Circulating interleukin-8 and osteopontin are promising biomarkers of clinical outcomes in advanced melanoma patients treated with targeted therapy.

BACKGROUND: Circulating cytokines can represent non-invasive biomarkers to improve prediction of clinical outcomes of cancer patients. Here, plasma levels of IL-8, CCL4, osteopontin, LIF and BDNF were determined at baseline (T0), after 2 months of therapy (T2) and, when feasible, at progression (TP), in 70 melanoma patients treated with BRAF and MEK inhibitors. The association of baseline cytokine levels with clinical response, progression-free survival (PFS) and overall survival (OS) was evaluated. METHODS: Cytokine concentrations were measured using the xMAP technology. Their ability to discriminate between responding (Rs) and non-responding (NRs) patients was assessed by Receiver Operating Characteristics analysis. PFS and OS were estimated with the Kaplan-Meier method. The Cox proportional hazard model was used in the univariate and multivariate analyses to estimate crude and adjusted hazard ratios with 95% confidence intervals. RESULTS: CCL4 and LIF were undetectable in the majority of samples. The median osteopontin concentration at T0 and T2 was significantly higher in NRs than in Rs. The median T0 and T2 values of IL-8 were also higher in NRs than in Rs, although the statistical significance was not reached. No differences were detected for BDNF. In 39 Rs with matched T0, T2, and TP samples, osteopontin and IL-8 significantly decreased from T0 to T2 and rose again at TP, while BDNF levels remained unchanged. In NRs, none of the cytokines showed a significant decrease at T2. Only osteopontin demonstrated a good ability to discriminate between Rs and NRs. A high IL-8 T0 level was associated with significantly shorter PFS and OS and higher risk of progression and mortality, and remained an independent negative prognostic factor for OS in multivariate analysis. An elevated osteopontin T0 concentration was also significantly associated with worse OS and increased risk of death. Patients with high IL-8 and high osteopontin showed the lowest PFS and OS, and in multivariate analysis this cytokine combination remained independently associated with a three- to six-fold increased risk of mortality. CONCLUSION: Circulating IL-8 and osteopontin appear useful biomarkers to refine prognosis evaluation of patients undergoing targeted therapy, and deserve attention as potential targets to improve its clinical efficacy.

Elevation of IL-8 secretion induced by PEDV infection via NF-κB signaling pathway.

Porcine epidemic diarrhea virus (PEDV) is associated with severe enteritis, which contributes to high mortality in piglets. The aim of this study was to describe molecular mechanisms associated with proinflammatory cytokine(s) production during PEDV infection. We showed that infection of porcine intestine epithelial cell clone J2 (IPEC-J2) with PEDV induces a gradual increase in interleukin 8 (IL-8) production at different time points, as well as infection of Vero E6 with PEDV. The secretion of IL-8 in these two cell lines infected with PEDV is related to the activation of NF-κB. Furthermore, the cells expressing PEDV M or E protein can induce the upregulation of IL-8. These findings suggest that the IL-8 production can be the initiator of inflammatory response by the host cells upon PEDV infection.

Anti-Inflammatory Effect of Atorvastatin on Primary Human Endothelial Cells Incubated under Genotoxic Load.

The level of cytokine expression was measured in human coronary artery (HCAEC) and internal thoracic artery (HITAEC) endothelial cells exposed to 500 ng/ml alkylating mutagen mitomycin C (MMC) and 5 µM atorvastatin. It was found that treatment of MMC-exposed HCAEC with atorvastatin decreased secretion of macrophage migration inhibitory factor (MIF), IL-8, and IL8 gene expression, but increased the expression of SERPINE1 gene encoding the PAI-1 protein. In atorvastatin-treated HITAEC, the concentration of MIF protein and the expression of the IL8 and SERPINE1 genes were reduced. We can conclude that atorvastatin prevents proinflammatory activation of endothelial cells cultured under conditions of genotoxic load. However, the molecular mechanisms of this effect require further research.

Pro-inflammatory activity of Cutibacterium acnes phylotype IA1 and extracellular vesicles: An in vitro study.

