Search Results (10,567)

Background/Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by immune dysregulation that leads to widespread inflammation and damage across multiple organs. B lymphocytes play a vital role in SLE, with abnormal development and activation leading to autoreactive antibody production and immune complex formation, which damages tissues. Methods: The PPARα agonist WY14643 has anti-inflammatory effects in various inflammatory conditions, including CNS diseases. We investigated whether WY14643 decreases inflammatory mediator production in CD45R⁺ cells in the MRL/lpr mouse model of SLE. Flow cytometry was used to evaluate WY14643’s impact on the expression of IFN-γ, IL-6, iNOS, MCP-1, IL-1α, IL-2, Notch-1, Notch-3, GITR, and NF-κB p65 in splenic CD45R⁺ B cells. Additionally, we assessed the effect of WY14643 on the mRNA levels of these markers in the kidney using RT-PCR. Results: WY14643 decreased inflammatory markers such as CD45R⁺IFN-γ⁺, CD45R⁺IL-6⁺, CD45R⁺iNOS⁺, CD45R⁺MCP-1⁺, CD45R⁺IL-1α⁺, CD45R⁺IL-2⁺, CD45R⁺Notch1⁺, CD45R⁺Notch3⁺, CD45R⁺GITR⁺, and CD45R⁺NF-κB p65⁺ in splenic cells from MRL/lpr mice. Furthermore, WY14643 also lowered mRNA expression of IFN-γ, IL-6, iNOS, MCP-1, IL-2, IL-1α, Notch-1, Notch-3, GITR, and NF-κB p65 in the kidney. Conclusions: This study shows that WY14643 inhibits the production of inflammatory mediators and significantly reduces autoimmune features, including kidney inflammation, in MRL/lpr mice. Our results indicate that WY14643, a PPAR-α agonist, could be a potential therapy for lupus nephritis. Full article

Candida albicans is a ubiquitous commensal fungus that may be lethal once it gains access to the bloodstream, following a breach in protective barriers such as skin or gut lining. Intravenous injection of C. albicans (4.5 × 10⁴ yeasts/gm of mouse) leads reproducibly to systemic infection with a median survival of about 75 h. We studied the effects of two human innate immune effectors on the course of systemic infections. The soluble human pentraxin serum amyloid P component (hSAP) retards death in murine disseminated candidiasis. In contrast, another soluble pentraxin, human C-reactive protein (hCRP), hastens death. To examine the pathological basis for these differences, necropsies were performed, and the right kidney was removed for study. Candidiasis caused abundant collagen deposition (the precursor to fibrosis) and loss of contrast between the kidney medulla and cortex. Daily administration of subcutaneous hSAP following the intravenous injection of C. albicans preserved the discrete histological difference between cortex and medulla and lessened host collagen deposition. Yeasts and hyphae within abscesses were decorated with hSAP. Contrastingly, kidneys from animals administered C. albicans and hCRP showed extensive collagen deposition and loss of the boundary between the cortex and the medulla of the kidney. hCRP did not bind to fungi but bound to damaged tissue surrounding abscesses, leading to a more destructive infection with loss of tissue. Staining cells with antibodies to CD45 (to detect T-lymphocytes, myelocytes, monocytes, and macrophages) and antibodies to Ly-6G (neutrophils, and granulocytes) showed that hSAP retarded infiltration of inflammatory cells into diseased areas. The results are consistent with the hypothesis that early administration of hSAP represses the migration of inflammatory cells, dampens the production of collagen by fibroblasts, and dampens the overall immune response of the host to infection. In doing so, hSAP prolonged life, whereas hCRP facilitated the infectious process and hastened death. Full article

