Dengue remains a leading cause of child mortality in Indonesia. Identifying reliable biomarkers to predict disease severity is essential for early intervention. Macrophage Migration Inhibitory Factor (MIF) is a pro-inflammatory cytokine involved in the pathogenesis of dengue. This study aimed to assess the relationship between MIF levels and dengue severity in children, and to compare  the predictive value of MIF levels with C-Reactive Protein (CRP) and serum albumin levels. A cross-sectional study was conducted on 104 pediatric dengue patients hospitalized at Saiful Anwar General Hospital. Serum levels of MIF (ELISA), CRP, and albumin were measured upon admission. Patients were categorized into four severity grades (Grade 1–4) and also stratified into shock and non-shock groups. Statistical analyses included ANOVA, correlation analysis, and receiver operating characteristic (ROC) curve evaluation. MIF levels showed a significant stepwise increase with disease severity and were significantly higher in patients with shock (p < 0.001). CRP levels were also elevated in severe dengue, but the correlation with severity was moderate (r = 0.61, p < 0.05). In contrast, serum albumin levels were inversely associated with severity (r = –0.67, p < 0.05), with lower values observed in the shock group. ROC analysis demonstrated that MIF had the highest predictive accuracy for shock (AUC = 0.94), compared to CRP (AUC = 0.78) and albumin (AUC = 0.81). MIF is a robust biomarker for predicting dengue severity and shock in children, outperforming CRP and albumin in diagnostic performance. The integration of MIF with conventional markers may improve early risk stratification and clinical decision-making in pediatric dengue.

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Periodontitis is a common and persistent inflammatory disease resulting from a sophisticated relationship between oral bacteria and the body's immune system. Toll-like receptors (TLRs) act as crucial sensors within the immune response, playing a fundamental role in the disease's initiation and progression. This review examines periodontitis, highlighting the limited understanding of TLR activation mechanisms and the therapeutic potential of TLR inhibitors. The discussion begins with a definition of TLRs, outlining their characteristics, types, distribution, and activation mechanisms. It then details the manifestation of TLRs in periodontitis, including alterations during inflammation and their correlation with disease severity. TLR activity is influenced not only by microbial stimuli but also by epigenetic factors and miRNAs, which mediate gene expression changes linked to inflammation. Various miRNAs have been shown to regulate TLR signaling pathways, thereby modulating the inflammatory response in periodontal tissues. Additionally, epigenetic modifications further complicate the landscape of immune regulation in periodontitis, affecting TLR expression and function. This interplay between TLRs, miRNAs, and epigenetic changes underscores the systemic implications of periodontal disease, contributing to broader health issues. Consequently, the review explores innovative strategies to modulate TLR signaling and discusses future challenges in TLR research in relation to periodontitis treatment. In summary, a more profound understanding of TLR-driven immune responses, along with the regulatory roles of miRNAs and epigenetic factors, is essential for developing targeted therapies and advancing treatment options for periodontitis.

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To examine the immunopathological mechanisms underlying heart failure with preserved ejection fraction (HFpEF) in elderly patients and evaluate exercise training as an immunomodulatory intervention for managing disease complications. A narrative literature review was conducted using PubMed, Embase, and Cochrane Library databases (2010–2023), focusing on immune dysfunction, aging, and exercise interventions in HFpEF. HFpEF pathophysiology in elderly patients involves complex interactions between innate and adaptive immunity, characterized by elevated pro-inflammatory cytokines, NLRP3 inflammasome activation, and immune cell dysfunction. Major complications—frailty syndrome, sarcopenia, and malnutrition—share common inflammatory pathways that perpetuate disease progression. Exercise training fundamentally alters this inflammatory profile through multiple mechanisms: suppressing pro-inflammatory cytokine production (TNF-α, IL-1β, IL-6), promoting anti-inflammatory immune cell phenotypes, and enhancing tissue regenerative capacity. Unlike pharmacological interventions targeting single pathways, exercise exerts pleiotropic effects across the immune-inflammatory network, simultaneously addressing cardiac dysfunction and systemic complications. Structured exercise programs effectively interrupt inflammatory cascades, improve functional capacity, and enhance quality of life in elderly HFpEF patients. Exercise training represents a cornerstone intervention that directly targets the fundamental immunopathology of HFpEF. Implementation of specialized exercise-based cardiac rehabilitation programs tailored to elderly patients is urgently needed to optimize clinical outcomes in this growing population.

