Elevated levels of interleukin‐35 and interleukin‐37 in adult patients with obstructive sleep apnea

BackgroundSystemic inflammation has a critical role in the pathogenesis of obstructive sleep apnea (OSA). Interleukin (IL)‐35 and IL‐37 have been identified as novel immune‐modulating cytokines with anti‐inflammatory activities in numerous types of inflammatory disease. The present study aimed to examine the serum levels of IL‐35 and IL‐37 in patients with OSA, and to investigate their associations with the severity of OSA.MethodsA total of 97 patients, including 67 cases of OSA and 30 age‐ and gender‐matched healthy control subjects, were enrolled in the present study. All subjects were evaluated by overnight polysomnography. Serum IL‐35, IL‐37, and pro‐inflammatory cytokine IL‐1β levels were examined by ELISA.ResultsCompared with those in the control subjects, serum IL‐35, IL‐37, and IL‐1β levels were significantly elevated in patients with mild, moderate, or severe OSA. Furthermore, a severity‐dependent increase in serum IL‐35 and IL‐37 levels was observed in patients with OSA. IL‐35 and IL‐37 levels were positively correlated with the apnea‐hypopnea index (r = 0.742 and 0.578, respectively; both p < 0.001), while they were negatively correlated with the mean oxygen saturation (r = −0.461 and −0.339, respectively; both p < 0.001) and lowest oxyhaemoglobin saturation (r = −0.616 and −0.463, respectively; both p < 0.001) in patients with OSA. In addition, a positive correlation was observed between IL‐35 or IL‐37 and IL‐1β levels (all p < 0.001).ConclusionThe serum levels of IL‐35 and IL‐37 were significantly increased in patients with OSA and associated with the severity of OSA, implying that IL‐35 and IL‐37 may have a protective role in OSA by counteracting inflammatory responses.     

MiR‐221‐3p and miR‐92a‐3p enhances smoking‐induced inflammation in COPD

BackgroundSmoking is likely to facilitate airway inflammation and finally contributes to chronic obstructive pulmonary disease (COPD). This investigation was intended to elucidate miRNAs that were involved in smoking‐induced COPD.MethodsAltogether 155 COPD patients and 77 healthy volunteers were recruited, and their serum levels of miR‐221‐3p and miR‐92a‐3p were determined. Besides, human bronchial epithelial cells (16HBECs) were purchased, and they were treated by varying concentrations of cigarette smoke extract (CSE). The 16HBECs were, additionally, transfected by miR‐221‐3p mimic, miR‐92a‐3p mimic, miR‐221‐3p inhibitor or miR‐92a‐3p inhibitor, and cytokines released by them, including TNF‐α, IL‐8, IL‐1β, and TGF‐β1, were monitored using enzyme linked immunosorbent assay (ELISA) kits.ResultsChronic obstructive pulmonary disease patients possessed higher serum levels of miR‐221‐3p and miR‐92a‐3p than healthy volunteers (p < 0.05), and both miR‐221‐3p and miR‐92a‐3p were effective biomarkers in diagnosing stable COPD from acute exacerbation COPD. Moreover, viability of 16HBECs was undermined by CSE treatment (p < 0.05), and exposure to CSE facilitated 16HBECs’ release of TNF‐α, IL‐8, IL‐1β, and TGF‐β1 (p < 0.05). Furthermore, miR‐221‐3p/miR‐92a‐3p expression in 16HBECs was significantly suppressed after transfection of miR‐221‐3p/miR‐92a‐3p inhibitor (p < 0.05), which abated CSE‐triggered increase in cytokine production and decline in viability of 16HBECs (p < 0.05).ConclusionMiR‐221‐3p and miR‐92a‐3p were involved in CSE‐induced hyperinflammation of COPD, suggesting that they were favorable alternatives in diagnosing COPD patients with smoking history.     

