Interleukin Research Articles

The Predictive Role of Inflammatory Biomarkers and Their Correlation with the Biochemical Profile in Patients with Vasculopathy Undergoing Surgery

Inflammation is involved in the pathomechanism of vascular diseases. Pro-inflammatory cytokines are important in perioperative monitoring. The aim of the study was the perioperative assessment of biochemical tests and inflammatory markers in patients with vasculopathy, focusing on the identification of subjects prone to complications. The study was performed between 2020 and 2023 at the Clinical County Hospital in Târgu Mureș on enrolled diabetic and non-diabetic patients with vasculopathy and lower limb surgery (amputation or necrectomy). Pre- and postoperative inflammatory markers, biochemical, and hematological tests (n = 62) were performed. Positive correlation was found between preoperative C-reactive protein (CRP) and interleukin-6 (IL-6) levels, and between preoperative triglyceridemia and glycemia/cholesterolemia. Positive correlation was present between pre- and postoperative values of IL-6, tumor necrosis factor-alfa (TNF-α), CRP, and fibrinogen. Preoperative TNF-α values positively correlated with malondialdehyde (MDA) levels, postoperative TNF-α values with transaminase enzymes. Diabetic patients presented higher IL-6 results compared to non-diabetic subjects. We can conclude that dynamic assessment of inflammatory markers is appropriate for monitoring perioperative course. Half of the subjects presented moderately increased preoperative IL-6 levels, and one quarter had critically high values, which might predict prolonged hospitalization. The assessment of oxidative stress, inflammatory markers and biochemical parameters enables the identification of patients prone to complications, so they can benefit from more complex management.

Harnessing the regenerative potential of interleukin11 to enhance heart repair

Balancing between regenerative processes and fibrosis is crucial for heart repair, yet strategies regulating this balance remain a barrier to developing therapies. The role of Interleukin 11 (IL11) in heart regeneration remains controversial, as both regenerative and fibrotic functions have been reported. We uncovered that il11a, an Il11 homolog in zebrafish, can trigger robust regenerative programs in zebrafish hearts, including cardiomyocytes proliferation and coronary expansion, even in the absence of injury. Notably, il11a induction in uninjured hearts also activates the quiescent epicardium to produce epicardial progenitor cells, which later differentiate into cardiac fibroblasts. Consequently, prolonged il11a induction indirectly leads to persistent fibroblast emergence, resulting in cardiac fibrosis. While deciphering the regenerative and fibrotic effects of il11a, we found that il11-dependent fibrosis, but not regeneration, is mediated through ERK activity, suggesting to potentially uncouple il11a dual effects on regeneration and fibrosis. To harness the il11a’s regenerative ability, we devised a combinatorial treatment through il11a induction with ERK inhibition. This approach enhances cardiomyocyte proliferation with mitigated fibrosis, achieving a balance between regenerative processes and fibrosis. Thus, we unveil the mechanistic insights into regenerative il11 roles, offering therapeutic avenues to foster cardiac repair without exacerbating fibrosis.

Impact of DPP-4 inhibitors on interleukin levels in type 2 diabetes mellitus.

Accumulating evidence had implicated pathological involvement of interleukins (ILs) in progression and complications in patients with type 2 diabetes mellitus (T2DM). Dipeptidyl peptidase-4 inhibitors (DPP-4i) produced favorable effects on glucose homeostasis in T2DM. This study aimed to evaluate the impact of DPP-4i on interleukins (ILs) concentrations in T2DM. PubMed, Embase and the Cochrane library were systematically searched for relevant articles from inception to May 31, 2024. Related searching items were used including DPP-4i, T2DM and randomized controlled trials (RCTs). Placebo- or active agents-controlled human studies were screened. All the RCTs were identified if they provided detailed information on changes of ILs during DPP-4i treatment. A total of 14 RCTs involving 850 participants were identified. Pooled estimates revealed that DPP-4i significantly lower IL-6 concentrations (-0.54 pg/mL, 95% CI, -0.82 to -0.25, I2 = 10%, P = 0.0003) compared to placebo. Similar effects were demonstrated for IL-1β (-16.33 pg/mL, 95% CI, -19.56 to -13.11, I2 = 0%, P<0.00001), whereas the effect on IL-18 was not statistically significant (-13.55 pg/mL, 95% CI, -76.95 to 49.85, I2 = 0%, P = 0.68). Subgroup analysis on IL-6 demonstrated that marked effects were found in groups of basal IL-6 concentrations (< 5 pg/mL), BMI (≥ 28 kg/m2) and type of DPP-4i (linagliptin). DPP-4i favorably decreased concentrations of IL-6 in patients with T2DM. The impact of DPP-4i on IL-1β and IL-18 needed to be explored with more studies. Further trials should be performed to elucidate this anti-inflammatory effect of DPP-4i during treatment of T2DM.

