Serum IL-6 Levels Research Articles

Diagnostic value of miR-34a in Mycoplasma pneumoniae pneumonia in children and its correlation with rehabilitation effect

BackgroundMycoplasma pneumoniae pneumonia (MPP) is responsible for 20 to 40% of all cases of pneumonia acquired by children and shows an increasing incidence year by year. The aim of this study was to investigate the expression of miR-34a in children with MPP and its diagnostic value, and further explore the relationship between miR-34a and the rehabilitation effect of children with MPP.MethodsThe expression level of miR-34a was detected by RT-qPCR, and the clinical value of miR-34a was analyzed by ROC analysis. In addition, the levels of IL-6, IL-18 and TNF-α in serum of children with MPP were detected by ELISA kit, and the correlation with miR-34a was analyzed.ResultsElevated levels of miR-34a were observed in the serum of children with MPP, and significantly higher expression levels were observed in children with severe symptoms and poor rehabilitation. The study suggested that miR-34a has potential as a diagnostic marker for MPP in children, helping to distinguish between mild and severe cases and predicting rehabilitation from MPP in children. In addition, miR-34a expression was positively correlated with IL-6, IL-8, and TNF-α levels.ConclusionsmiR-34a is closely related to MPP in children and miR-34a may be used as a clinical biomarker for MPP in children.

Astragaloside IV suppresses the proliferation and inflammatory response of human epidermal keratinocytes and ameliorates imiquimod-induced psoriasis-like skin damage in mice.

The primary pathological features of psoriasis include excessive epidermal keratinocytes and infiltration of inflammatory cells, which are pivotal targets for psoriasis therapy. Astragaloside IV (AS-IV), the principal active compound of astragalus, exhibits anti-inflammatory, antioxidant, and immune-modulatory properties. This study aims to investigate AS-IV's anti--psoriatic effects and underlying mechanisms. Normal human epidermal keratinocytes (NHEKs) were stimulated with a combination of TNF-α, IL-17A, IL-1α, IL-22, and oncostatin M (M5) to replicate psoriatic keratinocyte pathology in vitro. Cell proliferation was assessed using CCK8 and EDU staining. Pro-inflammatory cytokine levels were measured via qRT-PCR. In addition, an imiquimod (IMQ)-induced psoriasis mouse model was utilized. Skin histology changes were evaluated with HE staining, while IL-6 and TNF-α levels in mouse serum were quantified using ELISA. NF-κB pathway protein expression was analyzed by western blotting. The results demonstrated that AS-IV inhibited M5-induced proliferation of NHEKs. AS-IV reduced M5-stimulated IL-1β, IL-6, IL-8, TNF-α, IL-23, and MCP-1 expression in NHEKs. Moreover, M5-induced phosphorylation of IκBα and p65 was significantly attenuated by AS-IV. Furthermore, AS-IV application ameliorated erythema, scale formation, and epidermal thickening in IMQ-induced psoriasis-like mouse models. AS-IV also decreased IL-6 and TNF-α levels in mouse serum and inhibited IκBα and p65 phosphorylation in skin tissues. However, prostratin treatment reversed these effects. These findings underscore AS-IV's capacity to mitigate M5-induced NHEK proliferation and inflammation. AS-IV shows promise in alleviating IMQ-induced psoriasis-like skin lesions and inflammation by suppressing the NF-κB pathway.

Study on the Immunomodulatory effect of Qixian Decoction in an Asthmatic Mice Model Based on Serum Metabolomics