The abnormal level and prognostic potency of multiple inflammatory cytokines in PCI‐treated STEMI patients

ObjectiveInflammatory cytokines modulate atherogenesis and plaque rupture to involve in ST‐segment elevation myocardial infarction (STEMI) progression. The present study determined eight inflammatory cytokine levels in 212 percutaneous coronary intervention (PCI)‐treated STEMI patients, aiming to comprehensively investigate their potency in estimating major adverse cardiac event (MACE) risk.MethodsSerum tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, IL‐8, IL‐10, IL‐17A, vascular cell adhesion molecule‐1 (VCAM‐1), and intercellular adhesion molecule‐1 (ICAM‐1) of 212 PCI‐treated STEMI patients and 30 angina pectoris patients were determined using enzyme‐linked immunosorbent assay.ResultsTNF‐α (52.5 (43.9–62.6) pg/ml versus 46.4 (39.0–59.1) pg/ml, p = 0.031), IL‐8 (61.6 (49.6–81.7) pg/ml versus 46.7 (32.5–63.1) pg/ml, p = 0.001), IL‐17A (57.4 (45.7–77.3) pg/ml versus 43.2 (34.2–64.6) pg/ml, p = 0.001), and VCAM‐1 (593.6 (503.4–811.4) ng/ml versus 493.8 (390.3–653.7) ng/ml, p = 0.004) levels were elevated in STEMI patients compared to angina pectoris patients, while IL‐1β (p = 0.069), IL‐6 (p = 0.110), IL‐10 (p = 0.052), and ICAM‐1 (p = 0.069) were of no difference. Moreover, both IL‐17A high (vs. low) (p = 0.026) and VCAM‐1 high (vs. low) (p = 0.012) were linked with increased cumulative MACE rate. The multivariable Cox''s analysis exhibited that IL‐17A high (vs. low) (p = 0.034) and VCAM‐1 high (vs. low) (p = 0.014) were independently associated with increased cumulative MACE risk. Additionally, age, diabetes mellitus, C‐reactive protein, multivessel disease, stent length, and stent type were also independent factors for cumulative MACE risk.ConclusionIL‐17A and VCAM‐1 high level independently correlate with elevated MACE risk in STEMI patients, implying its potency in identifying patients with poor prognoses.     

IL‐23/IL‐17 axis and soluble receptors isoforms sIL‐23R and sIL‐17RA in patients with rheumatoid arthritis‐presenting periodontitis

BackgroundRheumatoid arthritis (RA) and periodontitis (P) are chronic inflammatory diseases characterized by joint and radiographic bone loss, respectively. IL‐23 and IL‐17 have an essential role in the immunopathogenesis of RA, and P. IL‐23 stimulates Th17 cells through which produces IL‐17, IL‐21, and RANKL. IL‐17 stimulates fibroblasts to produce RANKL, which initiates bone loss in the joints in RA and the periodontal tissue in periodontitis. The aim of this study was to determine the expression pattern of IL‐23/IL‐17 axis and soluble receptors isoforms sIL‐23R and sIL‐17RA of patients with RA presenting P (RAP).Material and methodsHealthy subjects (HS) (n = 42), patients with P (n = 40), RA (n = 20), and patients with RAP (n = 40) were included. Plasma samples were obtained to evaluate the IL‐23, IL‐17A, sIL‐23R, and sIL‐17RA by ELISA technique. A nonparametric Mann‐Whitney U test was used to compare the differences between groups. A Chi‐square was used to compare gender, grade and stage of periodontitis, and DAS28‐ESR between the groups. Spearman''s rank correlation coefficient was used to study the association between the molecules and clinical parameters.ResultsIL‐23 levels were increased in the RAP group, and lower sIL‐23R levels were found in the RAP groups. However, IL‐17A was lower in the P and RAP group but not in RA patients. RAP group showed a decrease IL‐17A levels in advanced stages of the periodontal disease.ConclusionThese results suggest that IL‐23 and IL‐17A tend to downregulate their expression patterns when patients present both rheumatoid arthritis and periodontitis.     

Association between serum inflammatory parameters and the disease severity in COVID‐19 patients