Fertility protective effects of Brillantaisia patula leaf extract against cyclophosphamide-induced ovarian damage in Wistar rats

BackgroundThe primary indication of infertility is the incapacity to conceive, and in females, the majority of instances of female infertility stem from ovulation disorders. This study evaluated the female fertility-enhancing effects and safety of aqueous leaf extract of Brillantaisia patula (ALEBP) in a cyclophosphamide (CYP) model of sterility in Wistar rats.MethodSixty-six female rats randomly allotted to six groups (n = 11) were administered with the appropriate regimen for 21 days and then mated with male rats. Group 1 (control) received distilled water. Groups 2–6 were treated with a single dose (200 mgkg− 1 body weight) of cyclophosphamide intraperitoneally and, in addition, received the same volume (0.5 mL) of distilled water, 18, 36, 72 mgkg− 1 body weight of ALEBP and 200 mg per body weight of vitamin C orally. Mating lasted 11 days; on day 20, the female Wistar rats were sacrificed. Data were analysed using One-way Analysis of Variance (ANOVA) followed by Dunett’s posthoc analysis, and GraphPad (at p < 0.05).ResultsResults herein showed that ALEBP significantly (p < 0.05) increased the diminution in activities/levels of glutathione peroxidase (GPx), reduced glutathione (GSH), total antioxidant capacity (TAC), cholesterol, alkaline phosphatase (ALP), acid phosphatase (ACP), estrogen (ES), and luteinising hormone (LH) induced by cyclophosphamide. ALEBP further reversed the increased level of malondialdehyde (MDA), tumour necrosis factor-α (TNFα), interleukin 8 (IL-8), and follicle-stimulating hormone (FSH) caused by cyclophosphamide (p < 0.05). In addition, ALEBP, while it significantly increased the cyclophosphamide-induced reduction in the number of implantations in each animal, the total number of viable fetuses, the total number of corpora lutea, and the fertility index, also significantly reduced the number of fetal resorptions in each animal and pre-implantation loss that was increased by cyclophosphamide. Moreover, the cyclophosphamide-induced degenerative and necrotic changes in the ovarian cells and uterus were reversed by ALEBP.ConclusionsConsidered as a whole, the aqueous leaf extract of Brillantaisia patula reversed oxidative stress and inflammatory side effects of cyclophosphamide, preserving ovarian function and fertility in the rats. This may suggest its exploration as a safe agent against toxic side effects of chemotherapy and fertility-related disorders of the uterus and ovary.

Cadmium-Induced Hepatotoxicity in Mice – Prophylactic Supplementation of Quercetin Exerts Hepatoprotective Effect by Modulating PI3K/Akt/NF-κB Signaling Pathway

This current study seeks to examine the pre-protective function of Quercetin in Cadmium (Cd)-induced liver damage, along with its modulation of the PI3K/Akt/NF-κB signaling pathway. A total of 60 male C57BL/6J mice were randomly assigned to four groups: control (C), quercetin (Q, 100 mg/kg/day), Cd (Cd, 2.5 mg/kg/day), and quercetin and Cd (Q+Cd). Before receiving Cd treatment, quercetin was administered intragastrically for 4 weeks. In the present study, liver markers, oxidative stress parameters, pro-inflammatory cytokines, liver histopathology, apoptotic markers and PI3K/Akt/NF-κB signaling molecules were examined. We observed that the body weight of the Cd-treated mice dramatically rise after 4 weeks of quercetin pre-administration, and the Cd concentration was significantly decreased. Liver function markers like alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) were significantly reduced in quercetin treatment in Cd-induced mice. Additionally, we observed that quercetin reduced Cd-mediated liver injury in mice by assessing the level of malondialdehyde (MDA), and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH) concentrations and the histological alterations. By monitoring tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), quercetin successfully reduced the inflammatory cytokines that the Cd metal caused in the liver. Additionally, in the liver tissues of Cd-mediated, quercetin could enhance the expression of Bcl-2 and decrease the expression of p-Akt, p-PI3K, Bax, Caspase-9, Caspase-3, NF-κB. In conclusion, quercetin protects against Cd induced liver injury via several pathways, including oxidative stress, inflammation and apoptosis, and its protective effect correlates with antioxidant activity.