Acne is a chronic inflammatory skin condition that involves Cutibacterium acnes (C. acnes), which is classified into six main phylotypes (IA1, IA2, IB, IC, II and III). Acne development is associated with loss of C. acnes phylotype diversity, characterised by overgrowth of phylotype IA1 relative to other phylotypes. It was also shown that purified extracellular vesicles (EVs) secreted by C. acnes can induce an acne-like inflammatory response in skin models. We aimed to determine if the inflammatory profile of EVs secreted by C. acnes phylotype IA1 from an inflammatory acne lesion was different from C. acnes phylotype IA1 from normal skin, thus playing a direct role in the severity of inflammation. EVs were produced in vitro after culture of two clinical strains of C. acnes phylotype IA1, T5 from normal human skin and A47 from an inflammatory acne lesion, and then incubated with either human immortalised keratinocytes, HaCaT cells, or skin explants obtained from abdominoplasty. Subsequently, quantitative PCR (qPCR) was performed for human ß-defensin 2 (hBD2), cathelicidin (LL-37), interleukin (IL)-1ß, IL-6, IL-8, IL-17α and IL-36γ, and ELISA for IL-6, IL-8 and IL-17α. We found that EVs produced in vitro by C. acnes derived from inflammatory acne lesions significantly increased the pro-inflammatory cytokines and anti-microbial peptides at both transcriptional and protein levels compared with EVs derived from normal human skin. We show for the first time that C. acnes EVs from inflammatory acne play a crucial role in acne-associated inflammation in vitro and that C. acnes phylotype IA1 collected from inflammatory acne lesion and normal skin produce different EVs and inflammatory profiles in vitro.

Serum Concentrations of Chemokines CCL20, CXCL8 and CXCL10 in Relapsing-Remitting Multiple Sclerosis and Their Association with Presence of Antibodies against Epstein-Barr Virus.

Epstein-Barr virus (EBV) infection and various chemokines, including CCL20, CXCL8 and CXCL10 are considered to participate in the pathogenesis of multiple sclerosis (MS), and several studies point to a direct regulatory effect of EBV on the expression of these chemokines. In our study we hypothesized that serum concentrations of CCL20, CXCL8 and CXCL0 are induced in patients with relapsing-remitting MS (RRMS) in comparison to healthy individuals, and that they are associated with EBV infection. Serum concentrations of CXCL8 and CXCL10 were lower in RRMS patients in relapse in comparison to healthy controls. Although potential effects of corticosteroid therapy introduced in a subgroup of RRMS patients prior to sampling were excluded by subgroup comparison, this possibility has to be considered while interpreting the results. We found an inverse association between serum concentrations of CXCL8 and anti-Epstein-Barr Virus Nuclear Antigen (EBNA) IgG and decreased expression of CXCL8 in peripheral blood mononuclear cells (PBMC) in relapse compared to remission. Lower serum concentrations of CXCL8 and CXCL10 in RRMS patients and decreased peripheral production of CXCL8 in relapse may indicate compensatory anti-inflammatory counter-regulation in MS.

Relationship between Respiratory Microbiome and Systemic Inflammatory Markers in COPD: A Pilot Study.

The respiratory microbiome may influence the development and progression of COPD by modulating local immune and inflammatory events. We aimed to investigate whether relative changes in respiratory bacterial abundance are also associated with systemic inflammation, and explore their relationship with the main clinical COPD phenotypes. Multiplex analysis of inflammatory markers and transcript eosinophil-related markers were analyzed on peripheral blood in a cohort of stable COPD patients (n = 72). Respiratory microbiome composition was analyzed by 16S rRNA microbial sequencing on spontaneous sputum. Spearman correlations were applied to test the relationship between the microbiome composition and systemic inflammation. The concentration of the plasma IL-8 showed an inverted correlation with the relative abundance of 17 bacterial genera in the whole COPD cohort. COPD patients categorized as eosinophilic showed positive relationships with blood eosinophil markers and inversely correlated with the degree of airway obstruction and the number of exacerbations during the previous year. COPD patients categorized as frequent exacerbators were enriched with the bacterial genera Pseudomonas which, in turn, was positively associated with the severity of airflow limitation and the prior year's exacerbation history. The associative relationships of the sputum microbiome with the severity of the disease emphasize the relevance of the interaction between the respiratory microbiota and systemic inflammation.

Corrigendum: Immune dysregulation is an important factor in the underlying complications in Influenza infection. ApoH, IL-8 and IL-15 as markers of prognosis.

[This corrects the article DOI: 10.3389/fimmu.2024.1443096.].

The lipid-metabolism enzyme ECI2 reduces neutrophil extracellular traps formation for colorectal cancer suppression.

