Cytokine Storm Syndrome Associated with Systemic Juvenile Idiopathic Arthritis.

The cytokine storm syndrome (CSS) associated with systemic juvenile idiopathic arthritis (sJIA) has widely been referred to as macrophage activation syndrome (MAS). In this chapter, we use the term sJIA-associated CSS (sJIA-CSS) when referring to this syndrome and use the term MAS when referencing publications that specifically report on sJIA-associated MAS.

Anti-Interferon-γ Therapy for Cytokine Storm Syndromes.

A vast body of evidence provides support to a central role of exaggerated production of interferon-γ (IFN-γ) in causing hypercytokinemia and signs and symptoms of hemophagocytic lymphohistiocytosis (HLH). In this chapter, we will describe briefly the roles of IFN-γ in innate and adaptive immunity and in host defense, summarize results from animal models of primary HLH and secondary HLH with particular emphasis on targeted therapeutic approaches, review data on biomarkers associated with activation of the IFN-γ pathway, and discuss initial efficacy and safety results of IFN-γ neutralization in humans.

IL-1 Family Blockade in Cytokine Storm Syndromes.

Interleukin-1 is a prototypic proinflammatory cytokine that is elevated in cytokine storm syndromes (CSSs), such as secondary hemophagocytic lymphohistiocytosis (sHLH) and macrophage activation syndrome (MAS). IL-1 has many pleotropic and redundant roles in both innate and adaptive immune responses. Blockade of IL-1 with recombinant human interleukin-1 receptor antagonist has shown efficacy in treating CSS. Recently, an IL-1 family member, IL-18, has been demonstrated to be contributory to CSS in autoinflammatory conditions, such as in inflammasomopathies (e.g., NLRC4 mutations). Anecdotally, recombinant IL-18 binding protein can be of benefit in treating IL-18-driven CSS. Lastly, another IL-1 family member, IL-33, has been postulated to contribute to CSS in an animal model of disease. Targeting of IL-1 and related cytokines holds promise in treating a variety of CSS.

Spirulina platensis shields the submandibular gland from cadmium toxicity by bolstering antioxidant defenses and maintaining its structural integrity.

Cadmium (Cd), an element categorized as a non-essential transitional metal, has potential hazards to the health of both human beings and animals. Spirulina platensis (SP), a type of blue-green algae, possesses a high concentration of essential antioxidants. The present study aimed to explore the possible defensive role of SP against Cd-induced submandibular gland injury in rats by assessment of biomarkers related to both oxidative stress and inflammatory processes, which were further explored through histopathological examination of submandibular gland tissue. Consequently, the study included 32 mature rats, subdivided into four different groups as follows: control, SP, Cadmium chloride (CdCl2), and CdCl2/SP. The duration of the study was 24days. The results revealed that CdCl2 induced submandibular gland injury as shown by the oxidant/antioxidant imbalance and increased inflammatory reactions, in addition to, histopathological changes and overexpression of BAX immunostaining. Concurrent SP administration to CdCl2-treated rats significantly improved all these effects. We concluded that concurrent SP supplement improved the submandibular gland injury provoked by CdCl2.

Bacillus coagulans BACO-17 ameliorates in vitro and in vivo progression of Rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease that causes persistent inflammation involving the joints, cartilage, and synovium. In individuals with RA, alterations in the composition of intestinal bacteria suggest the vital role of gut microbiota in immune dysfunction. Multiple therapies commonly used to treat RA can also alter the diversity of gut microbiota, further suggesting the modulation of gut microbiota as a prevention or treatment for RA. Therefore, a better understanding of the changes in the gut microbiota that accompany RA should facilitate the development of novel therapeutic approaches. In this study, B. coagulans BACO-17 not only significantly reduced paw swelling, arthritis scores, and hind paw and forepaw thicknesses but also protected articular cartilage and the synovium against RA degeneration, with a corresponding downregulation of TNF-α expression. The inhibition or even reversing of RA progression highlights B. coagulans BACO-17 as a novel therapeutic for RA worth investigating.

Interleukin-1α inhibits transforming growth factor-ß1 and ß2-induced extracellular matrix production, remodeling and signaling in human lung fibroblasts: Master regulator in lung mucosal repair.

