Interleukin Research Articles

Interleukin 29 is a novel antiangiogenic factor in angiogenesis.

Angiogenesis is tightly controlled by growth factors and cytokines in pathophysiological settings. Despite the importance of Interleukin 29 (IL-29), a newly identified cytokine of type III interferon family, its role in angiogenesis remains unknown. We aimed to elucidate IL-29's impact on angiogenesis under both and physiological and pathological conditions. We employed various assays to evaluate IL-29's effect on proliferation, apoptosis, migration and tube formation of human umbilical vein endothelial cells (HUVEC) in vitro. IL-29's angiogenic effect was assessed using mouse aortic rings ex vivo, and oxygen-induced retinopathy (OIR) mouse model in vivo. Signaling pathways possibly involved in IL-29-induced angiogenesis were investigated by Western blot. Finally, IL-29's impact on tube formation was blocked by inhibiting IL-29/interleukin 10 receptor 2 (IL-10R2) binding. IL-29 treatment inhibited endothelial cell migration, tube formation and vessel sprouting, without affecting proliferation or apoptosis. Notably, IL-29 (100ng/ml) attenuated vessel growth in pathological angiogenesis in OIR mice, accompanied by decreased expression of vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1α (HIF-1α). Mechanistically, IL-29 activated Stat3 signaling pathway, and blocking IL-29/IL-10R2 binding remarkably reversed IL-29's anti-angiogenic effect on tube formation. Our findings demonstrated that IL-29, at a relative low concentration, modulates angiogenesis in both physiological and pathological contexts. Targeting IL-29 or its receptor IL-10R2 offers a promising strategy for angiogenesis regulation in various conditions.

Effect of ketorolac on serum GDF-15 and IL-8 in patients with pancreatic cancer with cachexia.

713 Background: Cancer cachexia deteriorates the quality of life, chemotherapy tolerance and survivability of pancreatic cancer (PC) patients. Although a prevalent condition affecting PC patients, there are no approved therapies for cachexia and its mechanism of action is poorly understood. Elevated growth differentiation factor 15 (GDF-15), a stress-induced cytokine, has been associated with the pathogenesis of cachexia. Similarly, prior studies have displayed positive correlations between the proinflammatory factor interleukin-8 (IL-8) and PC cachexia. This abstract focuses on the exploratory endpoints (serum GDF-15 and IL-8 levels) of a feasibility trial on ketorolac as a treatment for PC cachexia. Methods: Patients took ketorolac 10 mg PO QID for 5 consecutive days, with weights measured on Day 1 (D1) and Day 6 (D6). Serum cytokines were drawn on D1 and D6. IL-8 was measured using a HDF15 assay (Eve Technologies). GDF-15 was measured using a human R-plex GDF-15 assay. Activity (e.g., number of steps) was measured via Fitbit. Differences in weight, activity, GDF-15, and IL-8 were analyzed using two-sample paired t-tests. Results: Twenty-nine patients were enrolled, of which 19 were evaluable. Median age was 70, 47.4% (9/19) were female, and 94.7% (18/19) were adherent with ketorolac. Statistically significant increases in both weight per baseline BMI and activity were observed from D1 to D6 (0.0716±0.1079 kg/BMI, p=0.012; 1423±2477 steps, p=0.0221). Of the 19 evaluable patients, 16 patients provided complete D1 and D6 pairs of serum cytokines. From D1 to D6, the mean GDF-15 level decreased by 277.5 pg/mL (p=0.529) and mean IL-8 decreased by 65.13 pg/mL (p=0.103). In all patients who gained weight (n=14), a trend toward reduced IL-8 from D1 to D6 was observed (79.57±39.57 pg/mL, p=0.065). Similarly, for patients who gained ≥ 1-kg from D1 to D6 (n=10), a trend toward reduced GDF-15 was observed (951.2±482.3 pg/mL, p=0.080). Patients with increased activity from D1 to D6 (n=12) had mean reductions of 157.7 pg/mL (p=0.643) and 70.17 pg/mL (p=0.179) in GDF-15 and IL-8, respectively. Conclusions: Given the growing literature suggesting associations between inflammatory cytokines and cancer cachexia, it is critical to investigate treatments that may possibly alter cytokine levels. Although our findings suggest that ketorolac aids in weight gain and increased activity, larger sample sizes are needed to determine whether these differences are related to reductions of specific serum cytokines. However, given reductions that trended towards significance for both GDF-15 and IL-8 serum levels within subsets of patients that gained weight on ketorolac, further studies investigating these cytokines are warranted to hopefully provide insight on the mechanistic action of ketorolac in cachexia. Clinical trial information: NCT05336266 .

The primiparous IgA and IL-5 colostrum concentration based on maternal factor: corroborate the inflammation pathways to IgA colostrum synthesis.

