📋 Browse Articles

Acute respiratory distress syndrome (ARDS) is a lung inflammatory condition associated with the accumulation of fluid edema and cell infiltrates into the alveolar space along with dysregulation of the immune response. Current therapeutics are limited to palliative care, i.e., mechanical ventilators, thus highlighting the need to develop targeted therapeutic for ARDS. Interleukin-27 (IL-27) is a multifunctional cytokine with the capability for immune modulation. Our interest lies in exploring the properties of IL-27, particularly as an anti-inflammatory cytokine that functions as an antagonist of IL-6 signaling, as an inducer of anti-viral genes, as a promoter of tissue repair, and as a regulator of both the innate and adaptive immune responses, possessing promising potential as a therapeutic for ARDS. To overcome the challenge of repeated administration due to the short half-life of cytokines, we utilized a cell-based gene therapy approach. An IL-27-expressing plasmid was transfected into adipose mesenchymal stromal cells (ASC) that serve as the gene therapy carriers. For in vitro studies, we treated mono- and co-culture lung lipopolysaccharide (LPS)-induced lung epithelial and monocytes/macrophages cell line with IL-27-expressing ASC (IL-27 ASC) conditioned media (CM) to determine the effects on pro-inflammatory gene expression. For in vivo studies, male C57BL/6 mice were intratracheally injected with LPS (5 mg/kg) and treated either PBS, ASC, or IL-27 ASC (5 × 10 IL-27 ASC CM reduced pro-inflammatory gene expression of lung epithelial and macrophages cultured in both mono- and co-culture systems. Additionally, IL-27 ASC were able to reduce pro-inflammatory markers, decrease cell infiltration into the lungs, promote genes and immune cells involved in tissue repair, and rebalance innate and adaptive immunity in an LPS-induced in vivo model. Collectively, our in vitro and in vivo results show promising potential for IL-27 cell-based gene therapy as a treatment for ARDS. Show less

This review explores the roles of interleukin-30 (IL-30) and interleukin-27 (IL-27) in inflammation and autoimmune diseases, with a focus on psoriasis. The two coexisting cytokines should be analysed in conjunction as their actions are antagonistic Show less

Obesity arises from an imbalance between adipogenesis and adipocyte thermogenesis. Interleukin-27 (IL-27), a heterodimer cytokine, is known to promote thermogenesis in brown adipose tissue. However, its role in adipogenesis remains unclear. This study aims to investigate the effects of IL-27 on adipogenesis both in vitro and in vivo, and to elucidate the underlying mechanisms. In vitro, an adipogenic differentiation model of adipose-derived mesenchymal stem cells (ADSCs) demonstrate that IL-27 is non-cytotoxic to ADSCs and inhibits ADSCs adipogenic differentiation. In vivo, using a high-fat diet (HFD)-induced obese mouse model and a targeted adipose tissue-specific IL-27 overexpression adeno-associated viral (AAV) vector, we confirm that IL-27 suppresses adipogenesis, prevents weight gain, and improves glucose and lipid metabolic homeostasis in obese mice. Additionally, the inhibition of adipogenesis by IL-27 is mediated through HDAC6 activation of the TGFβ/Smad3 signaling pathway. Our study suggests that IL-27 is a potential therapeutic target for obesity and metabolic disorders. Show less

Neurodevelopmental disorders such as attention deficit and disruptive behaviour disorders (ADHD), autism spectrum disorder (ASD), and schizophrenia have been increasingly prevalent recently. Previous research has demonstrated that inflammatory activity from autoimmune diseases is involved in neurological diseases. However, some studies question the association between inflammatory activities and neurodevelopmental disorders. Herein, we attempt to clarify this relationship using Mendelian randomization (MR) analysis. We used systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and type 1 diabetes mellitus (T1D) to represent autoimmune diseases. First, we conducted MR analysis to examine associated SNPs between autoimmune and neurodevelopmental disorders. Second, we performed bidirectional MR analysis to identify 429 types of signalling peptides and proteins or relevant receptors with causality reported diseases. Finally, we compared the genes with the gene loci identified in the available TWAS-hub site. The MR results of autoimmune diseases on neurodevelopmental disorders did not present any significant association in all models. However, we identified 20-45 factors in ADHD, ASD, and schizophrenia, including semaphorin 3, IL-27 receptor subunit alpha, and fibroblast growth factor 16, which were considered clinically significant pro-inflammatory mediators. GO and KEGG enrichment analyses revealed unequal integrities among the three neurodevelopmental diseases, and we failed to identify a shared pathway linking autoimmune diseases and neurodevelopmental disorders. TWAS analysis indicated that CHRNA5 potentially mediates inflammatory activities in schizophrenia. According to our data, we failed to identify an association between autoimmune diseases and neurodevelopmental disorders. However, we demonstrated that some pro-inflammatory factors are involved in neurodevelopmental disorders. Show less

