Search Results (275)

Diagnosing and prognosing immune-mediated airway diseases, like hypersensitivity pneumonitis (HP) and sarcoidosis, is complicated due to their overlapping symptoms and the lack of definitive biomarkers. Hence, we wanted to compare bronchoalveolar lavage (BAL) cytokine and chemokine profiles from 92 patients with different immune-mediated and inflammatory airway diseases, namely, HP, sarcoidosis, non-allergic asthma, amiodarone lung, and EGPA. We also compared pulmonary function parameters, BAL’s cellularity, and lymphocyte immunophenotypes. We found significant differences across all measured lung functions (VC, VC%, FEV1, FEV1%, and Tiff%) and in the number of macrophages, lymphocytes, neutrophils, and eosinophils. Furthermore, we showed significant differences in CD4, CD8, and CD4/8 across all included ILDs and OLDs; however, no significant differences were found in CD3, CD19, NK, or NKT. We identified nine biomarkers (IL-1β, IL-6, IL-8, IL-13, VEGF, angiogenin, C4a, RANTES, and MCP-1) that significantly differ in the BAL of patients with HP and sarcoidosis and showed that RANTES and IL-6 are associated with fibrotic outcome. We have demonstrated that interstitial and obstructive lung diseases differ in cytokine and cellular lung imprint, which may, in the future, enable the determination of the disease subtype and thus the identification of targets for the treatment of individuals or subgroups within diseases. Full article

Type 2 diabetes mellitus (T2DM) is a major public health concern that significantly increases the risk of diabetic retinopathy (DR), a leading cause of visual impairment worldwide. This study aimed to identify molecular markers of inflammation (INF) and angiogenesis (ANG) in the aqueous humor (AH) of patients with non-proliferative diabetic retinopathy (NPDR). We conducted an observational, multicenter, case–control study including 116 participants classified into T2DM with NPDR, T2DM without DR, and non-diabetic controls (SCG) undergoing cataract surgery. AH samples were collected intraoperatively and analyzed for 27 cytokines using multiplex immunoassay. Eighteen immune mediators were detected in AH samples, and several were significantly elevated in the NPDR group, including the interleukins (IL) -1β, -6, -8, -15, -17, as well as the granulocyte–macrophage colony stimulating factor (GM-CSF), basic fibroblast growth factor (bFGF), interferon gamma-induced protein (IP-10), macrophage inflammatory protein 1 beta (MIP-1b), monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell-expressed and -secreted protein (RANTES), and the vascular endothelial growth factor (VEGF). These molecules are involved in retinal INF, blood–retinal barrier breakdown, and pathological neovascularization. Our findings reveal a distinct pro-INF and pro-ANG profile in the AH of NPDR patients, suggesting that these cytokines may serve as early diagnostic/prognostic biomarkers for DR. Targeting these molecules could provide novel therapeutic strategies to mitigate retinal damage and vision loss in diabetic patients. Full article

At weaning, piglets deal with numerous changes and stressors, which can lead to reduced feed intake, digestive disturbances, and gut inflammation. In this context, there is a compelling need to develop new and innovative nutritional strategies aimed at restoring intestinal balance in piglets after weaning and controlling the weaning-associated intestinal inflammation. This study investigated the effect of a diet, including a synbiotic additive (a mix of grape seed and camelina meals as the prebiotic and a lactobacilli mixture as the probiotic) on intestinal inflammation in piglets after weaning. An acute inflammation was induced by the intraperitoneally challenge with Escherichia coli lipopolysaccharide (LPS). The experimental groups were as follows: Control group (piglets fed a conventional corn-soybean meal-based diet), LPS group (piglets fed the Control diet and challenged with 80 µg/b.w. of LPS), SYN group (piglets fed a basal diet, including 5% prebiotic mix and 0.1% probiotic mix, SYN diet), and SYN+LPS group (piglets fed the SYN diet and challenged with 80 µg/b.w. of LPS). Using genomic and proteomic techniques, genes and proteins related to intestinal inflammation were measured in both the jejunum and colon. The results showed that the LPS challenge induced an exacerbated inflammatory response in the jejunum and colon of piglets, inducing an overexpression of a large palette of inflammation-related mediators, including lactate dehydrogenase (LDH) activity, cytokines (e.g., interleukin (IL)—IL-1β, IL-6, tumor necrosis factor alpha—TNF-α), and chemokines (e.g., monokine induced by interferon-gamma—MIG, regulated on activation, normal T cell expressed and secreted—RANTES). All these effects are prevented by the SYN diet, which controls the amplitude of intestinal inflammation induced by the LPS challenge in piglets. Overall, these results suggested that piglets, after weaning, fed the synbiotic diet are less susceptible to the LPS challenge. This diet might be used as a nutritional strategy to alleviate intestinal inflammation in piglets after weaning. Full article

