Levels Of Interleukin Research Articles

Clinical utility of the neutrophil elastase inhibitor sivelestat for the treatment of ALI/ARDS patients with COVID-19

BackgroundSivelestat, a neutrophil elastase inhibitor, is postulated to mitigate acute lung injury in patients following emergency surgery. However, its efficacy in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) induced by coronavirus disease 2019 (COVID-19) remains uncertain. This study aims to evaluate the pulmonary protective effects of sivelestat in COVID-19 patients with ALI/ARDS. MethodsA retrospective study was conducted involving 2454 COVID-19 patients between October 5, 2022, and February 1, 2023. Of these, 102 patients received sivelestat (0.2 mg/kg/h), while 2352 age- and sex-matched controls were identified. Propensity score matching (PSM) analysis was used to match sivelestat and non-sivelestat subgroups in ratios of 1:1 and 1:3 for sensitivity analysis. The primary outcome was a composite of effective outcomes, including 30-day mortality. Secondary outcomes included changes in partial pressure of arterial oxygen (PaO2), the ratio of PaO2 to the fraction of inspired oxygen (PaO2/FiO2), and various cytokine levels. Safety evaluations included assessments of liver function, kidney function, and leukopenia. ResultsIn the propensity score-matched analysis, the sivelestat group had a higher proportion of severe/critical patients (87.26 % vs. 51.02 %, P < 0.001), more ARDS patients (4.9 % vs. 0.43 %, P < 0.001), and more patients with interstitial lung disease (4.9 % vs. 1.49 %, P = 0.023), but fewer patients with stroke (17.65 % vs. 19.86 %, P < 0.001). Oxygen therapy rates were similar between the groups (79.41 % vs. 80.95 %, P = 0.9). The relative risk reduction in 30-day mortality was 88.45 % (95 % confidence interval [CI] 81.23%–93.21 %) for severe/critical COVID-19 patients treated with sivelestat. Sivelestat significantly decreased cytokine levels of interferon alpha (IFNα), interleukin-1 beta (IL-1β), and interleukin-2 (IL-2).In the sivelestat group, the mortality rate was significantly reduced with standard oxygenation and HFNC therapy(P < 0.05). The treatment with sivelestat did not increase side effects. ConclusionThe administration of the neutrophil elastase inhibitor sivelestat may improve clinical outcomes in COVID-19 patients with ALI/ARDS. These findings suggest that sivelestat could be considered an effective treatment option to alleviate pulmonary inflammatory injury caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Effects of microencapsulated plant essential oils on growth performance, immunity, and intestinal health of weaned Tibetan piglets.

Plant essential oils (PEOs) have received significant attention in animal production due to their diverse beneficial properties and hold potential to alleviate weaning stress. However, PEOs effectiveness is often compromised by volatility and degradation. Microencapsulation can enhance the stability and control release rate of essential oils. Whether different microencapsulation techniques affect the effectiveness remain unknown. This study aimed to investigate the effects of PEOs coated by different microencapsulation techniques on growth performance, immunity, and intestinal health of weaned Tibetan piglets. A total of 120 Tibetan piglets, aged 30 days, were randomly divided into five groups with four replicates, each containing six piglets. The experimental period lasted for 32 days. The groups were fed different diets: a basal diet without antibiotics (NC), a basal diet supplemented with 10 mg/kg tylosin and 50 mg/kg colistin sulfate (PC), 300 mg/kg solidified PEO particles (SPEO), 300 mg/kg cold spray-coated PEO (CSPEO), or 300 mg/kg hot spray-coated PEO (HSPEO). The results showed that supplementation with SPEO, CSPEO, or HSPEO led to a notable decrease in diarrhea incidence and feed to gain ratio, as well as duodenum lipopolysaccharide content, while simultaneously increase in average daily gain, interleukin-10 (IL-10) levels and the abundance of ileum Bifidobacterium compared with the NC group (p < 0.05). Supplementation with SPEO, CSPEO, or HSPEO significantly elevated serum immunoglobulin G (IgG) levels and concurrently reduced serum lipopolysaccharide and interferon γ levels compared with the NC and PC groups (p < 0.05). Serum insulin-like growth factor 1 (IGF-1) levels in the SPEO and HSPEO groups significantly increased compared with the NC group (p < 0.05). Additionally, CSPEO and HSPEO significantly reduced jejunum pH value (p < 0.05) compared with the NC and PC groups (p<0.05). Additionally, Supplementation with HSPEO significantly elevated levels of serum immunoglobulin M (IgM) and interleukin-4 (IL-4), abundance of ileum Lactobacillus, along with decreased serum interleukin-1 beta (IL-1β) levels compared with both the NC and PC groups. Our findings suggest that different microencapsulation techniques affect the effectiveness. Dietary supplemented with PEOs, especially HSPEO, increased growth performance, improved immune function, and optimized gut microbiota composition of weaned piglets, making it a promising feed additive in piglet production.

