Pancreatic cancer is one of the most common malignant neoplasms, the incidence has increased in the population among patients who have recovered from various SARS-CoV-2 strains with subsequent post-COVID syndrome symptoms development. Given the heterogeneity of cancer development mechanisms within the population, the individual complex treatment implementation is essential for the correction of impaired immunometabolic processes. The aim is to assess pathological changes in humoral and cellular markers of innate and adaptive immunity in groups of patients with non-metastatic and metastatic pancreatic cancer. 64 patients (38 to 79 years) with pancreatic cancer were examined: group 1—non-metastatic (n = 44); group 2—metastatic (n = 20). The following research methods were used: ELISA (enzyme-linked immunosorbent assay), flow cytometry, immunoturbidimetry, spectrophotometry, light microscopy, impedance spectrometry. In first group patients had an increase in the C3 component complement, IL-1β, TNF-α, TLR4, TLR9 and DAMPs (Damage-Associated Molecular Patterns) cytotoxic oligonucleotide fraction. In second group patients had an increase in cortisol, C3 component complement, TLR9, oligopeptide and oligonucleotide DAMPs fractions and a maximum increase in the T regulatory cells CD3+CD4+CD25+СD127-. In both groups was increase in NK cells CD3-CD56+CD16+ and a wide spectrum of antinuclear antibodies to altered nuclear structures that acquired antigenic properties. In both groups, we identified cohorts of patients who with significant changes in the studied parameters set, had a decrease in serum electrical conductivity (on average by 45%). Individual changes in immunometabolic markers in patients of different ages with non-metastatic and metastatic pancreatic cancer have diagnostic and prognostic value.
Pediatric tuberculosis remains difficult to monitor using objective biomarkers. Total serum adenosine deaminase (ADA) reflects cellular immune activation, whereas vitamin D and zinc may modify antimycobacterial immunity. This pilot randomized trial evaluated whether adjunctive vitamin D or zinc altered serum ADA during the intensive phase of pediatric tuberculosis treatment. Thirty-three treatment-naive children with tuberculosis were randomized equally to standard anti-tuberculosis treatment (ATT) alone, ATT plus zinc, or ATT plus vitamin D. Total serum ADA was measured at baseline and after two months. The prespecified completer analysis compared change scores, while the primary adjusted analysis used analysis of covariance (ANCOVA) with post-treatment ADA as the outcome and baseline ADA as a covariate. A multiple-imputation intention-to-treat sensitivity analysis included all randomized participants. Twenty-two participants completed follow-up (ATT, n = 8; zinc, n = 8; vitamin D, n = 6). Unadjusted ADA decreased in all groups and most markedly in the vitamin D arm, but the between-group difference in change was not significant (p = 0.364). Baseline-adjusted ANCOVA also showed no treatment-group difference (F2,18 = 0.79; p = 0.470). Compared with ATT alone, the adjusted effects were −4.35 U/L for vitamin D (95% CI −15.70 to 7.00) and +2.26 U/L for zinc (95% CI −8.07 to 12.59). The intention-to-treat sensitivity analysis produced the same overall interpretation. In this underpowered pilot trial, adjunctive vitamin D or zinc did not significantly reduce total serum ADA beyond standard therapy. The large crude decline in the vitamin D arm was attenuated after adjustment for baseline imbalance and regression to the mean. Larger multicentre trials should confirm micronutrient repletion, measure ADA2, and prespecify methods for missing data.
