural compounds derived from the Lamiaceae family possess antimicrobial and anti-inflammatory properties that may modulate wound recovery. This study aimed to evaluate the dual modulatory effects of Satureja montana and Origanum vulgare hydrolate-loaded hydrogels on modulation of infection and skin recovery in an experimental rabbit model of S. aureus-infected burns. Methods: Full-thickness (grade IIIa) thermal burns were induced in 25 male New Zealand White rabbits, followed by inoculation with S. aureus (10⁸–10⁹ CFU/mL). Animals were divided into five groups: sham control, burn-infection control, standard-of-care intervention, Satureja montana hydrolate intervention, and Origanum vulgare hydrolate intervention. Treatments were applied twice daily for 14 days. Bacterial load (CFU/g), biochemical markers, histological parameters, and multiplex immunohistochemical indices (Ki-67, CD68, CD163) were analyzed. Results: Both hydrolate-based formulations exhibited pronounced antibacterial effects, significantly reducing S. aureus counts by day 14 compared to untreated burns (p < 0.001). Immunohistochemical analysis revealed enhanced cell proliferation and a rapid shift from pro-inflammatory M1 (CD68+) to reparative M2 (CD163+) macrophages, indicating effective immune resolution. The hydrolate-loaded hydrogels effectively combined antimicrobial activity with tissue-regenerative and immunomodulatory effects. The S. montana formulation demonstrated superior performance, representing a promising adjunctive therapy for infected burn wounds. Conclusions: This study represents the first comparative in vivo evaluation of S. montana and O. vulgare hydrolate-loaded hydrogels in a complex S. aureus-infected burn model. Full article

Postbiotics, which are preparations of inanimate microorganisms and their components, have emerged as a promising functional ingredient in animal health and nutrition. Postbiotics are primarily composed of microbial cell fractions, metabolites, enzymes, vitamins, polysaccharides, and short-chain fatty acids. Unlike probiotics, postbiotics do not contain live microorganisms, which strengthens their greater stability and safety in feed/food formulations. Postbiotics offer several beneficial effects, including antioxidant, anti-inflammatory, immune-modulatory, and antimicrobial actions. They enhance antioxidant enzymes, neutralize reactive oxygen species, and inhibit lipid peroxidation, thereby protecting tissues from oxidative damage. Postbiotics also inhibit pro-inflammatory molecules like TNF-α and IL-6, while enhancing the anti-inflammatory cytokine IL-10, promoting the maturation and function of immune cells, and increasing secretory IgA production. They suppress a variety of pathogenic bacteria, including Escherichia coli, Salmonella, Staphylococcus, Campylobacter, etc., both in vitro and in vivo. Moreover, they increase beneficial gut bacteria and improve the digestion and integrity of the intestine. This article outlines the beneficial effects of postbiotics in animals including poultry, swine, canine, feline, horses, and ruminant animals, either as feed/food or as a supplement. The integration of postbiotics into animal feed improves growth performance, feed conversion ratios, and disease resistance in animals. Thus, the multifunctional benefits of postbiotics make them a valuable tool for healthy companion animals and sustainable livestock production, supporting both animal welfare and productivity without the drawbacks associated with antibiotic growth promoters. Full article

Background/Objectives: Cancer’s complexity can be rationalized through the “hallmarks of cancer,” which define the key biological capabilities driving malignancy. Induced hyperthermia—an adjunctive therapy that elevates body temperature above the normal setpoint for a defined period—has been explored for its modulatory effects on these hallmarks. This systematic review aims to evaluate the effects and mechanisms of induced hyperthermia on tumor cells through the established hallmarks of cancer framework. Methods: A systematic search following the Cochrane guidelines and PRISMA assessment tool was conducted in PubMed and Cochrane Library (2000–2025) to identify reviews on the effects of induced hyperthermia on cancer hallmarks. Studies’ predefined inclusion criteria were independently evaluated by two external teams and graded using PRISMA standards. Results: From the 2015 records screened, 103 studies met the inclusion criteria. Evidence indicates that induced hyperthermia modulates seven of the ten cancer hallmarks. The most well-supported mechanisms of action include (1) the immune system activation (39–41 °C)—enhancing antigen presentation, activating innate/adaptive immune cells, promoting tumor infiltration—and (2) genome instability and mutation (41 °C)—impairing DNA repair pathways and increasing tumor vulnerability. Both hallmarks provide evidence clarifying the mechanistic pathways through which induced hyperthermia exerts its effects. Conclusions: Induced hyperthermia exerts multifaceted, temperature-dependent effects on cancer biology, predominantly through immune activation and genomic destabilization. While it enhances the therapeutic sensitivity of other treatment modalities (e.g., chemotherapy, radiotherapy) and antitumor responses, excessive heating may induce immune suppression and thermotolerance. Optimizing temperature parameters and identifying biomarkers are essential for integrating hyperthermia into targeted and multimodal cancer therapies. Full article