AbstractThe study aimed to investigate the immunomodulatory effect of Qixian Decoction (QXT) in an asthmatic model. In this study, ovalbumin (OVA)-induced asthma in female SPF BALB/c mice was established. Mice were randomly divided into four groups (n = 8): a control group, an OVA model group, a low-dose Qixian Granules (KLL) group, and a high-dose Qixian Granules (KLH) group. Mice in the KLL and KLH groups were given the Qixian Granules at a dose of 8 and 16 g/kg, respectively. After the treatment, the lung pathology was evaluated. The expression of inflammatory factors was determined. Serum metabolomics was used to investigate the overall regulation of QXT on the metabolism of asthmatic mice. Our data showed that QXT significantly increased the expression levels of Th1-related interferon-γ, Treg-related interleukin (IL)-10, and transforming growth factor-β1 while decreasing Th1-related tumor necrosis factor α levels in bronchoalveolar lavage fluid, and Th2-related IL-4 and IL-5 levels in serum when compared with the model group (all p < 0.05). Serum metabolomics revealed 28 potential biomarkers associated with nine pathways. Compared with the control group, 19 different metabolites in the KLL group and 18 different metabolites in the KLH were reversed. QXT's therapeutic effect against asthma might be related to glycerophospholipid metabolism and arachidonic acid metabolism. In conclusion, QXT could ameliorate inflammation of the OVA-induced asthmatic mice, mainly by regulating the expression of immune-related factors, probably through regulating the Th1/Th2 immune balance and promoting the proliferation of Treg.

Alpinia officinarum Hance extract relieved sepsis-induced myocardial ferroptosis and inflammation by inhibiting lncRNA MIAT/TRAF6/NF-κB axis.

Sepsis is generally triggered by a dysfunctional host response to infection, and it can result in life-threatening organ dysfunction. Alpinia officinarum Hance (AO) exhibits regulatory functions in some diseases. However, whether AO extract (AOE) plays a promoting role in sepsis--triggered myocardial injury is unclear. This study was aimed at investigating the regulatory effects of AOE on myocardial ferroptosis and inflammation in sepsis, and the regulation effects on the lncRNA MIAT/TRAF6/NF-κB axis. Lipopolysaccharide (LPS) was used to treat mice for establishing an in vivo sepsis model. The pathological changes in heart tissues were observed through hematoxylin-eosin (HE) staining. The levels of CK-MB, cTnl, MDA, SOD, IL-1β, IL-18, IL-6, and TNF-α in serum were detected through enzyme-linked immunosorbent assay (ELISA). The level of Fe2+ was assessed, and the protein expressions (ACSL4, GPX4, TRAF6, p-P65, and P65) were examined through western blot. The expressions of lncRNA MIAT and TRAF6 were measured through real-time quantitative polymerase chain reaction (RT-qPCR). Our results demonstrated that AOE treatment ameliorated sepsis-triggered myocardial damage by reducing the disordered cardiomyocytes, the destroyed sarcolemma, and the CK-MB and cTnl levels. In addition, AOE treatment inhibited sepsis-induced myocardial ferroptosis and inflammation by regulating Fe2+, ACSL4, GPX4, IL-1β, IL-18, IL-6, and TNF-α levels. Moreover, the improvement effect of AOE was strengthened with the increase in the dose of AOE (25, 50, 100 mg/kg). It was also revealed that AOE treatment retarded the lncRNA MIAT/TRAF6/NF-κB axis. Rescue assays manifested that overexpression of MIAT reduced the cardioprotective effect of AOE. In conclusion, AOE relieved sepsis-induced myocardial ferroptosis and inflammation by inhibiting lncRNA MIAT/TRAF6/NF-κB axis. These findings may provide a potential therapeutic drug for the treatment of sepsis.

Buzhong Yiqi decoction attenuates acquired myasthenia by regulating the JAK2/STAT3/AKT signaling pathway, inhibiting inflammation, and improving mitochondrial function.

Acquired myasthenia (AM), a debilitating autoimmune disease, is typically characterized by skeletal muscle fatigue and weakness. Despite advances in myasthenia gravis treatment, current approaches remain unsatisfactory and many result in unexpected side effects. Traditional Chinese medicine has shown great potential in the treatment of myasthenia gravis, including relieving myasthenic symptoms, improving patients' quality of life, and reducing Western medicine side effects. This study investigates the protective effects and mechanism of BZYQD in mice with acquired myasthenia. BZYQD alleviates the reduced grip strength and increased expression of MAFbx and MuRF-1 in mice with acquired myasthenia. It also reduces levels of pro-inflammatory factors IL-1β, IL-6, and TNF-α in the mouse serum. In addition, BZYQD reduces ROS accumulation and the mitochondrial ROS production rate, while increasing ATP levels and mitochondrial membrane potential in mice with acquired myasthenia. Moreover, BZYQD decreases the expression of p-JAK2, p-STAT3, and p-AKT in the skeletal muscle of mice with acquired myasthenia. In summary, BZYQD reduces inflammation, enhances mitochondrial function, and regulates the JAK2/STAT3/AKT signaling pathway to treat acquired myasthenia.