The tumor microenvironment (TME) plays a major role in cancer progression, immune evasion, and resistance to immunotherapy. Coumarins, a structurally diverse class of natural and synthetic compounds, have attracted increasing attention because of their anticancer, anti-inflammatory, antioxidant, and immunomodulatory properties, suggesting potential applications in TME-oriented cancer immunotherapy. This review aimed to summarize the immunotherapeutic potential of natural and synthetic coumarin derivatives in modulating TME and enhancing anticancer immune responses. A narrative review of the literature was conducted focusing on the effects of coumarin derivatives on immune-cell regulation, immune checkpoint signaling, angiogenesis, extracellular matrix remodeling, metabolic reprogramming, and hypoxia-related pathways within TME. Evidence from preclinical studies involving natural and synthetic coumarins was critically evaluated. Preclinical findings indicate that coumarin derivatives can modulate several components of TME by promoting M1 macrophage polarization, activating dendritic cells and natural killer cells, enhancing T-cell–mediated immunity, and suppressing immunosuppressive cell populations such as regulatory T cells and M2 macrophages. Several coumarins also demonstrated the ability to inhibit tumor glycolysis, attenuate hypoxia-associated immune resistance, normalize angiogenesis, and regulate inflammatory signaling pathways. Synthetic coumarins showed additional promise through structural optimization and targeted delivery approaches, while their potential complementary effects with immune checkpoint inhibitors remain to be established experimentally. However, available evidence remains limited, and further mechanistic and translational investigations are required. Natural and synthetic coumarins represent promising multifunctional immunomodulators capable of reshaping TME and improving anticancer immune responses. Their diverse biological activities support their future development as adjuncts or enhancers of cancer immunotherapy.
Cancer immunotherapy has been a successful therapeutic approach by improving the ability of the immune system to recognise and destroy tumour cells. However, the accurate prediction of patient-specific immunotherapy responses still remains a major challenge because of the heterogeneous tumour microenvironment (TME), in which complex interactions among Tumour-Associated Macrophages (TAMs), Myeloid-Derived Suppressor Cells (MDSCs), Dendritic Cells (DCs), cytokines, and immune checkpoint molecules exhibit highly nonlinear and dynamic behaviour. Current machine learning and deep learning models typically represent immune biomarkers as static feature vectors, which restricts their ability to model temporal immune dynamics and complex biological interactions. To overcome these limitations, this paper proposes a framework of Fish Swarm Optimised Spiking Neural Network (FSO-SNN) for precision immunotherapy response prediction. We pre-process multi-source immune and clinical datasets using missing-value estimation, normalisation, redundancy removal, and immune feature integration to create biologically meaningful representations. Temporal spike encoding allows biologically inspired modelling of dynamic immune signalling in the TME, while Fish Swarm Optimisation is employed to identify informative immune biomarkers and to optimise the synaptic parameters of the Spiking Neural Network. Experiment evaluation demonstrates that the proposed FSO-SNN outperforms conventional machine learning, deep learning, graph neural network, and standard spiking neural network models, achieving 98.74% accuracy, 98.51% precision, 98.83% recall, 98.67% F1 score and 99.31% AUC. The results presented demonstrate that the proposed framework is accurate and computationally efficient in predicting immunotherapy response, and it offers a promising computational tool for future precision oncology research, yet external validation and prospective clinical studies are required prior to its routine clinical application.
Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental disorder characterized by executive dysfunction, visuomotor impairment, and visuospatial deficits. Emerging evidence suggests that neuroinflammatory mechanisms may contribute to this cognitive heterogeneity. This exploratory methodological study aimed to illustrate the application of advanced multivariate statistical approaches to a reconstructed neuropsychological dataset and to discuss the resulting analytical patterns within the context of current neuroimmune research. A reconstructed dataset derived from published summary statistics of a previously reported case-control study of 80 children (40 with ADHD and 40 controls) was analyzed focusing on the Bender–Gestalt Test and the Rey–Osterrieth Complex Figure Test. Descriptive statistics, principal component analysis, cluster analysis, multiple regression, mediation analysis, and correlation network visualization were performed. The exploratory multivariate analyses illustrated how advanced statistical methods can identify latent neuropsychological structures within a reconstructed dataset. Principal component analysis summarized the major dimensions of variability, cluster analysis explored alternative cognitive profile solutions, and regression analysis identified variables associated with visuoconstructive performance. Although immune biomarkers were not assessed, the observed cognitive profiles may be interpreted within the current neuroimmune framework as hypothesis-generating. This methodological study illustrates the potential of advanced multivariate analyses for exploring reconstructed neuropsychological datasets. The results should be considered exploratory and hypothesis-generating and require validation using original participant-level data before any clinical or biological interpretation.