Abnormalities in ether lipid metabolism as well as the formation of neutrophil extracellular traps have recently been recognized as detrimental factors affecting tumorigenesis and progression. However, the role of abnormal ether lipid metabolism in colorectal cancer (CRC) evolution has not been reported. Here we show that the lipid metabolism-related gene enoyl-CoA δ-isomerase 2 (ECI2) plays a tumor-suppressor role in CRC and is negatively associated with poor prognosis in CRC patients. We mechanistically demonstrate that ECI2 reduces ether lipid-mediated Interleukin 8 (IL-8) expression leading to decreased neutrophil recruitment and neutrophil extracellular traps formation for colorectal cancer suppression. In particular, ECI2 inhibits ether lipid production in CRC cells by inhibiting the peroxisomal localization of alkylglycerone phosphate synthase (AGPS), the rate-limiting enzyme for ether lipid synthesis. These findings not only deepen our understanding of the role of metabolic reprogramming and neutrophil interactions in the progression of CRC, but also provide ideas for identifying potential diagnostic markers and therapeutic targets for CRC.

Skin inflammatory signatures, as measured by disordered spatial redness patterns, predict current and future skin ageing attributes.

Facial skin redness can be an indicator of skin inflammation, however the physiological connection between facial redness and inflammatory status, as well as its role in age-related skin changes, remains poorly understood. This study aims to investigate the association between the pattern of facial skin redness and biological inflammatory status, as well as age-related changes occurring in the skin. Four studies were conducted recruiting healthy Northern Asian females. Disordered spatial patterns of facial skin redness signals were assessed using image analysis, i.e., the a* gradient algorithm, which quantifies the disordered shape and pattern of localized redness signals on facial skin. This redness pattern was compared with (1) inflammatory protein markers (IL-1Ra/ IL-1α and IL-8) measured from stripped corneocyte samples, (2) gene expression profiles obtained through transcriptome analysis using skin biopsy samples, and (3) the distribution pattern of blood vessel measured using a photoacoustic microscope. The association between the skin redness pattern and current and future ageing-related skin changes was examined through a longitudinal study tracking the same subjects for 10 years. A significant correlation was observed between the a* gradient and the levels of inflammatory cytokines (IL-1Ra/IL-1α and IL-8). Transcriptome analysis revealed upregulation of genes related to acute inflammation, chronic inflammation, cellular senescence, and angiogenesis in subjects with higher a* gradients. The high a* gradient group exhibited an extension of blood vessel diameter and increased blood vessel density, while the medium a* gradient group only exhibited blood vessel extension. Lastly, the 10-year longitudinal study demonstrated that the a* gradient was associated with current and future skin ageing-related attributes, such as increased skin texture and wrinkle formation. The spatial pattern of localized redness on the skin reflects the biological inflammatory status, and this inflammatory condition helps predict current and future age-related skin changes.

Predictive Value of Interleukin 6 and Interleukin 8 in Response to Treatment of Hepatitis C Virus.

BACKGROUND: Chronic hepatitis C (CHC) infection is a major public health problem in many low- and middle-income countries. The study aimed to find out how interleukin IL-6 and IL-8 levels in the blood affect the virological response to directacting antivirals (DAAs) and to find useful clinical or immunological markers for the response to HCV treatment. METHODS: CHC patients from a real Egyptian population (n = 4,300), who were treated during the Egyptian national initiative to eliminate HCV at the Sherbin Central Hospital, Dakahlia Governorate, Ministry of Health, Egypt, were enrolled in our study. They were all patients who did not obtain a sustained virological response (SVR) (n = 75; non-responder; the response rate was 98.26%), and a total of 100 patients were randomly selected from patients who obtained SVR (responder) and were age- and gender-matched (p > 0.05) with non-responder patients. Serum levels of IL-6 and IL-8 were measured by commercial ELISA kits. RESULTS: Non-responder patients were associated with significantly high levels of ALT, AST, ALP, and total bilirubin. Non-responders had significantly (p < 0.05) higher baseline IL-6 (16.7 ± 4.92 pg/mL) and IL-8 (37.81 ± 10.55 pg/mL) levels compared to responders (12.68 ± 2.06, 29.06 ± 5.94 pg/mL, respectively). There was a substantial (p < 0.05) association between the combination of two cytokines and a high likelihood of treatment failure, as indicated by all parameters examined, with the highest correlation values seen. CONCLUSIONS: The present study showed that increased IL-6 and IL-8 were associated with HCV treatment failure. Also, IL8 was associated with hepatic fibrosis.

