It is supposed that the primary or secondary dysfunction of macrophages may play an essential role in the pathogenesis of endometriosis. It is postulated that macrophage-derived cytokines and signaling molecules, such as IL-1 (interleukin), IL-6, and IL-12, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and MCP-1 (monocyte chemoattractant protein) may be involved in the process of endometriosis formation. This pilot study included 47 patients who underwent diagnostic–therapeutic laparoscopy at the II Department of Gynecology, Medical University of Lublin, Poland. Peritoneal fluid was obtained from patients in both the reference and study groups. The number and viability of the cells were assessed. The cells were labeled with monoclonal antibodies and assessed using flow cytometry. Interleukins of macrophage origin in the peritoneal fluid were determined using the enzyme-linked immunosorbent assay (ELISA) test. The peritoneal fluid showed fundamental changes in the concentration of the studied cytokines. We recorded the peritoneal fluid volume for each patient (median ∼5 mL in the endometriosis group vs. ∼4 mL in the reference group) and noted that a larger volume could dilute cytokine levels; cytokine concentrations were thus interpreted per mL of fluid. More than twice as high median IL-12 levels were detected in women in the reference group than in the study group. High levels of IL-1α and low levels of IL-12 in the study group compared to the reference group suggest an immunological component in the etiopathogenesis of endometriosis, although this pilot, exploratory study (n = 47) cannot establish this relationship definitively. All endometriosis cases were laparoscopically confirmed, but histopathological confirmation was obtained in only 20 of 28 cases (71.4%); the remaining 8 patients had superficial Stage I lesions that were not biopsied. This study aimed to assess the concentrations of IL-1α and IL-12 in the PF of women with endometriosis compared to those with idiopathic infertility.
Introduction:Ulcerative colitis (UC) is characterized by immune dysregulation and localized inflammation of the colonic mucosa. Despite advances in therapy, effective treatment remains difficult. This study aimed to investigate the immunomodulatory and therapeutic effects of chitosan nanoparticles (CS-NPs) loaded with quinic acid (QA) and ferulic acid (FA) in an experimental model of UC, focusing on the IL-32/IL-33/IL-34 cytokine axis and the NF-κB signaling pathway. Methods:Eighty male Wistar rats were randomly divided into 10 groups (n = 8 per group). Experimental acute colitis was induced in rats via intrarectal administration of 4% acetic acid (AA). After induction, the animals received CS-NPs loaded with QA and FA for seven consecutive days. IL-33, IL-34, and NF-κB mRNA expression were measured by real-time PCR. Additionally, tissue IL-32 levels were measured using an ELISA kit. Results:Induction of UC significantly increased IL-32 protein levels as well as the expression of IL-33, IL-34, and NF-κB. Oral administration with mesalazine, FA/QA/CS-NPs, QA/CS-NPs, FA/CS-NPs, FA/QA, QA, and FA significantly decreased IL-32 protein levels and the expression of IL-33, IL-34, and NF-κB relative to the model group. Conclusion:FA/QA-loaded CS-NPs exhibit anti-inflammatory effects in experimental UC, likely through modulation of the IL-32/IL-33/IL-34 cytokine axis and NF-κB signaling. These findings suggest that FA/QA/CS-NPs may serve as a promising herbal-based therapeutic candidate for the treatment of UC in humans.
Neuroinflammation is intricately associated with impaired neuronal function and is a contributing factor in the development of neurodegenerative diseases. Significant alterations in cellular metabolism often accompany these inflammatory changes. Although considerable research has focused on understanding these metabolic shifts in astrocytes and microglia, the precise mechanisms linking neuroinflammation and cellular metabolism in neurons remain poorly understood. This study explores the connection between neuroinflammation and neuronal cell metabolism through a lipopolysaccharide (LPS)-induced neuroinflammation model utilizing GT1-7 hypothalamic neuron cultures. Our findings indicate that LPS-induced neuroinflammation in GT1-7 hypothalamic neurons is marked by reduced oxidative phosphorylation (OXPHOS) and decreased endogenous fatty acid oxidation (FAO). In contrast, exogenous FAO increases, leading to elevated ATP production, while glycolysis remains unchanged. These metabolic changes are associated with increased inflammatory markers (IL-6, TNF-α) and oxidative stress indicators (ROS, NO), as well as decreased synaptic plasticity (as indicated by synaptophysin) and impaired cellular function, as evidenced by reduced gonadotropin-releasing hormone (GnRH) release. Our study highlights the intricate interplay between neuroinflammation and neuronal cell metabolism. These findings emphasize the significance of metabolic changes in neuroinflammatory processes, offering potential insights for therapeutic interventions in neurodegenerative diseases.
BackgroundPrenatal stress experienced by pregnant individuals adversely affects offspring's health. This study investigated the effects of the administration of Eucalyptus alba (E. alba) extracts during pregnancy on prenatal stress-induced neural oxidative stress and downregulation of immune response in rat neonates.Materials and MethodsForty-five pregnant albino rats were divided into nine groups, each consisting of five animals. Group 1 (normal) served as the control group; they were neither exposed to stress nor given any treatment. Group 2 (vehicle) was subjected to stress and administered 5 mL/kg of distilled water orally via gavage. Group 3 (positive control) was also stressed and treated with 1 mg/kg of diazepam intramuscularly every 24 h. Groups 4, 5, 6, 7, 8, and 9 were stressed and received either 100, 200, or 400 mg/kg of aqueous or ethanol plant extracts orally via gavage until delivery. Twenty-one days after birth, the offspring were sacrificed to assess serum cytokine levels, humoral and cell-mediated immune responses, and the total antioxidant activity of the plant extracts.ResultsThe vehicle control group exhibited increased inflammatory cytokine levels (NO, IL-1beta, IL-6, and TNF-alpha), which were significantly reduced by E. alba extracts (p < 0.001). E. alba extracts mitigated the decrease in spleen index and hemagglutination (HA) titer, as well as the increased hypersensitivity observed in the vehicle control group; increased lymphocyte percentage (p < 0.05); and reversed the decreases in NEU, MID, and TWBC observed in the vehicle control group. Notably, antioxidant level improved with the reductions in CAT and TBARS and increases in SOD and GSH (p < 0.001). Histopathological analysis revealed less severe damage in the spleen and external ear structures of rats treated with E. alba compared to the vehicle control group.ConclusionThe findings of this study demonstrate that the use of E. alba extracts during pregnancy prevents immunological dysregulation and oxidative stress in the nervous system caused by prenatal stress.
Hypoxia‐inducible factor‐2 α (HIF‐2 α ), a key regulator of cellular adaptation to hypoxia, modulates cellular metabolism, allowing cells to survive under hypoxic conditions. In immune responses, infected or inflamed tissues often exhibit hypoxia, and HIF‐2 α plays a vital role in helping immune cells adapt. HIF‐2 α also plays a dual and context‐dependent role in inflammation. HIF‐2 α exhibits both pro‐ and anti‐inflammatory effects in inflammation depending on cell type, disease microenvironment, and signaling pathways. This article describes how HIF‐2 α regulates immune cell function and its essential role in inflammation, as well as the effects of HIF‐2 α on the development of inflammation through different signaling pathways. Finally, it explores the potential of HIF‐2 α as a therapeutic target.