Despite the identification of several mediators of arteriogenesis, the growth of natural bypass, the role of lymphocytes, particularly T cells, in this process remains poorly defined. Among these, γδ T cells, which express alternative T cell receptors, have emerged as a key immune component. This study examined the roles of αβ and γδ T cells in arteriogenesis using a murine hindlimb model. While the absence of αβ T cells did not affect arteriogenesis, γδ T cell depletion markedly reduced vascular cell proliferation and perfusion recovery. Early phase analyses revealed impaired mast cell activation, whereas platelet–neutrophil aggregates and neutrophil extravasation were unaffected. In the later proliferative phase, γδ T cell depletion hindered perivascular M2-like (MRC1⁺) macrophage accumulation. Flow cytometric analysis of whole blood in wildtype mice revealed a temporal shift in γδ T cell populations from a CD27⁺/CD39⁻ phenotype, commonly associated with pro-inflammatory functions and IFNγ production, to CD39⁺ phenotypes, which have been linked to anti-inflammatory properties and IL-10 production. In rescue experiments, administration of IFNγ to γδ T cell-depleted mice restored mast cell activation, whereas IL-10 treatment reestablished M2-like (MRC1⁺) macrophage accumulation. These findings collectively identify γδ T cells as critical regulators of both early and late phases of arteriogenesis through coordinated inflammatory and regenerative mechanisms. Full article

The use of colored LED lights is a tool for controlling the development of lymphoid organs and the immune system in general. This study aims to analyze the effects of using simple and combined colored LED lights throughout a 6 week period (1–42 days of age). In this study, 336 one-day-old chicks were used, separated randomly into four groups with different sex and lighting systems, with each group being divided into four separate replicates (4 × 21 birds). The chicks in the WL-Male and WL-Female were exposed to white LED light (WL, 400–760 nm) for 6 weeks, while the chicks in the G-GxB-BL-Male and G-GxB-BL-Female were exposed to a combination of monochromatic lights as follows: green (560 nm) from 1 to 14 days of age, green and blue (480–560 nm) for 15–28 days of age, and blue lights (480 nm) for 29–42 days of age. The use of a mixture of green and blue LED lights (G-GxB-BL) resulted in a significant decrease in the average daily feed intake and feed conversion ratio compared to white light, without causing changes in the body weight of the chicks, average daily gain, mortality rate, and coefficient of variability. G-GxB-BL lights also improved the morphological development of the bursa of Fabricius (BF) compared to white light by significantly increasing the organ index and the lymphoid follicle area. At the same time, G-GxB-BL light compared to white light improved B lymphocytes proliferation in the BF by significantly increasing the lymphocyte density in lymphoid follicles, as well as the number of PCNA-positive cells. This light treatment had these results due to the activation of melatonin receptors, which led to a significant increase in Mel1a-positive cells and a significant decrease in the number of RORα-positive cells. These results demonstrate that G-GxB-BL lights improved the growth performance and immune response in the BF of broiler chickens. Full article

Background/Objectives: Tumor–stroma ratio (TSR) and tumor-infiltrating lymphocytes (TILs) were suggested as prognostic markers in oral squamous cell carcinoma (OSCC). Identification of markers assessable in preoperative biopsies that could guide treatment planning is of great importance. This study aimed to evaluate the concordance and prognostic impact of TSR and TILs in preoperative biopsies and matched resection specimens of OSCC. Methods: This study included 100 patients with OSCC. TSR and stromal TILs were evaluated on hematoxylin and eosin-stained slides of biopsies and paired resection specimens and categorized (into low TSR and high TSR; high TILs and low TILs). The agreement between resections and biopsies, and the prognostic significance and clinicopathological correlations of TSR and TILs, were investigated. Results: For TSR, substantial agreement between preoperative biopsies and surgical specimens (kappa correlation coefficient 0.713) was demonstrated. The assessment of TILs showed poor concordance between biopsies and resections (kappa correlation coefficient 0.372). For both biopsies and resections, Cox regression showed an independent negative prognostic impact of low TSR on disease-free, disease-specific, and overall survival. Independent prognostic value of TILs evaluated in biopsies was not found, and the negative prognostic impact of low TILs on disease-free and overall survival was observed only in the main resection specimens. Conclusions: TSR evaluated in preoperative biopsies was highly concordant with results in main resection specimens and may provide significant information for OSCC prognostication, risk stratification, and treatment decisions. In contrast, TILs evaluated in biopsies showed poor concordance with main resection specimens and failed to demonstrate prognostic significance. Full article