Psychosocial stress has been linked to myriad mental and physical health conditions. Stress-induced changes to functioning of the immune system is a plausible mechanism in this association. Psychosocial stress is a well-established contributor to immune dysregulation, though the extant literature to date falls short of addressing the role of distal relative to contemporary stress in immune function, particularly as they relate to distinctions between innate and adaptive immunity. The present study directly addressed this knowledge gap by characterizing vertically-integrated markers of immune functioning as a function of both recent chronic stress during adolescence and childhood adversity. In the present study, childhood adversity (before age 10) and recent psychosocial stressors (past 6 months) were characterized via semi-structured clinical interviews among 127 adolescent girls (aged 13-17; 31 % Black, 38 % Hispanic, 32 % NHW) who have all measures included in this report. Vertically-integrated markers of immune activity were also collected: an a priori subset of immune-related genes using genome-wide transcriptional profiling, an 11-plex of circulating cytokines (IL-6, TNF-α, IL-10, IL-8, IFN-γ, IL-1β, IL-1α, IL-27, MCP-1, IL-12p70, IP-10), and systemic inflammation (C-reactive protein; CRP). The association between recent chronic stress and intracellular immune outcomes differed based on childhood adversity. Genome-wide transcriptional profiling implicated myeloid lineage cells, specifically monocytes and dendritic cells, in differential patterns of gene expression among childhood adversity-exposed youth in the context of chronic stress. These differential patterns were also reflected in expression of proinflammatory genes and CRP such that among adolescents without exposure to childhood adversity, more recent chronic stress was associated with less proinflammatory gene expression, b = -0.45 (SE = 0.22), p = 0.04, 95 %CI [-0.87, -0.02], and somewhat higher CRP, b = 0.62 (SE = 0.35), p = 0.08, 95 %CI [-0.07, 1.31], while among adolescents with exposure to childhood adversity, more recent chronic stress was not associated with any immune activity markers. However, these patterns among circulating markers did not survive corrections for multiple comparisons. Immune adaptation in the context of chronic stress may indicate plasticity to environmental demands that conserves biological resources, which may be a source of resilience that is negatively impacted by childhood adversity. Show less

Adverse pregnancy outcomes represent a global health burden. Bacterial infection and subsequent inflammation in gestational membranes lead to immunological and physiological changes that contribute to adverse pregnancy outcomes. Although animal models of infection during pregnancy are useful to interrogate tissue and cellular level changes in host responses, these models also have numerous drawbacks, including cost, complexity, and ethical considerations. The advent of organ-on-a-chip models provides cutting-edge new approaches to model host-pathogen interactions in multicellular organ and tissue environments. In this work, we employ an organ-on-a-chip model of the maternal-fetal interface as a tool to study immunological responses to infection with the perinatal pathogen, Group B Show less

The interleukin-6 (IL-6) family of cytokines includes IL-6, IL-11, IL-27, IL-31, etc. These cytokines are intimately linked with inflammatory diseases and exhibit pleiotropic properties. Several factors, including air pollution, smoking, and an aging population, are contributing to the changing epidemiology of respiratory diseases. A high incidence of respiratory disease represents a significant burden on society and the economy. The prominent role of IL-6 family members in respiratory diseases has been extensively studied, and they influence the disease process through multiple mechanisms and has significant clinical relevance in respiratory diseases. Here, we describe the role of IL-6 family cytokines and their signaling pathways on various immune cells, as well as the research progress on IL-6 family cytokines in respiratory diseases in recent years. The aim of this review is to provide an in-depth analysis of the key role of the IL-6 family in respiratory diseases and to provide a solid theoretical basis for further research and clinical practice in this field. Show less