Immunoglobulin A (IgA) plays a crucial role in the maturation the neonatal mucosal barrier. The accumulation of IgA antibody-secreting cells (ASCs) in the lactating mammary gland facilitates the secretion of IgA antibodies into milk, which are then passively to the suckling newborn, providing transient immune protection against gastrointestinal pathogens. Physiologically, full-term infants are unable to produce IgA, required for mucosal barrier maturation for at least 10 days after birth. Prior studies declare that interleukin 5 (IL-5) responsible to encourage of IgA-producing B cells maturation during lactating periods. This purpose of this study was determine IgA and IL-5 colostrum concentration based on maternal factors. Ninety primiparous with full-term pregnancy and vaginal delivery were enrolled in a cross-sectional study. Colostrum samples were collected on the first day after delivery, followed by the measurement of IgA and IL-5 concentrations using ELISA. Sociodemographic and maternal factors were recorded based on participants' self-reports using a questionnaire. The results showed that mean of colostrum IgA concentration in primiparous 24.9 ± 0.3 years old (95%CI: 24.3-25.6) was 1.51 ± 0.15µg/mL, while colostrum IL-5 concentration was 82.37 ± 20.2pg/mL. The results showed that IgA levels were not significantly correlated with age, education, occupation, weight, height, body mass index (BMI), fish consumption, or smoking habits but were significantly related to baby sex disappointment and weight gain during pregnancy (P<.05). Meanwhile, the IL-5 concentration was significantly correlated with smoking habits, baby's birth weight, and maternal age. The composition of IgA and IL-5 in breast milk is strongly associated with several maternal factors including baby sex disappointment, weight gain during pregnancy, smoking habits, baby's birth weight, and maternal age. This maternal factor corroborate the recently evidence refer to inflammatory pathways involvement in colostrum IgA synthesis.

Exploring the mechanism and crosstalk between IL-6 and IL- 1β on M2 macrophages under metabolic stress conditions.

Macrophages are highly variable immune cells that are important in controlling inflammation and maintaining tissue balance. The ability to polarize into two major types-M1, promoting inflammation, and M2, resolving inflammation and contributing to tissue repair-determines their specific roles in health and disease. M2 macrophages are particularly important for reducing inflammation and promoting tissue regeneration, but their function is shaped mainly by surrounding cells. This is evident in obesity, diabetes, and chronic inflammation. Although many cytokines regulate macrophage polarization, interleukin-6 (IL-6) and interleukin-1β (IL-1β) are major players, but their effects on M2 macrophage behavior under metabolic stress remain unclear. This study describes the intricacies within M2 macrophages concerning IL-6 and IL-1β signaling when under metabolic stress. Though, more frequently than not, IL-6 is labelled as pro-inflammatory, it can also behave as an anti-inflammatory mediator. On the other hand, IL-1β is the main pro-inflammatory agent, particularly in metabolic disorders. The relationship between these cytokines and the macrophages is mediated through important pathways such as JAK/STAT and NFκB, which get perturbed by metabolic stress. Therefore, metabolic stress also alters the functional parameters of macrophages, including alterations in mitochondrial metabolism, glycolytic and oxidative metabolism. Phosphorylation alters the kinetics involved in energy consumption and affects their polarization and their function. However, it has been suggested that IL-6 and IL-1β may work in concert or competition when inducing M2 polarization and, importantly, implicate cytokine release, phagocytic activity, and tissue repair processes. In this review, we discuss the recent literature on the participation of IL-6 and IL-1β cytokines in macrophage polarization and how metabolic stress changes cytokine functions and synergistic relations. A better understanding of these cytokines would serve as an important step toward exploring alternative antiviral strategies directed against metabolic disturbance and, hence, approve further endeavors.

Effects of initial periodontal therapy on the formation of neutrophil extracellular traps in gingival crevicular fluid in patients with severe periodontitis.

This study aimed to observe the effects of initial periodontal therapy on the level of neutrophil extracellular traps (NETs) in gingival crevicular fluid (GCF) of patients with severe periodontitis and to analyze the factors related to the formation of NETs. Thirty-one patients with stage Ⅲ-Ⅳ periodontitis were recruited. Clinical periodontal parameters, including plaque index (PLI), gingival index (GI), probing depth (PD), and clinical atta-chment loss (CAL), were recorded before and 6-8 weeks after initial periodontal therapy. Levels of NETs in GCF were detected by immunofluorescence staining. Quantities of total bacteria, Porphyromonas gingivalis (P. gingivalis), Aggregatibacter actinomycetemcomitans (A. actionomycetemcomitans) and Prevotella intermedia (P. intermedia)in unattached subgingival plaque were determined by real-time quantitative PCR, and levels of tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) in GCF were explored by enzyme-linked immunosorbent assay. In addition, the correlations between the level of NETs and the above indicators were analyzed. After initial periodontal therapy, the level of NETs in GCF, PLI, GI, PD, and CAL; quantities of total bacteria, P. gingivalis, A. actinomycetemcomitans, and P. itermedia; and levels of IL-8 and TNF-α significantly decreased (P<0.05). We observed strong positive correlations between the level of NETs and PLI, GI, PD, CAL, the amount of total bacteria, P. gingivalis, TNF-α, and IL-8 (P<0.05). Initial periodontal therapy might decrease the level of NETs in GCF from patients with severe periodontitis, which might be positively correlated with the quantities of P. gingivalis andthe levels of TNF-α and IL-8 in GCF.