Evaluation of mucosal barrier disruption due to Staphylococcus lugdunensis and Staphylococcus epidermidis exoproteins in patients with chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a persistent inflammatory condition of the sinus mucosa. While Staphylococcus aureus has been shown to play a significant role in mucosal barrier disruption in CRS patients, coagulase-negative staphylococci (CoNS) such as Staphylococcus epidermidis and Staphylococcus lugdunensis are also implicated in CRS pathophysiology. This study investigates the effects of exoproteins secreted by planktonic and biofilm forms of clinical isolates of S. epidermidis and S. lugdunensis on the nasal epithelial barrier. Thirty-one clinical isolates of CoNS were grown in planktonic and biofilm forms, and their exoproteins were concentrated. The epithelial barrier structure was assessed by measuring transepithelial electrical resistance (TEER) and the permeability of fluorescein isothiocyanate-dextran. Toxicity and inflammatory response were also studied. Our findings demonstrate that exoproteins from all planktonic forms of S. lugdunensis disrupted the mucosal barrier, whereas only nine of 16 biofilm-derived exoproteins had similar effects. Conversely, 11 of 15 exoproteins from planktonic S. epidermidis significantly disrupted barrier integrity; however, biofilm exoproteins did not. The study also showed that some exoproteins from planktonic S. epidermidis significantly reduced cell viability, while exoproteins from planktonic and biofilm forms of S. lugdunensis and biofilm S. epidermidis did not induce any statistically significant change in cell viability. Notably, four of 16 biofilm exoproteins from S. lugdunensis induced higher interleukin-6 (IL-6) secretion, whereas none of the S. epidermidis isolates showed a significant increase in IL-6 secretion. Our results suggest that CoNS exoproteins may contribute to CRS etiopathogenesis.

IL1RAP Blockade With a Monoclonal Antibody Reduces Cardiac Inflammation and Preserves Heart Function in Viral and Autoimmune Myocarditis.

Currently, there are no therapies targeting specific pathogenic pathways in myocarditis. IL (interleukin)-1 blockade has shown promise in preclinical studies and case reports. We hypothesized that blockade of IL1RAP (IL-1 receptor accessory protein), a shared subunit of the IL-1, IL-33, and IL-36 receptors, could be more efficient than IL-1 blockade alone. We induced coxsackievirus B3 (CVB3)-mediated or experimental autoimmune myocarditis (EAM) in BALB/c mice, followed by treatment with an Fc (fragment crystallizable)-modified mIgG2a mouse anti-mouse IL1RAP monoclonal antibody (mCAN10). Myocarditis severity and immune infiltration were assessed by histology and flow cytometry. Cardiac function was measured by echocardiography. We used spatial transcriptomics (Visium 10× Genomics) to compare the gene expression landscape in the hearts of mCAN10-treated versus control mice. IL1RAP blockade reduced CVB3 and EAM severity. In EAM, the treatment prevented deterioration of cardiac function, measured on day 42 post-disease induction (left ventricular ejection fraction: 56.5% versus 51.0% in isotype controls [P=0.002] and versus 51.4% in mice treated with anti-IL-1β antibodies alone [P=0.003]; n=10-11 mice per group). In the CVB3 model, mCAN10 did not impede viral clearance from the heart and significantly lowered the numbers of CD4+ (cluster of differentiation 4) T cells (P=0.025), inflammatory Ly6C+CCR2+ (lymphocyte antigen 6 complex, locus C/C-C motif chemokine receptor 2) monocytes (P=0.038), neutrophils (P=0.001) and eosinophils (P<0.001) infiltrating the myocardium. The spatial transcriptomic analysis revealed reduced canonical IL-1 signaling and chemokine expression in cardiac immune foci in CVB3-infected mice treated with IL1RAP blockade. Blocking IL1RAP reduces acute CVB3 myocarditis and EAM severity and preserves cardiac function in EAM. We conclude that IL1RAP blockade is a potential therapeutic strategy in viral and autoimmune myocarditis.