Background: Docetaxel (Doc) resistance in prostate cancer (CaP) patients is associated with the secretion of proinflammatory cytokines that induce an interaction between tumor cells and macrophages. Tumor cell-derived cytokines released in response to increased intracellular concentrations of Doc attract monocytes and macrophages to the tumor site and induce Doc resistance. Objectives: To generate Doc-resistant CaP cell line LNCaP-Doc/R and determine if we could modulate/reduce proinflammatory signals by administering Doc, encapsulated in a PLGA: Chitosan core-shell hierarchical nanoparticle (HNP-Doc) in the resistant and naive CaP Cells. Methods: LNCaP-Doc/R cells were generated by intermittent increasing concentration of Doc, proliferation, growth curve and cytotoxicity of Doc and HNP-Doc were evaluated followed by LNCaP and LNCaP-Doc/R (Doc resistant) CaP cells co-cultured with U937 monocytes with either free Doc or HNP-Doc encapsulated Doc, and various cytokine levels were measured in the conditioned media to assess the cytokine levels. Results: Our results show that LNCaP-Doc-R cells had slower growth in the lag phase, needed a 90-fold increase in Doc concentration to achieve 50% killing. Basal levels of cytokines secreted by LNCaP and LNCaP-Doc/R cells in response to free Doc and HNP-encapsulated Doc differed considerably, with free Doc-treated cells demonstrating, on average, 2–7-fold higher pro-inflammatory cytokine levels as compared to HNP-encapsulated Doc. The levels of pro-inflammatory cytokines, such as IFNγ, IL-1α, and RANTES, were increased ~2.38, ~2.75, and ~5.75-fold, respectively, in free Doc-treated CaP cells and were significantly lower when Doc was delivered via HNP. Further, LNCaP-Doc/R cells co-cultured with U937 had significantly lower markers of macrophage differentiation in response to HNP-encapsulated Doc treatment as opposed to free Doc treatment. Conclusions: Based on this analysis, we conclude that Doc treatment in vitro is associated with a proinflammatory response involving cytokines linked to macrophage recruitment and activation, with a lesser proinflammatory response with HNP-encapsulated Doc treatment. Full article

Wild soybean (Glycine soja, GS) is a traditional medicine used to treat inflammation. In this study, the anti-atopic properties of GS leaf and stem extract on skin inflammation were evaluated in the Dermatophagoides farinae-extract-induced mouse model and keratinocytes. Oral administration of the GS extract reduced scratching, dermatitis score, transepidermal water loss, thickness of epidermis, inflammatory cell accumulation, and serum concentrations of thymic stromal lymphopoietin and immunoglobulin E. GS downregulated the expression of inflammatory gene markers of atopic dermatitis (AD), including interleukin (IL)-6; regulated on activation, normal T cell expressed and secreted (RANTES); thymus- and activation-regulated chemokine (TARC); and macrophage-derived chemokine (MDC) and upregulated the expression of filaggrin, a keratinocyte differentiation marker, in skin tissue. GS downregulated Janus kinase 1, signal transducer and activation of transcription (STAT) 1, and STAT3 pathways. Using ultra-performance liquid chromatography, we identified seven flavonoids in GS extract, including apigenin, epicatechin, genistein, genistin, daidzin, daidzein, and soyasaponin Bb. GS, apigenin, and genistein reduced the expression of IL-6, MDC, TARC, and RANTES and increased filaggrin via the downregulation of STAT3 phosphorylation in interferon-γ/tumor necrosis factor-α-stimulated keratinocytes. Our results suggest that GS leaf and stem extract ameliorates AD-like skin inflammation by regulating the immune response and restoring skin barrier function. Full article