Predicting Delirium in Older Adults with Community-Acquired Pneumonia: A Retrospective Analysis of Stress Hyperglycemia Ratio and Its Interactions with Nutrition and Inflammation

BackgroundCommunity-acquired pneumonia (CAP) increases mortality risk in older patients, often complicated by delirium. Key risk factors include malnutrition and glucose metabolism disorders. This study examines the Stress Hyperglycemia Ratio (SHR) as a predictive marker for delirium in older CAP patients and its role in clinical risk management. MethodsIn this retrospective study, we analyzed patients aged 65 and older diagnosed with CAP at the Second People's Hospital of Lianyungang. Delirium was evaluated using the Confusion Assessment Method (CAM) based on DSM-5 criteria. We assessed clinical data, including nutritional status, SHR, and Interleukin-6 (IL-6) levels. Nutritional status was measured using the Mini Nutritional Assessment Short Form (MNA-SF). Statistical analyses including logistic regression, Receiver Operating Characteristic (ROC) analysis, and mediation analyses were used to ascertain the predictive value of SHR and its interaction with other delirium risk factors. ResultsThe average age of the cohort was 84.20 ± 5.15 years, with a delirium incidence of 19.68% and a 28-day mortality rate of 11.16%. Both SHR and IL-6 were significant risk factors for delirium, while higher MNA-SF scores were protective. An SHR of 1.12 or greater indicated an elevated risk of delirium. Combined assessments of SHR, IL-6, and MNA-SF enhanced predictive accuracy, achieving an AUC of 0.723. SHR and IL-6 independently and synergistically influenced the relationship between nutritional status and delirium onset. ConclusionSHR is a crucial risk factor for delirium in older CAP patients, interacting with nutritional and inflammatory markers. Integrating SHR with nutritional and inflammatory assessments can enhance early risk identification and improve clinical outcomes for this vulnerable group.

Phase Ib study of gevokizumab (GEVO) in combination with standard-of-care (SoC) anticancer therapies in patients (pts) with metastatic colorectal cancer (mCRC), metastatic gastroesophageal cancer (mGEC), and metastatic renal cell cancer (mRCC).

135 Background: GEVO, a humanized monoclonal antibody, binds to interleukin-1β (IL-1β) and inhibits its activity. We report results from a phase Ib study of GEVO + SoC anticancer therapies in pts with mCRC/mGEC/mRCC. Methods: This open-label study enrolled pts aged ≥18 years in cohorts A (first line mCRC, [A]), B (second line [2L] mCRC, [B]), C (2L mGEC, [C]) and D (2L/third line mRCC, [D]). The primary objectives were to determine the pharmacodynamically-active dose (PAD) of GEVO monotherapy in A/B, the safety and tolerability, and the recommended dose for expansion (RDE) of GEVO + SoC in A/B/C/D, and the efficacy of GEVO + SoC at RDE in A/B/C measured by the progression-free survival (PFS) rate. The proof of concept (PoC) criteria for PFS rates were ≥42% at 15 months (m) (lower 80% CI limit ≥29%) in A, ≥48% at ~9 m (lower 80% CI limit ≥37%) in B, ≥51% at 6 m (lower 60% CI limit ≥38%) in C. The relationship between baseline levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and IL-1β, and on-treatment decrease of circulating tumor DNA (ctDNA) levels with clinical response was explored. Results: As of March 1, 2023, 71 (A), 62 (B), 26 (C) and 7 pts (D) were treated. The PAD was established as 120 mg GEVO intravenous (IV) every 4 weeks (Q4W) and the RDE as 120 mg GEVO IV Q4W + SoC. There were 2 dose-limiting toxicities: grade 4 decreased neutrophil count (1 pt in C) and grade 3 hyponatremia (1 pt in D). The most frequent grade ≥3 treatment-related adverse events (≥15% of all pts) were neutropenia (A/B: 21.1%/22.6%), decreased neutrophil count (A/B/C: 18.3%/17.7%/15.4%) and hyponatremia (D: 28.6%). The PFS rates were 29.0% (80% CI: 20.4, 38.2), 39.4% (80% CI: 29.8, 48.9), 20.0% (60% CI: 13.3, 27.6) in A/B/C, respectively. In B, median PFS and overall survival (OS) were significantly longer in pts with baseline hs-CRP &lt;10 mg/L (low [L]) than ≥10 mg/L (high [H]), IL-6 &lt;9.58 pg/mL (L) than ≥9.58 pg/mL (H), and IL-1β &lt;0.12 pg/mL (L) than ≥0.12 pg/mL (H). In A + B, a median on-treatment decrease of ctDNA fraction by &gt;72% (H) was associated with significantly longer OS. Conclusions: The safety and tolerability of GEVO combinations was acceptable. The primary PFS rates did not meet the PoC criteria. Baseline levels of hs-CRP, IL-6 and IL-1β in pts with 2L mCRC, and on-treatment reduction of ctDNA in pts with 1L + 2L mCRC may have prognostic value. Clinical trial information: NCT03798626 . Variables PFS HR (95% CI) p-value OS HR (95% CI) p-value Ahs-CRP L / HIL-6 L / HIL-1β L / H 1.74 (0.81, 3.73)1.38 (0.70, 2.72)1.50 (0.74, 3.01) 0.1550.3520.259 1.99 (0.66, 5.98)1.73 (0.71, 4.20)0.98 (0.38, 2.52) 0.2210.2250.973 Bhs-CRP L / HIL-6 L / HIL-1β L / H 2.56 (1.27, 5.18)2.92 (1.33, 6.40)2.41 (1.13, 5.13) 0.0090.0070.022 3.04 (1.40, 6.60)3.25 (1.43, 7.36)3.60 (1.54, 8.44) 0.0050.0050.003 A + BctDNA decrease L / H 0.65 (0.39, 1.10) 0.108 0.45 (0.24, 0.83) 0.011

