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.     

Development of quantum dot‐based fluorescence lateral flow immunoassay strip for rapid and quantitative detection of serum interleukin‐6

BackgroundInterleukin‐6 (IL‐6) is an inflammatory factor that increases rapidly in response to infectious diseases including sepsis. The aim of this study is to develop a quantum dot (QD)‐based fluorescence lateral flow immunoassay (LFIA) strip that can rapidly and accurately detect IL‐6 levels.MethodsQD‐based LFIA strips were fabricated by conjugating CdSe/ZnS QDs to the IL‐6 antibody. Performance verification and clinical sample analysis were carried out to evaluate the newly developed strip.ResultsQD‐based LFIA strips were successfully fabricated. The test strip''s linear range was 10–4000 pg/ml, with a linear correlation coefficient of R ² ≥ .959. The sensitivity of the test strip was 1.995 pg/ml. The recovery rate was 95.72%–102.63%, indicating satisfying accuracy. The coefficient of variation (CV) of the intra‐assay was 2.148%–3.903%, while the inter‐assay was 2.412%–5.293%, verifying the strip''s high precision. The cross‐reaction rates with various interleukins (IL‐1α, IL‐1β, IL‐2, IL‐4, and IL‐8) and interferon‐γ (IFN‐γ) were all <0.1%. When the strip was placed in a 50°C oven for 1, 2, 3, and 4 weeks, the test results were not significantly altered compared to storage at room temperature. Furthermore, 200 clinical serum samples were analyzed to compare the strip with the Beckman chemiluminescence immunoassay (CLIA) kit, which revealed a high correlation (n = 200, R ² = .9971) for the detection of IL‐6.ConclusionsThe QD‐based test strip can rapidly and quantitatively detect IL‐6 levels, thus meeting the requirement of point‐of‐care test (POCT) and showing excellent clinical prospects.     

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.     

Combination of C‐reactive protein,procalcitonin, IL‐6, IL‐8, and IL‐10 for early diagnosis of hyperinflammatory state and organ dysfunction in pediatric sepsis

BackgroundAlthough early diagnosis and management are critical for prognosis of pediatric sepsis, there are no specific diagnostic biomarkers for the hyperinflammatory state and organ dysfunction, important stages of sepsis.MethodsWe enrolled 129 children with infection into three groups: non‐sepsis infection (33), Sepsis 1.0 (hyperinflammatory state, 67), and Sepsis 3.0 (organ dysfunction, 29). Another 32 children with no infections were included as controls. Serum C‐reactive protein (CRP), procalcitonin (PCT), interleukin (IL)‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐12p70, IL‐17, tumor necrosis factor (TNF)‐α, interferon (IFN)‐α, and IFN‐γ were assessed to diagnose the two stages, and their diagnostic capacities were evaluated using receiver operating characteristic (ROC) curves. We also examined whether combining biomarkers improved diagnostic efficiency.ResultsSignificantly higher CRP, PCT, and IL‐6 levels were detected in the Sepsis 1.0 than the non‐sepsis infection group (p < 0.001). The areas under the curve (AUCs) for diagnosing Sepsis 1.0 were 0.974 (CRP), 0.913 (PCT) and 0.919 (IL‐6). A combination of any two biomarkers increased diagnostic sensitivity to ≥92.54% and specificity to 100.00%. Significantly higher PCT, IL‐8, and IL‐10 levels were found in the Sepsis 3.0 than the Sepsis 1.0 group (p ≤ 0.01), with AUCs for diagnosing Sepsis 3.0 0.807 (PCT), 0.711 (IL‐8), and 0.860 (IL‐10). Combining these three biomarkers increased diagnostic sensitivity to 96.55% and specificity to 94.03%.ConclusionIn pediatric sepsis, combining any two of CRP, PCT, and IL‐6 can accurately diagnose the hyperinflammatory state and increase diagnostic specificity. Early diagnosis of organ dysfunction requires a combination of PCT, IL‐8, and IL‐10.     