Intrahepatic immune responses are often insufficient to control hepatitis virus infections. A recent study by Venzin and colleagues demonstrates a detailed mechanism by which an intrahepatic tricellular network and the cytokine IL-27 can augment virus-specific immunity. Show less

Obesity is turning into a more critical problem for public health. Vitamin D The study aims to examine the influence of VD Firstly, a small sample population study was conducted to compare the disparities in serum 25(OH)D A correlation was identified between serum 25(OH)D The study shows that VD Show less

Hyperactivation of cutaneous macrophages promotes the development of chronic pain. Stimulation of nociceptive regions promotes neuroplasticity, which affects pain perception and related physiological responses. However, the specific mechanisms by which cutaneous macrophages sense and elicit nociceptive responses are unknown. Here, we exacerbated the reduction of systemic pain threshold after chronic heart failure (CHF) by silencing follistatin-like 1 (FSTL1), especially the abnormal cutaneous nociceptive sensation at PC6 acupoint, the site associated with cardiac involvement pain. The upregulation of P2Y6 and interleukin-27 expression is intimately linked to the activation of skin macrophages. Hyperactivation of P2Y6 receptor (P2Y6R) may be associated with MHC II M1 Show less

Tuberculosis (TB) is a serious public health concern in many regions of the world and the only approved vaccine to prevent TB is the live-attenuated BCG vaccine. Despite being widely used, the BCG vaccine fails to prevent pulmonary TB in adults. The BCG vaccine is administered during the neonatal period when levels of the immunosuppressive cytokine interleukin (IL)-27 are elevated, and previous studies have demonstrated that the source of IL-27 can impact downstream immune responses. We therefore sought to characterize the specific subpopulations of myeloid cells that produce IL-27 following BCG vaccination. To investigate this, we administered the BCG vaccine to neonatal IL-27p28eGFP mice that report IL-27 production. Our studies demonstrated that BCG vaccination steadily increased IL-27 production throughout the weeks post-vaccination. We also showed that a predominantly CD11b+ F4/80+ population of IL-27 producers increased MHC class II expression following BCG vaccination in both the spleen and the lung. However, producers of IL-27 in these tissues differ, with a population of CD11c+ MHC II+ cells emerging in the spleen and a subset of Ly6G/C+ MHC II+ emerging in the lung. 10x scMultiome analysis further validated the increase in MHC class II expression and demonstrated improved antigen presentation functionality following vaccination. The sequencing analysis also revealed subpopulations of IL-27 producers with immunosuppressive functions such as a population of macrophages with increased Mrc1 expression post-vaccination. Our findings suggest that IL-27 producers are a heterogenous population of myeloid cells that impact the development of protective immune responses induced by the BCG vaccine. Show less

Immunosenescence is accelerated by chronic infectious and autoimmune diseases and could contribute to the pathobiology of multiple sclerosis (MS). How MS and disease-modifying therapies (DMTs) impact age-sensitive immune biomarkers is only partially understood. We analyzed 771 serum samples from 147 healthy controls and 289 people with MS (PwMS) by multiplex immunoassays. We determined cytomegalovirus (CMV) serostatus and collected retrospective clinical information. We performed unsupervised and multivariable analyses. Unsupervised analyses revealed that MS immune profile was characterized by low relative levels of anti-inflammatory/neuroprotective factors IL-4, IL-10, TNF, and β-NGF but high levels of growth factors EGF and bFGF. Serum levels of IL-4, β-NGF, IL-27, BDNF, and leptin were significantly influenced by sex and/or CMV status. IL-4 and β-NGF levels were lower in untreated PwMS compared to controls, while EGF and bFGF levels were influenced by age and markedly elevated in PwMS in multivariable analysis. Samples from treated PwMS, but not untreated PwMS, showed lower levels of BDNF and TNF than controls. Initiation of high efficacy DMTs, but not low efficacy DMTs, was associated with reduced levels of bFGF and EGF. Samples associated with distinct DMTs exhibited specific profiles for age-sensitive immune markers. Finally, lower levels of IL-6, TNF, IL-10, and β-NGF were observed at baseline in PwMS who subsequently experienced clinical failure after DMTs initiation. Age, sex, CMV status, and specific DMTs significantly influence levels of age-sensitive immune biomarkers associated with MS and must be considered when investigating inflammation-related biomarkers. This work was supported by a Grant for Multiple Sclerosis Innovation by Merck KGaA (ID: 10.12039/100009945). Show less