Objectives: To evaluate the association between fecal calprotectin (FC) levels and routinely available blood-based inflammatory indices measured during the same clinical episode in pediatric patients, as well as to assess the diagnostic performance of a novel composite parameter, the Gastrointestinal Inflammation Index (GII). Methods: This retrospective cross-sectional study included pediatric patients who underwent simultaneous testing for FC, complete blood count, C-reactive protein, and albumin between 2022 and 2025. Hematological inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), red cell distribution width (RDW), platelet mass index (PMI), systemic immune-inflammation index (SII), and the newly developed GII, were calculated. Correlations between FC and inflammatory indices were analyzed. Receiver operating characteristic (ROC) curve analysis was performed to evaluate diagnostic performance, and multivariate logistic regression was used to identify independent predictors of FC positivity. Results: Elevated FC levels were significantly associated with higher C-reactive protein levels, lower albumin concentrations, and increased values of RDW, PMI, SII, and GII (all p < 0.001). GII scores increased progressively across FC categories. In ROC analysis, GII demonstrated the highest discriminatory ability for predicting FC positivity (AUC = 0.660), followed by SII and PMI. In multivariate logistic regression analysis, only NLR remained an independent predictor of FC positivity (OR = 0.65, 95% CI: 0.44–0.97; p = 0.033). Conclusions: Blood-based inflammatory indices show significant associations with fecal calprotectin levels in pediatric inflammatory bowel disease. The novel GII may reflect the integrated systemic inflammatory burden related to intestinal involvement, while NLR appears to be a robust and practical independent marker. These indices may serve as adjunctive, rapid, and cost-effective supportive tools in clinical decision-making, although their moderate diagnostic performance limits their use as standalone screening markers. Full article

The Comarca Lagunera region faces groundwater quality issues due to elevated concentrations of heavy metals that exceed permissible limits set by Mexican regulations. This study aimed to evaluate arsenic concentrations in drinking water and goat milk, as well as their possible association with DNA fragmentation in goat lymphocytes in the Comarca Lagunera (Durango and Coahuila, Northern Mexico). Water, milk, and blood samples were collected from 120 goats (Capra hircus) and analyzed using atomic absorption spectrophotometry (water and milk samples) and the comet assay (blood). Arsenic concentration in drinking water varied among locations, with the highest value detected in El Venado (San Pedro, Coahuila), while other sites showed concentrations close to permissible limits. Arsenic concentrations in goat milk were generally low and mostly below the LOQ, which limited the ability to assess arsenic transfer into milk. DNA fragmentation was observed in lymphocytes; however, no statistically significant association was found between arsenic concentrations and DNA damage. These results indicate that, under the conditions of this study, DNA damage cannot be directly attributed to arsenic exposure and may be influenced by other environmental or biological factors. Further studies with larger sample sizes and additional variables are recommended. Full article

Objectives: Soft tissue sarcomas (STS) are biologically heterogeneous malignancies with unpredictable clinical behavior. Although tumor size, histological grade, and surgical margin status remain the main determinants of prognosis, additional biomarkers that integrate tumor biology and host-related factors are needed. The hemoglobin × albumin × lymphocyte/platelet (HALP) score reflects systemic inflammation and nutritional status. This study aimed to evaluate the association between preoperative HALP score and oncological as well as surgical outcomes in patients undergoing curative resection for STS. Materials and Methods: A retrospective cohort study was conducted including 46 consecutive patients who underwent surgery for STS between 2017 and 2025. HALP scores were calculated using preoperative laboratory parameters, and patients were stratified into low- and high-HALP groups according to the cohort median (24.9). Overall survival (OAS) and disease-free survival (DFS) were analyzed using the Kaplan–Meier method and Cox proportional hazards models. Surgical margin status and postoperative complications were also compared. Results: Patients with low HALP scores had significantly larger tumors, higher rates of non-R0 resection, and increased major complications (p < 0.05). Recurrence and mortality were more frequent in the low-HALP group. Kaplan–Meier analysis demonstrated significantly shorter OAS (log-rank p = 0.0034) and DFS (log-rank p = 0.0318) in patients with low HALP scores. In univariate Cox analysis, HALP was significantly associated with survival outcomes; however, in multivariate analysis, histological grade and surgical margin status remained independent prognostic factors, while HALP lost independent significance. Conclusions: A low preoperative HALP score is associated with aggressive tumor characteristics, increased surgical morbidity, and poorer survival in STS patients. Although HALP did not retain independent significance in multivariable analysis, its strong association with tumor aggressiveness and survival suggests that it may reflect the systemic manifestation of high-risk tumor biology. As a simple and cost-effective biomarker derived from routine laboratory parameters, HALP may support preoperative risk stratification and help identify patients with biologically aggressive disease. Full article

