Search Results (1,563)

Hemocyanins are oxygen-transporting proteins found in crustaceans and other arthropods, playing key roles in immune defense and metabolic regulation. Due to their stability and bioactive properties, Hcs have gained increasing interest in biotechnological and biomedical applications. However, detailed biophysical characterization is crucial to understanding their functional potential. In this study, the hemocyanin was extracted and purified from Macrobrachium acanthurus (HcMac) using ultracentrifugation and size-exclusion chromatography. The molecular mass of HcMac was determined by SDS-PAGE electrophoresis, MALDI-TOF mass spectrometry, and analytical ultracentrifugation. Spectroscopic analyses, including UV-Vis absorption, fluorescence emission, and light scattering intensity, were used to assess the structural stability of the compound under various pH conditions. HcMac was identified as a hexameric protein (~450 kDa) composed of monomeric subunits of 75 and 76 kDa. The protein maintained its oligomeric stability and oxygen-binding affinity in the pH range of 5.0–7.4. However, extreme pH conditions (below 4.4 and above 7.5) induced structural alterations, leading to dissociation and conformational changes, as evidenced by fluorescence emission and UV-Vis spectra. The isoelectric point was determined to be between pH 4.3 and 5.3, consistent with other crustacean HCs. These findings reinforce the structural robustness of HcMac and suggest its potential for biotechnological applications. The high stability of HcMac under physiological pH conditions indicates its suitability for biomedical research, including immunomodulatory and antimicrobial applications. Future studies integrating bioinformatics, proteomics, and immunological assays will be essential to explore the therapeutic potential of HcMac. Full article

Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease that involves progressive loss of voluntary muscle and ultimately, respiratory function, which is the primary cause of death in ALS patients. Respiratory vital capacity (VC) measurements are objective, reproducible, and directly related to survival. Respiratory function is known to be negatively affected in individuals with excess abdominal fat contributing to a chronic innate immune inflammatory state. To test whether ALS patients might have a body mass index (BMI) related VC response to the innate immune system regulator NP001, clinical results from two NP001 phase 2 trials were evaluated in an intent-to-treat manner, stratified by BMI measurements. Slowing of progressive VC loss and extension of overall survival (OS) occurred primarily in ALS patients who were overweight with a BMI ≥ 25 (70% of patients in the phase 2 trials). Innate immune dysfunction is a characteristic of ALS patients ≤ 65 years of age, and in this group both VC and OS changes in response to NP001 were most significant. This study represents a novel approach to ALS, wherein VC and OS were both significantly improved through immunologic, not neurologic modulation with NP001, a precursor to the dominant regulator of inflammation, taurine chloramine. Full article

Background: Tuberculosis (TB) and diabetes mellitus (DM) comorbidity (TB-DM) presents a significant global health challenge, with diabetes increasing susceptibility to TB, worsening clinical outcomes, and impairing immune responses. Among these dysfunctions, macrophages—the primary immune cells responsible for pathogen recognition, phagocytosis, and bacterial clearance—exhibit profound alterations in TB-DM. However, the complex interplay between metabolic dysregulation, immune impairment, and macrophage dysfunction remains poorly defined. Objective: This scoping review systematically maps the literature on macrophage dysfunction in TB-DM, identifying key immunological impairments affecting phagocytosis, cytokine production, antigen presentation, macrophage polarisation, reactive oxygen species (ROS) and nitric oxide (NO) regulation, and chronic inflammation. Methods: A systematic search was conducted in PubMed, Web of Science, and Embase, covering studies from 2014 to 2024. Inclusion criteria focused on human studies investigating macrophage-specific mechanisms in TB-DM. Data extraction and synthesis were performed using Covidence, with findings grouped into key immunological themes. Results: A total of 44 studies were included, revealing significant impairments in macrophage function in TB-DM. Findings indicate reduced NO production, variable ROS dysregulation, altered M1/M2 polarisation, defective antigen presentation, and chronic inflammation. Elevated IL-10 and VEGF were associated with immune suppression and granuloma destabilisation, while eicosanoids (PGE2, LXA4) contributed to sustained inflammation. Conclusions: Macrophage dysfunction emerges as a central driver of immune failure in TB-DM, creating a self-perpetuating cycle of inflammation, immune exhaustion, and bacterial persistence. Understanding these mechanisms is essential for developing biomarker-driven diagnostics, host-directed therapies, targeted immunomodulation, and improving TB outcomes in diabetic populations. Future research should explore macrophage-targeted interventions to enhance immune function and mitigate TB-DM burden. Full article

