Inhibitory effects of N-acetyl-L-cysteine on brain inflammation in mice with periodontitis and Alzheimer’s disease / 西安交通大学学报(医学版)

【Objective】 To explore the effects of periodontitis on the brains of Alzheimer’s disease (AD) mice and the effects of N-acetyl-L-cysteine (NAC) on the periodontium and the brain of AD mice with experimental chronic periodontitis (CP). 【Methods】 Ten wild-type C57 mice were in the blank control group (Group C57), and another 40 3-month-old APP/PS1 transgenic mice were randomly divided into four groups: AD+CP group, AD+CP+NAC group, AD+NAC group, and AD group. The periodontitis model was established in mice in AD+CP group and AD+CP+NAC group by silk ligation. At the same time, mice in AD+CP+NAC group and AD+NAC group were injected with NAC (200 mg/kg). The height of alveolar bone loss was detected after 3 weeks, and the cell morphology of the hippocampus was observed. We determined the expression levels of NLRP3 inflammasome and amyloid-β (Aβ) in the hippocampus as well as the expression levels of interleukin (IL)-1β and IL-18 in the hippocampus and gums by ELISA. 【Results】 Compared with AD group, the height of alveolar bone loss in AD+CP group was higher (P<0.05), and the expression levels of IL-18 in the gum and IL-1β and NLRP3 in the hippocampus were increased significantly (P<0.05). In addition, compared with AD+CP group, the height of alveolar bone loss in AD+CP+NAC group was reduced significantly (P<0.05), the expression levels of IL-1β and IL-18 in the gum were reduced significantly (P<0.05) as well as the expression levels of IL-1β and Aβ in the hippocampus were reduced significantly (P<0.05). Compared with C57 group, the neurons in the hippocampus of AD+CP group were more loose and disordered, and the activation of microglia was increased, while the disarrangement of cells in AD+CP+NAC group was less than that in AD+CP group. 【Conclusion】 Periodontitis can aggravate brain inflammation in AD mice. NAC can effectively reduce alveolar bone resorption in AD mice caused by periodontitis as well as reduce the levels of inflammatory factors in the gum and hippocampus. NAC can effectively reduce the alveolar bone absorption of AD mice caused by periodontitis, reduce the level of inflammatory factors in the gingiva and hippocampus, and reduce the damage of nerve cells in the hippocampus.

Clinical analysis of long-term survival and influencing factors of chimeric antigen receptor T-cell therapy in relapsed/refractory acute B-cell lymphoblastic leukemia / 中华血液学杂志

Objective: To analyze the survival and influencing factors of chimeric antigen receptor (CAR) T-cell therapy in relapsed/refractory acute B-cell lymphoblastic leukemia (R/R B-ALL) . Methods: Clinical information of patients who received CAR-T-cell therapy and achieved complete remission of R/R B-ALL between May 2015 and June 2018 at the Shaanxi Provincial People's Hospital was obtained. Kaplan-Meier analysis was used to evaluate the overall survival (OS) and leukemia-free survival (LFS) times of patients, and Cox regression analysis was performed to analyze the prognostic factors that affect patient survival after CAR-T therapy. Results: Among the 38 patients with R/R B-ALL, 21 were men, with a median age of 25 (6-59) years and a median OS time of 18 (95% CI 3-33) months. Multivariate Cox regression analysis showed that positive MLL-AF4 fusion gene expression was an independent risk factor for OS and LFS (OS: HR=4.888, 95% CI 1.375-17.374, P=0.014; LFS: HR=6.683, 95% CI 1.815-24.608, P=0.004). Maintenance therapy was a protective factor for OS and LFS (OS: HR=0.153, 95% CI 0.054-0.432, P<0.001; LFS: HR=0.138, 95% CI 0.050-0.382, P<0.001). In patients with MRD negative conversion, LFS benefit (HR=0.209, 95% CI 0.055-0.797, P=0.022) and OS difference was statistically insignificant (P=0.111). Moreover, patients with high tumor burden were risk factors for OS and LFS at the level of 0.1 (OS: HR=2.662, 95% CI 0.987-7.184, P=0.053; LFS: HR=2.452, 95% CI 0.949-6.339, P=0.064) . Conclusion: High tumor burden and high-risk genetics may affect the long-term survival rate of patients with R/R B-ALL receiving CAR-T, and lenalidomide-based maintenance therapy may improve their prognosis.

Effects of aralosdie C on excitation-contraction coupling of ischemia / reperfusion cardiomyocytes and role of CaMK II regulation / 中国药理学通报

Aim To investigate the effects of aralosdie C (SMC)isolated from aralosides on contractile func-tion and calcium transients in ischemia / reperfusion(I/R)-induced rat myocardial injury and the role of CaMK II. Methods The cardiomyocytes were divided into control group,I/ R group,I/ R + SMC group,KN-93+ I/ R + SMC group. The effect of SMC on the con-tractile function and calcium transient of I/ R cells was measured by cell shrinkage and ion concentration sim-ultaneous detection system. Results SMC(8 μmol· L - 1 )improved the contractile function of I/ R cardio-myocytes and the calcium transients,and SMC in-creased the rate of calcium transient and [Ca2 +]i up /down regulation significantly. While CaMK II was blocked by KN-93,the effect of SMC on contractile function and calcium transients was weakened. Con-clusions SMC can significantly improve the systolic function and calcium transients of cardiomyocytes in I/R rats,and the protective effect of SMC on cardiomyo-cytes may be related to CaMK II.