Crohn’s disease (CD) is frequently accompanied by T-cell lymphopenia and impaired mucosal immunity, conditions that may predispose to intestinal microsporidiosis by Encephalitozoon cuniculi. This prospective case–control study examined the interplay between IL-7/IL-7 receptor (IL-7R) signaling and anti-E. cuniculi immune responses in 50 CD patients and 50 matched healthy controls. Serum IL-7 and anti-E. cuniculi IgG, IgM, IgA and IgE were quantified by ELISA, while intestinal expression of IL-7, CD127 (IL-7Rα) and CD132 (IL-7Rγ) was assessed by RT-PCR. Protein levels of IL-7 and caspase-3 were evaluated by Western blot, and lymphocyte subsets and apoptosis by flow cytometry. CD patients showed reduced anti-E. cuniculi IgG and IgM levels but increased seropositivity, indicating compromised humoral quality despite greater exposure. Compared with controls, CD was associated with decreased serum IL-7, increased mucosal IL-7, downregulated CD132, and diminished caspase-3, suggesting a disrupted IL-7/IL-7R-apoptosis pathway. In CD, IgA- and IgE-skewed responses correlated differentially with caspase-3 and CD56⁺ γδ T cells, while E. cuniculi seropositivity independently predicted a shorter surgery-free interval. These findings identify a profound dysregulation of the IL-7/IL-7R-CD132-caspase-3 axis in CD and implicate E. cuniculi exposure as a potential marker of impaired mucosal immunity and adverse outcomes. Full article

Background: Treatment response to neoadjuvant therapy in rectal cancer exhibits a considerable degree of interpatient heterogeneity. Select components of the tumour immune microenvironment have been identified as predictive biomarkers of therapeutic response, for which more evidence is required for future clinical prediction models. Aim: The research aimed to identify key tumour immune microenvironment biomarkers predictive of the response to neoadjuvant therapy through the systematic appraisal of existing literature. Methods: A structured search was performed across PubMed, Ovid Embase, and Cochrane databases to retrieve primary studies investigating the association between the tumour immune microenvironment and pathological complete response (pCR) or tumour regression grade (TRG) in patients with rectal cancer. Studies were screened against predefined inclusion and exclusion criteria. Results: Fifteen studies satisfied the inclusion criteria, with cohorts ranging between 24 and 298 participants with predominantly stage II–III disease. Considerable heterogeneity was observed in both types and methods of quantification of biomarkers. Biomarkers assessed in pretreatment biopsies included tumour-infiltrating lymphocytes (TILs), investigated by subtype (cluster of differentiation (CD)8+, CD4+, forkhead box protein 3+ (FOXP3)) or as a composite measure, as well as programmed death-ligand 1 (PD-L1), PD-1+, natural killer (NK) cells, CD163+, and CD68+. Findings showed that high densities of TILs—particularly the CD8+ subtype—consistently correlated with improved tumour regression. FOXP3+ and CD163+ were inconsistently associated with reduced treatment response. NK cells and CD68+ cells were less frequently investigated and yielded non-significant findings. Conclusions: CD8+ TILs have the potential to serve as predictive biomarkers of therapeutic response to neoadjuvant treatment in patients with rectal cancer. Inconsistent findings with FOXP3+ Tregs and CD163+ macrophages reinforce the need for their further investigation. Full article