Childhood allergy and anxiety/depression in early adulthood: A longitudinal study in the ALSPAC birth cohort.

Allergic disease and common mental disorders frequently co-occur. However, little is known about the longitudinal impact of childhood allergy on the subsequent risk of developing anxiety or depression, and the possible biological mechanisms for this. We performed longitudinal analyses of data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. The baseline sample comprised n=5256 children with allergy data available at age 7yrs. We used multivariable regression to test associations between childhood allergy at age 7yrs and: a) four inflammatory markers at age 9yrs; b) depression and anxiety measures between ages 10-24yrs. Allergy measures included biological markers (total serum immunoglobulin E (tIgE), number of positive skin prick tests (SPTs)), and presence of eczema, asthma and/or food allergy (mother reported). Inflammatory markers were interleukin-6 (IL-6), C-reactive protein (CRP), IL-4 and IL-13. We used structural equation modelling to test whether inflammatory markers mediated the association between tIgE and depression/anxiety. tIgE and having≥1 positive SPT at age 7 were associated with IL-6 levels at age 9 (adjusted β=0.09; 95% CI 0.06-0.13; p<0.001 and adjusted β=0.06; 95% CI 0.03-0.09; p<0.001 respectively), but not with CRP, IL-4 or IL13 levels. We found no strong evidence of an association between childhood allergy and subsequent depression/anxiety during adolescence and early adulthood. This finding was consistent across biological and mother-reported allergy measures. Biological markers of childhood allergy are associated with IL-6, a key inflammatory cytokine. However, childhood allergy may not have a large long-term effect on subsequent depression/anxiety.

Phoenixin's Influence on HPG Axis and Inflammation in Elite Ice Hockey Athletes: A Cross-Sectional Analysis.

The neuropeptide phoenixin (PNX) may be involved in regulating the hypothalamic-pituitary-gonadal (HPG) axis and inflammatory responses. This study aims to investigate the role of PNX in the regulation of HPG axis function in ice hockey players and its impact on body composition. This cross-sectional study included 65 male ice hockey players aged 18-22, divided into untrained, non-elite athlete, and elite athlete groups. Body composition was assessed using bioelectrical impedance analysis, and plasma levels of PNX, gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), testosterone, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) were measured by enzyme-linked immunosorbent assay. Elite ice hockey players exhibited significantly higher lower limb and core skeletal muscle mass, skeletal muscle index, and testosterone levels, aligning with the high-intensity intermittent nature of hockey training. Compared to the non-training group, ice hockey training groups showed elevated levels of PNX, GnRH, testosterone, and TNF-α, along with reduced levels of LH and IL-6. PNX concentration positively correlated with lean body mass, skeletal muscle mass, skeletal muscle index, serum GnRH, and testosterone levels, and negatively correlated with serum LH and IL-6 levels. In conclusion, PNX may enhance skeletal muscle mass in ice hockey players, particularly in the lower limbs and core muscles, by promoting HPG axis activity while inhibiting inflammatory responses and reducing HPG axis suppression. These findings provide new insights into the physiological adaptation mechanisms of ice hockey players, potentially aiding in the optimization of training strategies and improvement of athletic performance.