Immune dysregulation is an important factor in the underlying complications in Influenza infection. ApoH, IL-8 and IL-15 as markers of prognosis.

Introduction: Influenza virus infection can cause a range of clinical symptoms, including respiratory failure (RF) and even death. The mechanisms responsible for the most severe forms of the disease are not yet well understood. The objective is to assess the initial immune response upon admission and its potential impact on infection progression. Methods: We conducted a prospective observational study of patients with influenza virus infection who required admission to a tertiary hospital in the 2017/18 and 2018/19 flu seasons. Immune markers, surrogate markers of neutrophil activation, and blood levels of DNase I and Apolipoprotein-H (ApoH) were determined in the first serum sample available during hospital care. Patients were followed until hospital discharge or death. Initially, 792 patients were included. From this group, 107 patients with poor evolution were selected, and a random control group was matched by day of admission. Results: Patients with poor outcomes had significantly reduced ApoH levels, a soluble protein that regulate both complement and coagulation pathways. In multivariate analysis, low plasma levels of ApoH (OR:5.43; 2.21-13.4), high levels of C- reactive protein (OR:2.73: 1.28-5.4), hyperferritinemia (OR:2.83; 1.28-5.4) and smoking (OR:3.41; 1.04-11.16), were significantly associated with a worse prognosis. RF was independently associated with low levels of ApoH (OR: 5.12; 2.02-1.94), while high levels of IL15 behaved as a protective factor (OR:0.30; 0.12-0.71). Discussion: Therefore, in hospitalized influenza patients, a dysregulated early immune response is associated with a worse outcome. Adequate plasma levels of ApoH are protective against severe influenza and RF and High levels of IL15 protect against RF.

Conformational preferences of heparan sulfate to recognize the CXCL8 dimer in aqueous medium: degree of sulfation and hydrogen bonds.

The sulfation pattern and epimerization of the long-chain sulfated polysaccharide heparan sulfate (HS) cause structural diversity and regulate various physiological and pathological processes when binding with proteins. In this work, we performed a series of molecular dynamics simulations of three variants of the octadecasaccharide HS with varying sulfation positions in aqueous medium in their free forms and in the presence of the chemokine CXCL8 dimer. The free energy of binding depicts the sulfation at the 6-O position of GlcNAc (HS6S), and both 3-O and 6-O positions of GlcNAc (HS3S6S) of HS variants are more likely to bind with the CXCL8 dimer than the triply sulfated HS2S3S6S, which is sulfated at the 2-O position of GlcUA additionally along with 3-O and 6-O positions of GlcNAc. Binding between HS and CXCL8 was driven by electrostatic and van der Waals interactions predominantly regardless of the sulfation pattern; however, unfavorable entropic contribution suppressed the interaction between HS and CXCL8. The contribution of different amino acid residues to the binding energetics suggested that basic amino acids line up the binding site of CXCL8. This study further acknowledges the role of interfacial water that is structured and bound with HS through hydrogen bonds, exhibiting differential hydrogen bond relaxation dynamics compared to when the HS molecules are free. Moreover, this study identifies that with the increase in sulfation, the HS-water hydrogen bond relaxation occurs faster with the complexation, while the reverse trend is followed in their free forms. Significant structural adaptation of the different sulfated HS molecules, as verified from the free energy landscapes generated from various reaction coordinates, root-mean-square-deviations, end-to-end distances, including ring pucker angles, dihedral flexibility, and the high conformational entropy cost arising from the glycosidic bonds, suggests that the different sulfated variants of HS undergo significant structural transformation to bind with CXCL8. The presence of a CXCL8 dimer imposes the bound forms of HS to adopt non-linear structures with skew-boat conformations. The atomistic details of the study would help in understanding the selectivity and conformational diversity, as well as the role of solvents in the recognition of CXCL8 by different sulfated variants of HS molecules.

Para-Hydroxycinnamic Acid Mitigates Senescence and Inflammaging in Human Skin Models.