The geriatric population is increasing worldwide, including in Indonesia which has reached 11.01% in 2021 as the leading country in the geriatric population in Southeast Asia. Consequently, there is an increased risk of having severe infection, malignancy, and autoimmunity. Aging of immunity (immunosenescence) is responsible not only for those conditions but also affects the immune response to vaccination. The study's purpose was to analyze the correlation between immunosenescence and a decreased cellular immune response between 6 and 24 weeks after the second dose of CoronaVac vaccination in the geriatric population. This was an observational analytical study with a prospective cohort design. 73 geriatric subjects (≥ 60 years old) who had already received a second dose of CoronaVac were included. All the subjects had blood taken at 6 and 24 weeks after the second dose of CoronaVac. Serum sCD28, sCD80, and sCTLA-4 were used as immunosenescence markers. The decrease in cellular immunity was measured by the decreasing level of serum neopterin between 6 and 24 weeks following vaccine administration. There is a moderate correlation between sCD28, sCD80, and sCTLA-4 with serum neopterin at weeks 6 and 24. We also found a significant correlation between the decrease in neopterin at 6 and 24 weeks with sCD80 (p = 0.016, r = 0.282) but not with sCD28 (p = 0.078, r = 0.207) or sCTLA-4 (p = 0.017, r = 0.279). sCD80 and sCTLA-4 correlated with a more rapid decrease in neopterin level after CoronaVac vaccination in the geriatric population.
The co-circulation of dengue virus (DENV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in endemic regions poses significant immunological challenges, particularly in the context of cross-reactivity and vaccine design. Leveraging an in-silico pipeline, this study sought to identify conserved antigenic determinants between DENV serotype 1 (DENV-1) and SARS-CoV-2 that may underlie molecular mimicry and immunological cross-reactivity. Viral protein sequences were obtained from UniProt, structurally modeled via SWISS-MODEL, and aligned using PRALINE. Conserved regions were mapped and visualized using PyMOL to identify accessible surface-exposed epitopes. Strikingly, up to 42% sequence identity was observed between DENV-1 polyproteins and SARS-CoV-2 proteins, including the nucleoprotein (N), spike (S), and nonstructural proteins NS7a and NS7b. Several conserved patches displayed surface accessibility, reinforcing their potential to elicit cross-reactive B or T cell responses. These findings highlight a critical concern in co-endemic settings: pre-existing DENV immunity could alter the outcome of SARS-CoV-2 infection or vaccination through heterologous immune responses, potentially contributing to antibody-dependent enhancement (ADE) or atypical inflammatory profiles. From an immunotherapeutic perspective, the identification of shared epitopes underscores the need for precision design in vaccines and monoclonal antibody therapies to avoid unintended immunopathology. While this bioinformatic study provides a foundational framework for predicting cross-reactive epitopes, experimental validation using serological assays, neutralization tests, and T cell activation studies are imperative. Ultimately, a deeper understanding of DENV–SARS-CoV-2 molecular mimicry may inform the development of safer and more effective immunotherapeutic strategies in regions burdened by both pathogens.