Trajectory of peripheral inflammation during index ECT in association with clinical outcomes in treatment-resistant depression.

Electroconvulsive therapy (ECT) is a highly efficacious intervention for severe and intractable depression. Evidence suggests ECT provokes an initial acute inflammatory response that subsequently decreases with repeated administration. However, relationships between inflammatory changes and clinical effects are unclear. Improved understanding of these processes may provide critical insight into effective intervention for treatment-resistant depression (TRD). Plasma inflammatory markers were assessed at pre-treatment (T1), after the second ECT session (T2), and after ECT index series completion (post-treatment/T3) in TRD (n=40). Changes were examined over time and in association with post-treatment Responder/Non-responder status (≥50% reduction in global depression severity) and percent change in affective, cognitive and neurovegetative depressive symptom domains. C-reactive protein (CRP) and interleukin-6 (IL-6) increased from pre-treatment to T2, and decreased from T2 to post-treatment. Neither early (%T2-T1) nor total (%T1-T3) change in inflammation predicted clinical outcomes, however, the interaction between early/acute inflammatory response and post-treatment inflammation (relative to baseline) was associated with clinical outcomes. Larger initial increases in IL-6 predicted greater reductions in both affective and cognitive symptoms in subjects with higher post-treatment IL-6; those with lower post-treatment IL-6 trended toward the opposite. The same was found between changes in CRP and neurovegetative symptoms. Though preliminary, these results demonstrate how processes involved in the acute inflammatory response to ECT may differentially influence clinical outcomes depending on overall trajectory of inflammation following ECT. Findings also highlight the importance of examining symptom-specific changes in depression when studying treatment mechanisms, rather than relying solely on global measures of severity.

Exploring the role of inflammatory biomarkers in trigeminal neuralgia.

Trigeminal neuralgia (TN) is a severe facial pain disorder with complex etiology. Inflammation has been suggested as a contributing factor to TN pathogenesis. This study investigates the causal relationship between inflammatory biomarkers, including 41 circulating inflammatory cytokines, C-reactive protein (CRP), and procalcitonin (PCT), and TN using Mendelian randomization (MR) analysis. A two-sample MR approach was employed using genome-wide association study (GWAS) data from 8293 Finnish individuals for inflammatory cytokines and data from the FinnGen database for TN. Instrumental variables (IVs) were selected based on genome-wide significance and clumping thresholds to avoid linkage disequilibrium. Inverse variance weighting (IVW) was used as the primary method, complemented by MR Egger regression, weighted median, simple mode, and weighted mode methods. Additionally, Bayesian Weighted MR (BWMR) and Multivariable MR (MVMR) were utilized to validate the findings and explore potential confounders. The present MR analysis identified significant causal associations for three inflammatory cytokines with TN. Stem cell growth factor beta (SCGF-β) (OR=1.362, 95% CI=1.049-1.770, p=0.021) and Interleukin-4 (IL-4) (OR=1.533, 95% CI=1.014-2.316, p=0.043) were positively associated with TN, while Interleukin-16 (IL-16) (OR=0.720, 95% CI=0.563-0.921, p=0.009) had a protective effect. CRP levels were also linked to TN risk (OR=0.751, 95% CI=0.593-0.951, p=0.017). No significant causal effect of PCT on TN was observed. Sensitivity analyses confirmed the robustness of these findings, showing no evidence of horizontal pleiotropy or heterogeneity. This study highlights specific inflammatory biomarkers that may play pivotal roles in TN pathogenesis. SCGF-β and IL-4 are potential therapeutic targets due to their facilitative effects on TN, while IL-16 could offer protective benefits. CRP's association with TN further supports the involvement of systemic inflammation in this condition. These findings provide novel insights into TN's inflammatory mechanisms, suggesting new avenues for targeted interventions.

Proposing Bromo-epi-androsterone (BEA) for perioperative neurocognitive disorders with Interleukin-6 as a druggable target.

