Serum Tumor Necrosis Factor Research Articles

Sex hormone-dependent and independent regulation of serum BAFF and TNFα in a cohort of transgender men and women.

The risk of inflammatory diseases is sex dependent, but it remains unknown whether this is due to impact of sex hormones or sex chromosomes. Transgender individuals represent a unique cohort for studying relative influence of endocrine and chromosomal factors. Here we compared serum levels of B-cell activating-factor (BAFF) and tumor necrosis factor α (TNFα) in transgender men (TM), transgender women (TW), cisgender women (CW) and cisgender men (CM). BAFF and TNFα were measured in the serum of 26 CW, 30 CM, 27 TM and 16 TW individuals. To determine the responsiveness of immune cells, TNFα was measured in bacterial lipopolysaccharide (LPS) treated peripheral leukocytes. BAFF was higher in CF (998 pg/mL) and TW (973 pg/mL) compared to CM (551 pg/mL) (p<0.0001), and TM (726 pg/mL) (p<0.0001). No difference in BAFF levels was shown between subjects grouped according to the number of X chromosomes. TNFα was higher in CM (174 pg/mL) than TW (2.3 pg/mL) (p=0.027) and TM (27.4 pg/mL) (p=0.028). LPS-induced TNFα was higher in CM (2524 pg/mL) and TM (2078 pg/mL) than in CW (1332 pg/mL) (both p<0.0001) and TW (1602 pg/mL) (both p=0.009). Sex hormones and sex chromosomes have different impact on cytokines involved in sex-dependent inflammatory response. Concentration of BAFF and LPS stimulated TNFα secretion depended on sex hormone levels, whereas basal TNFα was regulated by both sex hormone-dependent and -independent factors.

Exposure to Particulate Matter in the Broiler House Causes Dyslipidemia and Exacerbates It by Damaging Lung Tissue in Broilers

The high concentration of particulate matter (PM) in broiler houses seriously endangers the biological safety of broilers and causes low growth performance, deserving more attention. This study aimed to investigate the effects of PM collected from a broiler house on the lung and systemic inflammatory responses and liver lipid anabolic process in broilers. Broilers were systemically exposed to fresh air (control) and 4 mg·m-3 and 8 mg·m-3 total suspended particles (TSP). Lung, liver, and serum were sampled after 7 (E7) and 14 (E14) days of PM exposure and 7 days after self-recovery (R 7). Corresponding kits were used to assay the inflammatory cytokines and serum biochemical indicators. The expression levels of genes related to lipid metabolism were detected by real-time polymerase chain reaction (RT-PCR) assay. The results showed a significant decrease in the average daily gain in broilers for 7 days of PM exposure (p < 0.05) and clear lung and liver inflammations in PM groups. In addition, upregulation of lung interleukin (IL)-1β and IL-8 and serum low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) occurred after 7 days of PM exposure (p < 0.05), and upregulation of lung serum tumor necrosis factor (TNF)-α and cholesterol (CHOL) occurred after 14 days of PM exposure (p < 0.05). A decrease in serum total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-px) levels was found after 14 days of PM exposure (p < 0.05), and the GSH-px level was maintained until 7 days after cessation of exposure (p < 0.05). Seven days after cessation of exposure, the expression levels of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2) and fatty acid synthase (Fas) genes significantly increased (p < 0.05) and decreased (p < 0.05), respectively. These results demonstrate that exposure to PM in broiler houses can induce systemic inflammation and dyslipidemia through local pulmonary inflammation and also exert toxic effects on the liver by disturbing the expression of genes involved in the hepatic lipid anabolic process.

Efficacy of etanercept in rheumatoid arthritis patients and its effects on interleukin 6 and serum tumor necrosis factor α

Purpose: To study the effects of etanercept (ETA) on the clinical manifestations and serum levels of TNF-α and IL-6 in rheumatoid arthritis (RA) patients.&#x0D; Methods: A retrospective analysis was performed on the medical files of 138 active RA patients admitted to Guangdong Second Provincial General Hospital, Guangzhou, China for rheumatic diseases from January 2016 to February 2019. Out of the total subjects, 58 patients were administered conventional methotrexate (MTX) as routine treatment (control group), while the remaining 80 patients (classified as study group) received subcutaneous injection of etanercept (ETA). Health Assessment Questionnaire (HAQ) score, and TNF-α and IL-6 serum concentrations of the two groups before and after treatment were assessed.&#x0D; Results: Pre-treatment HAQ score was comparable in both groups (p &gt; 0.05). However, at 3, 6, 9 and 12 weeks post-treatment, HAQ scores decreased in the two groups. The mean score was significantly lower in study group than in control group (p &lt; 0.001). Pre-treatment serum levels of IL-6 and TNF-α in both groups were comparable. However, after treating for 3, 6, 9 and 12 weeks, serum IL-6 and TNF-α decreased significantly, with lower values in the study group than in control group (p &lt; 0.001).&#x0D; Conclusion: ETA has a higher efficacy and safety than MTX for the treatment of joint inflammation and and also achieved greater improvement of joint function. However, further clinical trials are recommended prior to wider application in clinical practice.

