Search Results (639)

Inflammatory cytokines and proteins are essential indicators of immune status and disease progression; however, conventional assays rely on invasive sampling and complex processing, restricting their use in real-time monitoring. Here, we present a 3D-printed poly(methyl methacrylate) (PMMA) microneedle-based biosensing platform integrated with a tyramide signal amplification–enhanced enzyme-linked immunosorbent assay (TSA–ELISA) for noninvasive and highly sensitive detection of inflammatory biomarkers in interstitial fluid. The microneedles exhibit precise geometry, adequate mechanical strength, and excellent biocompatibility, facilitating efficient skin penetration and biomarker capture. Stepwise chemical functionalization ensured stable antibody immobilization, while TSA significantly amplified detection signals. The platform achieved reliable, reproducible, and multiplex detection of cytokines and albumin in both healthy individuals and patients with inflammatory skin conditions. Notably, the measured cytokine level in lesional skin of eczema patients was 97.7 pg/mL, showing a significant difference from the 62.8 pg/mL observed in healthy subjects. This MN-based TSA–ELISA system offers a robust and minimally invasive strategy for monitoring inflammation-related biomarkers, holding great potential for clinical diagnostics and personalized healthcare applications. Full article

Early detection of lung cancer remains a major unmet clinical need, as most patients are diagnosed at advanced stages when curative treatment options are limited. Circulating cytokines and interleukins represent promising molecular biomarkers for the non-invasive diagnosis and monitoring of tumor development. In this study, we investigated the diagnostic potential of plasma interleukins in distinguishing early-stage non-small cell lung cancer (NSCLC) from healthy individuals and patients with chronic obstructive pulmonary disease (COPD). Quantitative analyses demonstrated significantly elevated plasma levels of IL-1RA, IL-6, IL-8, IL-10, and IL-17A in NSCLC patients compared with healthy controls. Among these, a composite biomarker panel comprising IL-6, IL-10, IL-8, and IL-1RA exhibited the highest diagnostic performance, outperforming individual cytokines and other combinations. This interleukin-based signature also differentiated NSCLC from COPD with strong specificity, underscoring its potential clinical applicability. These findings highlight the molecular and translational relevance of plasma interleukin profiling as a non-invasive diagnostic approach for early lung cancer detection, potentially enabling earlier intervention and improved patient outcomes. Full article

Combined oral contraceptives (COCs) remain one of the most popular reversible contraceptive methods worldwide. Still, regardless of the drug composition and duration of therapy, almost all COCs are associated with the risk of venous thrombosis. This review highlights the main pathogenetic mechanisms of thrombosis development during oral contraceptive use. Increase the production of certain clotting factors; a decrease in antithrombin and protein S levels; acquired resistance to activated protein C; a reduction in tissue factor pathway inhibitor (TFPI); indirect endothelial activation; inhibition of endogenous fibrinolysis; regulation of tissue factor by estradiol-sensitive microRNA; homocysteine imbalance caused by decreased intestinal reabsorption of folates and vitamin B-12; reduced bioavailability of nitric oxide (NO) due to high homocysteine levels; higher blood pressure, water retention, insulin resistance, increased levels of pro-inflammatory C-reactive protein (CRP) and uric acid, and antifibrinolytic (plasminogen activator inhibitor 1 type, PAI-1) biomarkers as consequences of NO deficiency; increased platelet adhesiveness and ADP-induced aggregation, which promote fibrinogen binding; and increased expression of pro-inflammatory cytokines are the main thrombotic effects of COCs use. Clinicians should carefully evaluate each patient’s individual risk factors when prescribing COCs and conduct regular monitoring to reduce the risk of complications. Full article