Cognitive impairment following surgery is a significant complication, affecting multiple neurocognitive domains. The term "perioperative neurocognitive disorders" (PND) is recommended to encompass this entity. Individuals who develop PND are typically older and have increases in serum and brain pro-inflammatory cytokines notwithstanding the type of surgery undergone. Surgical trauma induces production of small biomolecules, damage-associated molecular patterns (DAMP), particularly the DAMP known as high molecular group box 1 protein (HMGB1). Mechanistically, peripheral surgical trauma promotes pro-inflammatory cytokines that stimulate central nervous system (CNS) inflammation by disrupting the blood-brain barrier (BBB) causing functional neuronal disruption that leads to PND. PND is strongly linked to elevations in serum and CNS pro-inflammatory cytokines interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα); these cytokines cause further release of HMGB1 creating a positive feedback loop that amplifies the inflammatory response. The cytokine IL-6 is necessary and sufficient for PND. Dehydroepiandrosterone (DHEA) is a principal component of the steroid metabolome and is involved in immune homeostasis. DHEA has been shown to suppress expression of several pro-inflammatory cytokines by regulation of the NF-kB pathway. Bromo-epi-androsterone (BEA) is a potent synthetic analog of DHEA; unlike DHEA, it is non-androgenic, non-anabolic and is an effective modulator of immune dysregulation. In a randomized, placebo-controlled clinical trial, BEA effected significant and sustained decreases in IL-1β, TNFα and IL-6. This article presents BEA as a potential candidate for clinical trials targeting PND and further suggests the use of BEA in elective total hip arthroplasty as a well-documented surgical entity relevant to the management of PND.

Roles of S100A1 and S100A10 from hybrid grouper (Epinephelus lanceolatus♂ × Epinephelus fuscoguttatus♀) in the immune response to Vibrio infection

The S100 proteins are highly conserved EF-hand calcium-binding proteins found only in vertebrates. In the current study, two S100 genes (S100A1 and S100A10) were successfully identified and characterized from hybrid grouper Epinephelus lanceolatus♂ × Epinephelus fuscoguttatus♀. The deduced S100A10 protein contained two EF-hand domains, and S100A1 only possessed the N-terminal EF-hand. Phylogenetic analysis revealed that S100A1 and S100A10 from hybrid grouper were evolutionarily closely related to their counterparts in other selected vertebrates. Quantitative real-time PCR results revealed that the transcripts of S100A1 and S100A10 mRNA were ubiquitously distributed in all the examined tissues. After Vibrio alginolyticus infection, the expression of S100A1 and S100A10 in the spleen increased significantly. Moreover, overexpression of S100A1 and S100A10 could not only regulate the expression of interleukin 8 (IL-8), IL-10, and IL-16 in the head kidney, liver, and spleen, change the activities of acid phosphatase, catalase, lysozyme, and superoxide dismutase in serum, but also reduce the promoter activities of interferon 3 and nuclear factor kappa-B in vitro. Taken together, this study indicated that S100A1 and S100A10 participate in the immune response of hybrid grouper against bacterial infection.

The combination of RL-QN15 and OH-CATH30 promotes the repair of acne via the TLR2/NF-κB pathway.

Acne is a prevalent and chronic inflammatory skin disease, and its treatment remains a huge clinical challenge. In the present study, we evaluated the therapeutic potential of combining the peptides RL-QN15 and OH-CATH30 for the treatment of acne in mice. Results indicated that the topical application of RL-QN15 and OH-CATH30 significantly inhibited the proliferation of Propionibacterium acnes (P. acnes) and alleviated acne-induced edema. Furthermore, the combined treatment suppressed the overexpression of proinflammatory cytokines induced by P. acnes, including interleukin -1 beta (IL-1β), interleukin -6 (IL-6), interleukin -8 (IL-8), tumor necrosis factor-alpha (TNF-α) induced by P. acnes and facilitated collagen deposition, thereby effectively mitigating skin damage associated with acne. Mechanistically, the combination of RL-QN15 and OH-CATH30 inhibited the expression of toll-like receptor 2 (TLR2) and activation nuclear factor kappa-B (NF-κB) signaling pathway (phosphorylation of P65 and IκB) in both mice and RAW 264.7cells. These results suggested that this combination may inhibit the excretion of inflammatory factors and facilitate the collagen deposition by TLR2/NF-κB signaling. Overall, our study demonstrates the potent therapeutic effects of the combined application of RL-QN15 and OH-CATH30, highlights the TLR2/NF-κB pathway as a key target in acne treatment, and provides a novel strategy for developing innovative acne therapeutics.

Comparative analysis of the performance, egg quality and ovarian immune function of fast and slow feather strains in tianfu green shell laying hens at various stages of egg production.