Correlation between Serum Levels of Factor I, CD59, Interferon-gamma, and Interleukin-6 with the Response to Rituximab in Iraqi Patients with Rheumatoid Arthritis

Background: Rituximab is a chimeric IgG1 kappa immunoglobulin that has been genetically modified to incorporate human constant region sequences together with murine light- and heavy-chain variable region sequences. People use it to treat rheumatoid arthritis and certain malignancies. Objective: The study aimed to assess the potential association between the serum levels of Factor I, CD59, interleukins (IL)-6, and interferon-gamma (IFN)-γ and the response to Rituximab treatment in Iraqi rheumatoid arthritis patients. Methods: A cross-sectional study was conducted at the rheumatology center at Baghdad Teaching Hospital. Ninety adult patients who have been diagnosed with rheumatoid arthritis and are receiving Rituximab intravenous infusions were included. The enrolled patients were divided into a responder group (45 patients) and a non-responder group (45 patients). The response to Rituximab was assessed according to the 28-joint Disease Activity Score (DAS28). Results: The serum levels of Factor I and CD59 were significantly higher in the non-responders group in comparison to the responders group. In addition, the serum IL-6 and IFN-γ levels were significantly elevated in the non-responders group in comparison to the responders group. The estimated marker serum levels showed a strong, significant correlation with the 6-month change in DAS28. Conclusions: In Rituximab nonresponder RA patients, serum levels of Factor I, CD59, Factor H, IL-6, and IFN-γ are higher, and they have good potential to be used in the assessment of the response to Rituximab therapy.

Myristica fragrans Houtt. methanol extract as a promising treatment for Cryptosporidium parvum infection in experimentally immunosuppressed and immunocompetent mice.

Cryptosporidiosis is a major waterborne disease affecting ruminants and humans worldwide. It causes diarrhea and neonatal mortality in buffalo calves, and watery diarrhea and mortality in children and immunodeficient patients. This study aimed to investigate the efficacy of Myristica fragrans methanolic extract in treatment of C. parvum infection in comparison with nitazoxanide (NZX) (a Food and Drug Administration-approved drug control) in immunosuppressed and immunocompetent mice. One hundred laboratory-bred male Swiss albino mice were equally divided into immunocompetent and immunosuppressed groups. Each group was further divided into five subgroups: (1) non-infected and non-treated control, (2) infected and non-treated control (infected with Cryptosporidium parvum oocysts 3 × 103), (3) NZX-treated (100 mg/kg, 200 μL/mouse), (4) M. fragrans Houtt. methanol extract-treated (500 mg/kg), and (5) combination-treated (NZX + M. fragrans extract). Number of oocysts/g of feces, serum immunoglobulin (Ig) G level, and interferon (IFN)-γ, and interleukin (IL)-4 levels were used to evaluate the therapeutic effect. C. parvum oocyst shedding in stool samples was significantly decreased in all treatment groups, with 79.7%, 81.2 %, and 85.5 % reduction in immunocompetent mice treated with NZX, M. fragrans, and their combination, respectively. In immunosuppressed mice, oocyst shedding was reduced by 77.7%, 80.5 %, and 83.7 % upon NZX, M. fragrans, and their combination treatments, respectively. The serum IgG level was lowest in mice treated with a mixture of M. fragrans and NZX, followed by those treated with NZX, and was highest in mice treated with M. fragrans alone. Regarding cytokine levels, all groups treated with M. fragrans had low levels of IFN-γ and IL4 on day 21 post-infection. Collectively, the treatment of cryptosporidiosis with M. fragrans extract was successful in mice, as demonstrated by the measured parameters. M. fragrans reduced C. parvum oocyst shedding and serum IgG, IFN-γ, and IL-4 levels in immunocompetent and immunosuppressed mice.

Oleanolic acid attenuates obesity through modulating the lipid metabolism in high-fat diet-fed mice.