Deficiency of muscle-generated brain-derived neurotrophic factor causes inflammatory myopathy through reactive oxygen species-mediated necroptosis and pyroptosis

Idiopathic inflammatory myopathy (commonly known as myositis) is a group of immune-related diseases characterized by muscle damage, weakness, and fatigue with unknown causes. Although overactivated innate immunity is a widely believed cause of myositis onset, the mechanism that provokes and maintains a high immune response in myositis patients is still unclear. This study aims to test if brain-derived neurotrophic factor (BDNF) deficiency per se is sufficient to cause myositis and determine its underlying mechanism. We found that ablating BDNF production in skeletal muscle is sufficient to trigger myositis development in mice. Muscle-specific Bdnf knockout (MBKO) mice displayed extensive myocyte necrosis, mononuclear cell infiltration, and myophagocytosis. In association with these damages, elevated production of pro-inflammatory cytokines such as interleukin (IL) 23, IL-1β, IL-18, and tumor necrosis factor α (TNFα) was found in the muscle of MBKO mice. Disruption of sarcolemma integrity was also detected in MBKO mice, which is a result of necroptosis executioner Mixed lineage kinase domain-like protein (MLKL) and pyroptosis executioner Gasdermin D (GSDMD) activation. Mechanistically, diminishing BDNF synthesis in myotubes enhances the accumulation of mitochondrial reactive oxygen species (mtROS), which sensitizes the cells towards TNFα-induced receptor-interacting protein kinase (RIPs) activation and promotes the formation of NLR family pyrin domain containing 3 (NLRP3)-containing inflammasome. BDNF deficiency-induced cell death could be alleviated by scavenging mtROS, suppressing the activity of GSDMD, or inhibiting receptor-interacting kinase 3 (RIP3). Similarly, supplementation of BDNF mimetics, suppression of RIP3 activity, increasing the intramyocellular antioxidant, or enhancing mitophagy ameliorated the myopathies of MBKO mice and improved their muscle strength. Together, our study demonstrates that insufficient BDNF production in mouse muscle causes the development of pathological features of myositis via enhancing oxidative stress, necroptosis, and pyroptosis in myofibers.

Genetically predicted serum ferritin mediates the association between inflammatory cytokines and non-alcoholic fatty liver disease

ObjectiveInvestigating the causal relationship between inflammatory cytokines and Non-alcoholic fatty liver disease(NAFLD) and identifying and quantifying the role of serum ferritin as a potential mediator.MethodsGenetic summary statistics were derived from open genome-wide association study (GWAS) databases. We conducted a two-sample Mendelian randomization (MR) analysis to investigate the relationship between inflammatory cytokines (8,293 individuals) and NAFLD (8,434 cases, 770,180 controls). Furthermore, we used two-step MR to quantitate the proportion of the effect of serum ferritin-mediated inflammatory cytokines on NAFLD. In this study, we primarily utilized inverse-variance-weighted Mendelian randomization (MR-IVW) and reverse MR analysis methods, while other methods were also performed for sensitivity analysis, false discovery rate (FDR) &amp;lt;0.0012 as statistical significance in MR analyses.ResultsOur results indicated that high levels of Eotaxin, regulated upon activation normal T cell expressed and presumably secreted(RANTES), Interleukin-2(IL-2), macrophage migration inhibitory factor(MIF), tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) and Stem cell factor(SCF) were associated with increased risks of NAFLD, while high Cutaneous T cell-attracting chemokine(CTACK) and Interleukin-16(IL-16) levels that reduced the risk of NAFLD.The proportion of genetically predicted NAFLD mediated by ferritin was 2.1%(95% CI = 1.39%−5.61%).ConclusionIn conclusion, our study identified a causal relationship between inflammatory cytokines and NAFLD, with a small proportion of the effect mediated by ferritin, but a majority of the effect of inflammatory cytokines on NAFLD remains unclear. Further research is needed on additional risk factors as potential mediators.

Evaluating the Diagnostic and Prognostic Value of Interleukin-6 (IL-6) and Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) in Systemic Inflammatory Response Syndrome (SIRS) and Sepsis in Adults

Evaluating the Diagnostic and Prognostic Value of Interleukin-6 (IL-6) and Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) in Systemic Inflammatory Response Syndrome (SIRS) and Sepsis in Adults

A highly sensitive and selective label-free impedimetric immunosensor for the detection of interleukin-6 based on AuNPs@pDA@NiCo2S4@MoS2 nanocomposite.