Phosphorylation of Atg31 is required for autophagy

Autophagy is an evolutionarily conserved cellular process which degrades intracellular contents. The Atg17-Atg31-Atg29 complex plays a key role in autophagy induction by various stimuli. In yeast, autophagy occurs with autophagosome formation at a special site near the vacuole named the pre-autophagosomal structure (PAS). The Atg17-Atg31-Atg29 complex forms a scaffold for PAS organization, and recruits other autophagy-related (Atg) proteins to the PAS. Here, we show that Atg31 is a phosphorylated protein. The phosphorylation sites on Atg31 were identified by mass spectrometry. Analysis of mutants in which the phosphorylated amino acids were replaced by alanine, either individually or in various combinations, identified S174 as the functional phosphorylation site. An S174A mutant showed a similar degree of autophagy impairment as an Atg31 deletion mutant. S174 phosphorylation is required for autophagy induced by various autophagy stimuli such as nitrogen starvation and rapamycin treatment. Mass spectrometry analysis showed that S174 is phosphorylated constitutively, and expression of a phosphorylation-mimic mutant (S174D) in the Atg31 deletion strain restores autophagy. In the S174A mutant, Atg9-positive vesicles accumulate at the PAS. Thus, S174 phosphorylation is required for formation of autophagosomes, possibly by facilitating the recycling of Atg9 from the PAS. Our data demonstrate the role of phosphorylation of Atg31 in autophagy.

Comparative study on the ability of adhesion and invasion of different fimA genetypes of Porphyromonas gingivalis to oral epithelial cells / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To compare the ability of adhesion and invasion to epithelial cells by Porphyromonas gingivalis (Pg) strains with different fimA separated from Chinese.</p><p><b>METHODS</b>Cultured method and antibiotic protection method were used to determine the adhesive and invasive ability of Pg with different fimA genetypes. The adhesion was observed by scanning electron microscope.</p><p><b>RESULTS</b>All the strains adhered and invaded to KB cells, and the adhesion rate ranged from 0.523% to 37.125% and invasive rate from 0.017% to 3.750%.The adhesive and invasive ability among different fimA genotypes showed no significant difference (P > 0.05).</p><p><b>CONCLUSIONS</b>There is no significant correlation between fimA genotype and ability in adhesion and invasion to KB cells.</p>

Invasion of four common periodontal pathogens into vascular endothelial cells in vitro / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To investigate the adhesive and invasive ability of four common periodontal pathogens, Pg33277, Pi25611, Aa29522 and Fn10953 in human umbilical vein endothelial cells (HUVEC).</p><p><b>METHODS</b>The model of infection of HUVEC by periodontal pathogens was established in vitro. The invasive ability of four periodontal pathogens in HUVEC was tested by scanning electron microscope (SEM) and antibiotic protection assays-colony-forming units (CFU).</p><p><b>RESULTS</b>All of the four periodontal pathogens were found to adhere to HUVEC by SEM and invaded HUVEC at invasion numbers of (0.8 +/- 0.1) x 10(8), (4.1 +/- 0.5) x 10(6), (1.6 +/- 0.3) x 10(6) and (5.0 +/- 0.4) x 10(6) CFU/L respectively by antibiotic protection assays-CFU. The invasion efficiencies were (0.400 +/- 0.050)%, (0.021 +/- 0.003)%, (0.008 +/- 0.002)% and (0.025 +/- 0.002)%, respectively. The invasive ability of Pg33277 was significantly greater than those of the other three periodontal pathogens (P < 0.001). There was no difference in invasive abilities among Pi25611, Aa29522 and Fn10953 (P > 0.05).</p><p><b>CONCLUSIONS</b>All of the four common periodontal pathogens, Pg33277, Pi25611, Aa29522 and Fn10953 could adhere to and invaded HUVEC, with Pg33277 being the strongest.</p>

Detection of luxS gene of quorum sensing signal system in periodontal pathogen / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To detect the presence and distribution of luxS gene in quorum sensing signal system in the periodontal pathogens.</p><p><b>METHODS</b>The total DNA of Porphyromonas gingivalis (Pg), Fusobacterium nucleatum (Fn), Actinobacillus acitinomycetimcomtans (Aa) were extracted. The presence of luxS was detected by polymerase chain reaction (PCR). The products of PCR were detected by electrophoresis, sequenced and identified by a Blast search of the GenBank database.</p><p><b>RESULTS</b>Electrophoresis, sequencing and Blast searching indicated that the PCR products of Pg were highly consistent with the luxS gene in GenBank. The sequencing result of Fn was also identified with the target gene. The PCR product of Aa was the same as reference through electrophoresis.</p><p><b>CONCLUSIONS</b>Pg, Fn, Aa contain luxS gene. Further studies may be required to investigate the functions of luxS in the periodontal pathogens.</p>