As a natural pentacyclic triterpenoid, oleanolic acid has hepatoprotective, anti-inflammatory, and antioxidant activities. This work performed the invitro experiments and animal assay to explore whether oleanolic acid alleviates lipid accumulation induced by high-fat diet by mediating PPARγ. Oil red O staining showed that oleanolic acid can reduce lipid accumulation in HepG2 cells, which were treated with oleic acid and palmitic acid. Immunofluorescence, western blot analysis, and RT-qPCR showed that oleanolic acid could promote nuclear translocation of PPARγ and reduce the expression level of PPARγ, C/EBP-β, and SREBP-1c. The results of invivo experiments indicated that dietary intervention with oleanolic acid can effectively improve the fat accumulation in liver tissue and attenuate the level of IL-6 and TNF-α in serum caused by high-fat diet. Meanwhile, oleanolic acid did not cause lesions in vital organs at the experimental concentrations. In addition, the computer simulation indicated that oleanolic acid could directly bind to PPARγ with a reasonable and stable docking conformation. The above research results can provide new evidence for oleanolic acid to prevent nonalcoholic fatty liver disease.

Correlation Between Gut Microbiota Composition and Serum Interleukin 17 (IL-17) in Mice With Type 2 Diabetes and Experimental Periodontitis.

Objective To preliminarily explore the composition characteristics of gut microbiota in mice with type 2 diabetes mellitus (T2DM) and experimental periodontitis, and their correlation with serum IL-17 levels, aiming to provide new insights and evidence for related experimental studies. Methods A total of 42 SPF-grade C57BL/6J mice were randomly selected, with 24 used for T2DM modeling. Successfully modeled T2DM mice were divided into the T2DM group (ND group, n=8) and T2DM with experimental periodontitis group (PD group, n=8). Non-T2DM mice were divided into the blank control group (NC group, n=8) and the experimental periodontitis group (NP group, n=8). After modeling, body weight and fasting plasma glucose (FPG) were measured weekly. Each group of mice underwent an oral glucose tolerance test (OGTT) and an insulin tolerance test (ITT). Six weeks after modeling experimental periodontitis, serum IL-17 levels were measured using ELISA, intestinal inflammation was assessed using HE staining, and gut microbiota composition in cecal contents was analyzed by 16S rRNA sequencing to determine its correlation with serum IL-17 levels. Results FPG in the PD group was higher than in the ND group, with a statistically significant difference in the 12th week (p<0.05). The glucose tolerance level in the PD group was lower than in the ND group (p<0.01). Compared with the NC group, other groups showed varying degrees of inflammatory cell infiltration in the intestinal mucosa, and serum IL-17 levels were lower in both the ND and PD groups compared to the NC group (p<0.01), with the PD group also lower than the NP group (p<0.01). The Shannon and Pielou-e indices of gut microbiota in the PD group were significantly lower than those in the NP group (p<0.05). In terms of microbiota composition, Firmicutes were increased in both the ND and PD groups compared to the NC and NP groups (p<0.05), while Bacteroidetes were decreased (p<0.05). Proteobacteria were increased in the PD group compared to the ND group (p<0.05). The abundance of Bacteroidetes and the Bacteroidetes/Firmicutes ratio was moderately positively correlated with serum IL-17 levels (p<0.01) and moderately negatively correlated with blood glucose levels (p<0.01); serum IL-17 levels were strongly negatively correlated with blood glucose levels (p<0.01). Conclusion Comorbidity of experimental periodontitis and T2DM may exacerbate glucose metabolism impairment in T2DM mice by increasing the abundance of Proteobacteria and intestinal mucosal damage. Serum IL-17 levels may serve as an indicator of gut microbiota dysbiosis in T2DM mice with experimental periodontitis.

Association of Interleukin-6 gene (rs1800795) variant with waist-hip-ratio and Insulin resistance: A cross-sectional study in adult women