BACKGROUND: Lung fibroblasts play a central role in maintaining lung homeostasis and facilitating repair through the synthesis and organization of the extracellular matrix (ECM). This study investigated the cross-talk between interleukin-1 alpha (IL-1α) and transforming growth factor-ß (TGF-ß) signaling, two key regulators in tissue repair and fibrosis, in the context of lung fibroblast repair in the healthy lung. RESULTS: Stimulation of lung fibroblasts with TGF-ß1 and TGF-ß2 induced collagen-I and fibronectin protein expression (p < 0.05), a response inhibited with co-treatment with IL-1α (p < 0.05). Additionally, TGF-ß1 and TGF-ß2 induced myofibroblast differentiation, and collagen-I gel contraction, which were both suppressed by IL-1α (p < 0.05). In contrast, interleukin (IL)-6, IL-8 and thymic stromal lymphopoietin induced by IL-1α, were unaffected by TGF-ß1 or TGF-ß2. Mechanistically, IL-1α administration led to the suppression of TGF-ß1 and TGF-ß2 signaling, through downregulation of mRNA and protein for TGF-ß receptor II and the downstream adaptor protein TRAF6, but not through miR-146a that is known to be induced by IL-1α. DISCUSSION: IL-1α acts as a master regulator, modulating TGF-ß1 and TGF-ß2-induced ECM production, remodeling, and myofibroblast differentiation in human lung fibroblasts, playing a vital role in balancing tissue repair versus fibrosis. Further research is required to understand the dysregulated cross-talk between IL-1α and TGF-ß signaling in chronic lung diseases and the exploration of therapeutic opportunities. METHODS: Primary human lung fibroblasts (PHLF) were treated with media control, or 1 ng/ml IL-1α with or without 50 ng/ml TGF-ß1 or TGF-ß2 for 1, 6 and 72 h. Cell lysates were assessed for the expression of ECM proteins and signaling molecules by western blot, miRNA by qPCR, mRNA by RNA sequencing and cell supernatants for cytokine production by ELISA. PHLFs were also seeded in non-tethered collagen-I gels to measure contraction, and myofibroblast differentiation using confocal microscopy.

Correlation of brain tissue volume loss with inflammatory biomarkers IL1ß, P-tau, T-tau, and NLPR3 in the aging cognitively impaired population.

Background: Blood inflammatory biomarkers have emerged as important tools for diagnosing, assessing treatment responses, and predicting neurodegenerative diseases. This study evaluated the associations between blood inflammatory biomarkers and brain tissue volume loss in elderly people. Methods: This study included 111 participants (age 67.86 ± 8.29 years; 32 men and 79 women). A battery of the following blood inflammatory biomarkers was measured, including interleukin 1-beta (IL1ß), NACHT, LRR, and PYD domains-containing protein 3 (NLRP3), monomer Aß42 (mAß), oligomeric Aß42 (oAß), miR155, neurite outgrowth inhibitor A (nogo-A), phosphorylated tau (P-tau), and total tau (T-tau). Three-dimensional T1-weight images (3D T1WI) of all participants were prospectively obtained and segmented into gray matter and white matter to measure the gray matter volume (GMV), white matter volume (WMV), and gray-white matter boundary tissue volume (gwBTV). The association between blood biomarkers and tissue volumes was assessed using voxel-based and region-of-interest analyses. Results: GMV and gwBTV significantly decreased as the levels of IL1ß and T-tau increased, while no significant association was found between the level of P-tau and the three brain tissue volumes. Three brain tissue volumes were negatively correlated with the levels of IL1ß, P-tau, and T-tau in the hippocampus. Specifically, IL1ß and T-tau levels showed a distinct negative association with the three brain tissue volume losses in the hippocampus. In addition, gwBTV was negatively associated with the level of NLRP3. Conclusion: The observed association between brain tissue volume loss and elevated levels of IL1ß and T-tau suggests that these biomarkers in the blood may serve as potential biomarkers of cognitive impairment in elderly people. Thus, IL1ß and T-tau could be used to assess disease severity and monitor treatment response after diagnosis in elderly people who are at risk of cognitive decline.