Efficacy of the combination of carbamazepine and pulsed-radiofrequency in the treatment of trigeminal neuralgia

Purpose: To investigate the effect of the combination of carbamazepine and pulsed-radiofrequency therapy on trigeminal neuralgia (TN) and changes in inflammation status in vivo.&#x0D; Methods: Ninety-seven trigeminal neuralgia patients treated in Wuhan Fourth Hospital from January 2018 to January 2021 were analyzed retrospectively. Forty-five patients treated with pulsed-radiofrequency therapy alone were designated as the control group (CG), while 52 who underwent carbamazepine and pulse-radiofrequency combination therapy were enrolled in the study group (SG). Changes in serum inflammatory factors, viz, interleukin (IL)-6, IL-1β, and tumor necrosis factor α (TNF-α), were recorded before and after treatment. Similarly, changes in pain visual analog scale (VAS) score, quality of life score, and oxidative stress index were assessed before and after treatment; so also were changes in clinical efficacy and incidence of adverse reactions.&#x0D; Results: After treatment, VAS score, and levels of IL-6, IL-1β, and TNF-α in SG were lower than those in CG, while the score of quality of life in SG was higher (p &lt; 0.05). The clinical efficacy of SG was higher than that of CG, but there was no significant difference in incidence of adverse reactions (p &lt; 0.05).&#x0D; Conclusion: The therapeutic combination of carbamazepine and pulsed-radiofrequency is more effective than pulsed-radiofrequency alone in the short-term treatment of TN in patients. It produces better relief of pain, reduces inflammation and improves patients’ quality of life. However, it does not affect the incidence of adverse reactions.

Proactive monitoring of anti-TNF agents improves follow-up of paediatric patients with Crohn disease

Introduction and aimsThe incidence of paediatric inflammatory bowel disease has increased in recent decades. The aim of the present study was to evaluate the role of proactive and serial monitoring of tumour necrosis factor (TNF) inhibitor levels to maintain clinical remission and mucosal healing in the follow-up of paediatric patients with Crohn disease (CD). MethodsProspective study that included all patients diagnosed with CD and treated with adalimumab or infliximab between May 2015 and November 2020 who underwent serial and proactive monitoring of TNF inhibitor levels. ResultsThe study included 30 patients, 21 male (70%). The mean age at diagnosis was 11.3 years (SD, 2.0), the mean age at initiation of TNF inhibitors was 12.6 years (SD, 1.9) with a mean duration of follow-up of 27.1 ± 9.1 months. Clinical remission was defined as a weighted Pediatric Crohn’s Disease Activity Index (wPCDAI) of less than 12.5 and mucosal healing as a Mucosal Inflammation Non-invasive Index (MINI) of less than 8. During the follow-up, patients were in clinical remission in 87.1% of the visits, presented with mild disease in 11.4% and with moderate disease in 1.5%, and mucosal healing was assumed in 83% of the visits. The rates of clinical remission and mucosal healing at 1, 2, and 3 years of follow-up were 83.3%, 95.8%, 92.8%, and 86.7%, 87.5% and 85.7%, respectively. ConclusionsProactive and serial monitoring of serum TNF inhibitor levels may make it possible for patients to maintain clinical remission and mucosal healing in the maintenance phase, with individualised optimization of the required dosage and minimization of secondary loss of response.

The Relationship Between Cytokine Concentrations and Severity Scoring Index for Crimean-Congo Hemorrhagic Fever.