Background/Objectives: Immune cells are integral to bone homeostasis, including the repair and remodeling of bone tissue. Chronic dysregulation within this osteoimmune network can lead to bone marrow defects of the jaw (BMDJ), particularly fatty degenerative osteonecrosis of the jaw (FDOJ). These localized pathologies are implicated in systemic immune dysfunctions. Methods: This study is designed to determine whether BMDJ/FDOJ samples are indicative of medullary bone pathology by evaluating FDOJ gene expression patterns using quantitative real-time PCR. Results: Comparative analyses between pathological and healthy samples evaluated the dysregulation of key molecular pathways. BMDJ/FDOJ samples showed significant upregulation of inflammatory mediators, including CCL5/RANTES, VEGF, IGF and KOR, and downregulation of structural proteins, such as collagen types I, II and IV, and osteogenesis-associated factors, such as SP7. Conclusions: The study provides new insights into the molecular mechanisms of BMDJ/FDOJ by identifying potential molecular changes suggesting a pro-inflammatory state in the affected jawbone which may contribute to systemic immune dysregulation. The findings are consistent with morphologic observations of BMDJ/FDOJ in degenerated jawbone and underscore the need for integrative approaches in dentistry and medicine while highlighting BMDJ/FDOJ as a potential target for therapeutic and preventive strategies against systemic diseases and emphasizing its clinical significance. Full article

G protein-coupled receptor 75 (GPR75), a novel member of the rhodopsin-like G protein-coupled receptor (GPCR) family, has been identified across various tissues and organs, where it contributes to biological regulation and disease progression. Recent studies suggest potential interactions between GPR75 and ligands such as 20-hydroxyeicosatetraenoic acid (20-HETE) and C-C motif chemokine ligand 5 (CCL5/RANTES); however, its definitive endogenous ligand remains unidentified, and GPR75 is currently classified as an orphan receptor by International Union of Basic and Clinical Pharmacology (IUPHAR). Research on GPR75 deorphanization has underscored its critical roles in disease models, particularly in metabolic health, glucose regulation, and stability of the nervous and cardiovascular systems. However, the signaling pathways of GPR75 across different pathological conditions require further investigation. Importantly, ongoing studies are targeting GPR75 for drug development, exploring small molecule inhibitors, antibodies, and gene silencing techniques, positioning GPR75 as a promising GPCR target for treating related diseases. This review summarizes the recent advancements in GPR75 deorphanization research, examines its functions across tissues and systems, and highlights its links to metabolic, cardiovascular, and neurological disorders, thereby providing a resource for researchers to better understand the biological functions of this receptor. Full article

Background and aims: The CC5, CXC3, and CC2 chemokines (CK) are known to play a role in the pathogenesis of autoimmune hepatitis (AIH). However, no data are available on their potential utility as markers of disease progression or response to treatment. Material and methods: We analyzed their role as markers of remission in a population of patients with AIH. We retrospectively investigated the kinetics of RANTES (CCL5), IP-10 (CXCL10), and MCP-1 (CCL2) in 48 patients with AIH at the time of treatment initiation and also in 32 at biochemical, clinical and histological remission. Forty-nine healthy donors (HDs) served as controls. Results: At baseline, IP-10 and MCP-1 levels were higher in AIH patients than in HDs (261 vs. 101 pg/mL and 689 vs. 330 pg/mL, p < 0.01), and RANTES levels showed no differences. Correlations were observed between RANTES and IgG concentrations (r = 0.36 p = 0.04) and between IP-10 and Ishak’s grade (r = 0.52 p = 0.02). At remission, in 32 patients, while IP-10 and MCP-1 values showed a significant decrease from baseline reaching HD levels (261 vs. 106 pg/mL and 689 vs. 387 pg/mL, p < 0.01), RANTES did not. However, two kinetics patterns emerged, with 20 patients showing lower and 12 higher baseline RANTES values compared to HDs (29,450 pg/mL and 70,960 pg/mL vs. 52,010 pg/mL, p < 0.01). The former required longer treatment to reach remission and had higher Ishak’s grades than the latter (p < 0.01). Conclusions: RANTES, IP-10, and MCP-1 may help in predicting response to treatment and stable remission and in supporting the decision if and when to discontinue immune suppressive therapy. Full article

Acute brain injury includes different pathologies: stroke, traumatic injury, subarachnoidale haemorhhage. In the pathophysiology of acute brain injury, secondary injury with hyperactivation of glia plays a crucial role. Activated glial cells induce prolonged inflammation that impacts the recovery and further cognitive functions of patients. In our study, we have examined the neuroprotective impact of exogenous neuropeptides—Cerebrolysin on astrocytes under different conditions. In a model that simulates central nervous system damage associated with brain injury, stroke, and subarachnoid hemorrhage, the U87MG human brain cancer (glioblastoma astrocytoma like) cells were treated with Cerebrolysin and exposed to conditions of continuous and cyclic hypoxia and red blood cell lysate overload. The activity and expression of cyclooxygenases COX-1 and COX-2 and on cytokines (IL-8, IL-1β, IL-6, IL-10) and chemokines (CCL5/RANTES, CXCL9/MIG, CCL2/MCP-1, and CXCL10/IP-10) concentration were assessed. Cerebrolysin lowers IL-1β and IL-6 and increases IL-10 under all conditions. Cerebrolysin may exhibit a neuroimmunotrophic function, reducing inflammation under conditions that replicate traumatic brain injury and hemorrhagic insults to the central nervous system. By modulating both pro-inflammatory and anti-inflammatory cytokines, Cerebrolysin can help create a more balanced immune response conducive to tissue repair and reduced secondary damage. Its ability to lower harmful mediators like IL-1β and IL-6 while enhancing protective factors such as IL-10 suggests a promising therapeutic strategy in stroke, traumatic brain injury, and subarachnoid hemorrhage. Alongside other mechanisms such as neurotrophic factor enhancement and glial cell regulation, this cytokine modulation underscores the therapeutic potential of Cerebrolysin in a variety of central nervous system disorders. Full article