Glioblastoma (GBM) remains the most aggressive primary brain tumor, characterized by extensive intra-tumoral heterogeneity, profound local immunosuppression, and a highly adaptive tumor microenvironment that resists conventional therapies. Immunotherapy for GBM tries to overcome these barriers by reactivating anti-tumor immunity through cellular, molecular, and immune-modulatory interventions. The therapeutic efficacy of the cell-based vaccines in patients with glioma and glioblastoma is primarily driven by tumor antigen-specific CD8⁺ T cell activation, orchestrated by CD4⁺ T cell help. Several whole-cell vaccine platforms (e.g., DCVax-L, CMV-targeted vaccines, and Cancer Transplant Immune Recognition Therapy (CTITR)) provide personalized formulations. CTITR consists of irradiated autologous and allogeneic glioma cells and their lysates, leveraging the inherent immunogenicity of allogeneic material to bypass the need for predefined tumor-specific antigen selection. This strategy promotes broad CD8⁺ T cell expansion, potentially exceeding 10⁹ antigen-specific cytotoxic T lymphocytes, sufficient for substantial tumor clearance. Such a preparation can start with approximately 1 g of surgically resected tumor tissue per patient to generate both autologous and allogeneic vaccine components. Clinical observations indicate that cell-based vaccine preparations can be effective in both newly diagnosed glioblastoma patients treated post-surgery and in patients with recurrent gliomas. Cell-based vaccines, including CTITR, offer novel, antigen-agnostic immunotherapeutic platforms that harness autologous DC and autologous and allogeneic glioma cells, and their lysates bypass the need for predefined tumor-specific antigen selection. Full article

Recent scientific reports have highlighted the physiological role, toxicological effects, and pathophysiological aspects of gasotransmitters, particularly hydrogen sulfide (H₂S), which is recognized as a new member of this family. Endogenous generation of H₂S in the skin occurs through both enzymatic and non-enzymatic pathways. The main enzymes involved in its endogenous production are cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MST) and cysteine aminotransferase. 3-MST and CSE are crucial for maintaining the epidermal barrier. H₂S may play a role in oncogenesis, acting as a gas signaling molecule that disrupts mitochondrial respiration and influences immune modulation, cell proliferation, apoptosis, tumor cell survival, and metastasis. Interestingly, H₂S exhibits dual effects in the biology of skin cancer, promoting tumor growth in some contexts and exerting antitumor activities in others. Data from the European Cancer Information System and Global Cancer Observatory show a significant global increase in skin cancer cases. The most common types of cutaneous malignancies, from both epidemiological and clinical perspectives, are basal cell carcinoma. squamous cell carcinoma, and melanoma. This review aims to evaluate the dysfunctional metabolism of H₂S and the specific profiles of the enzymes that synthesize H₂S in skin cancer. By comparing the roles of H₂S in normal cells with those in cancer cells, we can enhance current understanding of its implications in skin cancer biology. This research paves the way for new clinical strategies, including the development of H₂S-modulatory therapies tailored to the dynamics of tumor progression, which could help overcome therapeutic resistance. Full article