Innate immune memory after brain injury drives inflammatory cardiac dysfunction.

The medical burden of stroke extends beyond the brain injury itself and is largely determined by chronic comorbidities that develop secondarily. We hypothesized that these comorbidities might share a common immunological cause, yet chronic effects post-stroke on systemic immunity are underexplored. Here, we identify myeloid innate immune memory as a cause of remote organ dysfunction after stroke. Single-cell sequencing revealed persistent pro-inflammatory changes in monocytes/macrophages in multiple organs up to 3 months after brain injury, notably in the heart, leading to cardiac fibrosis and dysfunction in both mice and stroke patients. IL-1ß was identified as a key driver of epigenetic changes in innate immune memory. These changes could be transplanted to naive mice, inducing cardiac dysfunction. By neutralizing post-stroke IL-1ß or blocking pro-inflammatory monocyte trafficking with a CCR2/5 inhibitor, we prevented post-stroke cardiac dysfunction. Such immune-targeted therapies could potentially prevent various IL-1ß-mediated comorbidities, offering a framework for secondary prevention immunotherapy.

Construction of IRAK4 inhibitor activity prediction model based on machine learning.

Interleukin-1 receptor-associated kinase 4 (IRAK4) is a crucial serine/threonine protein kinase that belongs to the IRAK family and plays a pivotal role in Toll-like receptor (TLR) and Interleukin-1 receptor (IL-1R) signaling pathways. Due to IRAK4's significant role in immunity, inflammation, and malignancies, it has become an intriguing target for discovering and developing potent small-molecule inhibitors. Consequently, there is a pressing need for rapid and accurate prediction of IRAK4 inhibitor activity. Leveraging a comprehensive dataset encompassing activity data for 1628 IRAK4 inhibitors, we constructed a prediction model using the LightGBM algorithm and molecular fingerprints. This model achieved an R2 of 0.829, an MAE of 0.317, and an RMSE of 0.460 in independent testing. To further validate the model's generalization ability, we tested it on 90 IRAK4 inhibitors collected in 2023. Subsequently, we applied the model to predict the activity of 13,268 compounds with docking scores less than - 9.503 kcal/mol. These compounds were initially screened from a pool of 1.6 million molecules in the chemdiv database through high-throughput molecular docking. Among these, 259 compounds with predicted pIC50 values greater than or equal to 8.00 were identified. We then performed ADMET predictions on these selected compounds. Finally, through a rigorous screening process, we identified 34 compounds that adhere to the four complementary drug-likeness rules, making them promising candidates for further investigation. Additionally, molecular dynamics simulations confirmed the stable binding of the screened compounds to the IRAK4 protein. Overall, this work presents a machine learning model for accurate prediction of IRAK4 inhibitor activity and offers new insights for subsequent structure-guided design of novel IRAK4 inhibitors.

Canakinumab in Yao Syndrome: Insights From a Comprehensive Case Report and Literature Review .

Yao syndrome, a rare autoinflammatory disorder linked to mutations in the nucleotide-binding oligomerization domain-containing protein-2 (NOD2) gene, manifests through periodic fever, polyarthritis, dermatitis, gastrointestinal disturbances, and sicca-like symptoms. The therapeutic landscape is limited, primarily encompassing glucocorticoids, interleukin-1 (IL-1), and IL-6 inhibitors. This report details the case of a teenager with periodic fevers, arthritis, livedo reticularis, and NOD2 gene mutations R702W and IVS8+158C consistent with Yao syndrome. The individual demonstrated significant improvement with canakinumab therapy. This case report aims to enhance recognition and understanding of Yao syndrome's clinical spectrum and management options.

Preoperative Immune Cell Dysregulation Accompanies Ovarian Cancer Patients into the Postoperative Period.