Impact of Air Pollutants on Lung Function and Inflammatory Response in Asthma in Shanghai

Objective Air pollution is a leading public health issue. This study investigated the effect of air quality and pollutants on pulmonary function and inflammation in patients with asthma in Shanghai.Methods The study monitored 27 asthma outpatients for a year, collecting data on weather, patient self-management [daily asthma diary, peak expiratory flow (PEF) monitoring, medication usage], spirometry and serum markers. To explore the potential mechanisms of any effects, asthmatic mice induced by ovalbumin (OVA) were exposed to PM2.5.Results Statistical and correlational analyses revealed that air pollutants have both acute and chronic effects on asthma. Acute exposure showed a correlation between PEF and levels of ozone (O3) and nitrogen dioxide (NO2). Chronic exposure indicated that interleukin-5 (IL-5) and interleukin-13 (IL-13) levels correlated with PM2.5 and PM10 concentrations. In asthmatic mouse models, exposure to PM2.5 increased cytokine levels and worsened lung function. Additionally, PM2.5 exposure inhibited cell proliferation by blocking the NF-κB and ERK phosphorylation pathways.Conclusion Ambient air pollutants exacerbate asthma by worsening lung function and enhancing Th2-mediated inflammation. Specifically, PM2.5 significantly contributes to these adverse effects. Further research is needed to elucidate the mechanisms by which PM2.5 impacts asthma.

Huangqin Qingrechubi Capsule alleviates inflammation and uric acid and lipid metabolism imbalance in rats with gouty arthritis by inhibiting the PTEN/PI3K/AKT signaling pathway

To investigate the effects of Huangqin Qingrechubi Capsule (HQC) on inflammation and uric acid and lipid metabolism in rats with gouty arthritis (GA) and its mechanism. SD rat models of GA established by injecting monosodium urate into the right ankle joint were treated with saline, colchicine and HQC at low, medium and high doses (n=10) by gavage for 7 days. Toe swelling of the rats was detected at 4, 8, 24, 48 and 72 h after modeling, and synovial histological changes were observed with HE staining. Serum levels of interleukin-10 (IL-10), IL-18, tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), adiponectin, leptin, resistin and visfatin were measured by ELISA, and the levels of high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), total cholesterol (TC), and uric acid (BUA) were detected. RTqPCR and Western blotting were used to detect the mRNA expressions of phosphatase and tensin homolog (PTEN), phosphatidylinositol-3-kinase (PI3K) and protein kinase B (AKT) and the protein expressions of PTEN, PI3K, p-PI3K, AKT and p-AKT. The rat models of GA showed obvious toe swelling, which reached the peak level at 48 h. HE staining revealed massive inflammatory cell infiltration and synovial tissue hyperplasia. The rat models showed significantly increased expressions of TNF-α, TGF-β1, IL-18, TC, TG, leptin, resistin and visfatin, BUA, p-PI3K, and p-AKT and lowered levels of IL-10, APN, HDL-C, and PTEN. Treatment with HQC and colchicine obviously improved these changes and alleviated synovial pathologies and toe swelling in the rat models. HQC can improve inflammation and correct the imbalance of uric acid and lipid metabolism in GA rats possibly by inhibiting the PTEN/PI3K/AKT signaling pathway.

Relation of T Cell Profile with Vitamin D Receptor and Vitamin D-Binding Protein Gene Polymorphisms in Atopy.

Atopic diseases, including atopic dermatitis (AD) and allergic asthma (AA), are characterized by complex immune responses involving various T cells subsets and their cytokine profiles. It is assumed that single nucleotide polymorphisms (SNPs) in the Vitamin D receptor (VDR) gene and the Vitamin D-binding protein (GC) gene are related to the action of Vitamin D and, consequently, play a role in regulating the immune response. However, there is not enough data to unequivocally support the hypothesis about the relationship between T cells profile and VDR or GC SNPs. Two hundred sixty-six subjects (aged > 18 years) were involved in the study: 100 patients with mild or moderate AD, 85 patients with mild or moderate AA, and 81 healthy individuals. Blood cell counts were determined by standard methods. Flow cytometric analysis was used to evaluate CD4+ T-helper (Th) cell subtypes: Th2, Th1, Th17, and T regulatory (Treg) cells in peripheral blood. Measurements of cytokines, total immunoglobulin E (IgE), and Vitamin D levels in serum were evaluated by ELISA. Significantly higher levels of Th1, Th2, and Th17 cells, along with lower levels of Tregs, were found in patients with atopic diseases compared to healthy individuals. Additionally, higher serum levels of interleukin (IL) 5, IL-17A, and transforming growth factor-β1 (TGF-β1), as well as lower levels of IL-10, were observed in patients with atopic diseases than in control. The study established associations between VDR SNPs and immune profiles: the AA genotype of rs731236 was associated with increased Th2 and Th17 cells and a higher Th1/Th2 ratio; the GG genotype of rs731236 was linked to decreased serum IL-10 and TGF-β1 levels; and the TT genotype of rs11168293 was associated with increased IL-10 levels. Additionally, the GG genotype of GC gene SNP rs4588 was associated with reduced Th2 and Th17 lymphocytes, while the TT genotype of rs4588 was linked to decreased IL-10 levels. Furthermore, the CC genotype of rs7041 was associated with higher levels of Th2, Th17, IL-10, and IL-35, as well as reduced levels of TGF-β1, while the GG genotype of rs3733359 was associated with reduced IL-10 levels. In conclusion, our study demonstrates that the Vitamin D receptor gene single nucleotide polymorphisms rs731236 and rs11168293, along with polymorphisms in the Vitamin D-binding protein gene (rs4588, rs7041, rs3733359), are significantly associated with variations in T cell profiles in atopy. These variations may play a crucial role in promoting inflammation and provide insight into the genetic factors contributing to the pathogenesis of atopy.