A highly sensitive and selective label-free impedimetric immunosensor based on AuNPs@pDA@NiCo2S4@MoS2 nanocomposite modified on the surface of a screen-printed electrode (SPE) was designed for the detection of interleukin-6 (IL-6). The distribution of NiCo2S4 nanoparticles on MoS2 nanosheets was able to prevent them from agglomerating. The polydopamine (pDA) layer was coated on the surface of NiCo2S4@MoS2 nanosheets by self-polymerization, which improved the stability and biocompatibility of the nanomaterial. The excellent reduction ability of pDA promoted the synthesis of gold nanoparticles (AuNPs), which increased the amount of antibody adsorption and the conductivity of the material. Finally, the antibody (Ab) of IL-6 was immobilized on the surface of AuNPs@pDA@NiCo2S4@MoS2 nanocomposite. Electrochemical impedance spectroscopy (EIS) was used to detect the change of impedance before and after the immune response between Ab and IL-6 antigen (IL-6). Under the optimal experimental conditions, the relative change in impedance and the logarithmic concentration of IL-6 showed a good linear relationship in the range 1.00 to 1.00 × 106pg/mL, with a low detection limit of 0.97pg/mL. In addition, the proposed immunosensor performed with good reproducibility, stability, and specificity. It was successfully applied to the determination of IL-6 in patient's serum samples of head and neck carcinoma with recoveries of 98.40% to 106.5%. To sum up, the proposed label-free impedimetric immunosensor was successfully constructed for IL-6 detection in real samples.

Chemical analysis, antibacterial and anti-inflammatory effect of Achillea fragrantissima essential oil growing wild in Egypt

BackgroundAchillea fragrantissima (F. Asteraceae) is traditionally used to treat skin infections and inflammation. The present work intended to prepare essential oils (EOs) from A. fragrantissima aerial parts growing widely in Egypt and investigate its antibacterial activity against skin-related pathogens and in vitro cell-based anti-inflammatory activity.MethodsEOs of the fresh aerial parts were extracted by hydrodistillation (HD), microwave-assisted hydrodistillation (MAHD), and head-space (HS), while those of the dried ones were prepared by supercritical fluid (SF). The result EOs were analyzed using GC/MS. The antibacterial activity was evaluated alongside Pseudomonas aeruginosa ATCC 9027, Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 25923, Streptococcus pyogenes ATCC 12344, Clostridium perfringens ATCC 13124 by agar diffusion, microwell dilution, and biofilm formation tests. The anti-inflammatory activity was evaluated by measuring tumor necrosis factor-alpha (TNF-α), interleukin 2 (IL-2), and 6 (IL-6) in lipopolysaccharides (LPS)- stimulated RAW 264.7 cells using ELISA assays in addition, expression of nitric oxide synthase (iNOS) was measured via western blot.ResultsThe SF method gave the highest EO yield (1.50 mL v/w). Oxygenated components constituted the highest percentage in the four methods, 84.14, 79.21, 73.29 and 33.57% in the HS, HD, MAHD, and SF, respectively. Moreover, variation in the amount of identified compounds was apparent; in HS EO α-thujone (29.37%), artemisia ketone (19.59%), and santolina alcohol (14.66%) are major components, while α-thujone (20.38%) and piperatone (12.09%) were significant in HD. Moreover, ( +)-spathulenol (12.22%) and piperatone (10.48%) were significant in MAHD, while piperatone (14.83%) and β-sitosterol (11.07%) were significant in SF EO. HD, MAHD, and SF EOs exhibited susceptibility against P. aeruginosa (IZ = 9–14 mm), E. coli (11–13 mm), and C. perfringens (IZ = 10–14 mm) in agar diffusion assay. MAHD EOs demonstrated potent growth inhibition (MICs = 0.25–2 mg/mL), followed by HD EOs (MICs = 13–52 mg/mL) to all tested microorganisms in well microdilution assay. Also, they exert MBC values equal to or higher than the MICs. Furthermore, SF EOs inhibited the biofilm formation of all tested microorganisms by 65.12—80.84%. Specifically, MAHD and HD EOs efficiently suppress the biofilm of S. pyogenes (77.87%) and P. aeruginosa (60. 29%), respectively. Ultimately, HD and SF EOs showed anti-inflammatory activity by suppressing the TNF-α, IL-2, and IL-6 release and iNOS expression in LPS-stimulated RAW 264.7 macrophages.ConclusionA. fragrantissima EO is rich in oxygenated volatile compounds with antibacterial and anti-inflammatory activities. It is encouraged as a bioactive agent for adjusting skin infections, though additional studies are essential for their safety in clinical settings.