Obesity is a major contributing factor to metabolic disorders and public health problems worldwide. The goal of the current study was to determine if the Interleukin-6 gene rs1800795 variant is linked to waist-hip-ratio (WHR) and insulin resistance (IR) in North Indian adult women. The WHO guidelines were followed by 37 women who had a WHR &gt;0.85 and 35 women who had a WHR &lt;0.85, out of the 72 women who took part in the study. Every adult woman underwent anthropometric measures. Fasting blood glucose, serum Insulin, lipid levels, and IL-6 levels were measured, and IR was computed. The RFLP technique was used to polymorphise the IL-6 gene (174 G&gt;C) variant. The study group's Insulin, HOMA-IR, BMI, lipid profile, TC/HDL ratio, HDL/LDL ratio, and serum IL-6 level were shown to differ significantly from the control. The percentage frequency of the IL-6 mutant genotype GC+CC (89.19%) and mutant allele C (75.68%) was higher in the study group (WHR &gt;0.85). According to the findings, WHR, TC, TG, and HOMA-IR were substantially correlated (all p &lt;0.05) with the mutant genotype GC+CC of the IL-6 174 G&gt;C gene. This study indicates that the IL-6 rs1800795 gene (174 G&gt;C) variant was substantially linked with metabolic risk variables, such as WHR and HOMA-IR.

Yinqin Qingfei granules alleviate Mycoplasma pneumoniae pneumonia via inhibiting NLRP3 inflammasome-mediated macrophage pyroptosis.

Mycoplasma pneumoniae pneumonia (MPP) is a prevalent respiratory infectious disease in children. Given the increasing resistance of M. pneumoniae (MP) to macrolide antibiotics, the identification of new therapeutic agents is critical. Yinqin Qingfei granules (YQQFG), a Chinese patent medicine formulated specifically for pediatric MPP, lacks a clear explanation of its mechanism. The primary components of YQQFG were identified using LC-MS/MS. In vitro, RAW264.7 cells infected with MP underwent morphological examination via scanning electron microscopy. Drug-containing serum was prepared, and its intervention concentration was determined using the CCK-8 assay. The active components of YQQFG were molecularly docked with NLRP3 protein using Autodock Vina software. A RAW264.7 cell line overexpressing NLRP3 was created using lentivirus to pinpoint the target of YQQFG. In vivo, MPP model mice were established via nasal instillation of MP. Lung damage was assessed by lung index and H&E staining. Pyroptosis-associated protein levels in cells and lung tissue were measured by western blot, while interleukin (IL)-1β and IL-18 levels in cell supernatants and mouse serum were quantified using ELISA. Immunofluorescence double staining of lung tissue sections was conducted to assess the correlation between NLRP3 protein expression and macrophages. The expression of the community-acquired respiratory distress syndrome toxin (CARDS TX) was evaluated by qPCR. 25 effective components with favorable oral bioavailability were identified in YQQFG. Both in vitro and in vivo studies demonstrated that YQQFG substantially reduced the expression of the NLRP3/Caspase-1/GSDMD pathway, decreasing the release of IL-1β and IL-18, and inhibited MP exotoxin. Molecular docking indicated strong affinity between most YQQFG components and NLRP3 protein. Lentivirus transfection and immunofluorescence double staining confirmed that YQQFG significantly suppressed NLRP3 expression in macrophages, outperforming azithromycin (AZM). The combination of YQQFG and AZM yielded the optimal therapeutic effect for MPP. YQQFG mitigates inflammatory responses by suppressing NLRP3 inflammasome-mediated macrophage pyroptosis, thereby ameliorating MP-induced acute lung injury. YQQFG serves as an effective adjunct and alternative medication for pediatric MPP treatment.

Evaluation of the Effect of Low-Level Laser Therapy Versus Photodynamic Therapy on the Level of Serum IL-17 and Salivary IL-4 in Patients Suffering from Erosive/Atrophic Oral Lichen Planus: A Case Control Study

Evaluation of the Effect of Low-Level Laser Therapy Versus Photodynamic Therapy on the Level of Serum IL-17 and Salivary IL-4 in Patients Suffering from Erosive/Atrophic Oral Lichen Planus: A Case Control Study

Systemic and cerebro-cardiac biomarkers following traumatic brain injury: an interim analysis of randomized controlled clinical trial of early administration of beta blockers