Simultaneous disruption of circulating miR‐21 and cytotoxic T lymphocytes (CTLs): Prospective diagnostic and prognostic markers for esophageal squamous cell carcinoma (ESCC)

Background Esophageal squamous cell carcinoma (ESCC) as the most prominent type of esophageal cancer (EC) in developing countries encompasses a substantial contribution of cancer‐related mortalities and morbidities. Cytotoxic T lymphocytes (CTLs) are the major subset of effector T cells against cancer. However, the microRNAs involved in the development and regulation of CTLs could be disrupted in cancers such as EC.MethodsHere, we evaluated the population of IL‐10, TGF‐β, IFN‐γ, and IL‐17a‐producing CD3+CD8+ T cells, their association with the circulating levels of miR‐21 and miR‐29b, and their diagnostic and/or prognostic (after 160 weeks of follow‐up) utilities in 34 ESCC patients (12 newly diagnosed: ND, 24 under‐treatment: UT) and 34 matched healthy donors.ResultsThe population of IL‐10 and TGF‐β‐producing CTLs (CD8+ Tregs) were considerably expanded, in addition to the overexpression of miR‐21 in both groups (ND and UT) of ESCC patients, while the frequency of Tc17 and CD8+ Treg cells increased only in UT patients. The expression means of TGF‐β and IL‐10 in CTLs were considered to be excellent biomarkers (1 ≥ area under the curve: AUC ≥0.9) in distinguishing ESCC patients and associated subgroups from healthy subjects. Moreover, the lower expressions of TGF‐β, IL‐17a, IL‐10, and IFN‐γ in CTLs were associated with ESCC better prognosis.ConclusionsThe association between the impaired function of CD3+ CD8+ T cell subsets and miR‐21 expression could be introduced as novel therapeutic targets and powerful diagnostic and prognostic markers for ESCC.     

IL‐19 induced by IL‐13/IL‐17A in the nasal epithelium of patients with chronic rhinosinusitis upregulates MMP‐9 expression via ERK/NF‐κB signaling pathway

BackgroundTissue remodeling is a crucial characteristic of chronic rhinosinusitis (CRS). Imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) is crucial for the pathologic tissue remodeling in CRS. Elevation of interleukin (IL)‐19 or MMP‐9 levels in patients with CRS had been proven in previous studies. Here, we aimed to investigate the role of IL‐19 in mediating MMP‐9 expression in CRS.MethodsNasal tissue samples were collected from 45 individuals having chronic rhinosinusitis with nasal polyps (CRSwNP), 24 CRS without nasal polyps (CRSsNP), and 17 controls. Expression of IL‐19, its receptors (IL‐20R1/IL‐20R2), and MMP‐9 were investigated using RT‐qPCR and Immunofluorescence (IF). Human nasal epithelial cells (HNECs) were stimulated by IL‐19; ERK phosphorylation, nuclear factor‐κB (NF‐κB) pathway activation, and MMP‐9 level were detected by RT‐qPCR, enzyme‐linked immunosorbent assay, western blot, and IF. We also explored the effect of type1/2/3 cytokines on IL‐19 production by RT‐qPCR, and western blot.ResultsExpression levels of IL‐19, its receptors (IL‐20R1/IL‐20R2), and MMP‐9 were increased in nasal tissues from individuals with CRSwNP compared to those with CRSsNP as well as the controls. IL‐19 significantly elevated the production of MMP‐9 in HNECs. Furthermore, IL‐19 could activate the ERK and NF‐κB pathways, accompanied by increased MMP‐9 production in HNECs. Conversely, both ERK and NF‐κB inhibitors significantly attenuated the role of IL‐19 in MMP‐9 production. siRNA knockdown of IL‐20R1 suppressed ERK and NF‐κB pathway activation, thereby decreasing MMP‐9 expression. IL‐13 and IL‐17A were found to stimulate IL‐19 production in HNECs.ConclusionIL‐19, promoted by IL‐13 and IL‐17A, contributes to the upregulation of secretion of the tissue remodeling factor MMP‐9 in patients with CRS.     

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.     

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.     

Topical inflammasome inhibition with disulfiram prevents irritant contact dermatitis