Background: Disease-related malnutrition is highly prevalent among hospitalized patients and is associated with increased mortality, complications, and prolonged hospital stays. Early identification of patients at nutritional risk is therefore essential to improve clinical outcomes. The Controlling Nutritional Status (CONUT) score is an objective prognostic immunometabolic marker derived from serum albumin, total cholesterol, and lymphocyte count. This study aimed to evaluate the prognostic value of the CONUT score for in-hospital mortality and length of hospital stay (LOS) in hospitalized patients with moderate-to-severe nutritional risk and to determine whether incorporating CONUT improves the predictive performance of a clinical model based on routine admission variables. Methods: A retrospective observational cohort study was conducted, including 671 adult patients admitted to a tertiary university hospital with CONUT ≥ 6. Multivariable logistic regression was used to assess predictors of in-hospital mortality, while LOS was analyzed using multivariable linear regression. Model discrimination was evaluated using receiver operating characteristic (ROC) curve analysis and comparison of the area under the curve (AUC). Results: Higher CONUT scores were independently associated with increased in-hospital mortality. Each one-point increase in CONUT was associated with 28% higher odds of death (OR 1.28; 95% CI 1.13–1.46; p < 0.001). Patients with a severe CONUT score had significantly higher mortality compared with those with a moderate CONUT score (OR 1.77; 95% CI 1.12–2.81; p = 0.004). Incorporating CONUT into the clinical prediction model significantly improved discrimination, increasing the AUC from 0.728 to 0.753 (DeLong p = 0.035). Higher CONUT values were also associated with longer hospital stays: each additional point corresponded to a 5.4% increase in LOS (p = 0.009), and a severe CONUT score was associated with a 17.6% longer stay (p = 0.027). Conclusions: the CONUT score is independently associated with in-hospital mortality and prolonged hospitalization. While its incremental discriminative improvement is modest, its automated calculation from routine laboratory data makes it a practical and scalable tool for early risk stratification. Full article

Zinc oxide (ZnO), silver (Ag) and titanium dioxide (TiO₂) nanoparticles (NPs), are three of the most widely manufactured NPs, while composite NPs have gained popularity due to their enhanced properties. NP release in environmental matrices increases chances of bioavailability and subsequent impact on human health. The current study focuses on manufacturing, characterization and cyto-genotoxic assessment of Ag, ZnO/Ag, TiO₂ and TiO₂/Ag NPs with and without humic acids (HAs), aiming for a holistic approach that leads to a comprehensive profile of said NPs. It entails (a) the synthesis of the aforementioned NPs via single-nozzle Flame Spray Pyrolysis (SN-FSP); (b) the characterization of NPs (in powder form and in dispersion media) using Powder X-ray Diffraction (PXRD), Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS); and (c) the assessment of their genotoxicity and cytotoxicity against human lymphocytes in presence of two HAs, thus simulating actual environmental conditions, and without HAs, through the cytokinesis block micronucleus assay (CBMN) with cytochalasin-B. No genotoxicity was observed in any case, whereas cytotoxicity induction varied depending on the NP and the presence or absence of the two HAs. Therefore, it is indispensable to evaluate the toxic profile of NPs considering different environmental scenarios, while conducting an integrated characterization of NPs. Full article

Background: Accurate prognostic stratification remains essential for optimizing outcomes in hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT). The hemoglobin–albumin–lymphocyte–platelet (HALP) score is a composite biomarker reflecting systemic inflammation, nutritional status, and immune competence, and has demonstrated prognostic value in several malignancies. This study aimed to evaluate the predictive utility of the HALP score for survivals and recurrence in HCC patients undergoing LT. Methods: A total of 476 consecutive patients who underwent LT for HCC between 2006 and 2024 were retrospectively analyzed. Pretransplant HALP scores were calculated for all patients. Receiver operating characteristic (ROC) analysis identified an optimal cut-off value of 29 for recurrence prediction. Patients were stratified into HALP ≥ 29 and HALP < 29 groups. DFS and recurrence rates were compared. Prognostic performance was assessed using the concordance index (C-index) and area under the ROC curve (AUC). Outcomes were further compared with the Milan and Expanded Malatya criteria. Results: Of the 476 patients, 335 (70.4%) had HALP ≥ 29 and 141 (29.6%) had HALP < 29. The HALP ≥ 29 group demonstrated significantly higher 5- and 10-year DFS rates compared with the HALP < 29 group (67.1% vs. 58.5% and 49.5% vs. 33.5%, respectively; p < 0.001). Recurrence rates were significantly lower in the HALP ≥ 29 group (14.0% vs. 31.9%; p < 0.001). However, patients within the Milan and Expanded Malatya criteria showed superior long-term DFS and lower recurrence rates in the HALP ≥ 29 compared to the HALP < 29 group (p ≤ 0.037). HALP ≥ 29 was associated with lower tumor burden parameters and improved hepatic functional reserve. Despite its significance, HALP demonstrated inferior discriminative performance (C-index: 0.565) compared with the Milan (0.621) and Expanded Malatya (0.648) criteria. Patients beyond the Milan criteria (n = 233) with HALP ≥ 29 achieved a 5-year overall survival of 54.2%, compared with 37.8% with HALP < 29. Conclusions: Low HALP score is associated with poor DFS and a high post-transplant recurrence rate. Although it represents a non-invasive and cost-effective biomarker, its prognostic accuracy remains inferior to established transplant selection criteria, limiting its use as a standalone selection tool. However, individuals beyond Milan with HALP ≥ 29 achieved survival outcomes exceeding internationally accepted post-transplant benchmarks. Incorporating HALP into pre-transplant evaluation may help identify a biologically favorable subgroup among patients traditionally considered high risk based solely on tumor burden. Full article