This is an interim analysis of the Beta-blocker (Propranolol) use in traumatic brain injury (TBI) based on the high-sensitive troponin status (BBTBBT) study. The BBTBBT is an ongoing double-blind placebo-controlled randomized clinical trial with a target sample size of 771 patients with TBI. We sought, after attaining 50% of the sample size, to explore the impact of early administration of beta-blockers (BBs) on the adrenergic surge, pro-inflammatory cytokines, and the TBI biomarkers linked to the status of high-sensitivity troponin T (HsTnT). Patients were stratified based on the severity of TBI using the Glasgow coma scale (GCS) and HsTnT status (positive vs negative) before randomization. Patients with positive HsTnT (non-randomized) received propranolol (Group-1; n = 110), and those with negative test were randomized to receive propranolol (Group-2; n = 129) or placebo (Group-3; n = 111). Propranolol was administered within 24 h of injury for 6 days, guided by the heart rate (> 60 bpm), systolic blood pressure (≥ 100 mmHg), or mean arterial pressure (> 70 mmHg). Luminex and ELISA-based immunoassays were used to quantify the serum levels of pro-inflammatory cytokines (Interleukin (IL)-1β, IL-6, IL-8, and IL-18), TBI biomarkers [S100B, Neuron-Specific Enolase (NSE), and epinephrine]. Three hundred and fifty patients with comparable age (mean 34.8 ± 9.9 years) and gender were enrolled in the interim analysis. Group 1 had significantly higher baseline levels of IL-6, IL-1B, S100B, lactate, and base deficit than the randomized groups (p = 0.001). Group 1 showed a significant temporal reduction in serum IL-6, IL-1β, epinephrine, and NSE levels from baseline to 48 h post-injury (p = 0.001). Patients with severe head injuries had higher baseline levels of IL-6, IL-1B, S100B, and HsTnT than mild and moderate TBI (p = 0.01). HsTnT levels significantly correlated with the Injury Severity Score (ISS) (r = 0.275, p = 0.001), GCS (r = − 0.125, p = 0.02), and serum S100B (r = 0.205, p = 0.001). Early Propranolol administration showed a significant reduction in cytokine levels and TBI biomarkers from baseline to 48 h post-injury, particularly among patients with positive HsTnT, indicating the potential role in modulating inflammation post-TBI.Trial registration: ClinicalTrials.gov NCT04508244. It was registered first on 11/08/2020. Recruitment started on 29 December 2020 and is ongoing. The study was partly presented at the 23rd European Congress of Trauma and Emergency Surgery (ECTES), April 28–30, 2024, in Estoril, Lisbon, Portugal.

Circulating endocannabinoid levels in SARS-CoV-2 infection and their potential role in the inflammatory response

Plasma levels of endocannabinoids (eCBs) are very dynamic and variable in different circumstances and pathologies. The aim of the study was to determine the levels of the main eCBs and N-acylethanolamines (NAEs) in COVID-19 patients during the acute and post-acute phase of SARS-CoV-2 infection. Samples collected before December 31, 2020 were used for the determination of circulating eCB levels by liquid chromatography-tandem mass spectrometry (LC–MS/MS). The association between plasma eCB measurements and biochemical and hematological parameters, as well as serum IL-6 levels, was evaluated. Samples of 64 individuals were analysed, n = 18 healthy donors, n = 30 acute, and n = 16 post-acute patients. Plasma levels of 2-arachidonoylglycerol (2-AG), were significantly elevated in COVID-19 patients when compared to healthy individuals. Plasma N-palmitoylethanolamide (PEA) and N-arachidonoylethanolamide (AEA) levels were found to be decreased in post-acute patient samples. These results suggest that 2-AG plays an important role in the inflammatory cascade in COVID-19 disease; in addition, eCBs might be involved in the post-acute pathogenesis of COVID-19. This study provides evidence of altered levels of circulating eCBs as a consequence of SARS-CoV-2 infection.

Effect of Follicular T Helper and T Helper 17 Cells-Related Molecules on Disease Severity in Patients with Myasthenia Gravis.