ObjectiveMost patients infected with the novel coronavirus (SARS‐CoV‐2), as the causative agent of COVID‐19 disease, show mild symptoms, but some of them develop severe illness. The purpose of this study was to analyze the blood markers of COVID‐19 patients and to investigate the correlation between serum inflammatory cytokines and the disease severity.MethodsIn this prospective cross‐sectional study, 50 patients with COVID‐19 and 20 patients without COVID‐19 were enrolled. According to ICU admission criteria, patients were divided into two groups of non‐severe and severe. Differences in the serum levels of C‐reactive protein (CRP), IL‐6, and TNF‐α, as well as erythrocyte sedimentation rate (ESR), lymphocytes (LYM) count, and neutrophils (NEU) count between the two groups were determined and analyzed.ResultsOut of the 50 patients with COVID‐19, 14 were diagnosed as severe cases. There was no significant difference between the two groups of COVID‐19 patients in terms of gender and age. Blood tests of COVID‐19 patients showed a significant decrease and increase in NEU and LYM counts, respectively. There were significant differences in the serum levels of IL‐6, TNF‐α, and CRP between the severe and non‐severe groups, which were higher in the severe group.Also, there was a significant correlation between the disease severity and CRP with ESR (r = 0.79), CRP with IL‐6 (r = 0.74), LYM with NEU (r = −0.97), and ESR with TNF‐α (r = 0.7).ConclusionThe findings of this study, as the first study in Iran, suggest that the levels of IL‐6, TNF‐α, ESR, and CRP could be used to predict the severity of COVID‐19 disease.     

Hsa_circ_0054633 association of C peptide is related to IL‐17 and TNF‐α in patients with diabetes mellitus receiving insulin treatment

BackgroundChronic inflammation damaged the islet and resulted in dysfunction of T2D. Circular RNA is stable and better for biomarker in many diseases. Here, we aimed to identify potential circular RNA hsa_circ_0054633 that can be a biomarkers for the effects of insulin therapy in T2D.MethodsIn this retrospective case‐control study, patients were from Li Huili Hospital, Ningbo, China, from February 10, 2019, to August 15, 2019. We included 47 healthy adults, 46 new‐onset T2D with insulin resistance, and 51 patients with insulin therapy. Serum inflammation factors were tested by ELISA assays. We selected hsa_circ_0054633 as a candidate biomarker and measured its concentration in serum by qRT‐PCR. The Pearson correlation test was used to evaluate the correlation between this circRNA and clinical variables.ResultsClinical data indicated that serum C peptide was increased in T2D treatment with insulin. Serum hsa_circ_0054633 was decreased in insulin treatment group. Hsa_circ_0054633 was negative correlated with C peptide (r = −0.2841, p = 0.0433,). IL‐1 and IL‐6, IL‐17, and TNF‐α were higher in T2D patients and decreased after insulin treatment, only IL‐17 and TNF‐α showed a positive correlation to hsa_circ_0054633 (r = 0.4825, p < 0.0001, and r = 0.6190, p < 0.0001). The area under ROC curve was 0.7432, 0.5839, and 0.7573 for Hsa_circ_0054633, C peptide, and their combination.ConclusionHsa_circ_0054633 level was lower in T2D with insulin treatment than untreated and was a negative correlation with C peptide, and positively correlated with IL‐17 and TNF‐α, suggesting that hsa_circ_0054633 may be a potential early indicator of insulin treatment effect to improve inflammation condition.     

Inter‐alpha‐trypsin inhibitor heavy chain 4: A serologic marker relating to disease risk,activity, and treatment outcomes of rheumatoid arthritis

ObjectiveInter‐alpha‐trypsin inhibitor heavy chain 4 (ITIH4) regulates immunity and inflammation, but its clinical role in rheumatoid arthritis (RA) patients remains unclear. Hence, this study was conducted to explore the association of circulating ITIH4 with disease risk, clinical features, inflammatory cytokines, and treatment outcomes of RA.MethodsAfter the enrollment of 93 active RA patients and 50 health controls (HCs), their serum ITIH4 level was analyzed by enzyme‐linked immunosorbent assay (ELISA). For RA patients only, serum ITIH4 level at week (W) 6 and W12 after treatment was also analyzed. Besides, serum tumor necrosis factor‐alpha (TNF‐α), interleukin (IL)‐1β, IL‐6, and IL‐17A at baseline of RA patients were also detected by ELISA.ResultsITIH4 was downregulated in RA patients (151.1 (interquartile range (IQR): 106.2–213.5) ng/mL) than in HCs (306.8 (IQR: 238.9–435.1) ng/mL) (p < 0.001). Furthermore, ITIH4 was negatively related to C‐reactive protein (CRP) (r_s  = −0.358, p < 0.001) and 28‐joint disease activity score using erythrocyte sedimentation rate (DAS28‐ESR) (r_s  = −0.253, p = 0.014) in RA patients, but not correlated with other clinical features (all p > 0.05). Besides, ITIH4 was negatively linked with TNF‐α (r_s  = −0.337, p = 0.001), IL‐6 (r_s  = −0.221, p = 0.033), and IL‐17A (r_s  = −0.368, p < 0.001) in RA patients, but not correlated with IL‐1β (r_s  = −0.195, p = 0.061). Moreover, ITIH4 was gradually elevated in RA patients from baseline to W12 after treatment (p < 0.001). Additionally, the increment of ITIH4 at W6 and W12 was linked with treatment response and remission in RA patients (all p < 0.05).ConclusionCirculating ITIH4 possesses clinical utility in monitoring disease risk, inflammation, disease activity, and treatment outcomes of RA.     