Fluoride exposure has been shown to affect immune cell subsets and immune function, but its impact on macrophage polarization remains unclear. This study investigates the effects of low fluoride exposure on macrophage polarization and its underlying mechanisms through epidemiological surveys, animal experiments, and in vitro cell experiments. In the population-based epidemiological survey, we used mass cytometry to assess the impact of low fluoride exposure (0.570–2.027 mg/L) in the environment on human immune cell populations following the current water improvement and fluoride reduction measures. A rat fluorosis model was established by treating rats with sodium fluoride (NaF) in drinking water at concentrations of 0 mg/L, 5 mg/L, 10 mg/L, 25 mg/L, and 50 mg/L for 90 days., and morphological changes were assessed by hematoxylin–eosin (H&E) staining and transmission electron microscopy in the spleen of rats. Flow cytometry was used to analyze the proportion of macrophage subtypes in the spleen, while Western blot and immunofluorescence were performed to detect the expression of mitochondrial autophagy-related proteins. An M1 macrophage model was constructed in vitro by inducing THP-1 cells, and the effects of fluoride on macrophage-related cell markers and cytokines were assessed using flow cytometry and ELISA, respectively, following intervention with an autophagy inhibitor. Mitochondrial membrane potential and mitochondrial–lysosomal colocalization are analyzed through flow cytometry and confocal microscopy. The study aims to investigate the role of mitophagy in sodium fluoride-induced macrophage polarization. Epidemiological investigations revealed that low fluoride increases the proportion of blood monocytes, as well as the expression levels of CD68 (a macrophage surface marker), CD86 (an M1 macrophage marker), and the inflammatory cytokine IFN-γ in peripheral blood mononuclear cells (PBMCs). In the rats of NaF-treated groups, splenic tissues exhibited inflammatory infiltration, mitochondrial swelling, and increased autophagosome formation. Moreover, low fluoride activated the PINK1/Parkin-mediated mitophagy pathway, promoting an increase in the M2/M1 macrophage ratio. In vitro experiments further confirmed that autophagy inhibitors reversed the NaF-induced increase in the M2/M1 macrophage ratio. This study demonstrates that low fluoride induces inflammatory responses in the body and drives M1 macrophage polarization toward M2 macrophages via mitophagy. These findings highlight the potential immunological risks associated with low fluoride and provide mechanistic insights into the interplay among fluoride, mitophagy, and macrophage polarization. Full article

Respiratory virus infections, such as those caused by influenza viruses, respiratory syncytial virus (RSV), and coronaviruses, pose a significant global health burden. While the immune system’s adaptive components, including memory T cells, are critical for recognizing and combating these pathogens, recurrent infections and variable disease outcomes persist. Memory T cells are a key element of long-term immunity, capable of responding swiftly upon re-exposure to pathogens. They play diverse roles, including cross-reactivity to conserved viral epitopes and modulation of inflammatory responses. However, the protective efficacy of these cells is influenced by several factors, including viral evolution, host age, and immune system dynamics. This review explores the dichotomy of memory T cells in respiratory virus infections: their potential to confer robust protection and the limitations that allow for breakthrough infections. Understanding the underlying mechanisms governing the formation, maintenance, and functional deployment of memory T cells in respiratory mucosa is critical for improving immunological interventions. We highlight recent advances in vaccine strategies aimed at bolstering T cell-mediated immunity and discuss the challenges posed by viral immune evasion. Addressing these gaps in knowledge is pivotal for designing effective therapeutics and vaccines to mitigate the global burden of respiratory viruses. Full article

CD99 is a membrane protein critical for various immunological functions, including T-cell activation, protein trafficking, cell apoptosis, and leukocyte movement. It is also highly expressed in certain malignant tumors, contributing to the development, invasion, immune evasion, and adaptation of tumor cells to stress stimuli, including drug resistance. CD99 is crucial at the intersection of normal biological processes and pathological conditions like cancer. While research indicates that CD99 may interact homotypically, there is evidence of some heterotypic ligands that align with its roles. The development of multiple anti-CD99 antibodies has shed light on its functions, particularly regarding interactions between tumor cells that overexpress CD99 and immune cells expressing the same protein within the microenvironment. Anti-CD99 antibodies effectively eliminate tumors and attract immune cells to the tumor area. Additionally, CD99 influences the expression of specific immune checkpoint molecules, such as CD47, paving the way for potential combinations of anti-CD99 with immune checkpoint inhibitors. This review explores CD99’s role in normal physiology and cancer biology, focusing on how monoclonal antibodies affect CD99 expression and activity, thereby influencing cancer cells’ interactions with their microenvironment. It summarizes key findings about how these changes impact cancer cell behavior and the effectiveness of treatments. Full article