Contribution of T helper 1 and 2 cells-related cytokines to pathogenesis of myasthenia gravis (MG) is well known. Recently, the contribution of follicular T helper (Tfh) and T helper 17 cells-related molecules to the pathogenesis has gained importance. In this study, we aimed to evaluate the changes in Tfh- and Th17-related molecules before and after rescue therapy in patients with myasthenic crisis (cMG) and to reveal the molecular differences between stable MG and cMG patients. Patients with stable generalized MG (gMG) and cMG were classified according to Myasthenia Gravis Foundation of America (MGFA) classification. Serum samples were collected from cMG patients both before and after rescue therapy (plasmapheresis or intravenous immunoglobulin [IVIg]). Serum levels of Tfh- and selected Th17-related molecules (IL-22, IL-17A, CXCL13, sPD-L1, sICOSLG, and sCD40L) were analyzed by commercial ELISA kits. Twelve cMG (6 for IVIg, 6 for plasmapheresis) and 10 gMG patients were included in the study. A decrease in serum sPD-L1 and CXCL13 levels was observed in cMG patients after treatment, regardless of the treatment modality (p &lt; 0.05). In contrast, serum sICOSLG levels decreased only in patients treated with IVIg (p &lt; 0.05) and serum IL-22 levels increased in patients receiving plasmapheresis (p &lt; 0.05). cMG patients had higher serum IL-17A levels compared to stable patients (p &lt; 0.001) and its level was positively correlated with disease severity (r = 0.678, p = 0.001). Our results confirm the contribution of Tfh- and Th17-related cell pathways to MG pathogenesis. Both IVIg and plasmapheresis appear to be effective in reducing Tfh- and Th17-related cytokine/molecule levels in cMG patients. Increased serum IL-17A levels may contribute to disease severity.

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

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

Inflammasome Proteins Are Reliable Biomarkers of the Inflammatory Response in Aneurysmal Subarachnoid Hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) is caused by abnormal blood vessel dilation and subsequent rupture, resulting in blood pooling in the subarachnoid space. This neurological insult results in the activation of the inflammasome, a multiprotein complex that processes pro-inflammatory interleukin (IL)-1 cytokines leading to morbidity and mortality. Moreover, increases in inflammasome proteins are associated with clinical deterioration in many neurological diseases. Limited studies have investigated inflammasome protein expression following aSAH. Reliable markers of the inflammatory response associated with aSAH may allow for earlier detection of patients at risk for complications and aid in the identification of novel pharmacologic targets. Here, we investigated whether inflammasome signaling proteins may serve as potential biomarkers of the inflammatory response in aSAH. Serum and cerebrospinal fluid (CSF) from fifteen aSAH subjects and healthy age-matched controls and hydrocephalus (CSF) no-aneurysm controls were evaluated for levels of inflammasome signaling proteins and downstream pro-inflammatory cytokines. Protein measurements were carried out using Simple Plex and Single-Molecule Array (Simoa) technology. The area under the curve (AUC) was calculated using receiver operating characteristics (ROCs) to obtain information on biomarker reliability, specificity, sensitivity, cut-off points, and likelihood ratio. In addition, a Spearman r correlation matrix was performed to determine the correlation between inflammasome protein levels and clinical outcome measures. aSAH subjects demonstrated elevated caspase-1, apoptosis-associated speck-like protein with a caspase recruiting domain (ASC), IL-18 and IL-1β levels in serum, and CSF when compared to controls. Each of these proteins was found to be a promising biomarker of inflammation in aSAH in the CSF. In addition, ASC, caspase-1, and IL-1β were found to be promising biomarkers of inflammation in aSAH in serum. Furthermore, we found that elevated levels of inflammasome proteins in serum are useful to predict worse functional outcomes following aSAH. Thus, the determination of inflammasome protein levels in CSF and serum in aSAH may be utilized as reliable biomarkers of inflammation in aSAH and used clinically to monitor patient outcomes.

Effect of Saccharomyces boulardii on Liver Diseases: A Systematic Review.

We aimed to systematize the results of published studies on the use of Saccharomyces boulardii (SB) for the treatment of various liver disorders (CRD42022378050). Searches were conducted using PubMed and Scopus on 1 August 2022. The PubMed search was updated on 15 June 2024. The review included sixteen studies: ten experimental animal studies (EASs) and six randomized controlled trials (RCTs). The CNCM I-745 strain was used in 68.8% of the included studies. SB reduced the severity of many manifestations of cirrhosis, and lowered the Child-Pugh scores in RCT. SB reduced the serum concentrations of TNF-α, IL-1β, IL-6, and IL-4 in animals with metabolic dysfunction-associated steatotic liver disease (MASLD); lowered the serum TNF-α and IL-6 levels in experimental cirrhosis in rats; and reduced the CRP levels in decompensated cirrhosis. The EAS of MASLD revealed that SB reduced liver steatosis and inflammation and lowered the liver expression of genes of TNF-α, IL-1β, interferon-γ, and IL-10. In studies on experimental cirrhosis and MASLD, SB reduced the liver expression of genes of TGF-β, α-SMA, and collagen as well as liver fibrosis. SB reduced the abundance of Escherichia (Proteobacteria), increased the abundance of Bacteroidetes in the gut microbiota, prevented an increase in intestinal barrier permeability, and reduced bacterial translocation and endotoxemia.