Background/Objectives: Neutrophil-to-lymphocyte ratio (NLR) may predict outcomes after organ transplantation. This study evaluated the peri-transplant prognostic value of NLR in lung transplantation (LTx). Methods: This retrospective study included 282 LTx recipients (2012–2020). NLR measured on PODs 1, 3, 7, and 28 predicted 6-month mortality. Generalized estimating equations analyzed serial trends. Multivariable regression and ROC analysis identified predictors for a composite model, assessing discrimination and calibration. Results: Among 282 recipients (mean age, 54.2 years; male, 65.2%; idiopathic pulmonary fibrosis, 54.3%), 24.1% died within 6 months, most commonly from infection. Median NLR increased sharply after LTx (pre-LTx, 5.4; POD 1, 23.1; POD 3, 31.2), then decreased (POD 7, 18.8; POD 28, 8.7). Non-survivors had significantly higher preoperative and postoperative NLRs, particularly on POD 28. POD 28 NLR independently predicted 6-month mortality (multivariable analysis: OR, 1.05 per unit; 95% CI, 1.02–1.07; p < 0.001), alongside age and donor lung PaO₂/FiO₂ (P/F) ratio. Notably, a composite model combining these variables demonstrated significantly superior discrimination (area under the curve [AUC], 0.742; p = 0.001) compared to the NLR-only model (AUC, 0.698; p < 0.05). GEE demonstrated significantly steeper post-transplant NLR decline among survivors than non-survivors after adjusting for age (p = 0.02). Patients with NLR > 9.20 at POD 28 (area under the curve, 0.698; 95% CI, 0.615–0.782; sensitivity, 71.4%; specificity, 59.8%)—showed significantly lower survival on Kaplan–Meier analysis (p < 0.001, log-rank). Conclusions: Persistent NLR elevation on POD 28 independently predicts early mortality post-LTx and may support routine post-transplant risk stratification. Full article

Background and Objectives: This study investigated the prognostic value of the C-reactive protein–albumin–lymphocyte (CALLY) index in predicting all-cause mortality among patients undergoing transcatheter aortic valve implantation (TAVI) for severe aortic stenosis. Materials and methods: This retrospective single-center study included 303 patients who underwent TAVI. The CALLY index and other established prognostic scores were calculated at baseline. Patients were followed for a median of 21 months. The primary endpoint was all-cause mortality. Results: A total of 60 patients (19.8%) died during follow-up. The CALLY index demonstrated the highest predictive performance for all-cause mortality, with an AUC of 0.698 (95% CI: 0.628–0.768, p < 0.001). In multivariate Cox regression, a low CALLY index remained an independent predictor of mortality (HR: 3.80, 95% CI: 2.03–7.11, p < 0.001), along with reduced LVEF, chronic kidney disease, and diabetes mellitus. Kaplan–Meier analysis further confirmed markedly worse survival in the high-risk group (log-rank p < 0.001). Conclusions: The CALLY index was independently associated with mortality after TAVI and may represent a complementary biomarker for risk stratification in this population. Full article