Ovarian cancer (OC) poses a significant global health challenge with high mortality rates, emphasizing the need for improved treatment strategies. The immune system's role in OC progression and treatment response is increasingly recognized, particularly regarding peripheral blood mononuclear cells (PBMCs) and cytokine production. This study aimed to investigate PBMC subpopulations (T and B lymphocytes, natural killer cells, monocytes) and cytokine production, specifically interleukin-1 beta (IL-1ß), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNFα), in monocytes of OC patients both preoperatively and during the early postoperative period. Thirteen OC patients and 23 controls were enrolled. Preoperatively, OC patients exhibited changes in PBMC subpopulations, including decreased cytotoxic T cells, increased M2 monocytes, and the disbalance of monocyte cytokine production. These alterations persisted after surgery with subtle additional changes observed in PBMC subpopulations and cytokine expression in monocytes. Considering the pivotal role of these altered cells and cytokines in OC progression, our findings suggest that OC patients experience an enhanced pro-tumorigenic environment, which persists into the early postoperative period. These findings highlight the impact of surgery on the complex interaction between the immune system and OC progression. Further investigation is needed to clarify the underlying mechanisms during this early postoperative period, which may hold potential for interventions aimed at improving OC management.

Interleukin-1ß activates matrix metalloproteinase-2 to alter lacrimal gland myoepithelial cell structure and function.

The aim of the present study is to investigate the role of c-Jun N-terminal kinase (JNK) and matrix metalloproteinase-2 (MMP-2) in mediating the effects of interleukin-1ß (IL-1ß) on the function of lacrimal gland myoepithelial cells (MECs). MECs isolated from an α-smooth muscle actin-green fluorescent protein (SMA-GFP) transgenic mouse were treated with IL-1ß alone or in the presence of SP600125, a JNK inhibitor, or ARP100, an MMP-2 inhibitor. The GFP intensity and the cell size/area were measured, and on day 7, the SMA, calponin, and pro-MMP-2 protein levels and the MEC contraction were assessed. At baseline, the control and treated cells showed no differences in GFP intensity or cell size. Starting on day 2 and continuing on days 4 and 7, the GFP intensity and cell size were significantly lower in the IL-1ß-treated samples, and these effects were alleviated following inhibition of either JNK or MMP-2. Compared with the control, the levels of SMA and calponin were lower in the IL-1ß-treated samples, and both the JNK and MMP-2 inhibitors reversed this trend. The pro-MMP-2 protein level was elevated in the IL-1ß-treated samples, and this effect was abolished by the JNK inhibitor. Finally, oxytocin-induced MEC contraction was diminished in the IL-1ß-treated samples, and both the JNK and MMP-2 inhibitors reversed this effect. Our data suggest that IL-1ß uses the JNK/MMP-2 pathways to alter MEC functions, which might account for the diminished tears associated with aqueous-deficient dry eye disease.

IL-1ß Induces LDL Transcytosis by a Novel Pathway Involving LDLR and Rab27a.

BACKGROUND: In early atherosclerosis, circulating LDLs (low-density lipoproteins) traverse individual endothelial cells by an active process termed transcytosis. The CANTOS trial treated advanced atherosclerosis using a blocking antibody for IL-1ß (interleukin-1ß); this significantly reduced cardiovascular events. However, whether IL-1ß regulates early disease, particularly LDL transcytosis, remains unknown. METHODS: We used total internal reflection fluorescence microscopy to quantify transcytosis by human coronary artery endothelial cells exposed to IL-1ß. To investigate transcytosis in vivo, we injected wild-type and knockout mice with IL-1ß and LDL to visualize acute LDL deposition in the aortic arch. RESULTS: Exposure to picomolar concentrations of IL-1ß induced transcytosis of LDL but not of albumin by human coronary artery endothelial cells. Surprisingly, expression of the 2 known receptors for LDL transcytosis, ALK-1 (activin receptor-like kinase-1) and SR-BI (scavenger receptor BI), was unchanged or decreased. Instead, IL-1ß increased the expression of the LDLR (LDL receptor); this was unexpected because LDLR is not required for LDL transcytosis. Overexpression of LDLR had no effect on basal LDL transcytosis. However, knockdown of LDLR abrogated the effect of IL-1ß on transcytosis rates while the depletion of Cav-1 (caveolin-1) did not. Since LDLR was necessary but overexpression had no effect, we reasoned that another player must be involved. Using public RNAseq data to curate a list of Rab GTPases affected by IL-1ß, we identified Rab27a. Overexpression of Rab27a alone had no effect on basal transcytosis, but its knockdown prevented induction by IL-1ß. This was phenocopied by depletion of the Rab27a effector JFC1. In vivo, IL-1ß increased LDL transcytosis in the aortic arch of wild-type but not Ldlr-/- or Rab27a-deficient mice. The JFC1 inhibitor nexinhib20 also blocked IL-1ß-induced LDL accumulation in the aorta. CONCLUSIONS: IL-1ß induces LDL transcytosis by a distinct pathway requiring LDLR and Rab27a; this route differs from basal transcytosis. We speculate that induction of transcytosis by IL-1ß may contribute to the acceleration of early disease.