Activating α7nAChR suppresses systemic inflammation by mitigating neuroinflammation of the medullary visceral zone in sepsis in a rat model.

Our previous studies have shown that activating α7nAChRs suppresses systemic inflammation and immunity through the cholinergic anti-inflammatory pathway (CAP) in early sepsis. Now that the medullary visceral zone (MVZ) is the center of CAP and responsible for regulating systemic inflammation, what changes will occur in MVZ's pathology and function in sepsis, especially when interfering with α7nAChRs? Does activation of MVZ's α7nAChRs contribute to the inhibition of systemic inflammation? To clarify these issues, we explored the systemic inflammation and immunity state by detecting serum levels of TNF-α, IL-6, HMGB1, sCD14, and CD4+CD25+Treg and TH17 lymphocytes percentage, meanwhile, we analyzed the apoptosis of cholinergic and catecholaminergic neurons and the expressions of tyrosine hydroxylase (TH) and choline acetyltransferase (CHAT) in MVZ in sepsis and the interfering effects on α7nAChRs. In this study, we found that in sepsis, serum TNF-α, IL-6, HMGB1, sCD14, CD4+CD25+Treg, and TH17 lymphocytes significantly increased and the ratio of Treg/TH17 significantly decreased, cholinergic and catecholaminergic neurons underwent apoptosis with low expressions of TH and CHAT in MVZ; activation of α7nAChRs not only significantly decreased the levels of septic serum TNF-α, IL-6, HMGB1, sCD14, and TH17 lymphocytes (P ＜ 0.05), but also significantly reduced cholinergic and catecholaminergic neurons' apoptosis, and promoted expressions of TH/CHAT. Our study reveals that sepsis undermines MVZ through neuroinflammation which contributes to the uncontrolled systemic inflammation. Activating central α7nAChRs is not only helpful to restore MVZ's structure and function but also beneficial to subside the inflammatory storm in sepsis. Even if MVZ is damaged in sepsis, cholinergic neurons in MVZ still regulate the systemic inflammation stably.

Tofacitinib therapy in systemic lupus erythematosus with arthritis: a retrospective study.

To estimate the effectiveness and safety of tofacitinib in treating systemic lupus erythematosus (SLE) patients with arthritis. This research was a retrospective cohort study that focused on SLEpatients who had arthritis and were treated with tofacitinib at the Department of Rheumatology and Immunology from January 2020 to January 2022. Clinical outcomes, disease activity, immunological parameters, and adverse events were systematically evaluated pre- and post-treatment at 4, 12, and 24weeks. Twenty-two patients were analyzed. At the 4-week mark, 5 (22.7%) patients were partially relieved, and 17 (77.3%) unalleviated. By the 12-week assessment, CR off corticosteroids was observed in four patients (18.2%), and CR on corticosteroids was seen in six patients (27.3%), with an additional six (27.3%) maintaining partial remission. At 24weeks after treatment, three patients (13.6%) achieved CR off corticosteroids, ten patients (45.5%) achieved CR on corticosteroids, and all patients received remission. Compared to before treatment, The SLEDAI and PGA scores significantly improved. The level of C3 was increased significantly, and the absolute CD3+ T cell count, the 28-tender and the 28-swollen joint count, and the levels of serum IL-6 were significantly decreased at 24weeks after treatment. Tofacitinib demonstrates significant therapeutic potential in SLE patients with arthritis, with a safety profile, and the therapeutic mechanism of tofacitinib may be related to reducing IL-6 expression and inhibiting T cell activation. Key Points • Tofacitinib demonstrates significant therapeutic potential in SLE patients with arthritis • The therapeutic mechanism of tofacitinib may be related to reducing IL-6 expression and inhibiting T cell activation.