Interleukin-13 promotes cellular senescence through inducing mitochondrial dysfunction in IgG4-related sialadenitis / 国际口腔科学杂志·英文版

Immunoglobulin G4-related sialadenitis (IgG4-RS) is an immune-mediated fibro-inflammatory disease and the pathogenesis is still not fully understood. The aim of this study was to explore the role and mechanism of interleukin-13 (IL-13) in the cellular senescence during the progress of IgG4-RS. We found that the expression of IL-13 and IL-13 receptor α1 (IL-13Rα1) as well as the number of senescent cells were significantly higher in the submandibular glands (SMGs) of IgG4-RS patients. IL-13 directly induced senescence as shown by the elevated activity of senescence-associated β-galactosidase (SA-β-gal), the decreased cell proliferation, and the upregulation of senescence markers (p53 and p16) and senescence-associated secretory phenotype (SASP) factors (IL-1β and IL-6) in SMG-C6 cells. Mechanistically, IL-13 increased the level of phosphorylated signal transducer and activator of transcription 6 (p-STAT6) and mitochondrial-reactive oxygen species (mtROS), while decreased the mitochondrial membrane potential, ATP level, and the expression and activity of superoxide dismutase 2 (SOD2). Notably, the IL-13-induced cellular senescence and mitochondrial dysfunction could be inhibited by pretreatment with either STAT6 inhibitor AS1517499 or mitochondria-targeted ROS scavenger MitoTEMPO. Moreover, IL-13 increased the interaction between p-STAT6 and cAMP-response element binding protein (CREB)-binding protein (CBP) and decreased the transcriptional activity of CREB on SOD2. Taken together, our findings revealed a critical role of IL-13 in the induction of salivary gland epithelial cell senescence through the elevated mitochondrial oxidative stress in a STAT6-CREB-SOD2-dependent pathway in IgG4-RS.

In vitro and in vivo effects of 5-aminolevulinic acid-mediated photodynamic therapy against oral squamous cell carcinoma / 中华口腔医学杂志

Objective@#To investigate the in vitro and in vivo effects of 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy against oral squamous cell carcinoma (OSCC) and preliminarily explore the possible mechanisms.@*Methods@#SCC25 cells were divided into the control group (5-ALA of 0 mg/L) and the experimental group (5-ALA of 10, 25, 50, 100 and 150 mg/L). The production of protoporphyrin Ⅸ (PpⅨ) induced by 5-ALA in SCC25 cells was detected using the flow cytometry. SCC25 cells were divided into the control group (5-ALA of 0 mg/L), lazer alone group, 5-ALA alone group (5-ALA of 100 mg/L) and the 5-ALA combined with laser irradiation group (5-ALA of 5, 10, 25, 50 and 100 mg/L), the cytotoxicity of 5-ALA combined with laser irradiation (wave length 635 nm, power density 87 mW/cm2 and laser dose 10.4 J/cm2) was evaluated in SCC25 cells using the methyl thiazolyltetrazolium assay (incubation times of 4, 8 and 12 h in each group) and the induction effect of combination treatment on the cell apoptosis was assessed by the flow cytometry (incubation time of 12 h in each group). The intracellular production of reactive oxygen species (ROS) triggered by 5-ALA combined with laser irradiation was determined using a fluorescence probe method (incubation time of 12 h in each group). A mouse OSCC xenograft model bearing SCC25 tumor was built, and the mice were divided into control group (saline), 5-ALA group (5-ALA of 50 mg/kg) and 5-ALA combined with laser irradiation group (5-ALA of 10, 25 and 50 mg/kg). Antitumor effect of 5-ALA combined with laser irradiation (wave length 635 nm, power density 158 mW/cm2 and laser dose 94.8 J/cm2) was further measured.@*Results@#5-ALA induced the production of PpⅨ in SCC25 cells in a drug concentration (0-150 mg/L)-and incubation time (0-24 h)-dependent manner. When the 5-ALA concentration was 100 mg/L, the intracellular PpⅨ production was in a relatively stable state. Cell viability and apoptosis rate of 5, 10, 25, 50, 100 mg/L 5-ALA combined with laser irradiation are, respectively, (82.3±5.2)%, (3.13±0.38)%; (74.6±9.3)%, (5.38±0.55)%; (38.3±9.7)%, (17.97±2.72)%; (9.2±3.8)%, (24.47±3.37)%; (7.2±0.8)%, (43.01±5.96)%, which indicated that 5-ALA combined with laser irradiation notably inhibited the growth of SCC25 cells and also induced significant cell apoptosis compared with the control group [(96.3±6.0)%, (0.35±0.13)%, P<0.05]. After combination treatment (5-ALA of 5, 10, 25, 50 and 100 mg/L combined with laser irradiation, the mean fluorescence intensity of dichlorofluorescein is (1.46±0.12)×104, (2.16±0.30)×104, (3.57±0.34)×104, (81.70±13.05)×104, (113.00±7.35)×104, respectively, a large amount of ROS was produced in SCC25 cells compared with the control group [(0.96±0.15) ×104, P<0.05], which was in positive correlation with the intracellular PpⅨ content. 5-ALA (concentration of 10, 25 and 50 mg/kg) combined with laser irradiation greatly suppressed the tumor growth in SCC25 tumor-bearing mice compared to the control group (P<0.05).@*Conclusions@#5-ALA-mediated photodynamic therapy can trigger the generation of intracellular ROS that has significant cytotoxicity and apoptosis induction effect, and thus inhibit the tumor growth both in vitro and in vivo.