Para-hydroxycinnamic acid (pHCA) is one of the most abundant naturally occurring hydroxycinnamic acids, a class of chemistries known for their antioxidant properties. In this study, we evaluated the impact of pHCA on different parameters of skin aging in in vitro skin models after H2O2 and UV exposure. These parameters include keratinocyte senescence and differentiation, inflammation, and energy metabolism, as well as the underlying molecular mechanisms. Here we demonstrate that pHCA prevents oxidative stress-induced premature senescence of human primary keratinocytes in both 2D and 3D skin models, while improving clonogenicity in 2D. As aging is linked to inflammation, referred to as inflammaging, we analyzed the release of IL-6, IL-8, and PGE2, known to be associated with senescence. All of them were downregulated by pHCA in both normal and oxidative stress conditions. Mechanistically, DNA damage induced by oxidative stress is prevented by pHCA, while pHCA also exerts a positive effect on the mitochondrial and glycolytic functions under stress. Altogether, these results highlight the protective effects of pHCA against inflammaging, and importantly, help to elucidate its potential mechanisms of action.

Evaluation of effects of bisphenol analogs AF, S, and F on viability, proliferation, production of selected cancer-related factors, and expression of selected transcripts in Caov-3 human ovarian epithelial cell line.

Bisphenol A (BPA) has been a substantial additive in plastics until the reports on its adverse effects have led to its restrictions and replacement. Monitoring studies document the increasing occurrence of bisphenol analogs, however, data on their effects and risks is still insufficient. Based on the indications that BPA might contribute to ovarian cancer pathogenesis, we examined effects of the analogs AF (BPAF), S (BPS) and F (BPF) (10-9-10-4 M) on the Caov-3 epithelial cancer cells, including the impact on cell viability, proliferation, oxidative stress, and production and expression of several factors and genes related to ovarian cancer. At environmentally relevant doses, bisphenols did not exert significant effects. At the highest concentration, BPAF caused varied alterations, including decreased cell viability and proliferation, caspase activation, down-regulation of PCNA and BIRC5, elevation of IL8, VEGFA, MYC, PTGS2 and ABCB1 expressions. Only BPA (10-4 M) increased IL-6, IL-8 and VEGFA output by the Caov-3 cells. Each bisphenol induced generation of reactive oxygen species and decreased superoxide dismutase activity at the highest concentration. Although the effects were observed only in the supraphysiological doses, the results indicate that certain bisphenol analogs might affect several ovarian cancer cell characteristics and merit further investigation.

Prognostic impact of Interleukin-8 levels in lung cancer: A meta-analysis and a bioinformatic validation.

BACKGROUND: High interleukin-8 (IL-8) levels have been linked to poor prognosis in lung cancer, but conclusive data are lacking. MATERIALS AND METHODS: A comprehensive search was conducted on April 1st, 2023, from electronic databases, focusing on studies with IL-8 expression evaluations and the availability of hazard ratio (HR) and 95% confidence intervals (CI) for overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS) or adequate data for their estimation. Then, we examined IL-8 and CXCR1 RNA-seq data from The Cancer Genome Atlas (TCGA) dataset, and we correlated these data with OS. RESULTS: Among 2655 produced records, 10 manuscripts involving both non-small cell lung cancer and small cell lung cancer, were included in the analysis. Two manuscripts and one study included two and three different cohorts, respectively, for a total of 14 cohorts of patients. Overall, 4 cohorts evaluated IL-8 levels in patients treated with chemotherapy, 3 cohorts immunotherapy, 2 cohorts surgical patients and 4 cohorts other treatments; 1 cohort was removed, as the type of treatments was lacking. The 12 cohorts included in the OS analysis revealed that patients with high IL-8 levels have a lower OS probability, as compared to patients with low IL-8 levels (HR=1.75, 95 % CI 1.36-2.26). No significant difference between patients with high and low IL-8 levels was observed in the 8 cohorts available for PFS analysis. Sensitivity analysis according to treatment revealed significant PFS and OS differences for patients treated with chemotherapy or immunotherapy. Analysis of RNA-seq data from TCGA, confirmed the correlation between high IL-8 and CXCR1 expression and worse OS in patients with resected lung cancer. CONCLUSION: To the best of our knowledge, this study represents the first meta-analysis demonstrating a negative prognostic impact of high IL-8 level in lung cancer, particularly in patients treated with chemotherapy and/or immunotherapy.

Analysis of 12 kinds of cytokines in seminal plasma by flow cytometry and their correlations with routine semen parameters.