Artemisinin and its derivatives, used as front-line anti-malarial drugs, exhibit anti-inflammatory properties. They were found to suppress the generation and function of Th1 and Th17 cells while promoting the generation of Foxp3 + regulatory T cells (Tregs). However, the specific role of Artemotil (β-arteether) in modulating the generation and functions of CD4 + T cells, particularly Type 1 regulatory T cells (Tr1), remains to be explored. Tr1 cells are one of the key cell types that are essential for regulating inflammatory response through IL-10. In this study, we report that Artemotil selectively promotes generation of Tr1 cells induced by IL-27 by upregulating signature genes of Tr1 cells, such as c-Maf, AhR, prdm1, IRF-1, and Batf, while inhibiting the Th1, Th2, and Th17 cells generation. We found that co-administration of Artemotil with anti-CD3 antibody increases the induction of IL-10 and frequency of Tr1 cells while suppressing Th1 and Th17 cells in vivo. Artemotil suppresses T-cell-induced enteropathy and alleviates the signs of colitis associated with the increased frequencies of Tr1 cells. Taken together, our data suggest that Artemotil provides protection in T-cell-mediated colitis by increasing the expansion of Tr1 cells and inhibiting the generation of Th1 and Th17 cells. Show less

The characterization of physiological immune signatures in a population-based cohort is a prerequisite for identifying pathological immune signatures associated with inflammatory or autoimmune diseases. Here, 47 plasma cytokines, chemokines, and growth factors were quantified with a bead-based multiplex-assay (Merck HCYTA-60 K) using a FLEXMAP 3D™ instrument in 1175 individuals of the Study of Health in Pomerania (SHIP; TREND cohort, 532 men and 643 women, age: 20 to 81, BMI: 17.7 to 53.6). Associations of cytokine concentrations with age, sex, BMI, season, and blood cell parameters (BCP) were examined by multivariate regression models. The physiological cytokine concentrations differed strongly between analytes, with median concentrations ranging from 0.6 to 7820 pg/mL. Many cytokine levels showed a large dynamic range within the study population. Higher levels of the pro-inflammatory cytokines and chemokines IL-6, IL-8, CXCL9, CXCL10, IL-12p40, CCL2, CCL4, CCL11, IL-27, FLT3LG, and TNFα were significantly associated with increasing age. The strongest age-associated effects were seen for CXCL9 (β The generated cytokine atlas provides detailed information on cytokine variations in the general population and will provide a reference base for disease-related studies in the future. Furthermore, BCPs should be considered as potential confounders in association studies based on plasma cytokine levels. Show less

One vision-threatening side effect of systematic diabetes mellitus is diabetic retinopathy (DR). Recent studies have revealed that the development and progression of DR depend critically on inflammation resulting from diabetes. By attracting leukocytes to endothelium, the higher production of the inflammatory mediators induces degeneration of retinal capillaries, hence increasing vascular permeability and thrombosis probability. The leukocytes that are recruited eventually generate additional proinflammatory and proangiogenic substances, resulting in the increased infiltration of leukocytes in the retina. This process also leads to changes in the blood retinal barrier and the formation of new blood vessels, which helps to counteract the damage caused by the blockage of blood flow. IL-12 family members, IL-12, IL-23, IL-27, and IL-35, play a crucial role in regulating the responses of T helper (Th)1 and Th17 cell populations. The collected data from studies investigating the levels of IL-12 family members in the blood and eye tissues suggest that IL-12 is linked to DR, indicating that it may have a role in the development of DR as a sequential component of the immune response. This review specifically examines the possibility of using IL-12 family cytokines as a therapeutic approach for diabetes, taking into consideration their involvement in the development of DR. Show less

Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by high morbidity and mortality rates. Sepsis-induced ARDS involves excessive inflammatory responses, which are modulated by macrophages. This study aimed to elucidate the effect of Recombinant Mouse IL-27 Protein on macrophage ferroptosis and polarization, as well as its impact on sepsis-induced ARDS. A cecal ligation and puncture (CLP)-induced sepsis model was established using wild-type (WT) or IL27R In vitro, IL-27 alone did not alter the expression of proteins linked to the ferroptosis pathway or macrophage polarization. Contrastingly, the combination of IL-27 with LPS further amplified LPS-induced alterations in the ferroptosis pathway, thereby promoting macrophage M1 polarization and inhibiting M2 polarization. Additionally, IL-27 + LPS increased ROS levels in macrophages. A sepsis-induced ARDS mouse model was then established via CLP. In vivo, IL-27 exacerbated CLP-induced lung injury in WT mice. Additionally, it decreased the expression levels of ferroptosis-related proteins (Nrf2, HO-1, GPX4) and increased those of Ptgs2 in the lung tissue of septic mice. Besides, GSH and SOD levels in lung tissue were also reduced. Moreover, IL-27 also promoted M1 polarization and inhibited M2 polarization in macrophages. In IL27R Oltipraz may alleviate ARDS-related lung injury by up-regulating Nrf2 expression and concurrently inhibiting macrophage ferroptosis. Show less

Our aim was to explore the IL-27 effect in sepsis (SP)-related acute hepatic injury (AHI) as well as its possible mechanism. Herein, we utilized both wild-type (WT) and IL-27 receptor (WSX-1)-deficient (IL-27R The results revealed that IL-27 exacerbated systemic inflammation and liver damage in AHI mice by promoting M1 macrophage polarization, thereby increasing pro-inflammatory phenotype macrophages (M1). This further exacerbated the inflammatory response and pyroptosis in vivo and in vitro. Additionally, IL-27 down-regulated p-AMPK and SIRT1 protein expression while overexpressing macrophage inflammatory mediators including IL-1β/6 and TNFα. Furthermore, IL-27 promoted increased RAGE and caspase-11 protein expression, aggravating macrophage pyroptosis. Employing CC to block the AMPK pathway further aggravated M1 macrophage polarization and pyroptosis in vitro and in vivo, ultimately worsening liver injury. Here, IL-27 aggravates AHI by promoting macrophage M1 polarization to induce caspase-11-mediated pyroptosis in vitro and in vivo, which may be linked to the AMPK/SIRT1 signaling pathway. Show less

Fermented foods and ingredients, including furmenties derived from lactic acid bacteria (LAB) in dairy products, can modulate the immune system. Here, we describe the use of reconstituted skimmed milk powder to generate novel fermentates from Show less

The prevalence of metabolic diseases, such as obesity, has been steadily increasing in recent years, posing a significant threat to public health. Therefore, early identification and intervention play a crucial role. With the deepening understanding of the etiology of metabolic diseases, novel therapeutic targets are emerging for the treatment of obesity, lipid metabolism disorders, cardiovascular and cerebrovascular diseases, glucose metabolism disorders, and other related metabolic conditions. IL-27, as a multi-potent cytokine, holds great promise as a potential candidate target in this regard. This article provides a comprehensive review of the latest findings on IL-27 expression and signal transduction in the regulation of immune inflammatory cells, as well as its implications in obesity and other related metabolic diseases. Furthermore, it explores the potential of IL-27 as a novel therapeutic target for the treatment of obesity and metabolic disorders. Finally, an overview is presented on both the opportunities and challenges associated with targeting IL-27 for therapeutic interventions. Show less

Primary atopic disorders (PAD) are monogenic disorders caused by pathogenic gene variants encoding proteins that are key for the maintenance of a healthy skin barrier and a well-functioning immune system. Physicians face the challenge to find single, extremely rare PAD patients/families among the millions of individuals with common allergic diseases. We describe case scenarios with signature PAD. We review the literature and deduct specific clinical red flags for PAD detection. They include a positive family history and/or signs of pathological susceptibility to infections, immunodysregulation, or syndromic disease. Results of conventional laboratory and most immunological lab studies are not sufficient to make a definitive diagnosis of PAD. In the past, multistep narrowing of differential diagnoses by various immunological and other laboratory tests led to testing of single genes or gene panel analyses, which was a time-consuming and often unsuccessful approach. The implementation of whole-genomic analyses in the routine diagnostics has led to a paradigm shift. Upfront genome-wide analysis by whole genome sequencing (WGS) will shorten the time to diagnosis, save patients from unnecessary investigations, and reduce morbidity and mortality. We propose a rational, clinical landmark-based approach for deciding which cases pass the filter for carrying out early WGS. WGS result interpretation requires a great deal of caution regarding the causal relationship of variants in PAD phenotypes and absence of proof by adequate functional tests. In case of negative WGS results, a re-iteration attitude with re-analyses of the data (using the latest data base annotation)) may eventually lead to PAD diagnosis. PAD, like many other rare genetic diseases, will only be successfully managed, if physicians from different clinical specialties and geneticists interact regularly in multidisciplinary conferences. Show less