Introduction/Goal: Stress and negative emotions have been shown to exert a substantial impact on cancer patients, affecting their ability to adapt to therapy and the overall effectiveness. Elevated cortisol levels, a stress-induced hormone, have been shown to suppress immune system function, potentially reducing the body’s capacity to combat cancer cells. On the contrary, prolactin, a hormone that stimulates the immune system, has shown potential in this context but requires further study. The objective of this study was to investigate the acute physiological changes that occur during a single Conscious Connected Breathing (CCB) session, as part of a larger investigation on Integrative Breathwork Psychotherapy (IBP), a novel integrative psychosomatic intervention designed to improve psychosomatic and immune status in cancer patients. Methods: The project involved 93 breast cancer patients hospitalized for postoperative radiotherapy who participated in a ten-session IBP program. Fifty-six patients agreed to participate (response rate: 60%). During the experiment, 8 patients were excluded from the analysis. IBP consisted of small group sessions (up to six participants) conducted three times weekly. Each session included 45 min of CCB—defined as rhythmic circular nasal breathing at a depth exceeding resting tidal volume, without breath-holding, performed in a state of mindful acceptance—followed by 15 min of free emotional expression (verbal articulation of emerging feelings and sensations). This was a within-subject pre-post design: physiological measurements were obtained immediately before and 30 min into the tenth session (when participants had achieved technical proficiency) in all participants, who served as their own controls. Outcome measures included: arterialized capillary blood gas parameters (pH, pCO₂, pO₂, ctO₂, COHb, HHb, cH⁺), serum cortisol and prolactin concentrations, and immunoglobulin A (IgA). Results: During the CCB session, blood gas analysis revealed significant changes consistent with mild respiratory alkalosis: decreases in pCO₂ (p = 0.003), pO₂ (p < 0.001), cH⁺ (p < 0.001), ctO₂ (p < 0.001), COHb (p = 0.03), and HHb (p = 0.004), alongside an increase in pH (p < 0.001). Concurrently, prolactin levels increased significantly (p < 0.001), while cortisol (p < 0.001) and IgA (p < 0.001) decreased. Conclusions: This study is the first to analyze acute changes in capillary blood gas parameters and neuroendocrine balance during Conscious Connected Breathing sessions in cancer patients, revealing measurable immunostimulatory and stress-modulatory effects. The observed shift toward respiratory alkalosis, combined with increased prolactin and decreased cortisol, suggests that CCB may facilitate favorable neuroendocrine-immune interactions. These findings support the potential of breathwork as a complementary therapy for cancer patients. Further research is needed to explore underlying mechanisms and assess long-term psychological and immunological impacts. Full article

Background/Objectives: Allergic diseases are highly prevalent worldwide and represent a significant public health burden. Current therapies mainly alleviate symptoms without addressing underlying immune dysfunction, which has increased interest in nutritional bioactive compounds as preventive or modulatory agents. This review summarizes evidence on omega-3 polyunsaturated fatty acids, vitamin D, curcumin, ginger bioactives, quercetin, and epigallocatechin gallate (EGCG) in allergy prevention and management. Methods: A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science up to July 2025, including preclinical and clinical studies reporting immunological, mechanistic, and clinical outcomes. Results: Omega-3 fatty acids modulate Th2 responses, promote regulatory T cells, and generate specialized pro-resolving mediators, with modest clinical benefits observed in pregnancy and early life. Vitamin D contributes to immune tolerance and epithelial integrity, although supplementation trials remain heterogeneous. Curcumin inhibits NF-κB/MAPK signaling, enhances barrier function, and improves allergic rhinitis and dermatitis despite limited bioavailability. Ginger constituents ([6]-gingerol, [6]-shogaol) modulate Th1/Th2 balance, mast-cell activity, and oxidative stress, with early clinical evidence in rhinitis and asthma. Quercetin stabilizes mast cells, inhibits Lyn/PLCγ pathways, and improves rhinitis symptoms in small randomized trials using bioavailable formulations. EGCG stabilizes mast cells, attenuates FcεRI signaling, and reduces airway inflammation in preclinical models, though clinical data are scarce. Conclusions: Overall, preclinical findings consistently support the immunomodulatory potential of these compounds, while clinical results are promising but heterogeneous. Standardized formulations, long-term trials, and exploration of synergistic effects are required to confirm efficacy and safety, providing future research directions in allergy prevention. Full article

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, and current treatments are limited by significant side effects. Deer bone, which is rich in proteins and various active compounds, possesses anti-inflammatory and bone-health-promoting properties. However, its fermented product’s effects on RA treatment remain unexplored. In this study, we evaluated the therapeutic effects of probiotic-fermented deer bone aqueous extract (BbF) in an adjuvant arthritis (AA) rat model, combined with LPS-stimulated RAW264.7 macrophage models. In vivo experiments showed that BbF significantly reduced paw swelling, arthritis index, and improved bone mineral density. BbF also alleviated synovial hyperplasia and inflammatory cell infiltration. It suppressed pro-inflammatory cytokines (TNF-α, IL-1β, etc.) and inhibited macrophage migration and invasion. Transcriptomic analysis revealed significant enrichment of the Notch signaling pathway, and Western blot confirmed the downregulation of Notch3, Notch4, DLL4, and Jagged1 proteins. BbF also restored gut microbiota homeostasis, increasing beneficial bacteria such as Firmicutes and Clostridia, while decreasing potential pathogens like Proteobacteria, Gammaproteobacteria, and Escherichia-Shigella. Furthermore, BbF enhanced short-chain fatty acids (SCFCs) production, including butyrate and caproic acid. These results indicate that BbF alleviates RA by inhibiting the Notch signaling pathway and regulating gut microbiota, providing new insights for the development of functional foods with immune-modulatory properties. Full article