G‐CSF as a potential early biomarker for diagnosis of bloodstream infection

BackgroundCytokines play an important role in bacterial infection, and thus, we aim to find out cytokines that may be diagnostically significant in early stage of bacterial bloodstream infection.MethodsMice models infected with Staphylococcus aureus and Klebsiella pneumoniae were established. Then dynamic changes of nine serum cytokines were monitored within 48 hours after the infection. Cytokines with significant differences between the infected groups and control group were further analyzed. Clinical samples of patients who were suspected of bloodstream infection were collected. Then the diagnostic efficiency of screened cytokines was determined with receiver operating characteristic curve analysis.ResultsAs for mice models infected by Staphylococcus aureus and Klebsiella pneumoniae, six cytokines including IL‐1β, IL‐6, IL‐12p70, G‐CSF, IFN‐γ, and TNF‐α were significantly different (P < .05) between two bacterial infected groups. As for clinical samples, three cytokines including IL‐6, IL‐12p70, and G‐CSF showed significant differences between infection group (Staphylococcus aureus and Klebsiella pneumonia group) and negative control group. With the area under curve of 0.7350 and 0.6431 for G‐CSF and IL‐6, respectively, these two cytokines were significantly different between Staphylococcus aureus and Klebsiella pneumoniae infection groups. Combination of G‐CSF and IL‐6 could improve the AUC to 0.8136.ConclusionsG‐CSF cannot only identify bacterial bloodstream infection, but can also distinguish the infection of Staphylococcus aureus from Klebsiella pneumoniae. Further investigation should be performed concerning the diagnostic efficiency of G‐CSF in diagnosing different types of bacterial bloodstream infection.     

Comparison of IL‐6 measurement methods with a special emphasis on COVID‐19 patients according to equipment and sample type

BackgroundInterleukin‐6 (IL‐6) is a multifunctional cytokine associated with various diseases, including coronavirus disease (COVID‐19). Although IL‐6 levels can be assessed using serum samples, use of the AFIAS (Boditech Med Inc.) automated immunoassay analyzer enables quick and simple measurement of IL‐6 levels in both serum and whole blood specimens. This study aimed to assess the correlation between IL‐6 measurements obtained from the AFIAS IL‐6 assay and Elecsys IL‐6 assay (Roche Diagnostics). Additionally, utilization of the AFIAS IL‐6 assay was evaluated.MethodsThe IL‐6 levels from 113 serum samples quantified using two assay systems were evaluated for their degree of correlation. Meanwhile, the linearity, analytical sensitivity, and precision/reproducibility of the AFIAS IL‐6 assay were also assessed.ResultsQuantification of IL‐6 with the AFIAS IL‐6 and Elecsys IL‐6 assays showed excellent agreement (kappa 0.802) and were found to be correlated (y = −0.2781 + 1.068x; 95% confidence interval: 1.007–1.124). AFIAS IL‐6 showed good analytical performances. IL‐6 levels were significantly higher in deceased patients compared to those with non‐complicated disease and those who were intubated (p = 0.002 and p < 0.0001, respectively). Finally, IL‐6 levels more accurately predicted poor prognosis in patients, than did C‐reactive protein (area under the curve, 0.716 vs. 0.634).ConclusionThe overall analytical performance of the AFIAS assay was comparable to that of the Elecsys IL‐6 assay. In light of the ongoing COVID‐19 pandemic, the AFIAS may be an attractive tool for measuring IL‐6 levels.     