Polycystic ovary syndrome (PCOS) is a common female endocrinopathy associated with reproductive and metabolic abnormalities. PCOS is characterized by complex pathogenesis and pathophysiology. Its multifactorial etiology and heterogeneous presentation make effective treatment difficult. Endocrine abnormalities in PCOS create a vicious cycle of overriding dysfunction involving the hypothalamic-pituitary-ovarian (HPO) axis. Most research has primarily focused on identifying genetic, epigenetic, or immunological factors underlying PCOS. In recent years, new reports have emerged on the possible involvement of antibodies directed against HPO axis components in the development of PCOS. Some of these have been shown to be able to interfere with hormone receptors or receptor binding by targeting the key domains for their function. However, the evidence is heterogeneous and challenging to interpret, given the overall predisposition to high levels of various autoantibodies found in women with PCOS. This review focuses on autoantibodies affecting the HPO axis in PCOS and their potential role in the pathogenesis of PCOS. The authors discuss PCOS as a potential antibody-mediated autoimmune disease in light of recent reports on its possible pathogenesis. Full article

Alveolar macrophages (AMs) are immune cells located in the alveoli—the tiny air sacs in the lungs where gas exchange occurs. Their functions are regulated by various epigenetic mechanisms, which are essential for both healthy lung function and disease development. In the lung’s microenvironment, AMs play critical roles in immune surveillance, pathogen clearance, and tissue repair. This review examines how epigenetic regulation influences AM functions and their involvement in lung diseases. Key mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs, regulate gene expression in response to environmental signals. In healthy lungs, these modifications enable AMs to quickly respond to inhaled threats. However, when these processes malfunction, they could contribute to diseases such as pulmonary fibrosis, COPD, and pulmonary hypertension. By exploring how epigenetic changes affect AM polarization, plasticity, and immune responses, we can gain deeper insights into their role in lung diseases and open new avenues for treating and preventing respiratory conditions. Ultimately, understanding the epigenetic mechanisms within AMs enhances our knowledge of lung immunology and offers potential for innovative interventions to restore lung health and prevent respiratory diseases. Full article

Background: Despite advances in immunotherapy, non-small-cell lung carcinoma (NSCLC)’s clinical success is limited, possibly due to substantial immunological alterations in advanced cancer patients. This study examines the immunomodulatory effects of sEVs derived from lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) on T cells. Methods: SEVs were isolated from lung cancer cell lines and Jurkat-E6.1. SEV size and morphology were analyzed by NTA and TEM, respectively, while Western blotting confirmed sEV markers. SEV uptake was assessed, followed by resazurin assay, RNA isolation, quantification, cDNA preparation, RT-PCR, nano LC-MS, and bioinformatic analysis, before and after treating Jurkat-E6.1 cells with sEVs from A549 and SKMES1. Results: Cancer-derived sEVs were efficiently internalized by immune cells, reducing T-cell viability. The real-time PCR analysis showed downregulation of KI67, BCL2, BAX, TNFA, IL6, TGFβ, and IL10, suggesting reduced proliferation, dysregulated apoptosis, and impaired inflammatory and immunosuppressive signaling, and the upregulation of GZMB and IL2 suggests retained cytotoxic potential but possibly dysfunctional T-cell activation. Proteomic analysis revealed 39 differentially abundant proteins (DAPs) in ADC-treated T cells and 276 in SCC-treated T cells, with 19 shared DAPs. Gene Ontology (GO) analysis of these DAPs highlighted processes such as sEV biogenesis, metabolic pathways, and regulatory functions, with ADC sEVs influencing NAD metabolism, ECM binding, and oxidoreductase activity, while SCC sEVs affected mRNA stability, amino acid metabolism, and cadherin binding. The cytoplasmic colocalization suggests the presence of these proteins in the cellular and extracellular lumen, indicating the potential of further release of these proteins in the vesicles by T cells. Conclusion: Lung cancer-derived sEVs regulate T-cell activities through immunoregulatory signaling. The molecular interactions between sEVs and immune cells can reveal novel tumor immune regulatory mechanisms and therapeutic targets. Full article