Serum MicroRNA Levels as a Noninvasive Diagnostic Biomarker for the Early Diagnosis of Hepatitis B Virus-Related Liver Fibrosis

BACKGROUND/AIMS: To investigate the role of selected serum microRNA (miRNA) levels as potential noninvasive biomarkers for differentiating S0–S2 (early fibrosis) from S3–S4 (late fibrosis) in patients with a chronic hepatitis B virus (HBV) infection. METHODS: One hundred twenty-three treatment-naive patients with a chronic HBV infection who underwent a liver biopsy were enrolled in this study. The levels of selected miRNAs were measured using a real-time quantitative polymerase chain reaction assay. A logistic regression analysis was performed to assess factors associated with fibrosis progression. Receiver operating characteristic (ROC) curve and discriminant analyses validated these the ability of these predicted variables to discriminate S0–S2 from S3–S4. RESULTS: Serum miR-29, miR-143, miR-223, miR-21, and miR-374 levels were significantly downregulated as fibrosis progressed from S0–S2 to S3–S4 (p < 0.05), but not miR-16. The multivariate logistic regression analysis identified a panel of three miRNAs and platelets that were associated with a high diagnostic accuracy in discriminating S0–S2 from S3–S4, with an area under the curve of 0.936. CONCLUSIONS: The levels of the studied miRNAs, with the exception of miR-16, varied with fibrosis progression. A panel was identified that was capable of discriminating S0–S2 from S3–S4, indicating that serum miRNA levels could serve as a potential noninvasive biomarker of fibrosis progression.

Interleukin-23 levels in serum and dendritic cells and its relationship with prognosis of acute-on-chronic liver failure patients with chronic hepatitis B / 中华传染病杂志

Objective To study interleukin-23 (IL-23) levels in serum and dendritic cells of acute-on-chronic liver failure (ACLF) patients with chronic hepatitis B (CHB) and to explore its relationship with the prognosis.Methods Peripheral blood mononuclear cells and serum were collected from 40 ACLF patients with CHB (including survival group 27 cases and non-survival group 13 cases) and 26 healthy controls.Monocytes were induced to immature dendritic cell in vitro and TNF-α was added to induce dendritic cell maturation.IL-23 mRNA of dendritic cells was detected by real time polymerase chain reaction (PCR), and serum IL-23 level was measured by enzyme-linked immuno sorbent assay (ELISA).Differences among the parameters with normal distribution were compared using t test, those with non-normal distribution were compared using non-parametric Mann-Whitney U-test, and the relationship between two variables was assessed by Spearman′s rank correlation.Results International normalized rate (INR) and model for end-stage liver disense (MELD) scores in non-survival group of ACLF were higher than those in survival group (INR: 2.32 vs 1.64, U=69.00, P=0.002 2;MELD:36 vs 30, U=64.50, P=0.001 4).However, there were no significant differences between two groups at gender, age, alanin aminotransferase (ALT), aspartate aminotrans ferase (AST), bilirubin, creatinine, hepatitis B virus (HBV) DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and serum IL-23.IL-23 mRNA level in dendritic cells at baseline in non-survival group of ACLF was significantly higher than that in survival group (76 vs 43, U=71.50, P=0.002 8).After treatment, serum IL-23 was significantly declined in survival group ([160±75] ng/L vs [91±49] ng/L, t=4.012, P=0.000 2), but not in non-survival group.Significant positive correlation was observed between IL-23 mRNA level in dendritic cells and MELD score at baseline (r=0.7198,P<0.01).Conclusions Persistent high serum IL-23 level suggests poor prognosis in ACLF patients with CHB.IL-23 mRNA expression in dendritic cells has good consistency with MELD score and the patients with high IL-23 mRNA expression has poor outcome.