OBJECTIVE: To investigate the levels of 12 kinds of cytokines in seminal plasma and their correlations with routine semen parameters. METHODS: The remaining seminal plasma samples of 134 patients undergoing routine semen examination were collected for detecting cytokines. The parameters for sperm concentration, percentage of progressively motile sperm (PR), and motility were analyzed by a computer-assisted sperm analysis (CASA) system. According to the results of sperm concentration, PR and motility, 134 patients were divided into the normal routine semen parameters group, oligoasthenospermia group and azoospermia group. The levels of 12 kinds of cytokines in seminal plasma, including interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17, interferin (IFN)-α, IFN-γ, and tumor necrosis factor (TNF)-α, were detected by flow cytometry. Two seminal plasma samples were detected for 10 times, respectively, to calculate the coefficients of variation (CV) of each cytokine. The linear range of each cytokine was measured using the standard, and the correlation coefficient (r) was calculated. RESULTS: The r2 of 12 kinds of cytokines detected by flow cytometry were all greater than 0.99. The reproducibility of 2 seminal plasma samples showed that the CVs of all cytokines were lower than 15 % except for TNF-α in sample 1 (15.15 %). Seminal plasma IL-6 levels were negatively correlated with semen volume (P < 0.01). Seminal plasma IL-5 levels were positively correlated with sperm concentration (P < 0.01). Seminal plasma IL-8 levels were negatively correlated with sperm motility (P < 0.01). Seminal plasma IL-8, IL-17 and IL-12P70 levels were negatively correlated with sperm PR (P < 0.05). In addition to the significant negative correlation between IL-5 and IL-17 (P < 0.05), there was a significant positive correlation between the majority of other cytokines. The levels of seminal plasma IL-17 and IL-12P70 in the oligoasthenospermia group and IL-1ß and IL-12P70 in the azoospermia group were significantly higher than those in the normal routine semen parameters group (P ≤ 0.05), while the levels of IL-10 in the azoospermia group were significantly lower than that in the normal routine semen parameters group (P < 0.05). CONCLUSION: There are certain correlations between seminal plasma cytokines and routine semen parameters and strong correlations between different seminal plasma cytokines, suggesting that the imbalance between seminal plasma cytokines may affect sperm quality. However, it still needs to be further confirmed by large samples and multi-center clinical studies and related basic researches.

IL-8 Induces Neutrophil Extracellular Trap Formation in Severe Thermal Injury.

Neutrophil extracellular traps (NETs) have a dual role in the innate immune response to thermal injuries. NETs provide an early line of defence against infection. However, excessive NETosis can mediate the pathogenesis of immunothrombosis, disseminated intravascular coagulation (DIC) and multiple organ failure (MOF) in sepsis. Recent studies suggest that high interleukin-8 (IL-8) levels in intensive care unit (ICU) patients significantly contribute to excessive NET generation. This study aimed to determine whether IL-8 also mediates NET generation in patients with severe thermal injuries. IL-8 levels were measured in serum samples from thermally injured patients with ≥15% of the total body surface area (TBSA) and healthy controls (HC). Ex vivo NET generation was also investigated by treating isolated neutrophils with serum from thermal injured patients or normal serum with and without IL-8 and anti-IL-8 antibodies. IL-8 levels were significantly increased compared to HC on days 3 and 5 (p < 0.05) following thermal injury. IL-8 levels were also significantly increased at day 5 in septic versus non-septic patients (p < 0.001). IL-8 levels were also increased in patients who developed sepsis compared to HC at days 3, 5 and 7 (p < 0.001), day 10 (p < 0.05) and days 12 and 14 (p < 0.01). Serum containing either low, medium or high levels of IL-8 was shown to induce ex vivo NETosis in an IL-8-dependent manner. Furthermore, the inhibition of DNase activity in serum increased the NET-inducing activity of IL-8 in vitro by preventing NET degradation. IL-8 is a major contributor to NET formation in severe thermal injury and is increased in patients who develop sepsis. We confirmed that DNase is an important regulator of NET degradation but also a potential confounder within assays that measure serum-induced ex vivo NETosis.

The clinical significance of inflammatory mediators in predicting obesity and progression-free survival in patients with adult-onset Craniopharyngioma.