Polycystic ovarian syndrome (PCOS) is the most common reproductive metabolic disorder in women of reproductive age. However, the underlying mechanism is unclear, because the main symptoms vary with age and the pathogenesis is complex and multifactorial. In order to explore the gene expression and regulation networks, and identify potential biomarkers for diagnosis and treatment of PCOS, we conducted whole RNA sequencing of protein-coding genes, lncRNAs, and miRNAs in peripheral blood with case-control design. RNA sequencing and weighted gene co-expression network analysis (WGCNA) were performed on four pairs of PCOS cases and control peripheral blood samples. The results showed that there were significant differences in the expression levels of 341 mRNAs, 252 lncRNAs and 47 miRNAs between PCOS patients and control groups. Bioinformatics analysis showed that these differentially expressed genes (DEGs) were mainly involved in the metabolic, immune, endocrine, and nervous systems, and also identified potential WGCNA module related with PCOS. The DEGs of PCOS as reported in other published literatures were used to verify our DEGs in this study. These results suggest that the ceRNA regulatory relationship between The online version contains supplementary material available at 10.1007/s43657-024-00183-9. Show less

Systemic lupus erythematosus (SLE) is an autoimmune disorder that commonly affects the skin, kidneys, joints, and various other systemic tissues, with its development intricately linked to the process of immunosenescence. Quercetin (QC), a phytochemical that occurs naturally, demonstrates many different biological capabilities, such as antibacterial, antioxidant, and anti-inflammatory activities. Our investigation found that QC effectively reduced kidney damage and relieved mesenteric lymph nodes (mLNs) swelling in MRL/lpr lupus mice. Moreover, QC has been found to decrease the number of senescent follicular helper T (Tfh) cells, a pivotal kind of T cells that contribute to the progression of SLE. In vitro, QC exhibited the capacity to modulate mRNA expression levels, with the downregulation of IL-6, IL21-AS1, IL-27, BCL6, and BCL2L12, and the upregulation of FOXP1 and BIM. This modulation resulted in the suppression of Tfh cells differentiation and the enhancement of apoptosis in senescent CD4 Show less

To explore the influencing factors of osteoporosis (OP) in elderly patients with rheumatoid arthritis (RA). A total of 145 elderly patients with RA were divided into comorbidity group (with OP) of 79 patients and RA group (without OP) of 66 patients. Demographic data and laboratory parameters were collected from patients. Demographic characteristics and laboratory parameters were compared between the two groups. Multiple influencing factors of OP in RA patients were analysed. There were significant differences in age, BMI, primary disease duration, history of glucocorticoids (GC) administration, disease activity score in 28 joints (DAS-28), and Sharp score data between the two groups. There were significant differences in rheumatoid factor (RF), interleukin-27 (IL-27), procollagen I N-Terminal Propeptide (PINP), nuclear receptor of activator factor-κB ligand (RANKL), and 25-hydroxyvitamin D [25-hydroxyvitamin D, 25 (OH) D] data between the two groups (P < 0.05). Logistic analysis showed that age, primary disease duration, GC history, DAS-28, Sharp score, RANKL and 25 (OH) D were independent factors for OP in RA patients. The risk of OP in elderly RA patients is mainly related to age, primary disease duration, GC history, DAS-28, Sharp score, RANKL, and 25 (OH) D levels, and risk factors should be actively prevented. Show less