Inguinal hernia repair is performed over 20 million times annually, with outcomes reflecting mechanical reconstruction and immune activation. This study compared autoplasty and tension-free alloplasty for primary inguinal hernias, focusing on clinical outcomes and inflammatory responses. This prospective single-center study compared tissue-based autoplasty (Shouldice/Spasokukotsky) with tension-free mesh alloplasty (Lichtenstein) in 118 adults (mean age 46 ± 12.1 years; 93% male; autoplasty, n = 50; alloplasty, n = 68). Pain (verbal descriptor scale), complications, hospital stay, and systemic markers (C-reactive protein, neutrophil-to-lymphocyte ratio, interleukin-6, tumor necrosis factor-alpha, lymphocyte count) were assessed (p < 0.05). Alloplasty showed faster operation (48.4 ± 1.5 vs. 59.6 ± 2.6 min), less pain (day 1: 4.5 ± 0.5 vs. 5.7 ± 0.6; day 2: 1.1 ± 0.2 vs. 2.4 ± 0.3; day 5: 0.5 ± 0.1 vs. 1.2 ± 0.2), earlier walking (7.2 ± 2.1 vs. 21.4 ± 3.6 h), fewer complications (8.4% vs. 28.8%), and reduced hospitalization (3.6 ± 0.9 vs. 5.1 ± 1.2 days; all p < 0.05). Autoplasty showed higher inflammatory markers (C-reactive protein 32.5 ± 6.8 vs. 21.3 ± 5.4 mg/L; neutrophil-to-lymphocyte ratio 5.8 ± 1.2 vs. 3.9 ± 0.9; interleukin-6 48.7 ± 10.2 vs. 29.4 ± 8.6 pg/mL; tumor necrosis factor-alpha 26.5 ± 7.3 vs. 17.2 ± 5.8 pg/mL; all significant). Operative time was correlated with pain (r = 0.64; p < 0.01) and complications (r = 0.48; p < 0.05). Tension-free alloplasty improved recovery and reduced immune activation; however, non-randomization, single-center design, and limited follow-up constrain long-term inferences of the study.
Autoimmune manifestations of primary minor immunodeficiencies (PMDs)—highly prevalent conditions that may represent a population-level model of autoimmunity—have not been systematically analyzed. The study aims to evaluate the current evidence for associations between PMDs and autoimmune syndromes. A systematic search of PubMed (MEDLINE) for 1980–2025 was conducted using keywords related to PMDs and autoimmune syndromes. The search was performed in two stages: an initial broad screening and a subsequent refined search with specific disease-related terms. High-quality peer-reviewed studies most relevant to the study objectives were selected. Available evidence indicates that PMDs commonly manifest through autoimmune syndromes according to a principle of universality, with important geographic, ethnic, age-related, sex-related, and ontogenetic variation. The strength of PMD–autoimmunity associations varies widely, reflecting major heterogeneity in both disease mechanisms and study quality. Key factors influencing clinical and epidemiological findings include terminological inconsistencies, multiple autoimmune pathways, heterogeneity of PMD origin and evolution, overlap with other immunodeficiencies and comorbidities, variability of clinical phenotypes, difficulties distinguishing PMDs from secondary immunosuppression, and the absence of standardized diagnostic criteria for many PMDs. Elementary models of autoimmune induction in immunocompromised individuals are proposed, together with a framework for personalized assessment of autoimmune disease in the context of PMDs, and implications for rational immunotherapy are discussed. PMDs are associated with diverse autoimmune syndromes and likely represent a major etiological factor of human autoimmunity at the population level. However, this data should be validated in further studies.
Global organ shortages have intensified interest in donation after circulatory death (DCD). However, DCD kidneys are affected by warm ischemia, which amplifies ischemia-reperfusion injury via a reactive oxygen species-damage-associated molecular pattern-cytokine-endothelial cascade, increasing the risk of microvascular dysfunction and delayed graft function. This study developed an objective postmortem ex vivo model to compare asystolic early donors/rapid death (AED; warm ischemia ≤30 min) and asystolic extended/delayed donors (ASED; 60–120 min) using integrated morphofunctional, biochemical, and immuno-inflammatory indicators during hypothermic perfusion. In an ex vivo design, 145 DCD renal allografts (71 AED, 74 ASED) underwent standardized hypothermic rehabilitation, with evaluations at 30, 60, and 120 min. Oxidative stress was quantified by lipid peroxidation and antioxidant capacity, in addition to histopathology (tubular, endothelial, podocyte, nuclear injury) and composite indices for cytokine activation, endothelial injury, and immune activation. A multicriteria scoring algorithm was used to categorize rehabilitation effectiveness, and group differences were assessed using comparative tests. These findings support a dynamic, multicriteria viability framework, indicating that ASED kidneys are at a higher risk yet potentially salvageable under comprehensive perfusion rehabilitation, warranting prospective transplantation-linked validation. Lipid peroxidation increased over time, rising more in the ASED group, whereas glutathione showed limited compensatory change. The ASED kidneys demonstrated greater tubular degeneration, endothelial swelling, podocyte injury, and nuclear alterations, with higher oxidative, inflammatory, and immune activation scores. Despite the higher biological burden, positive integrated outcomes remained frequent (AED 89.2% vs. ASED 84.5%; RR: 0.982; OR: 1.07–1.16), and morphology-function correlations were strong (AED r = 1.0; ASED r = 0.9). These findings support a dynamic, multicriteria viability framework, indicating that ASED kidneys are at a higher risk yet potentially salvageable under comprehensive perfusion rehabilitation, warranting prospective transplantation-linked validation.