BackgroundThe pathogenesis of contact dermatitis, a common inflammatory skin disease with limited treatment options, is held to be driven by inflammasome activation induced by allergens and irritants. We here aim to identify inflammasome‐targeting treatment strategies for irritant contact dermatitis.MethodsA high content screen with 41,184 small molecules was performed using fluorescent Apoptosis associated speck‐like protein containing a CARD (ASC) speck formation as a readout for inflammasome activation. Hit compounds were validated for inhibition of interleukin (IL)‐1β secretion. Of these, the approved thiuramdisulfide derivative disulfiram was selected and tested in a patch test model of irritant contact dermatitis in 25 healthy volunteers. Topical application of disulfiram, mometasone or vehicle was followed by application of sodiumdodecylsulfate (SDS) for 24 h each. Eczema induction was quantified by mexameter and laser speckle imaging. Corneocyte sampling of lesional skin was performed to assess inflammasome‐mediated cytokines IL‐1β and IL‐18.ResultsDisulfiram induced a dose‐dependent inhibition of ASC speck formation and IL‐1β release in cellular assays in vitro. In vivo, treatment with disulfiram, but not with vehicle and less mometasone, inhibited SDS‐induced eczema. This was demonstrated by significantly lower erythema and total perfusion values assessed by mexameter and laser speckle imaging for disulfiram compared to vehicle (p < 0.001) and/or mometasone (p < 0.001). Also, corneocyte IL‐18 levels were significantly reduced after application of disulfiram compared to vehicle (p < 0.001).ConclusionWe show that disulfiram is a dose‐dependent inhibitor of inflammasome pathway activation in vitro and inhibitor of SDS‐induced eczema in vivo. Topical application of disulfiram represents a potential treatment option for irritant contact dermatitis.     

Th17 cell‐derived miR‐155‐5p modulates interleukin‐17 and suppressor of cytokines signaling 1 expression during the progression of systemic sclerosis

Background miR‐155‐5p is associated with autoimmune diseases. T helper 17 (Th17) cells, interleukin (IL)‐17, and suppressor of cytokines signaling 1 (SOCS1) have important roles in the pathogenesis of systemic sclerosis (SSc). The purpose of this study was to explore the role of miR‐155‐5p in the regulation of IL‐17 and SOCS1 expression in Th17 cells and the subsequent effect on SSc disease progression.MethodsTh17 cells were isolated from peripheral blood mononuclear cells of SSc patients and healthy controls (HCs). RT‐qPCR and western blotting were used to examine the expression patterns of miR‐155‐5p, IL‐17, and SOCS1. Luciferase reporter assays were performed to confirm SOCS1 as a target of miR‐155‐5p. RNA pull‐down assays were performed to detect the interaction of IL‐17 and SOCS1 with miR‐155‐5p. In situ hybridization was performed to analyze the co‐expression pattern of miR‐155‐5p and IL17A in Th17 cells.ResultsThe levels of Th17 cell‐derived miR‐155‐5p were significantly up‐regulated in SSc patients compared with HCs, and its levels were negatively correlated with SOCS1 levels. Meanwhile, miR‐155‐5p positively regulated IL‐17 expression levels in Th17 cells isolated from SSc patients as the disease progressed. Using pmirGLO vectors, SOCS1 was confirmed as a target of miR‐155‐5p. The binding status of IL‐17 and SOCS1 to miR‐155‐5p was related to SSc progression. An increase in the co‐localization of miR‐155‐5p and IL‐17 was associated with greater SSc progression.ConclusionsIL‐17 and SOCS1 expression modulated by Th17 cell‐derived miR‐155‐5p are critical for SSc progression, which may provide novel insights into the pathogenesis of SSc.     

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.     

Role of IL‐17 in atopy—A systematic review

Purpose of ReviewAtopy is defined as the genetic predisposition to react with type I allergic diseases such as food‐, skin‐, and respiratory allergies. Distinct molecular mechanisms have been described, including the known Th2 driven immune response. IL‐17A (IL‐17) is mainly produced by Th17 cells and belongs to the IL‐17 family of cytokines, IL‐17A to F. While IL‐17 plays a major role in inflammatory and autoimmune disorders, more data was published in recent years elucidating the role of IL‐17 in allergic diseases. The present study aimed to elaborate specifically the role of IL‐17 in atopy.MethodsA systematic literature search was conducted in MEDLINE, Embase, and Cochrane Central Register of Controlled Trials, regarding IL‐17 and atopy/allergic diseases.ResultsIn total, 31 novel publications could be identified (food allergy n = 3, allergic asthma n = 7, allergic rhinitis [AR] n = 10, atopic dermatitis [AD] n = 11). In all allergic diseases, the IL‐17 pathway has been investigated. Serum IL‐17 was elevated in all allergic diseases. In AR, serum and nasal IL‐17 levels correlated with the severity of the disease. In food allergies, serum IL‐17E was also elevated in children. In AD, there is a trend for higher IL‐17 values in the serum and skin specimen, while it is more expressed in acute lesions. In allergic asthma, serum IL‐17 levels were increased. In two studies, higher serum IL‐17 levels were found in severe persistent asthmatic patients than in intermittent asthmatics or healthy controls. Only one therapeutic clinical study exists on allergic diseases (asthma patients) using a monoclonal antibody against the IL‐17 receptor A. No clinical efficacy was found in the total study population, except for a subgroup of patients with (post‐bronchodilator) high reversibility.SummaryThe role of IL 17 in the pathogenesis of allergic diseases is evident, but the involvement of the Th17 cytokine in the pathophysiological pathway is not conclusively defined. IL‐17 is most likely relevant and will be a clinical target in subgroups of patients. The current data indicates that IL‐17 is elevated more often in acute and severe forms of allergic diseases.     