Background This study aimed to investigate the effects of serum high mobility group box-1 (HMGB1), interleukin (IL)-6, IL-8, IL-1β, IL-10, and tumor necrosis factor alpha (TNF-α) levels on disease severity and mortality in Crimean-Congo hemorrhagic fever (CCHF) patients. Materials and methods This study was performed prospectively in the intensive care unit (ICU) and infection ward of a tertiary hospital in the Republic of Türkiye.Patients aged 18 years and older diagnosed with CCHF were included. Results Our study included 30 patients, of whom 83.3% were male, where the mean age was 51.6±14.35 years. The most common clinical findings in patients were malaise (90%) and myalgia (63.3%). In our study, IL-1β levels were found to be 1173.6 (783.0-1823.0) pg/mL, IL-6 69.9 (56.8-133.1) pg/mL, IL-8 191.2 (152.8-516.9) pg/mL, TNF-α 129.5 (104.9-270.8), HMGB1 37.01 (29.26-75.18), and IL-10 190.1 (IQR: 147.8-387.8) pg/mL. The patients' median Severity Scoring Index (SSI) score was found to be 2.5 (1.8-5.5). There was a moderate correlation between the patients' SSI score and serum IL-6 (r=0.464, p=0.010), TNF-α (r=0.420, p=0.021), and IL-10 levels (r=0.518, p=0.003), and a weak correlation between serum HMGB1 (r=0.392, p=0.032). The correlation between SSI and creatine phosphokinase (CPK) levels (r=0.499, p=0.036) was observed to be moderate. Conclusion It was seen that IL-10, IL-6, TNF-α, HMBG-1, and CPK levels evaluated at the CCHF patients' time of admission to the clinic and SSI clinical score were found to be significantly related. It is clear that more studies with patients and groups of healthy volunteers are needed on this subject.

High-sensitivity cardiac troponin T is associated with disease activity in patients with inflammatory arthritis.

To investigate whether high-sensitivity cardiac troponin T (hsTnT) correlates to markers of disease activity in inflammatory arthritis (IA), and whether antirheumatic treatment influences hsTnT levels. We assessed 115 patients with active IA (64 rheumatoid arthritis (RA), 31 psoriatic arthritis and 20 ankylosing spondylitis) before and after using methotrexate (MTX) alone or tumor necrosis factor inhibitor (TNFi) with or without MTX co-medication (TNFi±MTX). All patients starting with TNFi had been previously unsuccessfully treated with MTX monotherapy. HsTnT (measured in serum by electro-chemiluminescence immunoassay (Roche Elecsys® Troponin T- high-sensitivity)), and other clinical and laboratory parameters were evaluated at baseline, and after 6 weeks and 6 months of treatment. Of markers of disease activity, baseline levels of hsTnT positively correlated with Physicians' Global Assessment Score of disease activity in the total patient cohort (p = 0.039). In RA group, hsTnT positively correlated with swollen joints, Disease Activity Score for 28 joints with ESR and serum tumor necrosis factor levels (p = 0.025, p = 0.008, p = 0.01, respectively). Median hsTnT at baseline was 5.0 ng/L, and did not change significantly at 6-week visit (6.0 ng/L, p = 0.37) and 6-month visit (6.0 ng/L, p = 0.18) with either antirheumatic therapy. HsTnT levels were associated with inflammatory markers for IA disease activity. However, while inflammatory markers significantly improved after antirheumatic treatment, hsTnT did not change during the 6-month follow-up period.

Ferulic acid attenuates pancreaticobiliary duct occlusion-induced inflammation in both pancreas and liver.

Acute pancreatitis is a systemic inflammatory disorder characterized by the hyperactivation of digestion enzymes and the release of proinflammatory cytokines. Ferulic acid (FA) is a hydroxycinnamic acid derivative that has recently been shown to have antioxidant and anti-inflammatory properties. The anti-inflammatory effects of FA were investigated in the pancreaticobiliary duct ligation (PBDL)-induced pancreatitis model. Wistar albino rats (250-300g; female = male) were divided into sham operation and PBDL groups. Some PBDL-performed animals were given intragastric saline or 250mg/kg FA or 500mg/kg FA 30min before the PBDL and for 3 consecutive days. Moreover, the control group received saline. Blood samples are collected at the 24th, 48th, and 72nd hours to measure serum tumor necrosis factor (TNF)-α, liver, and pancreatic enzymes. At the 72nd hour, rats were euthanized; pancreas, lung, and liver samples were collected, scored microscopically, and analyzed for myeloperoxidase activity, malondialdehyde, and glutathione levels. One-way ANOVA with Tukey-Kramer tests were used for statistical analysis. FA treatment reduced myeloperoxidase activity and prevented the depletion of glutathione in all three tissues. With FA treatments, high malondialdehyde levels in the pancreas and liver were reduced, as were serum TNF- α, amylase, lipase, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels. Additionally, FA ameliorated microscopic damage in the pancreas and liver significantly. According to the findings, FA protects endogenous antioxidant content, prevents neutrophil infiltration, and decreases lipid peroxidation in PBDL-induced pancreatitis. Furthermore, FA improves tissue damage induced by pancreatitis with its anti-inflammatory effects.