Association of alpha‐thalassemia and Glucose‐6‐Phosphate Dehydrogenase deficiency with transcranial Doppler ultrasonography in Nigerian children with sickle cell anemia

BackgroundStroke is a devastating complication of sickle cell anemia (SCA) and can be predicted through abnormally high cerebral blood flow velocity using transcranial Doppler Ultrasonography (TCD). The evidence on the role of alpha‐thalassemia and glucose‐6‐phosphate dehydrogenase (G6PD) deficiency in the development of stroke in children with SCA is conflicting. Thus, this study investigated the association of alpha‐thalassemia and G6PD(A⁻) variant with abnormal TCD velocities among Nigerian children with SCA.MethodsOne hundred and forty‐one children with SCA were recruited: 72 children presented with normal TCD (defined as the time‐averaged mean of the maximum velocity: < 170 cm/s) and 69 children with abnormal TCD (TAMMV ≥ 200 cm/s). Alpha‐thalassemia (the α‐3.7 globin gene deletion) was determined by multiplex gap‐PCR, while G6PD polymorphisms (202G > A and 376A > G) were genotyped using restriction fragment length polymorphism—polymerase chain reaction.ResultsThe frequency of α‐thalassemia trait in the children with normal TCD was higher than those with abnormal TCD: 38/72 (52.8%) [α‐/ α α: 41.7%, α ‐/ α ‐: 11.1%] versus 21/69 (30.4%) [α‐/ α α: 27.5%, α ‐/ α ‐: 2.9%], and the odds of abnormal TCD were reduced in the presence of the α‐thalassemia trait [Odds Ratio: 0.39, 95% confidence interval: 0.20–0.78, p = 0.007]. However, the frequencies of G6PDA⁻ variant in children with abnormal and normal TCD were similar (11.6% vs. 15.3%, p = 0.522).ConclusionOur study reveals the protective role of α‐thalassemia against the risk of abnormal TCD in Nigerian children with SCA.     

Lower level of IL‐28A as a predictive index of the artificial liver support system in effective treatment of patients with HBV‐ACLF

BackgroundHBV‐related acute‐on‐chronic liver failure (HBV‐ACLF) is the most common type of liver failure with high mortality. Artificial liver support system (ALSS) is an important mean to reduce the mortality of HBV‐ACLF but lacking index to assess its effectiveness. The cytokines are closely related to the prognosis of HBV‐ACLF patients with ALSS treatment, however, which is not fully understood.MethodsOne hundred forty‐two patients with HBV‐ACLF and 25 healthy donors were enrolled. The cytokine profile of peripheral blood was determined in the patients before and after ALSS treatment, and their relationship with effectiveness of ALSS treatment in HBV‐ACLF was analyzed.ResultsSerum IL‐28A levels were markedly lower in ALSS‐effective patients than those in non‐effective patients pre‐ALSS treatment. Similarly, serum IL‐6 was significantly lower in ALSS‐effective patients. Furthermore, for patients with effective treatment, serum IL‐28A levels were positively related with IL‐6 levels post‐ALSS (r = 0.2413, p = 0.0383). The ROC curve analysis showed that serum levels of IL‐28A (AUC = 0.6959 when alone or 0.8795 when combined with total bilirubin, platelet count and INR, both p < 0.0001) and IL‐6 (AUC = 0.6704, p = 0.0005) were useful indices for separating effective from non‐effective ALSS treatment of HBV‐ACLF patients. Multivariate logistic regression analysis demonstrated that lower level of IL‐28A was independently associated with higher effective rate of ALSS treatments.ConclusionsLower level of IL‐28A is a predictive biomarker for ALSS in effective treatment of HBV‐ACLF patients and IL‐28A may be potential target for the treatment of HBV‐ACLF.     

Blood T‐helper 17 cells and interleukin‐17A correlate with the elevated risk of postpartum depression and anxiety