IL-1 Receptor Dynamics in Immune Cells: Orchestrating Immune Precision and Balance.

IL-1, a pleiotropic cytokine with profound effects on various cell types, particularly immune cells, plays a pivotal role in immune responses. The proinflammatory nature of IL-1 necessitates stringent control mechanisms of IL-1-mediated signaling at multiple levels, encompassing transcriptional and translational regulation, precursor processing, as well as the involvement of a receptor accessory protein, a decoy receptor, and a receptor antagonist. In T-cell immunity, IL-1 signaling is crucial during both the priming and effector phases of immune reactions. The fine-tuning of IL-1 signaling hinges upon two distinct receptor types; the functional IL-1 receptor (IL-1R) 1 and the decoy IL-1R2, accompanied by ancillary molecules such as the IL-1R accessory protein (IL-1R3) and IL-1R antagonist. IL-1R1 signaling by IL-1ß is critical for the differentiation, expansion, and survival of Th17 cells, essential for defense against extracellular bacteria or fungi, yet implicated in autoimmune disease pathogenesis. Recent investigations emphasize the physiological importance of IL-1R2 expression, particularly in its capacity to modulate IL-1-dependent responses within Tregs. The precise regulation of IL-1R signaling is indispensable for orchestrating appropriate immune responses, as unchecked IL-1 signaling has been implicated in inflammatory disorders, including Th17-mediated autoimmunity. This review provides a thorough exploration of the IL-1R signaling complex and its pivotal roles in immune regulation. Additionally, it highlights recent advancements elucidating the mechanisms governing the expression of IL-1R1 and IL-1R2, underscoring their contributions to fine-tuning IL-1 signaling. Finally, the review briefly touches upon therapeutic strategies targeting IL-1R signaling, with potential clinical applications.

Examination of certain single-nucleotide polymorphisms of interleukins 1A and 1B in medication-related osteonecrosis of the jaw - An ambirectional cohort study.

AIM: The aim of this study was to examine particular single-nucleotide polymorphisms (IL-1A-889 C/T - rs1800587, IL-1B +3953 C/T - rs 1143634) of interleukins 1A and 1B in the development and prognosis of medication-related osteonecrosis of the jaw. MATERIALS AND METHODS: DentiGen Parodontitis Tests were applied for collecting samples. This test is suitable for sampling oral mucosa cells in order to detect interleukins 1A and 1B single nucleotide polymorphisms (IL-1A-889, IL-1B+3953). Genetic samples were evaluated in the Istenhegyi Genediagnostic Center using the DNA-hybridization method. Genetic samples were collected in the patient group and the control group. The role of gene polymorphisms in the development of the disease was investigated by comparing the genetic results for the patient and control groups. The investigation of gene polymorphisms in disease prognosis is based on stage improvement, recovery, and relapses following treatment. RESULTS: In total, 91 patients with MRONJ and 59 healthy controls were included in the study. 51 patients in the patient group and 37 controls had unfavorable allelic variants. No association (Mp = 1.42, SDp = 0.496, Mc = 1.35, SDc = 0.482, p = 0.52) was found between unfavorable polymorphisms and the development of the MRONJ. In the patient group, surgical therapy was required in 79 cases. Stage improvement was detected in 78 cases, recovery in 67 cases, and relapse in 33 cases. No stage improvement was found in one case, recovery in nine cases, or relapse in 34 cases. Of the 79 patients requiring surgical therapy, 49 had unfavorable allelic variants. No connection was found between the polymorphisms examined and stage improvement (Mp = 1.37, SDp = 0.486, Mnp = 2, SDnp = -, p = 0.800) or recovery (Mp = 1.39, SDp = 0.491, Mnp = 1.44, SDnp = 0.527, p = 0.990). However, a significant association (Mp = 1.21, SDp = 0.415, Mnp = 1.58, SDnp = 0.502, p < 0.001) was found between relapses and the presence of unfavorable allelic variants. CONCLUSION: Within the possible limitations of this study, it can be assumed that the analysis of certain single-nucleotide polymorphisms of interleukin-1 may have the potential to help define the risk stratification of MRONJ after surgical therapy.