Neonatal sepsis is a significant cause of mortality in children under 5 years of age globally, with the highest incidence reported in India. The challenges in diagnosing neonatal sepsis often result in the irrational use of antibiotics. The aim of the study was to determine the diagnostic efficacy of interleukin 27 (IL-27) as a novel biomarker for the early diagnosis of neonatal sepsis. This prospective cohort study was conducted at a tertiary care hospital in North India from May 2019 to April 2020. Eighty neonates suspected of sepsis were enrolled based on the sepsis screen criteria approved by the National Neonatal Forum of India. Blood samples were collected for culture and biomarker analysis, with C-reactive protein (CRP), procalcitonin (PCT), and IL-27 levels measured. The diagnostic performance of IL-27 was compared to that of CRP and PCT. Out of 80 neonates, 56% were male and 44% were female. Blood cultures were positive in 51.2% of cases. The most common pathogens isolated were Gram-negative bacteria (41%), fungi (34%), and Gram-positive bacteria (25%). IL-27 demonstrated a sensitivity of 78.05%, specificity of 61.54%, positive predictive value of 68.09%, and negative predictive value (NPV) of 72.73%. In comparison, PCT showed the highest sensitivity (82.93%), and CRP had the highest specificity (79.49%). IL-27 levels were notably higher in blood culture-positive cases. IL-27 is a promising biomarker for the early diagnosis of neonatal sepsis, showing comparable sensitivity and NPV to PCT, but with lower specificity than CRP. Show less

Bullous pemphigoid (BP) and prurigo nodularis (PN) are chronic pruritic skin diseases that severely impact patients' quality of life. Despite the widespread attention these two diseases have garnered within the dermatological field, the specific pathogenesis, particularly the molecular mechanisms underlying the pruritus, remains largely unclear. Limited clinical sequencing studies focusing on BP and PN have hindered the identification of pathological mechanisms and the exploration of effective treatment strategies. To address this gap, we collected a total of 23 peripheral blood mononuclear cell samples from BP and PN patients, as well as healthy controls, and performed RNA sequencing analysis. By integrating bioinformatics and machine learning techniques, we aimed to uncover the shared immune regulatory networks and pruritus-related mechanisms between BP and PN. Our study identified 161 differentially expressed genes shared between BP and PN, which were primarily enriched in immune activation and neural pathways, providing crucial molecular insights into the pruritus-related mechanisms of both diseases. Furthermore, using the machine learning algorithms of support vector machines and random forest, we pinpoint 7 crucial genes shared between the BP and PN databases. Among these, IL-27 emerged as a potential pivotal gene, as its mRNA expression levels strongly correlated with clinical parameters including pruritus scores, immunoglobulin E levels, and eosinophil counts. Validation experiments conducted on clinical samples from an additional 22 participants confirmed the upregulation of IL-27 expression in both BP and PN lesions. This study is the first to unveil the shared inflammatory and immune pathways common to BP and PN, highlighting the critical role of IL-27 in the pathogenesis of these conditions. Our findings not only enhance the understanding of the intricate relationship between BP and PN, but also provide a foundation for the development of novel therapeutic strategies targeting these two dermatological conditions. Show less

Interleukin (IL)-41, a type of cytokine also known as Metrnl, is involved in the pathogenesis of various inflammatory and immune-related diseases. However, its role in Ankylosing Spondylitis (AS), a field yet to be explored, remains a mystery. This study therefore assesses the diagnostic utility of IL-41 in patients with AS and examines the correlations among IL-41 levels, disease activity, and patients' demographic and clinical data. Such novel insights could have significant implications for the diagnosis and management of AS. Eighty-eight patients diagnosed with AS were enrolled from the Rheumatology Unit at Baghdad Teaching Hospital. Participants were categorized into two groups based on disease status: inactive (n = 44) and active (n = 44). Additionally, 44 matched healthy individuals were included as controls. Comprehensive medical histories were obtained, including disease duration, body mass index, sex, and age. Laboratory parameters related to the disease-such as C-reactive protein, human leukocyte antigen (HLA-B27), and rheumatoid factor-were also measured. Serum IL-41 levels were quantified using an enzyme-linked immunosorbent assay. The study revealed a significant difference in levels of IL-41 in patients with AS (17.721±0.705 ng/L) compared to controls (8.495±0.984 ng/L; P = 0.009). The mean serum IL-41 concentration was highest in the active group (23.037±5.268 ng/L), followed by the inactive group (12.411±1.672 ng/L; p = 0.001) and controls (8.495±0.984 ng/L). Serum IL-41 levels demonstrated strong validity for diagnosing AS, with a cutoff value of ≥ 9.35 ng/mL and an area under the curve of 0.991. The sensitivity, specificity, and accuracy were 97.7%, 79.5%, and 92.38%, respectively (p = 0.002). IL-41 is a potential new diagnostic biomarker for AS and associated with patient's disease activity. These insights could potentially transform the way we diagnose and manage AS, offering new avenues for improved patient care and outcomes. Show less