Translocation of probiotics via gut–lung axis enhanced pulmonary immunity of weaned piglets exposed to low concentrations of ammonia

ObjectiveLactobacillus salivarius is a probiotic bacteria strain in human and animal diets. The administration of probiotics to weaned piglets may improve their growth by optimizing the gastrointestinal bacterial composition. To further investigate the effect of bacterial communication between the gastrointestinal tract and lungs on bodily immunity, we reared weaned piglets in a low-ammonia gas environment. L. salivarius was supplemented to explore its effects on pulmonary immunity and its potential for bacterial translocation. ResultsOne hundred sixty weaned piglets were allocated to four groups: L. salivarius-supplemented, L. reuteri-supplemented, control, and antibiotic drug (aureomycin)-supplemented. The feeding duration was 28 d. The body weights of piglets administered a strain of Lactobacillus were better than those of the control (P < 0.01). The transcription level of immune factors interleukin 2 (IL-2), IL-4, interferon α (IFN-α), and tumor necrosis factor α (TNF-α) in cells of the ileum and lung was significantly higher (P < 0.01). Lung and ileal mucus tissues were isolated to sequence the bacterial composition, which suggested a higher richness in the lungs at the phylum level, which was not significant in the ileum. Functional bacteria were more abundant in the ileum and lungs. The proportion of the genera of Lactobacillus, Prevotella, Actinobacillus, and Prevotellaceae_ NK3B31_group increased in two tissues, and a lower ratio of Streptococcus, Escherichia-Shigella, and mycoplasma was detected. The correlation between the microbial genus composition and the levels of immune factors suggests that the abundance of Lactobacillus plays the same positive role in the lungs and ileum. Mycoplasmas play a negative role in ileal and pulmonary immunity. More Lactobacillus reuteri and anaerobic probiotic bacteria were detected in the lungs. ConclusionThe colonization of Lactobacillus salivarius and Lactobacillus reuteri in the membrane of the ileum optimized the ileal microbial composition, enrolled other probiotic bacteria translating to the lung, improved the abundance of pulmonary microbiota, and enhanced immunity after exposure to low concentrations of ammonia.

Effect of early administration of tetracosactide on mortality and host response in critically ill patients requiring rescue surgery: a sensitivity analysis of the STOPSHOCK phase 3 randomized controlled trial

BackgroundUndifferentiated shock is recognized as a criticality state that is transitional in immune-mediated topology for casual risk of lethal microcirculatory dysfunction. This was a sensitivity analysis of a drug (tetracosactide; TCS10) targeting melanocortin receptors (MCRs) in a phase 3 randomized controlled trial to improve cardiovascular surgical rescue outcome by reversing mortality and hemostatic disorders.MethodsSensitivity analysis was based on a randomized, two-arm, multicenter, double-blind, controlled trial. The Naïve Bayes classifier was performed by density-based sensitivity index for principal strata as proportional hazard model of 30-day surgical risk mortality according to European System for Cardiac Operative Risk Evaluation inputs-outputs in 100 consecutive cases (from August to September 2013 from Emilia Romagna region, Italy). Patients included an agent-based TCS10 group (10 mg, single intravenous bolus before surgery; n = 56) and control group (n = 44) and the association with cytokines, lactate, and bleeding-blood transfusion episodes with the prior-risk log-odds for mortality rate in time-to-event was analyzed.ResultsThirty-day mortality was significantly improved in the TCS10 group vs. control group (0 vs. 8 deaths, P < 0.0001). Baseline levels of interleukin (IL)-6, IL-10, and lactate were associated with bleeding episodes, independent of TCS10 treatment [odds ratio (OR) = 1.90, 95% confidence interval (CI) 1.39–2.79; OR = 1.53, 95%CI 1.17–2.12; and OR = 2.92, 95%CI 1.40–6.66, respectively], while baseline level of Fms-like tyrosine kinase 3 ligand (Flt3L) was associated with lower bleeding rates in TCS10-treated patients (OR = 0.31, 95%CI 0.11–0.90, P = 0.03). For every 8 TCS10-treated patients, 1 bleeding case was avoided. Blood transfusion episodes were significantly reduced in the TCS10 group compared to the control group (OR = 0.32, 95%CI 0.14–0.73, P = 0.01). For every 4 TCS10-treated patients, 1 transfusion case was avoided.ConclusionsSensitivity index underlines the quality target product profile of TCS10 in the runway of emergency casualty care. To introduce the technology readiness level in real-life critically ill patients, further large-scale studies are required.Trial registrationEuropean Union Drug Regulating Authorities Clinical Trials Database (EudraCT Number: 2007-006445-41).