Treatment-free remission (TFR) is a key therapeutic goal for chronic myeloid leukemia (CML) patients in deep molecular response (DMR). While predicting patient outcome remains challenging, different NK cell populations seem crucial. We conducted an immunological sub-study from the Argentina Stop Trial (AST), including 46 patients in 2019 (AST I) and 35 new patients between 2022 and 2023 (AST II). To characterize NK cell subsets in patients attempting TFR, peripheral blood mononuclear cell samples were collected before stopping treatment and phenotype and functional characteristics were assessed by flow cytometry. Non-relapsing patients from AST I exhibited NK cell subpopulations with cytomegalovirus-related memory features, high expression of cytotoxicity markers, and robust functionality. Remarkably, though clinical variables were very similar between cohorts, significant immune differences were observed. NK cell percentage and CD16 and CD57 receptor expression levels were significantly reduced in AST II (p = 0.0051; p = 0.0222; p = 0.0033, respectively), whereas NKp46, NKp44 and PD-1 expression levels were significantly increased (p = 0.0081; p < 0.0001; p < 0.0001, respectively). NK cells from AST II patients demonstrated higher overall functionality and more memory-like subpopulations, characterized mainly by the expression of CD57, NKG2C, NKp30 and NKp46 receptors among CD56^dim NK cells, also with enhanced functional performance. However, in AST II, we were unable to report an association with clinical outcome. Given the enrollment time of both cohorts and that they appear to be clinically homogeneous, we consider that COVID could be impacting the immune landscape; accordingly, serum samples from AST II, but not AST I, confirmed the presence of anti-SARS-CoV-2 IgG. The influence of the COVID pandemic and the different vaccine platforms on NK cells cannot be underestimated when evaluating the role of the immune system in cancer. Full article

Lauric acid (LA), a medium-chain fatty acid (C12), can promote growth performance and decrease oxidative damage and lipid deposition in animals. This study aimed to evaluate the effect of dietary supplementation of lauric acid as a functional ingredient on European seabass juveniles’ growth performance and intestine antioxidant and immunological status. For this purpose, four practical diets were formulated to be isoproteic and isolipidic, including 0, 0.5, 1, and 2% of LA, and fed to triplicate groups of European seabass juveniles (~12.7 g) for 61 days. Dietary LA supplementation did not affect growth performance, feed utilization, or whole-body composition, but feed intake increased at a concentration-dependent level. However, the plasmatic triglyceride content was increased at the higher level of LA supplementation. In the intestine, catalase and glutathione reductase activities and lipid peroxidation levels were lower in fish fed the 1% LA diet than in the control group. The hepatic LPO level was higher in fish fed 0.5% LA than in the control group. Fish fed the 1% LA diet presented lower intestinal expressions of caspase 3, tumor necrosis factor-alpha, interleukins 10, 6, and 1-β, and a lower plasma white blood cell number. Overall, up to 2% dietary supplementation of lauric acid as a functional ingredient showed a trend to improve European sea bass juveniles’ growth performance without affecting feed utilization. Moreover, 1% dietary inclusion of LA reduced intestinal lipid peroxidation and downregulated pro-inflammatory and anti-inflammatory genes, thus enhancing the intestine’s homeostatic status. Full article

The complex nature of immune system behavior in both autoimmune diseases and transplant rejection can be understood through the lens of avalanche dynamics in critical-point systems. This paper introduces the concept of the “immunological avalanche” as a framework for understanding unpredictable patterns of immune activity in both contexts. Just as avalanches represent sudden releases of accumulated potential energy, immune responses exhibit periods of apparent stability followed by explosive flares triggered by seemingly minor stimuli. The model presented here draws parallels between immune system behavior and other complex systems such as earthquakes, forest fires, and neuronal activity, where localized events can propagate into large-scale disruptions. In autoimmune conditions like systemic lupus erythematosus (SLE), which affects multiple organ systems including the kidneys in approximately 50% of patients, these dynamics manifest as alternating periods of remission and flares. Similarly, in transplant recipients, the immune system exhibits metastable behavior under constant allograft stimulation. This critical-point dynamics framework is characterized by threshold-dependent activation, positive feedback loops, and dynamic non-linearity. In autoimmune diseases, triggers such as UV light exposure, infections, or stress can initiate cascading immune responses. In transplant patients, longitudinal analysis reveals how monitoring oscillatory patterns in blood parameters and biological age markers can predict rejection risk. In a preliminary study on kidney transplant, all measured variables showed temporal instability. Proteinuria exhibited precise log–log linearity in power law analysis, confirming near-critical-point system behavior. Two distinct dynamic patterns emerged: large oscillations in eGFR, proteinuria, or biological age predicted declining function, while small oscillations indicated stability. During avalanche events, biological age increased dramatically, with partial reversal leaving persistent elevation after acute episodes. Understanding these dynamics has important implications for therapeutic approaches in both contexts. Key findings suggest that monitoring parameter oscillations, rather than absolute values, better indicates system instability and potential avalanche events. Additionally, biological age calculations provide valuable prognostic information, while proteinuria measurements offer efficient sampling for system dynamics assessment. This conceptual model provides a unifying framework for understanding the pathogenesis of both autoimmune and transplant-related immune responses, potentially leading to new perspectives in disease management and rejection prediction. Full article