Effect of reduced saturation and elevated D-dimer and interleukin 6 levels on vessel density and foveal avascular zone in patients with COVID-19 bilateral pneumonia.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can affect multiple organs, including the eyes. This study aimed to identify associations between vascular density (VD) and the foveal avascular zone (FAZ), assessed using optical coherence tomography angiography (OCTA), and baseline levels of D-dimers and interleukin 6 (IL-6) in patients with bilateral COVID-19 pneumonia, depending on oxygen saturation (SpO2) on admission. The study included patients with COVID-19 bilateral pneumonia due to SARS-CoV-2 infection who were hospitalized between March and May 2021. Ophthalmological examination was performed 2 months after hospitalization. Optical coherence tomography angiography was used for the automatic assessment of the central retinal VD and the manual assessment of FAZ. A significant monotonic negative relationship was observed between SpO2 . 90% and VD in some areas of the superficial capillary plexus (SCP) (p = 0.048) and choriocapillaris (p = 0.021), and the mean VD in the deep capillary plexus (DCP) (p = 0.048). No significant monotonic negative relationship was noted between SpO2 . 90% and the FAZ in the SCP (p = 0.075). However, there was a significant monotonic positive relationship between VD in the nasal choriocapillaris and D-dimer levels in patients with SpO2 . 90% (p = 0.003, respectively). Finally, a monotonic negative relationship was identified between foveal VD in the DCP and IL-6 levels in patients with SpO2 . 90% (p = 0.027). An OCTA study conducted 2 months after hospitalization for COVID-19 bilateral pneumonia showed reduced VD in those with SpO2 . 90% and elevated levels of D-dimers and IL-6 during hospitalization. Optical coherence tomography angiography testing can provide monitoring of ocular status in patients following SARS-CoV-2 infection, especially those who report visual disturbances.

Inter-alpha Inhibitor Proteins Modulate Microvascular Endothelial Components and Cytokines After Exposure to Hypoxia-Ischemia in Neonatal Rats.

Inter-alpha inhibitor proteins (IAIPs) are neuroprotective and attenuate lipopolysaccharide (LPS)-mediated blood-brain barrier (BBB) disruption in neonatal rodents. We investigated some mechanism(s) fundamental to neuroprotection by IAIPs including changes in cerebral endothelial components and inflammation. Postnatal day-7 rats exposed to sham surgery and placebo or carotid ligation plus 8% FiO2 (90min) were given IAIPs (30 or 60mg/kg) or placebo and were killed 6, 12, 24, or 36h after hypoxia-ischemia (HI). Proteins regulating BBB permeability to leukocytes (vascular cell adhesion molecule 1, VCAM-1), lipid-soluble (P-glycoprotein, PGP), and lipid-insoluble molecules (zonula occludens-1, ZO-1) were measured by immunoblot, and cytokines were measured in serum and cortex. HI resulted in reductions in ZO-1 and increases in VCAM-1, PGP, interferon-γ (IFN-γ), interleukin-12 (IL-12), vascular endothelial growth factor (VEGF), IL-α, and macrophage colony-stimulating factor (M-CSF) in cortex and increases in IL-4, IL-5, IL-10, and granulocyte colony-stimulating factor (G-CSF) in serum. IAIPs attenuated the reductions in ZO-1 and delayed increases in VCAM-1 and PGP in cortex and attenuated increases in cytokines in serum (IL-4, IL-5, IL-10, IFN-γ, G-CSF) and cortex (IL-1α, IL-12, IFN-γ, VEGF, M-CSF) after HI. We conclude that vascular endothelial proteins and cytokines exhibit sequential changes after HI and IAIPs modulate some of these HI-related changes in neonatal rats.

Ameliorating Immune-dependent Inflammation and Apoptosis by Targeting TLR4/MYD88/NF-ᵰ5B Pathway by Celastrol Mitigates the Diabetic Reproductive Dysfunction.