Evaluating the role of interleukin-2 and interleukin-12 in pediatric patients with concurrent Mycoplasma pneumoniae and Epstein-Barr virus infections.

Mycoplasma pneumoniae (MP) frequently causes respiratory infections in children, whereas Epstein-Barr virus (EBV) typically presents subclinical manifestations in immunocompetent pediatric populations. The incidence of MP and EBV co-infections is often overlooked clinically, with the contributory role of EBV in pulmonary infections alongside MP remaining unclear. To evaluate the serum concentrations of interleukin-2 (IL-2) and interleukin-12 (IL-12) in pediatric patients with MP pneumonia co-infected with EBV and assess their prognostic implications. We retrospectively analyzed clinical data from patients diagnosed with MP and EBV co-infection, isolated MP infection, and a control group of healthy children, spanning from January 1, 2018 to December 31, 2021. Serum IL-2 and IL-12 levels were quantified using enzyme-linked immunosorbent assay. Logistic regression was employed to identify factors influencing poor prognosis, while receiver operating characteristic (ROC) curves evaluated the prognostic utility of serum IL-2 and IL-12 levels in co-infected patients. The co-infection group exhibited elevated serum IL-2 and C-reactive protein (CRP) levels compared to both the MP-only and control groups, with a reverse trend observed for IL-12 (P < 0.05). In the poor prognosis cohort, elevated CRP and IL-2 levels, alongside prolonged fever duration, contrasted with reduced IL-12 levels (P < 0.05). Logistic regression identified elevated IL-2 as an independent risk factor and high IL-12 as a protective factor for adverse outcomes (P < 0.05). ROC analysis indicated that the area under the curves for IL-2, IL-12, and their combination in predicting poor prognosis were 0.815, 0.895, and 0.915, respectively. Elevated serum IL-2 and diminished IL-12 levels in pediatric patients with MP and EBV co-infection correlate with poorer prognosis, with combined IL-2 and IL-12 levels offering enhanced predictive accuracy.

The hypoglycemic effect of enzymatic modified dietary fiber from bamboo shoot on type 2 diabetes rats.

Bamboo shoot is a healthy food rich in dietary fiber (DF). However, its highly insoluble DF and fibrous texture limit its application in industrially processed foods. To achieve industrial processing of bamboo shoot, cellulase was used to improve the physical characteristics of bamboo shoot DF in this study. After enzymatic hydrolysis, the content of soluble DF (SDF) of bamboo shoot increased by 99.28% (from 5.53% to 11.02%) significantly (p<0.01). At the same time, the effect of enzymatic-modified bamboo SDF (EMBSDF) on streptozotocin-induced type 2 diabetes rats was explored. Results demonstrated that the high dose of EMBSDF (312.8mg/kg) treated rats showed significant improvements in terms of glucose tolerance and insulin sensitivity (p<0.01) compared with the diabetes rats. Meantime, it was observed that the levels of glucagon-like peptide-1, adiponectin and interleukin-4 of high dose of EMBSDF compared with diabetes rats were increased (p<0.01) by 57.79%, 159.13%, and 6.17%, respectively. The tumor necrosis factor-α, C-reactive protein, and leptin levels were decreased (p<0.01) by 62.89%, 31.53%, and 7.84%, respectively. Furthermore, apparent kidney and pancreas histology improvements were found in high-dose and mid-dose EMBSDF-treated diabetes rats. These results indicated that the modified DF significantly improved diabetes.

Autochthonous probiotic bacteria improve intestinal pathology and histomorphology, expression of immune and growth-related genes and resistance against Vibrio alginolyticus in Asian seabass (Lates calcarifer).