Background/Objectives: Long COVID (LC) causes persistent symptoms, including fatigue, musculoskeletal (MSK) pain, and a lower quality of life. It is hypothesised that chronic low-grade inflammation in LC could impact bone, joints, and muscle microcirculation, but evidence is limited. Our aim is to assess health-related quality of life (HRQoL) and circulating inflammation, bone turnover markers (BTM), and vitamin D in LC individuals to explore their potential association with MSK function. Methods: Prospective longitudinal cohort; LC n = 45, well-recovered (WR) n = 40; 12 ± 2 months follow-up. Baseline and follow-up assessments included evaluations of HRQoL and pain-rating questionnaires, and blood analysis of inflammatory and bone turnover markers (BTM). Results: More females were in the LC group. LC reported significantly lower HRQoL compared to WR, with no change over 12 months. LC had higher vitamin D levels at baseline, median 29.46 ng/mL (23.75; 35.06) compared to WR 20.36 ng/mL (15.995; 27.65) (p = 0.0021). Both groups experienced significant increases in vitamin D after 12 months: WR median from 21.4 ng/mL (16.34; 27.89) to 29.58 ng/mL (25.33; 41.74), (p =< 0.001) and LC median from 32.695 ng/mL (23.665; 35.1) to 35.89 ng/mL (30.1; 41.2), (p = 0.0023). Pain rating showed LC also experienced more hand pain at baseline median 1 (0; 5), (p = 0.003). There were no differences between groups in BTM or cytokines over time. Conclusions: This feasibility cohort showed that LC is associated with a reduction in HRQoL and joint symptoms; however, no significant changes were observed in the inflammatory markers, indicating the need for ongoing monitoring. Future studies should explore MSK, muscle function via imaging, and ways to enhance musculoskeletal health and well-being. Full article

Background: Long COVID—defined as the persistence of symptoms or the development of new symptoms beyond four weeks after acute SARS-CoV-2 infection—affects an estimated 10–30% of individuals recovering from COVID-19, posing a significant public health burden. Emerging evidence suggests that type I interferons (IFNs) (a critical group of cytokines in the antiviral defense) and hematologic alterations, such as lymphopenia and elevated inflammatory markers, are linked to both the severity of acute COVID-19 and the likelihood of developing long-term symptoms. The aim of this study is to explore the association between type I IFN signatures and long COVID. A second aim is to examine the relationship between laboratory findings during acute infection and long COVID. Methods: The study included 61 patients investigated for the presence of long COVID symptoms 16.5 ±1.5 months after acute infection. Patients were divided into two groups of higher symptom burden of long COVID and those with milder symptoms based on demographic, laboratory, and clinical data as well as type I IFN-inducible gene expression (MX-1, IFIT-1, and IFI-44) measured in peripheral blood by real-time PCR. Data collected during acute infection were recorded. Peripheral blood samples were collected during the acute phase of infection, within the first 48 h of hospital admission. IFN-inducible gene expression was measured prospectively at that time, and RNA was extracted immediately for subsequent analysis. Results: History of intubation emerged as a significant associated factor of severe long COVID, with 75% of intubated patients reporting >8 persistent symptoms approximately 16 months post-infection. Higher white blood cell (WBC) and neutrophil counts but lower eosinophil and monocyte counts in acute infection were found to be associated with a high burden of long COVID symptoms. Interestingly, absolute monocyte count was found to independently correlate with higher long COVID symptom burden. Lactate dehydrogenase (LDH) and serum glutamic-oxaloacetic transaminase (SGOT) also differed significantly between groups, with higher levels correlating with a high burden of long COVID symptoms. Notably, MX-1 transcript levels in peripheral blood at the time of acute infection were reduced in patients with a high burden of long COVID symptoms, suggesting that dysregulated immune responses during the acute phase may contribute to persistent symptoms. Conclusions: These findings suggest the potential association of hematological and immune markers with long COVID severity, as well as the importance of monitoring these parameters to identify at-risk patients for early interventions. Full article

Zearalenone (ZEN) is a mycotoxin commonly produced by Fusarium species and is often found in food and feed. It has been linked to reproductive problems in livestock and, less frequently, to hyperestrogenic effects in humans. However, information regarding the impact of ZEN on wild boars (Sus scrofa) remains scarce, despite this species being among the most frequently hunted game animals in Italy. The aim of this study was to assess the impact of ZEN on the hepatic system by examining nitrosative stress markers and the balance between pro- and anti-inflammatory cytokines in wild boars hunted in various areas of the Avellino province (Campania region, Italy) during the 2021–2022 hunting season. The findings revealed that exposure to ZEN was linked to a marked rise in both pro- and anti-inflammatory mediators, except for IL-10, which did not increase significantly. In addition, ZEN stimulated the expression of inducible nitric oxide synthase (iNOS), which, in turn, led to elevated nitric oxide (NO) concentrations in the liver. The immunohistochemical analysis revealed a predominance of CD3-positive T-cells in the hepatic inflammatory infiltrate of ZEN-exposed wild boars, highlighting the importance of structured wildlife monitoring to protect food safety and safeguard human and animal health. Full article