Background: Infertility is a multifactorial condition that causes significant emotional distress and financial burden for couples. Despite advances in assisted reproductive technologies (ARTs), many patients experience recurrent implantation failure (RIF) or pregnancy loss. Intralipid, an intravenous lipid emulsion, has been proposed as an adjunctive therapy due to its immune-modulatory effects, particularly in reducing elevated natural killer (NK) cell activity, which may be associated with poor reproductive outcomes. This study evaluated the effect of intralipid infusion on pregnancy rates and miscarriage rates in women with recurrent implantation failure undergoing in vitro fertilization (IVF). Materials and Methods: This was a retrospective study of women who had suffered from recurrent implantation failure and underwent IVF between September 2023 and September 2024. A comparative group undergoing IVF but who did not have recurrent implantation failure matched for age was selected. Outcomes of clinical pregnancy, miscarriage and livebirth rates were compared in both groups. Results: A total of 113 women undergoing IVF were identified and 51 received intralipid. Intralipid was initiated at varying stages of the IVF process, a day before embryo transfer (ET) (18 or 35.3%), on the day of ET (20 or 39.2%) and after ET (13 or 25.5%). The clinical pregnancy rate was 44.2% in the treatment group compared to 29% in the comparator group (p < 0.05) while the miscarriage rates were 13.7% versus 11.3% (p > 0.05). Elevated NK cells were present in 65.4% of the patients who received intralipid, but the correlation between NK cell levels and pregnancy outcomes was weak (Spearman ρ = 0.032). No adverse effects were reported in any of the women. Conclusions: Intralipid infusion increased the successful pregnancy rates in women who had recurrent implantation failure during IVF. The successful pregnancy rate was significantly higher than that in those undergoing ART who had not suffered from RIF. These findings support several studies on the potential benefit and safety of intralipids in women undergoing ART, but the numbers remain small and more prospective studies are needed to confirm these findings Full article

Cyclic lipopeptides (CLPs), produced by beneficial rhizobacteria such as Bacillus and Pseudomonas species, are specialized metabolites retaining key functions for the plant protective activity of the producers, which shows their potential as biocontrol agents in agriculture. Beyond their strong antimicrobial properties, CLPs can act as potent elicitors of plant immunity and systemic resistance. However, the molecular mechanisms underlying these immune-modulatory effects and the role of CLPs’ structural diversity remain poorly understood. Here, we demonstrate that specific structural features of surfactin-type CLPs critically influence their ability to trigger early immune responses in plants, including reactive oxygen species bursts, nitric oxide (NO) production, calcium fluxes, and systemic resistance. In Arabidopsis thaliana roots, we show that surfactin-induced NO generation requires calcium signaling. Moreover, we reveal that contrasting immune effects of CLPs may stem from the ecological lifestyles of their microbial producers, shedding light on the evolutionary basis of plant–microbe interactions. Altogether, our findings underscore the importance of CLP structural variation in shaping plant defense responses and highlight the potential for structure-informed design of next-generation biosourced small molecules with broad-spectrum efficacy as plant protectants. Full article

Periodontitis is a chronic, multifactorial inflammatory disease initiated by dysbiotic biofilms and driven by a dysregulated host immune response. Central to its pathogenesis is a complex network of cytokines, particularly interleukins, with both pro-inflammatory and anti-inflammatory roles. This narrative review comprehensively analyzes current knowledge on the molecular biology, cellular sources, immune pathways, and systemic effects of key interleukins in periodontitis. We highlight the dual roles of interleukins such as IL-17 and IL-10, discuss recent advances in understanding their regulatory networks, and explore translational perspectives, including diagnostic biomarkers and cytokine-targeted therapies. Emphasis is placed on dissecting the fine balance between destructive inflammation and protective resolution mechanisms, aiming to inform novel, immune-modulatory treatment strategies for periodontal disease. Full article