The study isolated two strains of intestinal autochthonous bacteria Lactiplantibacillus plantarum1 (MH155966.1) (L1) and Lactiplantibacillus plantarum2 (MH105076.1) (L2) from the Choobdeh Abadan region. The aim of this study was to investigate the effects of different strains of probiotic bacteria on the growth performance, digestive enzyme activity, histopathologic and histomorphometric characterization of the intestine, expression of immune and growth related genes, and evaluate Lates calcarifer resistance against Vibrio alginolyticus. To achieve this, for each treatment 60 L. calcarifer juveniles (75 ± 12g) were randomly distributed in three fiberglass tanks (300L) and fed for 45 days. The treatments were established as Diet 1 (control diet); L1 (diet with Lb. plantarum isolated 1); L2 (diet with Lb. plantarum isolated 2) with a bacterial concentration of 1 × 109 CFU/g. Nine fish from each treatment were sampled and examined, after euthanasia. The fish were placed 2cm from the beginning of the intestine for microscopic sampling of villi height, villi width and thickness of the epithelium, with 3 treatments: The result showed differences in the mean values of total weight were found at the end of the experiment. After 45 days of culture, the fish fed with L1 had higher (P < 0.05) growth performance than the other treatment groups. But at the end of the trial, in L2, the digestive enzyme activities were higher (P < 0.05) than the other treatment groups. The fishes fed diets supplemented with the L2 group, like the digestive enzyme activities test, presented an increase in the thickness of the epithelium of the intestine, and villus height, and villus width were greatest in L2. Fish feeding with L1 and L2 probiotics induced higher transcription levels of interleukin-10 (IL-10), granulocyte-macrophage colony-forming cells (GMCFC), epidermal growth factor (EGF), and Transforming Growth Factor Beta (TGF-β) genes in the gut, which may correlate with better immune and hematological parameters in these groups. The results of the challenge test revealed that the percentage of survival was significantly higher in L1 (76.2%) and L2 (80.95%) treatments than in the control (P < 0.05). These results indicate that host-derived probiotics (Lb. plantarum) have significant potential as important probiotics to enhance nutrient utilization, Digestive enzymes, and metabolism by increasing the gut surface area of Lates calcarifer juveniles at 45 days of culture.

Assessment of ventilatory functions and associated inflammatory markers among workers in slaughterhouses

ObjectiveMeat processing is among the most extensive industries globally. However, data on the effects of occupational exposure on the pulmonary health of slaughterhouse workers is limited. Ascertaining the impact of the slaughterhouse atmosphere on the breathing habits of laborers exposed to it and the inflammatory markers associated with it was the aim of the current investigation.MethodsA cross-sectional study was performed on 82 non-smoker subjects of 41 male workers working in one of the major slaughterhouses in Cairo, Egypt, matched to 41 controls of administrative personnel. An elaborate questionnaire encompassing medical and occupational history was administered to each participant in the research. General and local systemic examinations and ventilatory function tests were carried out, and serum levels of interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) were measured.ResultsRespiratory symptoms were more prevalent with a statistically significant decline in ventilatory function parameters (FVC%, FEV1%, FEV1/FVC, FEF 25%, FEF 50%, FEF 75%, and PEF%) among the exposed group compared to those of control. In addition, there was a significantly higher serum level of inflammatory markers (IL-6 and hsCRP) among the exposed group compared to the control group, with a negative correlation with ventilatory functions. Moreover, there was a positive association between levels of serum IL-6 and hsCRP and the age and duration of employment of workers.ConclusionThere was a notable increase in the prevalence of respiratory disorders and inflammatory markers among slaughterhouse workers. Additionally, there was a substantial decrease in ventilatory function parameters, which could be attributed to the bioaerosols they encountered in the workplace.

Ascites and Serum Interleukin-10 Levels as a Prognostic Tool for Ovarian Cancer Outcomes.

Interleukin-10 (IL-10) has been shown to be present at high levels in the ascites of ovarian cancer (OC) patients; however, little is known about its prognostic value. We sought to correlate IL-10 levels in ascites and sera of OC patients with clinicopathologic characteristics and oncologic outcomes. IL-10 levels and clinical data from biobanked ascites and serum samples of OC patients were evaluated. Receiver operating characteristic curves were used to quantify marker performance and identify IL-10-high and IL-10-low groups. Correlations between IL-10 levels and clinicopathologic data were performed. Survival outcomes were calculated, while the factors affecting them were also investigated. A total of 106 patients had ascites samples, of which 44 serum samples were also available. Mean ascites IL-10 levels were significantly higher in patients with serous histology compared to endometrioid histology (p = 0.024). Fold-change in ascites IL-10 during treatment positively correlated with clinical response, as determined by a change in serum cancer antigen (CA)-125 levels (p = 0.0126). Median progression-free survival (PFS) and overall survival (OS) were shorter in patients with high compared with low ascites IL-10 levels (PFS: 18 versus 60 months; p = 0.007, OS: 42 versus 85 months; p = 0.029). A significant positive correlation was seen between ascites and sera IL-10 levels (p = 0.019). In multivariable analyses, a high ascites IL-10 level was associated with a significantly worse prognosis (PFS hazard ratio (HR) = 1.93; p = 0.02). Patients with high ascites levels of IL-10 have worse outcomes, which are likely reflective of the immunosuppressive effect of IL-10. This highlights its potential role as an immunomodulator in the tumor microenvironment, leading to OC immune evasion.

Association of IL-9 Cytokines with Hepatic Injury in Echinococcus granulosus Infection.