Dry eye disease (DED) is a highly prevalent multifactorial disorder of the ocular surface that extends beyond local tear film pathology to involve systemic immune, neuroendocrine, and neurosensory mechanisms. Increasing evidence reveals a strong and bidirectional association between DED and psychiatric disorders, particularly depression, anxiety, post-traumatic stress disorder (PTSD), and sleep disturbances. This review synthesises the current knowledge on shared molecular, neuroimmune, and neuropathic pathways that underlie this comorbidity. Key mechanisms include hypothalamic–pituitary–adrenal (HPA) axis dysregulation, systemic and ocular inflammation, oxidative stress, mitochondrial dysfunction, and impaired neurotrophic signaling, especially reduced brain-derived neurotrophic factor (BDNF). Dysregulation of monoaminergic neurotransmitters such as serotonin and norepinephrine not only contributes to mood disturbances but also alters tear secretion and corneal pain perception. Corneal nerve changes and trigeminal–limbic sensitisation further reinforce the overlap between neuropathic ocular pain and affective dysregulation. Psychotropic medications, while essential for psychiatric care, may exacerbate ocular surface dysfunction through anticholinergic effects, altered neurotransmission, and tear film instability, highlighting the iatrogenic dimension of this interface. Conversely, tear-based biomarkers, including cytokines, serotonin, and BDNF, offer promising translational tools for patient stratification, diagnosis, and treatment monitoring across ocular and psychiatric domains. Recognising DED as part of a systemic, biopsychosocial continuum is critical for effective management. Multidisciplinary strategies that integrate ophthalmologic and psychiatric care, alongside novel therapies targeting shared molecular pathways, provide a framework for improving outcomes. Future research should prioritise longitudinal studies, biomarker validation, and personalised interventions to address this complex comorbidity. Full article

Cervical cancer remains a significant public health priority, particularly in low- and middle-income countries. In this context, liquid biopsy has emerged as a minimally invasive method for detecting and monitoring molecular biomarkers, offering advantages over traditional screening approaches. This systematic review included 21 studies published between 2015 and 2025 and was conducted in accordance with the PRISMA 2020 statement. The analysis examined the role of serum cytokines, circulating microRNAs (miRNAs), and circulating cell-free HPV DNA (cfHPV-DNA) in patients with cervical cancer or high-grade intraepithelial lesions. Circulating miRNAs—particularly miR-21, miR-29a, and miR-34a—are consistently associated with recurrence, tumor progression, and reduced survival. However, their immediate clinical translation remains limited by methodological variability and the lack of universal normalizers. In contrast, cfHPV-DNA, especially with ddPCR, exhibited the best study-level performance, with a specificity of 100% and a sensitivity of approximately 80–88%, across heterogeneous endpoints and analytic conditions. Consequently, cfHPV-DNA represents a promising tool for post-treatment surveillance and early detection of recurrence. Serum cytokines, such as TNF-α, IL-6, and IL-10, reflect inflammation and the tumor microenvironment. Nevertheless, their lack of standardization and variability across detection platforms restricts their reproducibility, positioning them as complementary rather than stand-alone markers. In conclusion, the evidence supports liquid biopsy as a promising tool in cervical cancer management; nonetheless, only cfHPV-DNA is currently ready for clinical application, whereas miRNAs and cytokines require multicenter validation and technical standardization before implementation. Full article

Background/Objectives: Crohn’s disease (CD) is a chronic immune-mediated disorder with heterogeneous response to biologic therapies. Ustekinumab (UST), an anti-IL-12/23 monoclonal antibody, is effective in CD, but predictive biomarkers of treatment response remain lacking. This study aimed to investigate cytokine dynamics during UST induction and to evaluate their association with clinical and biochemical outcomes in an observational cohort of CD patients. Methods: We prospectively recruited 31 adult patients with moderate-to-severe active CD initiating UST therapy at a tertiary referral center. Peripheral blood and stool samples were collected at baseline and weeks 4, 8, and 16. UST trough concentrations, C-reactive protein (CRP), fecal calprotectin (FC), hemoglobin, albumin, and 13 serum cytokines (including IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-17, IL-23, TNF-α, and OSM) were analyzed. Response was defined as a ≥70% reduction in FC at week 16, or, alternatively, CRP < 5 mg/L or a Harvey–Bradshaw Index < 3. Results: Eighteen patients (58%) achieved response at week 16. Responders showed significant reductions in FC, CRP, and disease activity, while non-responders exhibited limited biochemical improvement. Overall, UST induction was associated with a global decrease in proinflammatory cytokines, particularly TNF-α and IL-1β. Responders displayed distinct cytokine patterns, with higher IL-13 levels at week 8 and lower IL-8 concentrations at week 16 compared with non-responders. UST trough levels tended to be higher in responders, and inverse correlations were observed between drug concentrations and several cytokines, including IL-6, IL-8, IL-13, and IL-23. Conclusions: UST induction leads to measurable immunological changes in CD, with differential cytokine dynamics distinguishing responders from non-responders. These findings support the potential of cytokine signatures, in combination with therapeutic drug monitoring, as pharmacodynamic biomarkers to optimize personalized treatment strategies in CD. Full article