The value of serum TRAP1 in diagnosing small cell lung cancer and tumor immunity.

This study set out to investigate the clinical significance of serum tumor necrosis factor receptor-associated protein 1 (TRAP1) in diagnosing small cell lung cancer (SCLC) with different clinical stages, and to compare the diagnostic efficiency with neuron-specific enolase (NSE), carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). Besides, to analyze the role of serum TRAP1 in tumor immunity. A total of 91 patients with SCLC, 99 patients with non-small cell lung cancer (NSCLC), 102 patients with pulmonary nodules (PN), and 75 healthy people were included. The concentrations of serum TRAP1 was detected by enzyme-linked immunosorbent assay (ELISA). NSE, CEA, and CA19-9 were detected by chemiluminescence. The results showed that level of TRAP1 in Group SCLC was lower than other three groups (P < 0.01), whereas NSE in SCLC was significantly higher than the others (P < 0.01), and the levels of CEA and CA19-9 were higher than healthy people and PN patients (P < 0.01). There was a significant difference in TRAP1 levels between patients with limited-stage disease SCLC (LD-SCLC) and extensive-stage disease SCLC (ED-SCLC) (P < 0.0001). The sensitivity and specificity of TRAP1 in diagnosing LD-SCLC were 0.964 and 0.560, respectively, and the area under the curve (AUC) was 0.819. The sensitivity and specificity in diagnosing ED-SCLC were 0.810 and 0.868, respectively, and the AUC was 0.933, which showed high diagnostic value. The AUC of these two groups can be increased to 0.946 and 0.947 in combination of four biomarkers, effectively improving the diagnosis rate of SCLC. Our findings have revealed that serum TRAP1 has high diagnostic value for SCLC and high diagnostic sensitivity for LD-SCLC. It is a potential biomarker for SCLC. Combined detection can effectively improve the diagnosis rate of SCLC. TRAP1 may be secreted into the circulation by mature immune cells and participates in tumor immunity as a carrier of tumor antigens.

LncRNA XIST promotes insulin resistance in gestational diabetes mellitus via the microRNA-181b-5p/NDRG2 axis.

Many studies have explored the role of lncRNA X inactivation-specific transcript (XIST) in diabetes. This study was designed to unravel the regulatory mechanism of XIST on animal models of gestational diabetes mellitus (GDM) progression via the microRNA (miR)-181b-5p/N-myc downstream-regulated gene 2 (NDRG2) axis. XIST, miR-181b-5p, and NDRG2 expression levels in GDM mice were detected. The GDM mice were subjected to gain- and loss-of-function assays to examine the change of glucose metabolism indices (fasting blood glucose (FBG), fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR)), serum oxidative stress factors (glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA)), serum inflammatory factors (interleukin-1 β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α)), pathological changes of pancreatic tissues, and apoptotic cells in pancreatic islets in GDM mice. XIST and NDRG2 expression were elevated while miR-181b-5p expression was depleted in GDM mice. Down-regulated XIST or NDRG2 or up-regulated miR-181b-5p reduced the FBG level, HOMA-IR, and serum IL-1β, IL-6, and TNF-α, and MDA contents, elevated the FINS, GSH, and SOD level, mitigated pathological changes in pancreatic tissues, and decelerated apoptotic cells in pancreatic islets in GDM mice. Silenced XIST dampens insulin resistance in GDM mice via the modulation of the miR-181b-5p/NDRG2 axis.

Comprehensive evaluation of biopolymer immune implants for peritoneal metastasis carcinoma therapy.