Cystic echinococcosis (CE) is a zoonotic disease caused by the parasite Echinococcus granulosus (E. granulosus), which can lead to the formation of liver lesions. Research indicates that E. granulosus releases both Toll-like receptor 2 (TLR2) and Interleukin-9 (IL-9), which can potentially impair the body's innate immune defenses and compromise the liver's ability to fight against diseases. To investigate the role of TLR2 and IL-9 in liver damage caused by E. granulosus infection, samples were initially collected from individuals diagnosed with CE. Subsequently, BALB/c mice were infected with E. granulosus at multiple time points (4 weeks, 12 weeks, 32 weeks) and the expression levels of these markers was then assessed at each of these phases. Furthermore, a BALB/c mouse model was generated and administered anti-IL-9 antibody via intraperitoneal injection. The subsequent analysis focused on the TLR2/MyD88/NF-κB signaling pathway and the expression of IL-9 in E. granulosus was examined. A co-culture experiment was conducted using mouse mononuclear macrophage cells (RAW264.7) and hepatic stellate cells (HSCs) in the presence of E. granulosus Protein (EgP). The findings indicated elevated levels of IL-9 and TLR2 in patients with CE, with the activation of the signaling pathway significantly increased as the duration of infection progressed. Administration of anti-IL-9 in mice reduced the activation of the TLR2/MyD88/NF-κB signaling pathway, exacerbating liver injury. Moreover, EgP stimulates the TLR2/MyD88/NF-κB signaling pathway, resulting in the synthesis of α-SMA and Collagen I. The data suggest that infection with E. granulosus may stimulate the production of IL-9 through the activation of the TLR2/MyD88/NF-κB signaling pathway, which is mediated by TLR2. This activation stimulates RAW264.7 and HSCs, exacerbating liver injury and fibrosis.

PCSK9 inhibitor effectively alleviated cognitive dysfunction in a type 2 diabetes mellitus rat model.

The incidence of diabetes-associated cognitive dysfunction (DACD) is increasing; however, few clinical intervention measures are available for the prevention and treatment of this disease. Research has shown that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, particularly SBC-115076, have a protective effect against various neurodegenerative diseases. However, their role in DACD remains unknown. In this study, we aimed to explore the impact of PCSK9 inhibitors on DACD. Male Sprague-Dawley (SD) rats were used to establish an animal model of type 2 diabetes mellitus (T2DM). The rats were randomly divided into three groups: the Control group (Control, healthy rats, n = 8), the Model group (Model, rats with T2DM, n = 8), and the PCSK9 inhibitor-treated group (Treat, T2DM rats treated with PCSK9 inhibitors, n = 8). To assess the spatial learning and memory of the rats in each group, the Morris water maze (MWM) test was conducted. Hematoxylin-eosin staining and Nissl staining procedures were performed to assess the structural characteristics and functional status of the neurons of rats from each group. Transmission electron microscopy was used to examine the morphology and structure of the hippocampal neurons. Determine serum PCSK9 and lipid metabolism indicators in each group of rats. Use qRT-PCR to detect the expression levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) in the hippocampal tissues of each group of rats. Western blot was used to detect the expression of PCSK9 and low-density lipoprotein receptor (LDLR) in the hippocampal tissues of rats. In addition, a 4D label-free quantitative proteomics approach was used to analyse protein expression in rat hippocampal tissues. The expression of selected proteins in hippocampal tissues was verified by parallel reaction monitoring (PRM) and immunohistochemistry (IHC). The results showed that the PCSK9 inhibitor alleviated cognitive dysfunction in T2DM rats. PCSK9 inhibitors can reduce PCSK9, total cholesterol (TC), and low-density lipoprotein (LDL) levels in the serum of T2DM rats. Meanwhile, it was found that PCSK9 inhibitors can reduce the expression of PCSK9, IL-1β, IL-6, and TNF-α in the hippocampal tissues of T2DM rats, while increasing the expression of LDLR. Thirteen potential target proteins for the action of PCSK9 inhibitors on DACD rats were identified. PRM and IHC revealed that PCSK9 inhibitors effectively counteracted the downregulation of transthyretin in DACD rats. This study uncovered the target proteins and specific mechanisms of PCSK9 inhibitors in DACD, providing an experimental basis for the clinical application of PCSK9 inhibitors for the potential treatment of DACD.

Variants in the Late Cornified Envelope Gene Locus Are Associated With Elevated T-helper 17 Responses in Patients With Postinfectious Lyme Arthritis.