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.     

Human adipose and synovial mesenchymal stem cells improve osteoarthritis in rats by reducing chondrocyte reactive oxygen species and inhibiting inflammatory response

BackgroundWe explored the therapeutic effects of Adipose‐derived mesenchymal stem cells (ADMSCs) and Synovial‐derived mesenchymal stem cells (SDMSCs) on osteoarthritis (OA).MethodsSDMSCs and ADMSCs were co‐cultured with chondrocytes and stimulated with interleukin (IL)‐1β. An OA model was established on rats by intra‐articular injection with ADMSCs and SDMSCs. After 8 weeks, the joint diameter difference was detected, and histological staining was used to observe the pathological changes in cartilage tissue. Enzyme‐linked immunosorbent assay (ELISA) was used to detect the expressions of IL‐6, tumor necrosis factor (TNF)‐α and IL‐1β in joint fluid. The expressions of COL2A1, Aggrecan, Matrix metalloproteinase (MMP)‐13, SOX9, IL‐6, TNF‐α and IL‐1β were detected by qRT‐PCR and Western blotting in cartilage tissue. Reactive oxygen species (ROS) content in cells and cartilage tissues was detected by ROS kit.ResultsSDMSCs and ADMSCs co‐cultured with chondrocytes could reduce MMP‐13 expression, increase the expressions of COL2A1, Aggrecan and SOX9, as well as reverse the effects of IL‐1β on promoting ROS content and inflammatory factors levels. After the OA model was established, the injection of ADMSCs and SDMSCs reduced the differences in joint diameter and tissue lesions in OA rats. The OA model led to increased levels of IL‐6, TNF‐α and IL‐1β in joint fluid and cartilage tissue, while the injection of ADMSCs and SDMSCs inhibited the inflammatory factor levels in OA rats, and increased the expressions of COL2A1, Aggrecan and SOX9 in OA rats.ConclusionADMSCs and SDMSCs improve osteoarthritis in rats by reducing chondrocyte ROS and inhibiting inflammatory response.     

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.     

Th17, rather than Th1 cell proportion,is closely correlated with elevated disease severity,higher inflammation level,and worse prognosis in sepsis patients

ObjectiveThe current study aimed to investigate the prognostic value of T helper (Th) 1 and Th17 proportions in sepsis patients.MethodsTh1 and Th17 cells in blood CD4⁺ T cells were detected by flow cytometry in 210 sepsis patients and 100 healthy controls (HCs). Besides, serum interferon‐γ (IFN‐γ), tumor necrosis factor‐α (TNF‐α), and interleukin‐17 (IL‐17) levels in the enrolled sepsis patients were determined with enzyme‐linked immunosorbent assay.ResultsCompared with HCs, Th1 and Th17 proportions were elevated in sepsis patients (both p < .001). Meanwhile, Th1 proportion was strongly correlated with IFN‐γ (p < .001, r = .484) but weakly correlated with TNF‐α (p = .024, r = .156) and IL‐17 (p = .002, r = .212), while Th17 proportion showed faint correlation with IFN‐γ (p = .015, r = .168), but strong correlations with TNF‐α (p < .001, r = .602) and IL‐17 (p < .001, r = .498) in sepsis patients. Besides, Th1 proportion was weakly associated with APACHE II score (p = .030, r = .150), but Th17 proportion was closely associated with APACHE II score (p < .001, r = .322) and SOFA score (p < .001, r = .337) in sepsis patients. Regarding their prognostic value, Th1 proportion (p = .042) was slightly, while Th17 proportion (p < .001) was dramatically, increased in septic deaths compared with survivors, and Th17 possessed good predictive value for 28‐day mortality risk (AUC: 0.748, 95% CI: 0.659–0.836).ConclusionTh1 and Th17 proportions are elevated in sepsis patients compared with HCs, and Th17 proportion is correlated with increased disease severity, higher inflammation level, and worse prognosis in sepsis patients.