Immunotherapy has been widely used in the treatment of advanced stage cancers with spreading metastases, while the fully activation of immune system often requires sustained and long-acting immune stimulation by immunotherapeutic agents. In previous studies, we designed a biopolymer immune implant by dynamic covalent bonds and achieved sustained release of loaded immunotherapeutic agents, thus stimulated systemic immune activation and elicited immune memory effects. Herein, we further optimized the implants and carried out a comprehensive evaluation of the implants on peritoneal metastasis carcinoma (PMC) therapy. Our results showed that the implants fabricated with 8-arm polyethylene glycol amine (8-arm PEG-NH2) and 40% oxidation degree dextran (ODEX) exhibited a satisfactory degradation time for activating the antitumor immunity. The drug combination of oxaliplatin (OxP) and resiquimod (R848) could be sustainably released from the implants for 18days. The implants cured 75% of mice with PMC and elicited immune memory effects to resist tumor re-challenge without obvious side effects observed. Mechanism analysis revealed that the implants could serve as an in-situ vaccine to enhance the infiltration of activated dendritic cells (DCs), T cells and natural killer (NK) cells inside the tumor, as well as increase the serum tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ) and interleukin 12 (IL-12) levels. These results strongly support the clinical translation potential of this sustained released biopolymer immune implants for PMC therapy.

Continuous Monitoring of Serum Tumor Necrosis Factor-&amp;lt;i&amp;gt;α&amp;lt;/i&amp;gt; for Patients with TEMIS Treated by Nitrates Postconditioning during PCI

Continuous Monitoring of Serum Tumor Necrosis Factor-&amp;lt;i&amp;gt;α&amp;lt;/i&amp;gt; for Patients with TEMIS Treated by Nitrates Postconditioning during PCI

Glyceraldehyde-derived advanced glycation end-products are associated with left ventricular ejection fraction and brain natriuretic peptide in patients with diabetic adverse cardiac remodeling

Objectives: Glyceraldehyde-derived advanced glycation end-products (Glycer-AGEs) have a strong binding affinity for their cognate receptor and elicit oxidative stress and inflammation. However, it remains unknown whether the levels of Glycer-AGEs correlate with the severity of cardiac function and heart failure in patients with diabetic adverse cardiac remodeling (DbCR). Fourteen heart failure patients with type 2 diabetes mellitus (DM) without other cardiac disorders (DbCR group) were enrolled. Another 14 patients with idiopathic dilated cardiomyopathy (DCM) without DM were served as a control (DCM group). All patients were assessed for serum Glycer-AGEs, nitrotyrosine (NT), and tumor necrosis factor alpha (TNFα) and for plasma brain natriuretic peptide (BNP). The left ventricular ejection fraction (LVEF) was evaluated by echocardiography. Results: The mean serum levels of Glycer-AGEs, NT, and TNFα in the DbCR group were significantly higher than those in the DCM group (for Glycer-AGEs, p = .0073; for NT, p = .005; for TNFα, p < .0001, respectively). In the patients with DbCR, the levels of serum Glycer-AGEs and TNFα were closely associated with LVEF and BNP values. Conclusions: Both Glycer-AGEs and TNFα showed close associations with LVEF and the levels of BNP in patients with DbCR. Glycer-AGEs and TNFα may play a pathological role in the development of DbCR.

COULD GROWTH DIFFERENTIATION FACTOR-15 BE A NEW INFLAMMATORY PATHWAY IN PSORIASIS VULGARIS?

Amaç&#x0D; Psoriasis vulgaris kronik inflamatuvar bir hastalık olup,&#x0D; etyopatogenezde T hücrelerin önemli rol oynadığı inflamatuvar&#x0D; mekanizmalar rol almaktadır. Son yıllarda&#x0D; psoriasisin sadece deriye sınırlı olmayıp aynı zamanda&#x0D; bazı komorbiditeler ile ilişkili olduğu gösterilmiştir.&#x0D; Büyüme farklılaşma faktörü-15 (GDF-15), dönüştürücü&#x0D; büyüme faktörü beta süper ailesinin (TGF-ß) bir&#x0D; üyesidir ve inflamasyonla artmaktadır. Bu çalışmada;&#x0D; serum GDF-15 düzeyi ve bunun hastalığın etyopatogenezinde&#x0D; rolü olduğu düşünülen tümör nekrozis&#x0D; faktör alfa (TNF-α) ve diğer metabolik parametrelerle&#x0D; arasındaki ilişkinin değerlendirilmesi amaçlandı.&#x0D; Gereç ve Yöntem&#x0D; Çalışmaya 41 psoriasis vulgarisli hasta ve 41 sağlıklı&#x0D; kontrol dahil edildi. Tüm katılımcıların dermatolojik&#x0D; muayenesi yapıldı ve psoriasis alan ve şiddet indeksi&#x0D; (PAŞİ) skoru hesaplandı. Tüm katılımcıların boy,&#x0D; kilo ölçümleri, sistolik ve diastolik kan basınçları, bel&#x0D; ve kalça çevreleri, lipit profilleri, biyokimyasal parametreleri&#x0D; değerlendirildi. Serum GDF-15 ve TNF-α&#x0D; düzeyleri ELİSA yöntemi ile ölçüldü.&#x0D; Bulgular&#x0D; Hasta ve kontrol grubu arasında yaş, cinsiyet, lipit&#x0D; profilleri, biyokimyasal parametreler ve yüksek-sensitif&#x0D; C-reaktif protein (hs-CRP) düzeyleri açısından&#x0D; anlamlı fark gözlenmedi. Hasta grubunda kontrol grubuna&#x0D; kıyasla serum GDF-15 ve TNF-α düzeyleri anlamlı&#x0D; derecede yüksek bulundu (p