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Wound healing is a critical global clinical issue, particularly in surgical and emergency care settings, where infections lead to significant morbidity, extended hospitalization, and increased healthcare costs. This study investigated the impact of altitude deadaptation on immune responses during wound healing in rabbits. Animals with aseptic and purulent wounds were divided into three groups: control (Bishkek), short-term (3-day), and long-term (30-day) high-altitude exposure, followed by descent to Bishkek. Leukocyte profiles and plasma levels of pro-inflammatory interleukin-1 beta (IL-1β) and anti-inflammatory interleukin-10 (IL-10) were analyzed. Short-term high-altitude exposure followed by rapid descent induced a maladaptive immune response characterized by elevated IL-1β levels, peaking at 10.1 ± 0.3 pg/ml on day 1 in aseptic wounds and 31.1 ± 2.5 pg/ml on day 3 in purulent wounds, indicating prolonged inflammation. In contrast, long-term exposure resulted in immune exhaustion, with diminished IL-1β and IL-10 responses. IL-10 levels were disrupted in the short-term exposure group, showing an initial increase followed by a decrease, suggesting inadequate anti-inflammatory effects. Leukocyte counts paralleled cytokine patterns, with initial leukopenia followed by delayed leukocytosis in the short-term exposure group. These findings demonstrate that altitude deadaptation affects immune regulation, inflammation extension, and hinders wound healing.

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Hypothyroidism, characterized by insufficient thyroid hormone production, is frequently associated with iodine deficiency. Selenium is essential for thyroid hormone metabolism and immune regulation. This study examined the effects of iodinated casein and selenomethionine supplementation on thyroid function and immune-inflammatory markers in a rat model of hypothyroidism. Thirty-six male Wistar rats were divided into four groups: control, hypothyroid (induced by thyrozol), hypothyroid rats treated with iodinated casein and selenomethionine, and hypothyroid rats treated with iodinated casein only. After 10 days of supplementation, serum levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), calcitonin, and cytokines (IL-6, TNF-α, IL-10, IFN-γ) were assessed. Compared to the controls, the hypothyroid group showed elevated TSH levels, decreased T3 and T4 levels, and a pro-inflammatory cytokine profile. Treatment with both iodinated casein and selenomethionine improved TSH levels, partially restored T3 and T4 levels, and normalized cytokine levels, whereas iodinated casein alone was less effective. Calcitonin levels remained unchanged after combined supplementation. These findings suggest that supplementation with both micronutrients is more effective than iodine alone in restoring thyroid hormone balance and modulating immune responses in individuals with hypothyroidism.

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Allergic diseases are increasingly recognized as a worldwide public health problem, affecting countries at all levels of economic growth. In recent years, it has been proposed that allergic diseases result from excessive type 2 inflammation, which is driven by cooperative interactions between the innate and acquired immune systems. In this model, allergens, pathogen-associated molecular patterns (PAMPs), and proteases would all be considered allergen-associated substances.  In this study, the Japanese ceder allergen Cry j1 and the house dust mite (HDM) allergen Der f1 were selected as representative allergens; lipoteichoic acid (LTA) from Staphylococcus aureus as a PAMP; and V8 protease (V8) from S. aureus, fungal Alternaria extract (Alt), and HDM fecal extract Dff as proteases. The effects of ozone gas on these substances were investigated in terms of allergenicity, proinflammatory activity via innate immunity, and protease activity. Ozone gas inactivated the allergenicity of both Cry j1 and Der f1, and the protease activities of V8, Alt, and Dff, in a CT value (the product of concentration [C] and exposure time [T])-dependent manner. The proinflammatory activity of LTA via innate immunity was significantly inactivated after ozone exposure (301 ppm·min). Although this study was carried out in a small chamber at the basic research level, the results suggest that ozone gas can inactivate indoor allergy-related substances and may help alleviate allergic symptoms. With appropriate safety measures, such as using it in a closed system, this technology has great potential for practical application to allergy management.

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