BackgroundT‐helper (Th) cells regulate inflammation and immunity, which is implicated in psychological disorders. The current study aimed to explore the clinical role of blood Th1, Th2, and Th17 cells and their main secreted cytokines in postpartum depression (PPD) and postpartum anxiety (PPA).MethodsA total of 226 postpartum women were included. At 6 weeks postpartum, Edinburgh Postnatal Depression Scale (EPDS) and State Trait Anxiety Inventory 6 item version (STAI6) scores were assessed; meanwhile, blood Th1, Th2, and Th17 cells were detected by flow cytometry, serum interferon‐gamma (IFN‐γ), interleukin‐4 (IL‐4), and IL‐17A were detected by enzyme‐linked immunosorbent assay.ResultsThe incidence of PPD and PPA were 24.3% and 27.9%, respectively. Th17 cells and IL‐17A were positively correlated with EPDS score and STAI6 score (all p < 0.001). Besides, Th17 cells (p < 0.001) and IL‐17A (p = 0.002) were increased in PPD cases vs. non‐PPD cases, and they were also elevated in PPA cases vs. non‐PPA cases (both p < 0.05). However, Th1 cells, Th2 cells, IFN‐γ, and IL‐4 were not linked with EPDS score or STAI6 score (all p > 0.05); besides, they did not vary in PPD cases vs. non‐PPD cases or in PPA cases vs. non‐PPA cases (all p > 0.05). Multivariate logistic regression model analysis showed that Th17 cells were independently associated with an elevated risk of PPD (odds ratio [OR] = 1.600, p = 0.001) and PPA (OR = 1.371, p = 0.022).ConclusionBlood Th17 cells and IL‐17A are positively linked with the risk of PPD and PPA, indicating which may be involved in the development of PPD and PPA.     

Heterogeneity assessment of vaccine‐induced effects using point‐of‐care surrogate neutralization test for severe acute respiratory syndrome coronavirus 2

IntroductionCoronavirus disease (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has become a global pandemic even after vaccination. We aimed to identify immunological heterogeneity over time in vaccinated healthcare workers using neutralization antibodies and neutralizing activity tests.MethodsSerum samples were collected from 214 healthcare workers before vaccination (pre) and on days 22, 90, and 180 after receiving the first dose of BNT162b2 vaccine (day 0). Neutralization antibody (NAb, SARS‐CoV‐2 S‐RBD IgM/IgG) titers and two kinds of surrogate virus neutralization tests (sVNTs) were analyzed (UMIN000043851).ResultsThe NAb (SARS‐CoV‐2 S‐RBD IgG) titer peaked on day 90 after vaccination (30,808.0 μg/ml ± 35,211; p < 0.0001) and declined on day 180 (11,678.0 μg/ml ± 33,770.0; p < 0.0001). The neutralizing activity also peaked on day 90 and declined with larger individual differences than those of IgG titer on day 180 (88.9% ± 15.0%, 64.8% ± 23.7%, p < 0.0001). We also found that the results of POCT‐sVNT (immunochromatography) were highly correlated with those of conventional sVNT (ELISA).ConclusionsNeutralizing activity is the gold standard for vaccine efficacy evaluation. Our results using conventional sVNT showed large individual differences in neutralizing activity reduction on day 180 (64.8% ± 23.7%), suggesting an association with the difference in vaccine efficacy. POCT‐sVNT is rapid and user‐friendly; it might be used for triage in homes, isolation facilities, and event venues without restrictions on the medical testing environment.     

A novel biomarker for pleural effusion diagnosis: Interleukin‐36γ in pleural fluid

BackgroundNumerous studies have described the critical importance of interleukin (IL) ‐36γ in host defense against lung infections, but it is unknown whether it plays a role in infectious pleural effusion (IPE). This study aimed to examine the levels of IL‐36γ in pleural effusions of different etiologies and evaluate the diagnostic accuracy of IL‐36γ in the differential diagnosis of IPE.MethodsA total of 112 individuals was enrolled in this research. IL‐36γ levels in pleural fluids of all 112 patients were measured by enzyme‐linked immunosorbent assay (ELISA). We also characterized these markers'' diagnostic values across various groups.ResultsPatients with tuberculous pleural effusion (TPE) and parapneumonic effusion (PPE) had exhibited markedly higher IL‐36γ levels in their pleural fluid than the malignant pleural effusion (MPE) and transudative effusion patients. Furthermore, the IL‐36γ concentrations in TPE patients were evidently higher than in uncomplicated parapneumonic effusion (UPPE) patients but significantly lower than in complicated parapneumonic effusion (CPPE)/empyema patients. Pleural fluid IL‐36γ is a useful marker to differentiate TPE from UPPE, at a cut‐off value for 657.5 pg/ml (area under the curve = 0.904, p < 0.0001) with 70.0% sensitivity and 95.7% specificity.ConclusionsThe elevated IL‐36γ in pleural effusion may be used as a novel biomarker for infectious pleural effusion diagnosis, particularly in patients with CPPE/empyema, and is a potentially promising biomarker to differentiate between TPE and UPPE.     