Association between inflammation, reward processing, and ibuprofen-induced increases of miR-23b in astrocyte-enriched extracellular vesicles: A randomized, placebo-controlled, double-blind, exploratory trial in healthy individuals

Ibuprofen, a non-steroidal, anti-inflammatory drug, modulates inflammation but may also have neuroprotective effects on brain health that are poorly understood. Astrocyte-enriched extracellular vesicles (AEEVs) facilitate cell-to-cell communication and – among other functions - regulate inflammation and metabolism via microribonucleic acids (miRNAs). Dysfunctions in reward-related processing and inflammation have been proposed to be critical pathophysiological pathways in individuals with mood disorders. This investigation examined whether changes in AEEV cargo induced by an anti-inflammatory agent results in inflammatory modulation that is associated with reward-related processing. Data from a double-blind, randomized, repeated-measures study in healthy volunteers were used to examine the effects of AEEV miRNAs on brain activation during reward-related processing. In three separate visits, healthy participants (N = 20) received a single dose of either placebo, 200 mg, or 600 mg of ibuprofen, completed the monetary incentive delay task during functional magnetic resonance imaging, and provided a blood sample for cytokine and AEEV collection. AEEV miRNA content profiling showed that ibuprofen dose-dependently increased AEEV miR-23b-3p expression with greater increase following the 600 mg administration than placebo. Those individuals who received 600 mg and showed the highest miR-23b-3p expression also showed the (a) lowest serum tumor necrosis factor (TNF) and interleukin-17A (IL-17A) concentrations; and had the (b) highest striatal brain activation during reward anticipation. These results support the hypothesis that ibuprofen alters the composition of miRNAs in AEEVs. This opens the possibility that AEEV cargo could be used to modulate brain processes that are important for mental health.

The role of IL-33 and IL-1β in the development of persistent allergic rhinitis in overweight/obese children

BACKGROUND: Few works were devoted to the study of the role of cytokines in children with allergic rhinitis (AR) with comorbid obesity. AIMS: To study the level of cytokines interleukin (IL)1, IL-33, IL-6, tumor necrosis factor (TNF)-, and total IgE in the blood serum of overweight/obese children with intermittent and persistent AR. MATERIALS AND METHODS: This cross-sectional observational study analyzed 69 children aged 710 years with AR in the remission period and was conducted from November 2020 to February 2021. All children went through a comprehensive examination for 3 days, including the definition of the serum concentrations IL-1, IL-33, IL-6, TNF-, and total IgE. Before blood sampling, children did not use nasal glucocorticosteroids, antileukotriene drugs for the last 4 weeks, and antihistamines for the last 7 days. Bioimpedansometry was used to assess the body weight by calculating the %FM (percentage of body fat mass). RESULTS: The study included 44 children with AR and overweight/obesity (group I) and 25 children with AR and normal body weight (group II). The analysis of AR showed that in group I, intermittent AR was detected in 11 (25.0%) children (subgroup IA), whereas a persistent course was found in 33 children (75.0%) (subgroup IB). In group II, intermittent AR was detected in 13 (52.0%) children (subgroup IIA), whereas persistent AR in 12 children (48.0%) (subgroup IIB). The level of IL-1 in the blood serum was significantly higher in the subgroup IB than in subgroup IA (p=0.009). The concentration of IL-33 in children with persistent AR and obesity was significantly lower than that in children with intermittent AR and obesity (p=0.039). The level of IL-33 in the serum negatively correlated with %FM in group IA (r=-0.6673, p=0.035). The concentration of IL-1 negatively correlated with %FM in group IIB (r=-0,738, p=0,037). The levels of IL-6, TNF, and total IgE in obese children did not depend on the severity of AR. CONCLUSIONS: The predictors of persistent AR in children with obesity are a decrease in the level of IL-33 and an increase in IL-1 in the blood serum. The negative correlation between the degree of obesity and IL-33 concentration in children with intermittent AR opens a window of opportunity for the personified management of children with AR and comorbid obesity.