Type 2 diabetes mellitus (T2D) is a chronic metabolic disorder in which inflammation plays a central role in its onset, progression, and complications. Identifying reliable biomarkers is essential to improve risk prediction, disease monitoring, and early intervention. A total of 169 Ecuadorian participants were stratified into four clinical groups: non-diabetic controls (NDC), controlled T2D (C-T2D), uncontrolled T2D (NC-T2D), and diabetic kidney disease (DKD). Circulating levels of cytokines (IL-6, IL-8, TNF-α), adipokines (leptin, adiponectin), and PBMC-derived microRNAs (miR-146a, miR-155) were quantified. Associations with disease stage were evaluated using ROC curve analysis and logistic regression. Leptin showed the strongest association with T2D (OR = 13.76, 95% CI: 6.47–29.26), followed by IL-8 (OR = 6.73, 95% CI: 3.30–13.70) and IL-6 (OR = 4.43, 95% CI: 2.26–8.97). Adiponectin distinguished NC-T2D from DKD (OR = 4.15, 95% CI: 1.77–9.71), underscoring its potential as an indicator of renal complications. Interestingly, TNF-α levels declined across disease stages, possibly reflecting subclinical inflammation in Ecuadorian NDC with high rates of obesity and dyslipidemia. PBMC-derived miR-146a was upregulated in T2D patients, contrasting with prior serum-based studies and emphasizing the importance of compartment-specific analysis. miR-155 was elevated in C-T2D, suggesting a compensatory immune-regulatory mechanism that diminishes with poor glycemic control and advanced disease. Inflammatory cytokines, adipokines, and microRNAs act in distinct yet complementary ways in T2D. Leptin, IL-6, and IL-8 emerge as strong predictors of disease, while miR-146a and miR-155 provide additional insight into immune-inflammatory regulation. Integrated biomarker panels may enhance patient stratification and support personalized monitoring of T2D progression. Full article

Septic shock has an unacceptably high mortality rate and unmet need for new therapeutics. Murine models are crucial for research, yet methodologies often differ. This study characterised standard- and high-grade caecal ligation and puncture (CLP) murine models of septic shock by integrating ultraminiature arterial telemetry with comprehensive plasma biomarker analysis. Standard-grade and high-grade CLP was performed in 8–10 week old, male C57BL/6 mice (n = 98), with a subset implanted with arterial telemetry to monitor real-time circulatory function. Plasma markers of inflammation and organ damage were measured at multiple intervals up to 168 h post-CLP. Standard-grade and high-grade CLP showed distinct progressions; episodes of hypotension began 5–6 h after CLP in 30% of standard-grade and all high-grade CLP mice, with respective 168 h mortality of 40% and 71%. Recurrent episodes of hypotension 5–39 h after CLP were universally lethal. The coincidence of hypotension and elevated plasma lactate defined the onset of septic shock after high-grade CLP, which was always lethal. Inflammatory cytokines and markers of liver, renal, and cardiac damage were markedly elevated to 168 h after high-grade CLP, in contrast to standard-grade CLP, which returned to baseline by 48 h. Elevated plasma IL-6, TNFα, and corticosterone, along with reduced albumin, were significantly correlated with mortality. In conclusion, this research refines murine CLP models by providing a precise, dynamic map of the progression to septic shock. The high-grade CLP model consistently models early and late-stage physiological deterioration and serves as a robust model for evaluating the efficacy of novel therapies aimed at human septic shock. Full article

This study reports the development of a fiber-optic localized surface plasmon resonance (FO-LSPR) sensor incorporating a three-dimensional micropillar array functionalized with gold nanoparticles. The micropillar structures were fabricated on the fiber facet using a single-mask imprint lithography process, followed by nanoparticle immobilization to create a composite plasmonic surface. Compared with flat polymer-coated fibers, the micropillar array markedly increased the effective sensing surface and enhanced light trapping by providing anti-reflective conditions at the interface. Consequently, the sensor demonstrated superior performance in refractive index sensing, yielding a sensitivity of 4.54 with an R² of 0.984, in contrast to 3.13 and 0.979 obtained for the flat counterpart. To validate its biosensing applicability, Interleukin-8 (IL-8), a cancer-associated cytokine, was selected as a model analyte. Direct immunoassays revealed quantitative detection across a broad dynamic range (0.1–1000 pg/mL) with a limit of detection of 0.013 pg/mL, while specificity was confirmed against non-target proteins. The proposed FO-LSPR platform thus offers a cost-effective and reproducible route to overcome the surface-area limitations of conventional designs, providing enhanced sensitivity and stability. These results highlight the potential of the micropillar-based FO-LSPR sensor for practical deployment in point-of-care diagnostics and real-time biomolecular monitoring. Full article