A new silver amplification immunochromatography system compared with conventional rapid antigen assay for the diagnosis of influenza A and B / 中国感染与化疗杂志

Objective To analyze the consistency of two rapid antigen assays for the diagnosis of influenza A and B. We evaluated the clinical usefulness of silver amplification immunochromatography influenza virus detection kit.Methods Nasopharyngeal swab samples were collected from patients who were suspected of influenza at Huashan Hospital between January and February 2015. Two samples were collected from the same one patient. The samples were tested simultaneously by using IMMUNO AG Cartridge Flu AB kit (AG1) and commercial immunochromatographic assay kit, Clearview exact influenza A&B (CV). PCR method was used as reference.Results A total of 91 samples were tested, of which 7 were positive for influenza A and 53 positive for influenza B by AG1 system; 7 positive for influenza A and 50 positive for influenza B by CV system; and 8 positive for influenza A and 60 positive for influenza B by PCR. The sensitivity and specificity of the AG1 system were 87.5 % and 100 % for influenza A, and 88.3 % and 100 % for influenza B; while the CV system showed sensitivity and specficity of 87.5 % and 100 % for influenza A, 83.3 % and 100 % for influenza B. The AG1 system was 100 % consistent with the CV system in the positive rate of influenza A, and 94.3 % consistent with the CV system in the positive rate of influenza B.Conclusions The AG1 system is well consistent with the conventional immunochromatography-based diagnostic tests in diagnosis of influenza. The AG1 system is useful in earlier diagnosis of influenza due to fewer human error in result interpretation.

Association between postnatal weight gain and severe retinopathy of prematurity in preterm babies with very low birth weight / 中华眼底病杂志

Objective To analyze the association of postnatal weight gain proportion of very low birth weight (BW) preterm babies and the onset of severe retinopathy of prematurity,and investigate the optimal cut-off points and predictive ability of postnatal weight gain (WG) proportion for the onset of retinopathy of prematurity (ROP).Methods A retrospective cohort study.257 preterm infants underwent screening whose weight was less than 1500 g were enrolled in this study.Risk factors include BW,gestational age (GA),history of oxygen inhalation,need for blood transfusions,Apgar score in 1 to 10 minutes,embryo number,delivery mode,in vitro fertilization infants,and WG proportion within 6 weeks after birth and other systemic diseases were recorded.Their correlation with severe ROP is analyzed.Clinical outcomes were divided into severe ROP group (patients who suffered from ROP and required treatment) and mild and no ROP group (patients who suffered from ROP but do not require treatment and-patient without ROP).The severe ROP group included 18 patients and mild and no ROP group included 239 patients.Multiple logistic regression and receiver operating characteristic (ROC) curve were used to determine if the WG proportion was independently related to severe ROP development and if it was capable of predicting severe ROP.This study determines the predict value by comparing the area under the ROC curve (AUC) of independent risk factors.Results GA (t=-4.835,P＜0.001),BW(t=-5.192,P＜0.001),history of oxygen inhalation (x2=6.001,P=0.009),proportion of infants who had oxygen inhalation for more than 10 days(x2 =10.019,P=0.002),postnatal WG proportion at 1 week(t =-3.663,P＜ 0.001),postnatal WG proportion at 2 weeks(t=-3.425,P=0.001) had significant difference between two groups.Multiple logistic regression analysis revealed that GA (β =-0.858,P =0.008),BW (β =-0.005,P =0.010),postnatal WG proportion at 2 weeks (β=-8.745,P =0.035) were correlated to severe ROP significantly.And their area under the ROC were 0.836[95％ confidence interval (CI):0.752-0.920],0.826 (95％CI:0.947-0.903),0.744 (95％CI:0.598-0.891) respectively.The optimal cut-off points of GA,BW,and postnatal WG proportion at 2 weeks were 28.41 weeks,1241.96 g,12.80％ respectively.Conclusion Low WG proportion at 2 weeks of very low BW preterm babies is an important and independent risk factor for severe ROP and has certain predictive value of the onset of severe ROP.