Longitudinal change of serum inter‐alpha‐trypsin inhibitor heavy chain H4, and its correlation with inflammation,multiorgan injury,and death risk in sepsis

BackgroundInter‐alpha‐trypsin inhibitor heavy chain H4 (ITIH4) inhibits infection‐induced inflammation and multiorgan injury through several methods. The present study aimed to estimate the association of serum ITIH4 with inflammatory cytokines, multiorgan injury, and death risk in sepsis patients.MethodsSerum samples were collected to detect ITIH4 by enzyme‐linked immunosorbent assay in 127 sepsis patients at admission (baseline), day (D)1, D3, and D7 after admission, as well as in 30 healthy controls (HCs). Additionally, 28‐day mortality was recorded in sepsis patients.ResultsITIH4 was reduced in sepsis patients versus HCs (median [interquartile range]: 147.9 [78.2–208.8] vs. 318.8 [237.2–511.4] ng/ml) (p < 0.001). In sepsis patients, ITIH4 was associated with the absence of cardiovascular and cerebrovascular disease history (p = 0.021). Additionally, ITIH4 was negatively correlated with tumor necrosis factor‐α (p < 0.001), interleukin (IL)‐1β (p < 0.001), IL‐6 (p = 0.019), IL‐17A (p = 0.002), and C‐reactive protein (p = 0.001), but positively related to IL‐10 (p = 0.007). Moreover, ITIH4 was also inversely associated with Acute Physiology and Chronic Health Evaluation II score (p = 0.002), Sequential Organ Failure Assessment (SOFA) score (p < 0.001), SOFA‐respiratory system score (p = 0.023), and SOFA‐renal system score (p = 0.007). Interestingly, ITIH4 gradually increased from baseline to D7 (p < 0.001); besides, ITIH4 at baseline (p = 0.009), D1 (p = 0.002), D3 (p < 0.001), and D7 (p = 0.015) were all decreased in sepsis deaths versus sepsis survivors.ConclusionSerum ITIH4 is raised from baseline to D7 after disease onset, and it reflects the reduction of systemic inflammation, disease severity, and 28‐day mortality for sepsis. However, further verification is required.     

Arctigenin inhibits apoptosis,extracellular matrix degradation,and inflammation in human nucleus pulposus cells by up‐regulating miR‐483‐3p

BackgroundArctigenin (ATG) is the active ingredient of the Chinese herbal medicine Arctium lappa, with anti‐inflammatory and antioxidant effects. Excessive inflammation and cell apoptosis are important causes of intervertebral disc degeneration (IDD). Hence, this study probed into the possible role of ATG in IDD.MethodsInterleukin (IL)‐1β (10 ng/ml) was adopted to induce human nucleus pulposus cells (HNPCs) as a cell model for IDD. The effects of different concentrations of ATG (0, 2, 5, 10, 20, 50 μmol/L) on the viability of HNPCs and effects of ATG (10, 50 μmol/L) on the viability of IL‐1β‐induced HNPCs were detected by cell counting kit‐8 (CCK‐8). After IL‐1β‐induced HNPCs were transfected with miR‐483‐3p inhibitor and/or treated with ATG, cell viability and apoptosis were determined by CCK‐8 and flow cytometry; the expressions of miR‐483‐3p, extracellular matrix (ECM)‐related genes, and inflammation‐related genes were measured by quantitative real time polymerase chain reaction (qRT‐PCR), and expressions of ECM/apoptosis/NF‐κB pathway‐related proteins were quantified by Western blot.ResultsATG had no significant effect on the viability of HNPCs but could promote the viability of IL‐1β‐induced HNPCs. ATG inhibited apoptosis, ECM degradation, inflammation, and activation of NF‐κB pathway in HNPCs induced by IL‐1β, but promoted the expression of miR‐483‐3p. MiR‐483‐3p inhibitor reversed the above‐mentioned regulatory effects of ATG.ConclusionArctigenin suppresses apoptosis, ECM degradation, inflammation, and NF‐κB pathway activation in HNPCs by up‐regulating miR‐483‐3p.