Background/Objectives: A high-energy-density (HED) diet promotes body weight gain, fat accumulation, and gut dysbiosis, contributing to obesity. The aim of this study was to characterize the initial response to HED diet consumption, as well as identify any sex differences in body composition, systemic inflammation, gut microbiome, and fecal fat excretion in rats. Methods: Male and female Sprague-Dawley rats were fed a low-energy-density (LED) diet for 10 days and were then switched to an HED diet for four weeks. Food intake, body weight, and body composition were measured routinely. Serum samples were collected to measure inflammatory cytokines/chemokines. Fecal samples were collected for microbiome analysis and lipid content. Results: After the HED diet, all rats gained body weight and fat mass, with males exhibiting increased susceptibility to weight gain. Males displayed either a diet-induced obesity phenotype (DIO-P) or a diet-resistant (DR) phenotype, as characterized by their differential body weight gain. Males showed elevated TGF-β levels, while females exhibited increases in Interferon gamma-inducible protein 10 (IP-10), regulated on activation, normal T cell expressed and secreted (RANTES) protein, and basic fibroblast growth factor (FGFb). Changes in gut microbiota composition revealed a reduction in beneficial species, like Bacteroides uniformis and Parabacteroides distasonis, and an increase in species such as Akkermansia muciniphila. Sex differences in fat metabolism were shown in the greater fecal fat excretion observed in males. Conclusions: Our study demonstrates that short-term consumption of a high-energy diet elicits notable sex-specific differences in body weight, body composition, inflammatory markers, gut microbiota, and fat excretion in Sprague-Dawley rats. While we recognize that this study has a small sample size and a short-term intervention, our findings highlight the critical role of sex as a biological variable in diet-induced obesity research. Full article

The refrigeration (cold storage) of platelet components provides several benefits over room-temperature (RT) storage, extending the shelf-life up to 21 days. However, the effect of storage conditions on platelet activation in response to stimulation remains unclear. A paired study was conducted where buffy-coat platelet concentrates were pooled, split, and allocated to RT or cold storage (n = 6 in each group). Platelet samples were taken on days 1, 7, 14, and 21, which were tested without stimulation or following activation with TRAP-6, A23187, lipopolysaccharides, or Histone-H4. Imaging flow cytometry was used to assess the surface characteristics of platelets and extracellular vesicles (EVs). The supernatant concentration of EGF, RANTES, PF4, CD62P, IL-27, CD40L, TNF-α, and OX40L was examined using ELISA. Cold-stored platelets generated a greater proportion of procoagulant platelets and EVs than RT-stored platelets in response to stimulation. The supernatant of cold-stored components contained lower concentrations of soluble factors under basal conditions, suggesting that platelet granules were better retained. Cold-stored platelets released higher concentrations of soluble factors following stimulation with TRAP-6, A23187, or Histone-H4. Only cold-stored platelets responded to lipopolysaccharides. These data demonstrate that cold-stored platelets retain the capacity to respond to stimuli after 21 days of storage, which may facilitate improved functional post-transfusion. Full article