BACKGROUND: Craniopharyngioma (CP) is a rare malformational tumor characterized by high rates of recurrence and morbid obesity. However, the role of inflammatory mediators in obesity and the prognosis of patients with CP remains unknown. Therefore, the present study aimed to analyze associations of inflammatory mediators with weight-related outcomes and the prognosis of patients with CP. METHODS: A total of 130 consecutive patients with CP were included in this study. The expression levels of seven inflammatory mediators and the plasma leptin concentration were investigated. Clinical parameters, weight changes, new-onset obesity, and progression-free survival (PFS) were recorded. The relationships between inflammatory mediators, clinicopathologic parameters, weight-related outcomes, and PFS were explored. RESULTS: Compared with those in normal pituitary tissue, the expressions of inflammatory mediators in tumor tissue were higher. Higher expression levels of CXCL1 and CXCL8 were identified as independent risk factors for significant weight gain, and CXCL1 and TNF were identified as independent risk factors for new-onset postoperative obesity. Poor PFS was associated with higher expression levels of CXCL1, CXCL8, IL1A, IL6, and TNF. CONCLUSION: The present study revealed that inflammatory mediators are associated with morbid obesity in patients with CP. Inflammatory mediators may be the critical bridge between elevated leptin and weight-related outcomes. Additionally, PFS was associated with the expression of inflammatory mediators. Further research is needed to elucidate the underlying mechanisms of inflammatory mediators and their potential as targets for novel therapies for CP.

Unraveling shared molecular signatures and potential therapeutic targets linking psoriasis and acute myocardial infarction.

Psoriasis, a chronic inflammatory skin disorder, is associated with comorbidities such as acute myocardial infarction (AMI). However, the molecular mechanisms connecting these conditions are unclear. In this study, we conducted bioinformatics analyses using gene expression datasets to identify differentially expressed genes and hub genes associated with both psoriasis and AMI. Our findings emphasize the involvement of immune-related pathways in the pathogenesis of both conditions. Furthermore, we investigated the expression levels of hub genes in AMI patients and myocardial infarction (MI) mice. ELISA measurements revealed significantly higher levels of CXCL8, IL1B, S100A9, and S100A12 in the serum of AMI patients compared to normal individuals. Immunohistochemical staining of heart tissue from MI mice showed a progressive increase in the expression of CXCL8 and IL-1B as MI advanced, while S100A9 exhibited high expression at day 3 post-MI. mRNA expression analysis validated these findings. Additionally, we explored the skin lesions of psoriasis patients and found significantly higher expression of CXCL8, IL-1B, S100A9, and S100A12 in the affected skin areas compared to unaffected regions. These results highlight the consistent upregulation of hub genes in both AMI and psoriasis patients, as well as in myocardial infarction mice, underscoring their potential as reliable markers for disease diagnosis. Moreover, molecular docking simulations revealed potential interactions between simvastatin and key target proteins, suggesting a potential therapeutic avenue. Overall, our study uncovers shared molecular signatures and potential therapeutic targets, providing a foundation for future investigations targeting common pathways in psoriasis and AMI.

Olink Proteomics-Based Exploration of Immuno-Oncology-Related Biomarkers Leading to Lung Adenocarcinoma Progression.

INTRODUCTION: It is crucial to investigate the distinct proteins that contribute to the advancement of lung cancer. MATERIAL AND METHODS: We analyzed the expression levels of 92 immuno-oncology-related proteins in 96 pairs of lung adenocarcinoma tissue samples using Olink proteomics. The differentially expressed proteins (DEPs) were successively screened in tumor and paraneoplastic groups, early and intermediate-late groups by a nonparametric rank sum test, and the distribution and expression levels of DEPs were determined by volcano and heat maps, etc., and the area under the curve was calculated. RESULTS: A total of 24 DEPs were identified in comparisons between tumor and paracancerous tissues. Among them, interleukin-8 (IL8) and chemokine (C-C motif) ligand 20 (CCL20) as potential markers for distinguishing tumor tissues. Through further screening, it was found that interleukin-6 (IL6) and vascular endothelial growth factor A (VEGFA) may be able to lead to tumor progression through the JaK-STAT signaling pathway, Toll-like receptor signaling pathway and PI3K/AKT signaling pathway. Interestingly, our study revealed a down-regulation of IL6 and VEGFA in tumor tissues compared to paracancerous tissues. CONCLUSIONS: IL8 + CCL20 (AUC: 0.7056) have the potential to differentiate tumor tissue from paracancerous tissue; IL6 + VEGFA (AUC: 0.7531) are important protein markers potentially responsible for tumor progression.