Obesity is a global health and economic burden that affects disadvantaged groups and increases healthcare use. It involves adipocyte hypertrophy/hypoxia, adipokine imbalance, immune cell recruitment, pro-inflammatory polarization, signaling activation, systemic inflammation, oxidative stress, insulin resistance, and a higher cardiometabolic risk. This review synthesizes bariatric surgery as an immunometabolic intervention, integrating mechanistic, clinical, and translational findings. A literature search of PubMed/MEDLINE, Scopus, and Web of Science (through 2025), supplemented by Google Scholar, included peer-reviewed human and animal studies on metabolic or immunological mechanisms; technical surgical reports and non-peer-reviewed sources were excluded. Bariatric surgery consistently achieves broader metabolic and immunomodulatory, sustained weight loss and improved glycemic control and comorbidity profiles. Diabetes improvements partially preceded major weight loss via enhanced enteroinsular signaling, altered bile acid pathways, and microbiome remodeling. Surgery reduces systemic inflammation, reprograms cytokines, improves immune cell phenotypes, and lowers oxidative stress, leading to antioxidant status recovery. Comparative evidence indicates an efficacy–risk gradient: laparoscopic adjustable gastric banding is least effective; laparoscopic sleeve gastrectomy offers intermediate benefits with favorable safety; Roux-en-Y gastric bypass is widely supported with strong outcomes and manageable risks; and biliopancreatic diversion with duodenal switch yields maximal benefit but higher adverse-event and malabsorption burden. Bariatric surgery is an immunometabolic intervention that induces immune and metabolic remodeling, disrupting the obesity–inflammation–insulin resistance cycle via multi-system remodeling.
Neoantigen-based personalized vaccines have emerged as an important innovation in the field of precision oncology through utilizing unique tumor somatic mutations to stimulate a targeted anti-tumor immune response. Unlike common tumor antigens, neoantigens can be recognized by the immune system as foreign because they exist only on tumor cells and thus do not contribute to any autoimmune reactions as a result of central immune tolerance. The emergence of techniques in next-generation sequencing, mutational profiling, and bioinformatics has made it possible to precisely identify neoantigens. In addition, breakthroughs in vaccine technology, such as synthetic long peptides, dendritic cell vaccination, and nucleic acid vaccination, have facilitated its clinical application. Studies have shown that neoantigen-based personalized vaccines are safe and can induce potent T-cell-mediated anti-tumor immune responses, especially when combined with immune checkpoint inhibitors. Randomized trials have indicated their potential in decreasing cancer recurrence. There still remain some limitations in developing personalized neoantigen vaccines due to the problem of tumor heterogeneity, immune evasion, neoantigen prediction, immunosuppression environment in the tumors, and high cost and long manufacturing time for personalized vaccines. This paper provides an overview of current methods and new approaches for neoantigen identification and vaccine development.