Background: Recent studies have analyzed some cytokines in patients with papillary thyroid carcinoma (PTC), but simultaneous analysis of multiple cytokines remains rare. Nonetheless, the simultaneous assessment of multiple cytokines is increasingly recognized as crucial for understanding the cytokine characteristics and developmental mechanisms in PTC. In addition, studies applying artificial intelligence (AI) to discriminate patients with PTC based on serum multiple cytokine data have been performed rarely. Here, we measured and compared 46 cytokines in patients with PTC and healthy individuals, applying AI algorithms to classify the two groups. Methods: Blood serum was isolated from 63 patients with PTC and 63 control individuals. Forty-six cytokines were analyzed simultaneously using Luminex assay Human XL Cytokine Panel. Several laboratory findings were identified from electronic medical records. Student’s t-test or the Mann–Whitney U test were performed to analyze the difference between the two groups. As AI classification algorithms to categorize patients with PTC, K-nearest neighbor function, Naïve Bayes classifier, logistic regression, support vector machine, and eXtreme Gradient Boosting (XGBoost) were employed. The SHAP analysis assessed how individual parameters influence the classification of patients with PTC. Results: Cytokine levels, including GM-CSF, IFN-γ, IL-1ra, IL-7, IL-10, IL-12p40, IL-15, CCL20/MIP-α, CCL5/RANTES, and TNF-α, were significantly higher in PTC than in controls. Conversely, CD40 Ligand, EGF, IL-1β, PDGF-AA, and TGF-α exhibited significantly lower concentrations in PTC compared to controls. Among the five classification algorithms evaluated, XGBoost demonstrated superior performance in terms of accuracy, precision, sensitivity (recall), specificity, F1-score, and ROC-AUC score. Notably, EGF and IL-10 were identified as critical cytokines that significantly contributed to the differentiation of patients with PTC. Conclusions: A total of 5 cytokines showed lower levels in the PTC group than in the control, while 10 cytokines showed higher levels. While XGBoost demonstrated the best performance in discriminating between the PTC group and the control group, EGF and IL-10 were considered to be closely associated with PTC. Full article

(1) Background: Despite previous studies linking inflammatory cytokines to lung adenocarcinoma (LUAD), their causal mechanisms remain unclear. This study aims to explore the causal relationship between inflammatory cytokines and LUAD to fill this knowledge gap. (2) Methods: This study employs a comprehensive approach, integrating Mendelian randomization (MR) analysis, single-cell RNA sequencing (scRNA-seq), and transcriptomic sequencing (RNA-seq) data to investigate the relationship between inflammatory cytokines and LUAD. (3) Results: In forward MR analysis, elevated levels of hepatocyte growth factor (HGF), interleukin-1 receptor antagonist (IL-1RA), IL-5, monocyte chemoattractant protein-3, and monokine induced by interferon-γ were causally associated with an increased risk of LUAD. In reverse MR analysis, LUAD exhibited a positive causal relationship with the levels of regulated upon activation normal T cell expressed and secreted factor (RANTES) and stromal cell-derived factor-1α. The scRNA-seq data further identified specific cell populations that may influence LUAD onset and progression through the expression of particular inflammatory genes and intercellular communication. RNA-seq data analysis highlighted the role of the HGF gene in LUAD diagnosis, demonstrating its strong correlation with patient prognosis and immune cell infiltration within the tumor microenvironment. (4) Conclusions: The findings reveal a causal relationship between inflammatory cytokines and LUAD, with HGF emerging as a potential biomarker of significant clinical relevance. This study provides new insights into the molecular mechanisms underlying LUAD and lays the foundation for future therapeutic strategies. Full article

Chronic wounds present a large burden to our healthcare system and are typically marked by a failure to transition out of the inflammatory phase of wound healing. Venous leg ulcers (VLUs) represent the largest portion of chronic wounds. A pilot study of eleven (11) patients with VLUs seen over a 12-week period was undertaken utilizing RNA sequencing of wound biopsies and plasma cytokine levels to determine if biomarkers could be identified that would distinguish between wounds which heal versus those that do not. Chronic wounds were found to have increased expression of genes relating to epithelial-to-mesenchymal transition (EMT), cartilage and bone formation, and regulation of apical junction. Plasma cytokine levels showed predictive potential for IL-15 and RANTES, which were found to increase over time in patients with healed wounds. Further research is needed to validate these biomarkers as well as additional study of other chronic wound models, such as diabetic foot ulcers (DFUs). Full article

SARS-CoV-2, the pathogenic virus that induces COVID-19 disease, contains four structural proteins in its virion. The nucleocapsid (N) protein is one of the four structural proteins that play a crucial role in the assembly of viral RNA into ribonucleoprotein. In addition, the N protein contributes to viral pathogenesis. One of the functions attributed to the N protein is the triggering of cytokine release by lung epithelial cells, macrophages, and monocytes. This study addresses the cellular effects of the N protein of SARS-CoV-2 on cells of glial origin. We report the upregulation of the RANTES chemokine in A172 glioblastoma cells at both the mRNA and protein levels in response to exposure to SARS-CoV-2 nucleocapsid protein. The N protein did not have an effect on cell viability and cell migration. Full article