Inflammation parameters, monocyte subgroups and toll-like receptor expression before and after dialysis in patients with chronic kidney disease

Abstract Objectives The data of the monocyte subgroups and expressed toll like receptors (TLR) in the innate immune system response, which develop against chronic inflammation in patients with predialysis chronic kidney disease (CKD) and in patients who undergo dialysis treatment, are limited. We aimed to investigate the effect of the dialysis procedure on the current chronic inflammatory condition and which role of monocyte subgroups ratios, the expressions of TLR2/4 and serum Tumor necrosis factor alpha (TNF-α) levels involved in the innate immune response process. Methods We investigated monocyte subgroups, TLR2/TLR4 expressions and serum TNF-α levels in 30 predialysis CKD patients, 90 CKD patients undergoing dialysis and 30 healthy control subjects. Monocyte subgroup percentages and TLR2/TLR4 expressions were determined using the flow cytometry, serum TNF-α levels were investigated using the enzyme-linked immunosorbent assay (ELISA). Results In the dialysis patients, the percentages of classical (p=0.0001) and non-classical (p=0.078) monocytes were found to be higher when compared with the predialysis CKD patients. The percentages of TLR4 expression on non-classical monocytes was higher in dialysis and predialysis patients compared with the healthy controls (p&lt;0.0001, p=0.796). Serum TNF-α level was significantly higher in dialysis and predialysis patients compared with the healthy controls (p=0.013, p=0.022) and a positive correlation between the classical monocyte subgroup and TNF-α was observed (r=0.285, p=0.006). Conclusions Increased percentages of non-classical monocytes, TLR4 expressions and serum TNF-α levels observed in the predialysis CKD patients and dialysis patients might be related to inflammation.

Clinical characteristics and associated factors of pediatric acute disseminated encephalomyelitis patients with MOG antibodies: a retrospective study in Hangzhou, China

BackgroundTo explore the clinical characteristics and related factors of children with acute disseminated encephalomyelitis (ADEM) with positive anti-myelin oligodendrocyte glycoprotein (MOG) antibody.MethodsA retrospective study was conducted and enrolled pediatric ADEM patients who underwent serum MOG antibody detection from May 2017 to August 2020. The patients were divided into two groups: MOG- immunoglobulin G (IgG) positive (n = 35) and MOG-IgG negative (n = 50). We analyzed the clinical characteristics of MOG-IgG-positive ADEM pediatric patients and conducted a comparative analysis between the two groups.ResultsThirty-five patients (21 males and 14 females) in the MOG-IgG-positive group with encephalopathy, multifocal neurological symptoms, and typical magnetic resonance imaging (MRI) abnormalities were enrolled. They usually had a favorable outcome, while some suffered from relapse. Compared to the MOG-IgG-negative group, MOG-IgG-positive ADEM patients had a longer disease duration (median: 10 vs. 6 days), more meningeal involvement (31.4% vs. 8%) and frontal lobe involvement (82.8% vs. 68%), higher relapse rates (14.3% vs. 2%), lower serum tumor necrosis factor (1–12.4 pg/ml, median 1.7 vs. 1–34 pg/ml, median 2.2) and interferon-gamma (1–9.4 pg/ml, median 1.3 vs. 1–64 pg/ml, median 3) (P < 0.05, respectively). Multivariate logistic regression analysis showed that the longer disease duration, meningeal involvement and frontal lobe involvement were the correlated factors of patients with ADEM with MOG antibody (P < 0.05).ConclusionsOur findings provide clinical evidence that MOG-IgG positivity is associated with longer disease duration, meningeal involvement, and frontal lobe involvement.