The study evaluates the relationship with diabetes self-management behavior and retinal microvascular status and hypothesizes whether HbA1c has an indirect statistically significant association between diabetes self-management behavior and retinal microvascular status in individuals with type 2 diabetes. The second view is to determine whether the involvement of continuous glucose monitoring is a moderator of the relationship between the self-management behavior and the HbA1c. An empirical cross-sectional study involved 328 adults with type 2 diabetes. The model combined six indicators of self-management, three of the HbA1c indicators, four indicators of the Optical Coherence Tomography Angiography (OCTA)-based retinal microvascular indicators, and four indicators of the continuous glucose monitor activity. A Partial Least Squares Structural Equation Modeling (PLS-SEM) model was developed in Python and evaluated based on reliability, convergent and discriminant validity, bootstrapped path estimation, indirect effect test, moderation analysis, and predictive analysis. Better self-management behavior is related to lower HbA1c (β = −0.496, p = 0.001) and more desirable retinal microvascular situation (β = −0.144, p = 0.002). Worse retinal microvascular status was linked with higher levels of HbA1c (β = 0.584, p < 0.001). The self-management behavior indirectly related to retinal microvascular status via HbA1c was significant (β = −0.290, p < 0.001), and this could be attributed to partial mediation. The constant glucose monitoring involvement had a significant moderate effect on the association between self-management behavior and HbA1c (β = −0.120, p = 0.004). The results substantiate a composite behavioral, metabolic, and retinal imaging model with self-management behavior, HbA1c, and OCTA-generated retinal radiations being strongly correlated.
Chimeric antigen receptor (CAR) T-cell therapies and bispecific T-cell engagers have produced durable remissions in haematological malignancies that were previously considered refractory, and the bispecific class has now extended this approach to a solid tumour, extensive-stage small-cell lung cancer, through the delta-like ligand 3 engager tarlatamab. The shared mechanism of intense, sustained T-cell activation generates two characteristic and potentially fatal toxicities: cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). As bispecific agents shift toward subcutaneous and outpatient administration, an increasing proportion of treated patients present to emergency departments without immediate access to the treating cellular therapy centre, where the syndrome may not be recognised. This narrative review translates the consensus produced by haematology and cellular therapy societies into an operational framework for acute care. It synthesises the mechanism, epidemiology, grading, and initial management of CRS, ICANS, and related immune effector cell toxicities, drawing on the American Society of Transplantation and Cellular Therapy consensus, the American Society of Clinical Oncology guideline, the joint European recommendations, and pivotal and updated product trials. Recognition rests on a few disciplined habits: naming the therapy, treating fever in a recently treated patient as an emergency, grading CRS and ICANS while methodically excluding infection, and contacting the treating centre early. Management centres on tocilizumab for CRS, corticosteroids for ICANS, anakinra in refractory disease, and aggressive supportive care. Competence with these syndromes is becoming a general expectation of acute care rather than the exclusive concern of cellular therapy units.
Acne vulgaris is a chronic inflammatory skin disease in which a defect in the immune barrier function is a major extent of the pathological etiology. The aim of this randomized controlled trial was to assess the restorative benefits of supramolecular salicylic acid (SSA) with intense pulsed light (IPL) photon rejuvenation and its effects on the immune barrier function of the skin in acne patients. Moderate-to-severe acne was assigned to each patient, with three groups being treated for 12 weeks with either: The primary outcome was transepidermal water loss (TEWL) (continuous variable); secondary outcomes were stratum corneum hydration, sebum secretion, skin pH, pro- and anti-inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-10, TGF-β), Treg/Th17 cell ratio, microbiome Shannon diversity index, Global Acne Grading System (GAGS) score, lesion counts, and the Dermatology Life Quality Index (DLQI). The SSA+IPL group showed significant improvements compared to both monotherapy groups in all outcomes (all corrected p < 0.001). TEWL decreased by 47.0% (Cohen's d = 2.14; 95% CI: 1.67–2.61), stratum corneum hydration increased by 67.0%, and sebum secretion declined by 45.7%. Fifty-six to 58% reduction in pro-inflammatory cytokines was achieved, whereas IL-10 and TGF-β levels increased by 167.8% and 130.8% respectively. The ratio Treg/Th17 was raised by 331.3% and Shannon diversity index was raised by 52.1%. This multiple regression revealed that the Treg/Th17 ratio reestablishment, reduction of sebum and upregulation of IL-10 are independent factors of clinical efficacy (adjusted R2 = 0.763). The combination of SSA and IPL therapy can have a systemic effect on the regeneration of skin immune barrier function by overlapping mechanisms and deserves further testing in larger trials.
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.
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.
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.
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.
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.