This objective of this experiment was to compare and evaluate the performance, egg quality, and immune function of Tianfu green shell laying hens with varying feather growth rates, in order to provide a reference for their rational utilization. A total of 120 one-day-old healthy Tianfu green shell laying hens were classified into the early-feathering (EF) and late-feathering (LF) groups through phenotypic identification of feather length and qPCR molecular identification. Each group was subdivided into four replicates, with 30 chickens in each replicate. Under the identical feeding and management conditions, the live weight, tibial length, egg production performance, egg quality, serum biochemical indexes, immune protein content, and the expression of related genes in uterine and ovarian tissues were assessed and analyzed. The results indicated that LF hens exhibited significantly greater live weights at 4, 16, 27, and 43 weeks (P < 0.05) and longer tibia lengths at 4 and 16 weeks (P < 0.05) compared to EF hens, suggesting enhanced early growth performance. Conversely, EF hens demonstrated superior egg-laying performance, characterized by a higher laying rate during both peak (27 weeks) and late (43 weeks) laying periods (P < 0.05), despite their eggs being lighter in weight (P < 0.05). Furthermore, EF hens exhibited the production of eggs with significantly thicker and stronger shells during the peak laying period (P < 0.05), while no notable differences were observed in other egg quality parameters. Immunologically, EF hens demonstrated elevated peak serum levels of IgA, IgG, and IgM compared to LF hens. Additionally, the expression levels of IFN-γ and interleukin 6 (IL-6) genes in the ovaries were markedly higher in EF hens. These findings indicate that although LF hens excel in early growth stages, EF hens exhibit superior egg production capabilities and enhanced immune responses.

Non-bioartificial artificial liver support system in acute liver failure: A comprehensive systematic review and meta-analysis of randomized controlled trials.

Acute liver failure (ALF) poses a significant threat to patient health with high mortality rates. While Non-Bioartificial Artificial Liver Support system (NBALSS) has been utilized as a transitional intervention to liver transplant, its efficacy remains uncertain, It is also used as a last-line treatment for patients who are not candidates for liver transplantation. The aim of this study was to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of NBALSS in treating acute liver failure (ALF). The primary outcome was overall survival (OS), while the secondary outcome focused on inflammatory factor levels. We conducted a comprehensive search across various databases, including PubMed, EMbase, The Cochrane Library, Web of Science, CBM, Wanfang Database, VIP database, and CNKI database. The search spanned from the inception of the databases to July 2023. Two independent reviewers screened literature, extracted data, assessed bias risk in the selected studies and used GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) to rate the certainty of evidence. Random and fixed effects meta-analyses were used to determine the average effect of the interventions on ALF. The sensitivity analysis was conducted using the leave-one-out test. Additionally, subgroup analyses were carried out based on a singular NBALSS treatment or combined treatment of two NBALSS and follow-up duration. Twelve RCTs involving 824 patients were identified. The use of NBALSS was associated with a significantly improved overall survival (OS) [RR = 1.42, 95 %CI (1.26, 1.61), low certainty] and notable reductions in total bilirubin (TBIL) [MD = -57.60, 95 %CI (-79.60, -35.59), moderate certainty], alanine aminotransferase (ALT) [MD = -48.28, 95 %CI (-76.57, -19.98), low certainty], tumor necrosis factor (TNF-α) [MD = -1.49, 95 %CI (-2.24, -0.73), very low certainty], and interleukin 6 (IL-6) [MD = -178.72, 95 %CI (-277.37, -80.06), very low certainty]. However, the effects of NBALSS on interleukin-2 (IL-2) [MD = 1.33, 95 %CI (-0.33, 3.00), very low certainty], interleukin-8 (IL-8) [MD = -44.75, 95 %CI (-163.04, 73.55), very low certainty], and Sequential Organ Failure Score (SOFA) [MD = -4.06, 95 %CI (-8.92, 0.80), very low certainty] remained uncertain. Moderate to very low certainty of evidence indicates that NBALSS may improve OS and biochemical indexes, cytokines in patients with ALF. However, the certainty of evidence is limited by risk of bias, incositency and imprecision. High-quality and larger trials are needed to better determine the effect of NBALSS on patient-important outcomes.

Inhibition of hippocampal interleukin-6 receptor-evoked signalling normalises long-term potentiation in dystrophin-deficient mdx mice.

Duchenne muscular dystrophy (DMD), an X-linked neuromuscular disorder, characterised by progressive immobility, chronic inflammation and premature death, is caused by the loss of the mechano-transducing signalling molecule, dystrophin. In non-contracting cells, such as neurons, dystrophin is likely to have a functional role in synaptic plasticity, anchoring post-synaptic receptors. Dystrophin-expressing hippocampal neurons are key to cognitive functions such as emotions, learning and the consolidation of memories. In the context of disease-induced chronic inflammation, we have explored the role of the pleiotropic cytokine, interleukin (IL)-6 in hippocampal dysfunction using immunofluorescence, electrophysiology and metabolic measurements in dystrophic mdx mice. Hippocampal long-term potentiation (LTP) of the Schaffer collateral-CA1 projections was suppressed in mdx slices. Given the importance of mitochondria-generated ATP in synaptic plasticity, reduced maximal respiration in the CA1 region may impact upon this process. Consistent with a role for IL-6 in this observation, early LTP was suppressed in dystrophin-expressing wildtype slices exposed to IL-6. In dystrophic mdx mice, exposure to IL-6 suppressed mitochondrial-mediated basal metabolism in CA1, CA3 and DG hippocampal regions. Furthermore, blocking IL-6-mediated signalling by administering neutralising monoclonal IL-6 receptor antibodies intrathecally, normalised LTP in mdx mice. The impact of dystrophin loss from the hippocampus was associated with modified cellular bioenergetics, which underpin energy-driven processes such as the induction of LTP. The additional challenge of pathophysiological levels of IL-6 resulted in altered cellular bioenergetics, which may be key to cognitive deficits associated with the loss of dystrophin.