Postinfectious Lyme arthritis (LA) is associated with dysregulated immunity and autoreactive T- and B-cell responses in joints. Here we explored the role of host genetic variation in this outcome. The frequency of 253 702 single-nucleotide polymorphisms (SNPs) was determined in 147 patients with LA (87 with postinfectious LA and 60 with antibiotic-responsive LA), and for comparison in 90 patients with erythema migrans or the general population (n = 2504). Functional outcome of candidate SNPs was assessed by evaluating their impact on clinical outcome and on immune responses in blood and synovial fluid in patients with LA. Six SNPs associated with late cornified envelope (LCE3) genes were present at greater frequency in patients with postinfectious LA compared to those with antibiotic-responsive LA (70% vs 30%; odds ratio, 2; P < .01). These SNPs were associated with heightened levels of inflammatory Th17 cytokines in serum but lower levels of interleukin 27, a regulatory cytokine, implying that they may contribute to dysregulated Th17 immunity in blood. Moreover, in patients with postinfectious LA, the levels of these Th17 mediators correlated directly with autoantibody responses in synovial fluid, providing a possible link between LCE3 SNPs, maladaptive systemic Th17 immunity, and autoreactive responses in joints. Variation in the LCE3 locus, a known genetic risk factor in psoriasis and psoriatic arthritis, is associated with dysregulated systemic Th17 immunity and heightened autoantibody responses in joints. These findings underscore the importance of host genetic predisposition and systemic Th17 immunity in the pathogenesis of postinfectious (antibiotic-refractory) Lyme arthritis.

Major Adverse Cardiovascular Events: The Importance of Serum Levels and Haplotypes of the Anti-Inflammatory Cytokine Interleukin 10.

Cardiovascular diseases (CVDs) represent major medical and socio-economic challenges worldwide. There is substantial evidence that CVD is closely linked to inflammatory changes triggered by a complex cytokine network. In this context, interleukin 10 (IL-10) plays an important role as a pleiotropic cytokine with an anti-inflammatory capacity. In this study (a substudy of ClinTrials.gov, identifier: NCT01045070), the prognostic relevance of IL-10 levels and IL-10 haplotypes (rs1800896/rs1800871/rs1800872) was assessed regarding adverse cardiovascular outcomes (combined endpoint: myocardial infarction, stroke/transient ischemic attack, cardiac death and death according to stroke) within a 10-year follow-up. At baseline, 1002 in-patients with CVD were enrolled. Serum levels of IL-10 were evaluated utilizing flow cytometry (BD™ Cytometric Bead Array). Haplotype analyses were carried out by polymerase chain reactions with sequence-specific primers (PCR-SSP). In a survival analysis, IL-10 haplotypes were not proven to be cardiovascular prognostic factors in a 10-year follow-up (Breslow test: p = 0.423). However, a higher IL-10 level was associated with adverse cardiovascular outcomes (Breslow test: p = 0.047). A survival analysis considering adjusted hazard ratios (HRs) could not confirm this correlation (Cox regression: adjusted HR = 1.26, p = 0.168). In the present study, an elevated IL-10 level but not IL-10 haplotypes was linked to adverse cardiovascular outcomes (10-year follow-up) in a cohort of CVD patients.

Assessing the impact of opioid-free anesthesia using the modified Mulimix technique on postoperative pain in bariatric surgery patients: a correlative randomized double-blinded trial

Background &amp; objective: The effective management of postoperative pain in bariatric surgery poses significant challenges to the anesthesiologists and the surgeons. Opioids have been the mainstay of postoperative pain management; but recently, opioid-free anesthesia (OFA) has been a popular option in an effort to prevent the opioid related side-effects. The objective of this study was to assess the effects of OFA utilizing the modified mulimix technique on the levels of plasma interleukin-2 (IL-2) and interleukin-6 (IL-6). In addition, the study aimed to evaluate the duration of analgesia and the analgesic requirements during the first 24 hours postoperatively. Methodology: A total of 60 patients were randomly assigned to the OFA Group, which received opioid-free anesthesia, and the OBA Group, which received Opioid-Based Anesthesia. The modified Mulimix technique was used in both groups. Serum samples were collected from all patients during skin incision and after the surgical procedure. Subsequently, these samples were assessed for IL-2 and IL-6 levels. The postoperative analgesic consumption was compared in both groups. Results: Regarding serum IL-2 and IL-6 levels in the two study groups, there was a statistically significant difference after the conclusion of surgery, and the skin incision was made. Regarding the initial rescue analgesia postoperatively assessment, the OBA group demonstrated a substantially greater overall consumption of analgesics within the first 24 h. The study revealed a significant difference in VAS values between the OBA Group and the OFA Group at 2 h, 4 h, and 6 h postoperatively. Conclusion: The modified mulimix technique effectively reduces postoperative plasma inflammatory mediators, interleukin-2 and interleukin-6, and results in decreased postoperative pain, thus reducing the postoperative analgesia consumption Abbreviations: OBA - Opioid based anesthesia; OFA - opioid-free anesthesia; IL-2 - interleukin-2; IL-6 - interleukin-6; VAS - visual analogue scale Keywords: Bariatric surgery, interleukin, Mulimix, opioid, pain, immunological response. Citation: Seyam SHA, Hassan AE, Elsayed MM. Assessing the impact of opioid-free anesthesia using the modified Mulimix technique on postoperative pain in bariatric surgery patients: a correlative randomized double-blinded trial. Anaesth. pain intensive care 2024;28(4):721−726; DOI: 10.35975/apic.v28i4.2516 Received: March 04, 2024; Reviewed: May 18, 2024; Accepted: May 19, 2024