Studies on the metabolism and mechanism of acteoside in treating chronic glomerulonephritis

Ethnopharmacological relevanceActeoside (ACT) is the main ingredient derived from the leaves of Rehmannia glutinosa (Dihuangye). Dihuangye has the function of clearing heat, replenishing qi and activating blood, nourishing yin and tonifying kidney in traditional Chinese medicine. Recent studies have demonstrated that Dihuangye can be used to treat nephritis and ACT is a promising antinephritic agent. Aim of the studyTo clarify the metabolites of ACT in biological samples and investigate the renoprotective effect and mechanism of ACT in rats with chronic glomerulonephritis (CGN). Materials and methodsIn this study, the biotransformation of ACT in rat biological samples was clarified by quadrupole time-of-flight tandem mass spectrometry. The metabolites were validated by urine samples in nephropathy model rats. The effect of ACT and its metabolites was evaluated by glomerular podocyte injury due to high glucose. Based on an analysis of the ingredients in vivo, the potential therapeutic targets in the treatment of CGN were investigated by using network pharmacological analysis and molecular docking. Then, the renoprotective effect and mechanism of ACT were determined in rats in a passive Heymann nephritis (PHN) model. ResultsA total of 49 metabolites of ACT were detected and identified. Meanwhile, 21 metabolites were detected in nephropathy model rats. ACT was absorbed rapidly and transferred from the kidney, and the metabolites were eliminated via urine. The whole process lasted approximately 8 h. ACT had a significant protective effect on glomerular podocytes damaged by high glucose and 3,4-dihydroxyphenylacetic acid might be the main metabolite of ACT underlying its functions in vivo. The network pharmacology and molecular docking results showed 84 ACT-CGN targets, among which MAPK1, HRAS, AKT1, EGFR, and others were a highly correlated. In the PHN rat model, ACT significantly reduced the 24-h urine protein and serum creatinine concentrations, suppressed the leukocyte CD18 expression levels, decreased the serum tumor necrosis factor α (TNF-α) levels and tended to reduce serum interleukin 6 (IL-6) levels. ACT significantly reduced the platelet aggregation rate and inhibited the proliferative activity of splenic lymphocytes in response to the mitogen concanavalin A. Meanwhile, ACT inhibited transforming growth factor-β and fibronectin expression in renal tissues and dose-dependently inhibited TNF-α and IL-6 production in RAW264.7 mouse macrophages at doses ranging from 1.8 to 1330 μg/mL. ConclusionsACT had therapeutic effects on PHN rats, and its mechanism might be related to the inhibition of intercellular or intercellular-matrix adhesion, suppression of inflammatory response, regulation of immune function, improvement of tissue hemodynamics and hemorheology, and relief of fibrotic lesions.

Effect of intra-dialytic physical exercise on depression in prevalent hemodialysis patients

BackgroundDepression is associated with morbidity, death, diminished quality of life, decreased longevity, and even suicidal ideation in hemodialysis patients. Intra-dialytic exercise is considered as integral component of the clinical care management of hemodialysis patients as it improves hemodialysis effectiveness, reducing systemic inflammation, increasing exercise tolerance, decreasing depression and improving quality of life. The objective of this study was to assess the effect of intra-dialytic physical exercise on depression and physical activity in prevalent hemodialysis patients. This prospective cohort research comprised 50 hemodialysis patients maintained on regular hemodialysis 3 times/week with duration since starting dialysis (1–5 years), not practicing any previous physical activity, suffering from depressive symptoms, not maintained on antidepressants and separated into two groups: group I underwent intra-dialytic exercise for 3 months and group II was matched in age and gender but did not undertake any exercise.ResultsHamilton depression rating scale was significantly decreased in group I after completing the exercise program compared to baseline (P = 0.000), while there was no significant change in group II. Serum tumor necrosis factor alpha significantly decreased in group I compared to baseline (P = 0.000), while there was no significant change in group II. A positive correlation was found between serum tumor necrosis factor alpha and Hamilton depression rating scale (r = 0.676), (P = 0.000). Physical activity tests; 6-min walk test, rapid assessment of physical activity and peak volume of oxygen consumption were significantly improved in group I compared to baseline (P = 0.000), while there was no statistically significant difference in group II. Serum phosphorus and parathyroid hormone levels were significantly decreased in group I compared to baseline (P < 0.01), while urea reduction ratio was significantly increased in group I compared to baseline (P = 0.000), but there was no significant change in group II.ConclusionsIntra-dialysis exercise can improve depression and physical performance in hemodialysis patients. As positive correlation was found between serum tumor necrosis factor alpha and Hamilton depression rating scale, so tumor necrosis factor alpha may be considered as marker of depression in hemodialysis patients. Intra-dialytic exercise can improve dialysis efficacy by improving urea reduction ratio.