Methylation of Interleukin-1 receptor-associated kinase-3 and the risk of multiple sclerosis relapse/activity.

This study retrospectively investigated the impact of interleukin-1 receptor-associated kinase-3 (IRAK-3/IRAK-M) silencing by methylation on the likelihood of multiple sclerosis (MS) activity. This cross-sectional study included 90 patients with MS: 45 with active disease (Group 1), 45 in remission (Group 2), and 45 healthy controls. The study included quantitation of IRAK-3 methylation index (MI%), IRAK-3 mRNA, and myeloid differentiation factor88 (MyD88) and assessment of NF-κB activity. IRAK-3 MI% was significantly higher in group 1 compared to group 2, accompanied by lower IRAK-3 mRNA expression, elevated circulating MyD88, and increased NF-κB activity. IRAK-3 MI% correlated negatively with its transcript and positively with MyD88 and NF-κB activity. A logistic regression model was created to predict active demyelination. The C-index was 0.924, which indicates a very strong prediction model. Within the limitations of current work, IRAK-3 methylation level seems to be a promising candidate biomarker for identifying MS patients at risk of relapse.

SIGIRR suppresses hepatitis B virus X protein-induced chronic inflammation in hepatocytes.

Although antiviral drugs can effectively inhibit hepatitis B virus (HBV) replication, the maintenance of chronic inflammation in the liver is still considered to be an important cause for the progression of HBV-related liver disease to liver fibrosis and advanced liver disease. As an endogenous inhibitory receptor of IL-1R and TLR signaling pathways, single immunoglobulin interleukin-1-related receptor (SIGIRR) has been proven to reduce inflammation in tissues to maintain system homeostasis. However, the relationship between SIGIRR expression and HBV replication and inflammatory pathway activation in hepatocytes remains unclear. In this study, hepatitis B virus X protein (HBx) upregulated MyD88 in liver cells, promoting NF-κB signaling and inflammatory factor production with LPS treatment, and the cell supernatant accelerated the activation and collagen secretion of hepatic stellate cells. However, SIGIRR overexpression suppressed HBx-mediated MyD88/NF-κB inflammatory signaling activation and inflammatory cytokine production induced by LPS in hepatocytes and HBV replication hepatocytes. Although we did not find any effect of SIGIRR on HBV replication in vitro, this study investigated the role of SIGIRR in blocking the proinflammatory function of HBx, which may provide a new idea for the treatment of chronic hepatitis B.

Association between the IL1B-511 C>T polymorphism and the risk of hematologic malignancies: data from a meta-analysis.

The relationship between the IL1B-511C>T (rs16944) polymorphism and the risk of developing hematologic malignancies remains controversial. Thus, we performed a meta-analysis to evaluate the association between IL1B-511C>T polymorphism and the risk of developing hematologic malignancies. A comprehensive search was conducted to identify all eligible studies on IL1B-511C>T polymorphism and hematologic malignancies. Twelve case-control studies, with 2,896 cases and 3,716 controls, were selected for the analysis. The overall data failed to indicate a significant association between IL1B-511C>T polymorphism and the risk of hematologic malignancies (OR:1.06, 95% Confidence Interval [CI]: 0.93-1.22). Moreover, non-significant associations were observed in a stratified analysis according to neoplasm type (multiple myeloma, Hodgkin's lymphoma, and non-Hodgkin's lymphoma), ethnicity (European and Asian), and Hardy-Weinberg equilibrium. In summary, our results suggest that there is no association between the IL1B-511C>T polymorphism and the risk of hematologic malignancies. As such, further large-scale studies are needed to confirm our findings.