Nocardia, a rare but life-threatening pathogen, can invade multiple tissues and organs, such as lungs, brain, skin and soft tissue. In this study, we determined whether nitric oxide (NO) contributes to the severity of experimental pulmonary nocardiosis. BALB/c mice with or without aminoguanidine (AG) treatment were infected with N. farcinica through intranasal or intraperitoneal routes. Over experimental period, weight and mortality were monitored, and lung tissues were collected for NO production, cytokines detection, histopathological analysis, and bacterial load assessment. Next, alveolar MH-S macrophages were treated with various inhibitors to explore the impacts of NO, MAPK, and NF-κB against N. farcinica infection. AG treatment improved weight loss, lowered pulmonary bacterial load, and attenuated inflammatory response in infected mice. Similar effects were observed in alveolar MH-S macrophages. And all AG-treated mice survived infection. Furthermore, we suggest that NO is induced by N. farcinica through MAPK JNK and NF-κB signaling. Our study demonstrates the causative role of inducible NO on the severity of N. farcinica infection. Full article

Background: Interleukin-6 (IL-6) is a multifunctional cytokine implicated in various inflammatory and immune-mediated processes. Its involvement in systemic lupus erythematosus (SLE) has been increasingly investigated, particularly related to disease activity and tissue damage. This study aimed to quantify serum IL-6 levels in patients with SLE and assess their associations with clinical manifestations and laboratory parameters. Methods: A total of 88 patients diagnosed with SLE and 87 matched healthy controls were included. Serum IL-6 concentrations were measured by ELISA. Clinical data, SLEDAI scores, organ involvement, inflammatory markers, and autoantibody profiles were recorded. The statistical analysis involved non-parametric testing, correlation analysis, and linear regression. Results: IL-6 concentrations were higher in SLE patients than in controls (7.46 ± 6.73 vs. 5.30 ± 10.89 pg/mL). Significantly increased IL-6 levels were observed in patients with active disease (SLEDAI ≥ 6; p = 0.025) and renal (p = 0.001) involvement. Positive correlations were identified between IL-6 and ESR, creatinine, ANA, and specific autoantibodies (anti-dsDNA, SSA, and SSB). IL-6 also correlated with IL-10 (p = 0.010) but showed no significant association with IL-17A, TNF-α, CRP, or complement levels. Conclusions: Elevated IL-6 levels are associated with greater disease activity and specific organ involvement in SLE. These findings highlight IL-6 as a measurable indicator of immunological and clinical disease expression, supporting its relevance in disease monitoring. Full article

Blood pressure variability (BPV) is linked to cardiovascular disease (CVD) and systemic inflammation in adults, but its relevance in young, healthy populations remains unclear. This study examined the association between short-term BPV and inflammatory markers in 447 normotensive participants (mean age, 22.9 years) from the Georgia Stress and Heart (GSH) study, a cohort of Non-Hispanic Black and White individuals. Participants underwent 24 h ambulatory blood pressure monitoring and assessment of serum inflammatory markers, including hs-CRP, IFN-γ, IL-6, and TNF-α. BPV was quantified using average real variability (ARV), and generalized estimating equations (GEEs) were used to evaluate associations, adjusting for age, sex, race, and mean blood pressure. Diastolic BPV was significantly, positively associated with hs-CRP and TNF-α, whereas systolic BPV was not associated with any inflammatory marker. Specifically, 24 h diastolic BPV was positively associated with hs-CRP (p = 0.001) and TNF-α (p = 0.015), while daytime diastolic BPV was positively associated with hs-CRP (p = 0.002). Nighttime diastolic BPV was positively associated with both hs-CRP (p = 0.020) and TNF-α (p = 0.007). No significant associations were found between BPV and IL-6 or IFN-γ. These findings suggest diastolic BPV may be a marker of low-grade inflammation in healthy young adults and could represent an early cardiovascular risk factor that warrants longitudinal study. Full article