Exploring the potential of IL-10 for risk assessment and early intervention in pediatric ALL

Acute lymphoblastic leukemia (ALL), a leading cause of childhood cancer, targets immune system B and T cells. While understanding its causes is crucial, predicting susceptibility holds immense power for early diagnosis and intervention. This study explored the potential of interleukin 10 (IL-10), a key immune regulator, as a predictive tool in Egyptian children. Investigating 100 ALL patients and 100 healthy controls, we analyzed the IL10 gene polymorphism (-1082 A/G) and serum levels. Strikingly, both the G allele and higher serum IL-10 levels were significantly associated with increased ALL risk (p < 0.05, OR > 1). Moreover, IL-10 emerged as a remarkably accurate predictor, boasting an AUC of 0.995, with a sensitivity of 97% and specificity of 96%. These findings unveil the potential of IL-10 as a powerful predictive tool for pediatric ALL in the studied Egyptian population. Identifying individuals with the GG/AG haplotype and elevated IL-10 levels could enable early intervention and potentially improve outcomes. While further validation in larger and more diverse populations is needed, this study paves the way for personalized risk assessment and potentially revolutionizes how we combat this childhood killer.

Penilumamide, a novel SIRT1 activator, protects UVB-induced photodamages in HaCaT cells

ABSTRACT Ultraviolet-B (UVB) radiation is a major physical factor that induces structural changes in human skin. The aim of this study was to determine whether the novel silent information regulator 1 (sirtuin 1 SIRT1) protein activator, penilumamide, exerted any protective effects against UVB-induced skin damage using human HaCaT keratinocytes as a model. Enzymatic assays were performed to determine the SIRT1-activating ability of penilumamide, which was compared with that of resveratrol, a potent natural product SIRT1 activator with antioxidant and anti-inflammatory properties. Penilumamide markedly activated SIRT1 enzyme activity compared to resveratrol. To further investigate the protective effect of penilumamide against UVB-induced cytotoxicity, HaCaT cells were pretreated with penilumamide (10 μM) for 24 hr followed by irradiation with UVB (40 mJ/cm2). UVB (40 mJ/cm2) irradiation significantly reduced cell viability in a time-dependent manner, whereas pretreatment with penilumamide blocked this effect. Further, penilumamide decreased the levels of intracellular reactive oxygen species (ROS) generated by UVB irradiation in HaCaT cells. Pretreatment with penilumamide also prevented UVB irradiation-induced changes in mitochondrial membrane potential (ΔΨ m). In addition, pretreatment with penilumamide significantly reduced the expression levels of pro-inflammatory cytokines, interleukin (IL)-6, IL-8, and IL-10 and phosphorylation of nuclear factor-kB (NF-kB). These results indicate that penilumamide protects HaCaT cells from UVB-induced inflammation. Taken together data demonstrate that penilumamide exerted protective effects against UVB-induced ROS generation in HaCaT cells. Therefore, penilumamide may be considered to be used as a new SIRT1 activator to protect human keratinocyte against UVB-induced damage.

Interleukin-10 contrasts inflammatory synaptopathy and central neurodegenerative damage in multiple sclerosis.

Proinflammatory cytokines are implicated in promoting neurodegeneration in multiple sclerosis (MS) by affecting excitatory and inhibitory transmission at central synapses. Conversely, the synaptic effects of anti-inflammatory molecules remain underexplored, despite their potential neuroprotective properties and their presence in the cerebrospinal fluid (CSF) of patients. In a study involving 184 newly diagnosed relapsing-remitting (RR)-MS patients, we investigated whether CSF levels of the anti-inflammatory interleukin (IL)-10 were linked to disease severity and neurodegeneration measures. Additionally, we examined IL-10 impact on synaptic transmission in striatal medium spiny neurons and its role in counteracting inflammatory synaptopathy induced by IL-1β in female C57BL/6 mice with experimental autoimmune encephalomyelitis (EAE). Our findings revealed a significant positive correlation between IL-10 CSF levels and changes in EDSS (Expanded Disability Status Scale) scores one year after MS diagnosis. Moreover, IL-10 levels in the CSF were positively correlated with volumes of specific subcortical brain structures, such as the nucleus caudate. In both MS patients' CSF and EAE mice striatum, IL-10 and IL-1β expressions were upregulated, suggesting possible antagonistic effects of these cytokines. Notably, IL-10 exhibited the ability to decrease glutamate transmission, increase GABA transmission in the striatum, and reverse IL-1β-induced abnormal synaptic transmission in EAE. In conclusion, our data suggest that IL-10 exerts direct neuroprotective effects in MS patients by modulating both excitatory and inhibitory transmission and attenuating IL-1β-induced inflammatory synaptopathy. These findings underscore the potential therapeutic significance of IL-10 in mitigating neurodegeneration in MS.