Clinico-immunological evaluation of use of omega-3 fatty acids as nutraceutical approach in management of patients with chronic periodontitis: A randomized clinical trial.

Background: Subgingival bacterial colonization and biofilm formation are known to be the main etiology of periodontal disease progression. This biofilm elicits host response and the interaction between host defence mechanisms with plaque microorganisms and their products results in periodontal disease. Host modulatory therapy (HMT) is a form of treatment of periodontitis that focuses on treatment of the host in the host-bacteria interaction. Omega-3 fatty acids have emerged as a potential HMT agent to treat inflammation associated with periodontal disease. Methods: A total of 60 cases of chronic periodontitis were allocated into two groups; the test group (n = 30) were treated with scaling and root planing (SRP) and given a dietary supplementation of omega-3 fatty acid while the control group were treated with SRP alone. Clinical parameters carried out were plaque index (PI), gingival bleeding index (GBI), pocket probing depth (PPD) and clinical attachment level (CAL) and immunological parameter included interleukin-1ß level in saliva at baseline, 3 months and 6 months after therapy. Results: At 6 months, both the groups showed significant improvements with regards to all clinical and immunological parameters compared to baseline (all p < 0.05). However, test group presented with more favourable statistically significant results. Conclusion: The use of omega-3 fatty acid as nutraceutical agent to conventional method acted as beneficial therapeutic measures and effective in patients with chronic periodontitis when compared with SRP alone.

[Study on the risk factors of coal workers' pneumoconiosis and the mechanism of pyroptosis in peripheral blood].

Objective: To explore the risk factors of coal workers' pneumoconiosis, reveal the molecular mechanism of pyroptosis in peripheral blood of coal workers' pneumoconiosis patients, and provide new strategies and potential diagnostic biomarkers for the treatment of the disease. Methods: From January 1, 2020 to December 31, 2022, workers with suspected occupational diseases who were diagnosed with coal workers' pneumoconiosis in the Third People's Hospital of Xinjiang Uygur Autonomous Region were included in the study, including 77 patients with coal workers' pneumoconiosis stage Ⅰ, 10 patients with stage Ⅱ, 6 patients with stage Ⅲ, and 49 workers with dust-free lung disease as the control group. General information of the subjects was collected, blood samples were collected for routine blood and blood biochemical results, and plasma levels of interleukin (IL) -1ß and IL-18 were measured. Combined with the results of clinical examination, multi-factor ordered logistic regression analysis was carried out to evaluate the influencing factors of coal workers' pneumoconiosis. At the same time, the expression of pyroptosis related proteins in blood cells was detected to reveal the molecular mechanism of coal workers' pneumoconiosis. Results: All 142 subjects were male, with an average age of (51.65±6.31) years old and an average working age of (15.94±9.38) years. There were significant differences in smoking age (F=4.95, P=0.003) and lunch break distribution (H=8.84, P=0.031) among all groups. The hemoglobin content of stage Ⅰ patients was higher than that of stage Ⅱ patients, and the neutrophil percentage of stage Ⅲ patients was higher than that of the other 3 groups (P<0.05). The levels of total bilirubin and indirect bilirubin in stage Ⅰ patients were higher than those in control group, while the erythrocyte sedimentation rate in stage Ⅱ patients was higher than that in the other 3 groups (P<0.05). The levels of IL-18 and IL-1ß in stage Ⅲ of coal workers' pneumoconiosis were higher than those in the other 3 groups (P<0.05). Multiple logistic regression analysis showed that smoking age (OR=1.03, 95%CI: 1.00-1.06) and IL-1ß level (OR=4.61, 95%CI: 1.59-13.32) were independent risk factors for coal workers' pneumoconiosis (P<0.05). Compared with the control group, the expression levels of nucleotide-binding of oligomeric domain-like receptor protein 3 (NLRP3), Caspase-1, GSDMD, Caspase-4 and other proteins in stage Ⅲ of coal workers' pneumoconiosis were significantly increased (P<0.05) . Conclusion: Smoking age is a risk factor for coal workers' pneumoconiosis, IL-1ß may be a potential biomarker for the diagnosis of coal workers' pneumoconiosis, and pyroptosis may play a role in the development of peripheral inflammation of coal workers' pneumoconiosis.