This study aimed to examine the protective effect of celastrol on testicular dysfunction in diabetic rats and the potential underlying mechanisms. All rats included in the study were divided into four groups: a control group treated with sodium citrate buffer and vehicle), a celastrol-treated control group, a streptozotocin (STZ)-induced diabetic group following insulin resistance, and a celastrol-treated diabetic group. Serum glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol, interleukin (IL)-1β, tumor necrosis factor-alpha, and testosterone levels were measured. In addition, the levels of testicular homogenate superoxide dismutase and malondialdehyde were assessed. Furthermore, testicular tissue relative TLR4, NF-ᵰ5B, and MYD88 expression were quantitatively measured using polymerase chain reaction. Histopathological and immunohistochemical studies were also conducted. The results revealed that treatment with celastrol significantly reduced TLR4, MyD88, NF-ᵰ5B expressions and the levels of inflammatory mediators such as tumor necrosis factor-alpha and IL-1ᵯD in the testicular tissue of treated rats. These findings suggest has the potential to be effective in the treatment of diabetes-induced testicular injury by inhibiting testicular inflammation, apoptosis, and oxidative stress.

Promotion of a quality standard for Scutellariae radix based on the anti-inflammatory efficacy-oriented quality marker of the effect-constituent index.

The quality control of herbal medicines is key to their clinical efficacy. The multi-component and multi-effect characteristics of herbal medicines have prompted scholars to clarify various factors related to quality evaluation through various methods. Nevertheless, the relationship between chemical properties and their associated clinical efficacy is little reflected in the quality control techniques currently in use. To address the issue, a novel herbal quality standard system based on the efficacy-oriented Q-marker of the effect-constituent index (ECI) is promoted in this study, using Scutellariae Radix (SR), a widely used herbal medicine with anti-inflammation, anti-tumor, anti-viral and other therapeutic effects, as a case study. Combined with chromatographic analysis and bioassay, four Q-markers including baicalin, baicalein, wogonin and oroxylin A were selected based on the anti-inflammatory efficacy of SR. The ECI model of SR was constructed by combining the content determination of the Q-markers via ultra-high-performance liquid chromatography-triple quadrupole mass spectroscopy (UHPLC-QqQ-MS/MS) with the corresponding biological potency obtained from the anti-inflammatory effects on tumor necrosis factor (TNF)-α and interleukin (IL)-6 production. Correlation analysis showed that the ECI was significantly correlated with the measured anti-inflammatory activity (p < 0.01). The ECI exhibited a good ability to determine and predict the bioeffect-based quality grade for SR. Overall, the construction and application of the ECI for SR in this study provides a beneficial reference for quality evaluation methods of other herbs with distinct effects and active ingredients.

Concomitant parasite infections influence tuberculosis immunopathology and favor rapid sputum conversion of pulmonary tuberculosis patients

Immunopathology of human tuberculosis (TB) in a subgroup of patients is characterized by aberrantly high concentrations of inflammatory cytokines, for example Interleukin (IL)-6. Concomitant (co-)infections by parasites can affect host immunity, but the impact on immunopathology in TB patients is poorly defined. Here we characterized a group of patients with TB ( n = 76) from Ghana with different protozoan and helminth co-infections. Plasma cytokines were measured at the onset of disease and anti-mycobacterial treatment efficacy was monitored during disease course. A subgroup of TB patients had co-infections with protozoan (n = 19) or helminth (n = 16) parasites. Plasma analyses for candidate cytokines identified lower levels of IL-6 in parasite co-infected patients with TB. Moreover, it took less time for co-infected patients to become sputum-negative for Mycobacterium tuberculosis during treatment. These results indicated an influence of parasite co-infections on immunopathology in TB and suggested positive effects on treatment efficacy.

Associations Between Interleukin-10 Polymorphisms and Susceptibility to Sjögren's Syndrome: A Meta-Analysis.