Effects of combined use of compound acidifiers and plant essential oils in feed on the reproductive performance and physiological status of Xianjv chickens.

This study investigates the effects of combined compound acidifiers and plant essential oils on the production performance, egg quality, and health parameters of Xianjv chickens. A total of 240 healthy 34-week-old Xianjv chickens were randomly divided into 5 groups and given 5 different feed additives: a control group with a basal diet, and four experimental groups with varying doses of compound acidifiers (CA) and essential oils (EO). The results revealed that the addition of compound acidifiers and essential oils did not significantly affect average daily feed intake, egg production rate, or feed-to-egg ratio. However, supplementation with CA and EO significantly improved eggshell strength, albumen height, and Haugh unit, enhancing overall egg quality. Additionally, the combination of these additives enhanced serum antioxidant capacity by increasing levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), while reducing malondialdehyde (MDA) levels. It also lowered inflammatory cytokines such as interleukin-2 (IL-2) and interleukin-6 (IL-6) and improved intestinal health by enhancing digestive enzyme activities, including trypsin and lipase, in the duodenum and jejunum. The study concludes that the combined use of compound acidifiers and plant essential oils offers a promising alternative to antibiotics in poultry feed, improving egg quality and supporting better health status in Xianjv chickens. Nevertheless, careful optimization of the dosages and combinations is necessary to maximize their benefits without adversely affecting the birds' physiological balance.

The double-edged role of IL-18 in reproductive endocrine and reproductive immune related disorders.

Interleukin (IL)-18 is one of the members of IL-1 family cytokines, it was originally named as interferon gamma (IFN-γ) inducing factor. IL-18 is a pleiotropic immune regulator and has a bidirectional regulatory effect on immunity. It exerts a potent pro-inflammatory effect by inducing the expression of IFN-γ, also has an important anti-inflammatory role. In recent years, IL-18 has received widespread attention and become a research hotspot. Previous studies have described the roles of IL-18 in the pathogenesis of many diseases. However, the biologic activities of IL-18 and its role in the reproductive endocrine and reproductive immune related diseases are still not well understood, such as endometriosis (EMS), recurrent spontaneous abortion (RSA), polycystic ovary syndrome (PCOS), and infertility, which are closely related to inflammation and immunity. Here, we reviewed the research progress of IL-18 in these diseases in the past few years. This article provides an overview of the latest knowledge about the roles of IL-18 in these diseases, with a view to providing new possibilities for the diagnosis and treatment of reproductive endocrine and reproductive immune related disorders.

Exploring the anti‑inflammatory activity of boron compounds through the miR‑21/PTEN/AKT pathway in cecal ligation and puncture‑induced sepsis.

The present study investigated the impact of boric acid (BA) and borax (BX) on markers of inflammation and modifications in miR‑21/PTEN/AKT pathway genes in the liver and kidney tissues of Sprague Dawley male rats with sepsis induced by cecal ligation and puncture (CLP). A total of 60 male Sprague Dawley rats were randomly divided into 6 groups, each containing 10 animals as follows: Control, CLP (where the model was created), 20 mg/kg BX (CLP + BX1), 40 mg/kg BX (CLP + BX2), 20 mg/kg BA (CLP + BA1) and 40 mg/kg BA (CLP + BA2). Liver and kidney tissues were analyzed for histopathological changes, immunopositivity for tumor necrosis factor‑α, interleukin (IL)‑6 and IL‑10, and gene expression of microRNA‑21 (miR‑21), phosphatase and tensin homolog (PTEN) and AKT. Gene expression analysis in the liver tissues revealed a significant decrease in miR‑21, and a marked but not significant decrease in PTEN levels in the CLP group, while AKT expression was significantly increased in the CLP group, and was significantly decreased in CLP + BA1 group compared with in the CLP group. In the kidney tissues, miR‑21 levels were significantly decreased in the CLP group, but the CLP + BA2 group showed a significant increase compared with in the CLP group. These results suggest the potential therapeutic benefits of low‑dose BA and BX in ameliorating sepsis‑induced tissue damage, emphasizing the need for further exploration of their mechanisms of action.