Folliculin-interacting protein 1 (FNIP1) is a key regulator of cellular metabolism and immune homeostasis, integrating nutrient signaling with proteostasis. FNIP1 forms a complex with folliculin (FLCN) to regulate the mechanistic target of rapamycin complex 1 (mTORC1), functioning as a GTPase-activating protein (GAP) for RagC/D. Additionally, FNIP1 interacts with heat shock protein 90 (HSP90) and undergoes phosphorylation, glycosylation, and ubiquitination, which dynamically regulate its stability and function. Evidence from murine models suggests that FNIP1 loss disrupts immune cell development and mitochondrial homeostasis. However, FNIP1 deficiency in humans remains incompletely characterized, and its full phenotypic spectrum is likely underestimated. Notably, FNIP1-deficient patients exhibit immunological and hematological abnormalities, immune dysregulation, and metabolic perturbations, emphasizing its role in cellular adaptation to stress. Understanding the mechanistic basis of FNIP1 dysfunction in human tissues will be critical for delineating its contributions to immune and metabolic disorders and identifying targeted interventions. Full article

Background: The aim of our study is to evaluate the impact of SARS-CoV-2 vaccination on HIV viremia in patients treated under bictegravir-based therapy. Methods: We conducted a retrospective observational study in a tertiary hospital, analyzing data from 152 patients treated with BIC/TAF/FTC between 2020 and 2022. Patients were divided into two groups: “vaccinated” (110/152) and “unvaccinated” (42/152) against SARS-CoV-2. The outcomes considered were the presence of “blips” (detectable viremia ≥ 20 copies/mL), “rebound” (viremia ≥ 50 copies/mL), and virological failures. Results: A lower incidence of blips in the “vaccinated” group compared to the “unvaccinated” group (9.1% vs. 28.6%, p = 0.002), and a reduced risk of blips in the vaccinated group (OR 3.8, 95% CI 1.4–9.8) were noticed. The rebound rate was lower in the vaccinated group compared to non-vaccinated, with a statistically significant difference (respectively, 2.7% vs. 11.9%, p = 0.037). Conclusions: our data suggest that SARS-CoV-2 vaccination may stimulate an immune response that enhances CD4+ and CD8+ cell function, contributing to a reduction in the number of blips and maintaining good viro-immunological control in patients with HIV, supporting the importance of vaccination in this population. Full article

Background and Objectives: Bladder cancer (BLCA), intimately associated with the immune system, represents a substantial global health burden due to its high recurrence rates and limited therapeutic effectiveness. Although immunotherapy shows promise, challenges persist due to the lack of reliable therapeutic targets. This study aims to investigate potential immune-related biomarkers that could influence the tumor microenvironment in BLCA, using proteomic and in silico approaches. Materials and Methods: Tissue samples from BLCA patients (n = 27) and controls (n = 27) were collected from Şişli Hamidiye Etfal Training and Research Hospital. Proteomic analysis was performed by liquid chromatography/mass spectrometry (LC-MS)/MS to reveal the identities of differentially regulated proteins. Protein network analysis and hub protein detection were performed using Cytoscape (v.3.10.3), while functional annotation was carried out using EnrichR. The immunological analysis of hub proteins was performed in Sangerbox platform, and prognostic associations were evaluated through the Kaplan–Meier Plotter tool. Results: LC-MS/MS analysis identified 120 differentially regulated immune-related proteins. STRING analysis, using an immune response dataset (GO:0006955), highlighted the complement cascade as a significantly enriched pathway (p < 0.05). Proteins, namely C4A, CFB, C4B, C8B, CFH, CFI, C5, C4BPA, C3, and C2, that are known to play key roles in the complement system were identified. Immunological analysis with these proteins revealed the phenomena of immune infiltration and immune checkpoint gene associations (p < 0.05). Four hub genes—CFB, C4B, CFI, and C2—demonstrated a significant prognostic value for BLCA (p < 0.05). Conclusions: This study highlights the pivotal role of the complement system in the immune regulation of BLCA. CFI, C4A, and C4B emerged as potential target proteins for BLCA treatment, particularly in immunotherapy, for enhancing survival. Future research on these proteins and the complement system specifically focusing on BLCA may facilitate the development of targeted immunotherapies, ultimately improving treatment outcomes. Full article