This study sought to investigate the association between interleukin-10 (IL10) polymorphisms and susceptibility to Sjögren's syndrome. A systematic search of the Medline, Embase and Web of Science databases was conducted to identify relevant articles from inception to April 2024. No restrictions were placed on race, ethnicity or geographic area, but only studies published in English were included. A meta-analysis was conducted to evaluate the association among the IL10-1082 G/A (rs1800896), -819 C/T (rs1800871) and -592 C/A (rs1800872) polymorphisms, as well as their haplotypes and the risk of developing Sjögren's syndrome. The included studies involved 998 Sjögren's syndrome patients and 1576 controls. Ten studies were included in the meta-analysis. Meta-analysis of the IL10-1082 G/A polymorphism revealed no significant association with Sjögren's syndrome (odds ratio [OR]=1.115, 95% confidence interval [CI]: 0.888-1.401, p=0.343), with stratification by ethnicity yielding consistent results for Europeans and Latin Americans. Similarly, the IL10-819 C/T polymorphism was not associated with Sjögren's syndrome in any study subjects (OR=0.859, 95% CI: 0.648-1.138, p=0.290). The IL10-592 C allele also exhibited no association with Sjögren's syndrome (OR=1.131, 95% CI: 0.776-1.646, p=0.522). However, the GCC carrier status demonstrated a significant association with Sjögren's syndrome across all study subjects (OR=1.496, 95% CI: 1.200-1.865, p<0.001), particularly in Europeans (OR=1.444, 95% CI: 1.085-1.921, p=0.012) and Latin Americans (OR=1.324, 95% CI: 1.115-2.366, p=0.012). A significant protective effect of the homozygous ATA/ATA haplotype on Sjögren's syndrome was found in Europeans (OR=0.320, 95% CI: 0.121-0.846, p=0.022). This meta-analysis indicates a significant link between carrying the GCC haplotype of the IL10-1082 G/A, -819 C/T and -592 C/A polymorphisms and an increased susceptibility to Sjögren's syndrome. Conversely, the homozygous ATA/ATA haplotype appears to confer protection against the risk of Sjögren's syndrome, particularly in European populations.

SYNERGISTIC POTENTIAL OF NIGELLA SATIVA L. AND TRIGONELLA FOENUM-GRAECUM: INTEGRATED NETWORK PHARMACOLOGY FOR DIABETIC WOUND HEALING

Objective: Diabetes Mellitus (DM) is a metabolic disorder marked by elevated blood glucose levels, and one of the issues linked to DM involves the development of Diabetic Wounds (DW). DW is susceptible to infection and develops into chronic wounds if not treated properly. This study aimed to investigate the network pharmacology of N. sativa L. and T. foenum-graecum, emphasizing on their potential as DW treatment candidates. Methods: Various databases were used in this study, including PubChem, Dr. Duke's phytochemistry and Ethnobotany, and KNApSAcK Family. Swiss Target Prediction and Way2Drug PASS Online were utilized for biological activity and protein target prediction. The DW pathway's protein-protein interactions were examined with the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene Cards, and STRING databases. STRING was used to predict the metabolite's action. The relationship between metabolites and target proteins was predicted using STITCH, and Cytoscape was used to visualize the network. Result: The results showed that ten active ingredients (five active ingredients in N. sativa L. and five active ingredients in T. foenoem-graecum) contributed to DW healing by affecting Tumor Necrosis Factor (TNF), Interleukin-1beta (IL1B), JUN, Caspase 3 (CASP3), Interleukin-6 (IL-6), Alpha Kinase Threonine-1 (AKT1), Vascular Endothelial Growth Factor-A (VEGFA), and Mitogen-Activated Protein Kinase 3 (MAPK3) genes. Furthermore, the ten active ingredients correlated with twenty-eight intracellular proteins, resulting in a mechanism involving eight DW signalling pathways. Conclusion: Based on network pharmacology analysis, we determine that N. sativa L. and T. foenoem-graecum combination can potentially treat DW.

Epigenetic Mechanisms of the Anti-inflammatory Action of the Opioid Peptide Leutragin: Role of Sirtuin 1

Sirtuin 1 (SIRT1) is a class III histone deacetylase that plays a key role in resolving inflammation through known epigenetic mechanisms involving histone and nuclear factor κB (NF-κB) deacetylation. Deacetylation reduces the transcriptional activity of NF-κB and the associated production of pro-inflammatory cytokines such as interleukin 1β (IL-1β), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). In the present study, we show for the first time that biomodeling of acute lung inflammation by a single injection of lipopolysaccharide (LPS) induces synchronous oscillations of mRNA levels of cytokines IL-1β, TNF-α, IL-6 and SIRT1 deacetylase in the lungs, the maximum amplitudes of cytokine mRNA oscillations are observed between 1.5 and 5 hours, whereas high levels of SIRT1 mRNA are observed up to 24 hours, when cytokine mRNA oscillations have already faded, which is consistent with the hypothesis about the role of SIRT1 as a factor acting in the phase of inflammation resolution. The study shows that the mechanism of anti-inflammatory action of inhaled hexapeptide Leutragin, a δ-opioid receptor agonist, is related to its ability to increase SIRT1 mRNA expression and decrease the amplitudes of IL-1β, TNF-α, and IL-6 mRNA oscillations in the lungs, which generally leads to the resolution of inflammation in the conditions of biomodeling of acute lung inflammation.