OBJECTIVES: This study aimed to investigate the potential mediating role of plasma phosphorylated tau217 (p-tau217) in the association between periodontitis and mild cognitive impairment (MCI). METHODS: In this case-control study, patients diagnosed with MCI in the Neurology Department of the First Affiliated Hospital of Shandong Second Medical University from November 2023 to May 2024 were selected as the case group (MCI group). Cognitively normal (CN) volunteers, matched for age and education level and recruited from the physical examination center during the same period, served as the control group (CN group). The general demographic data of the study participants were collected. The Beijing versions of the Montreal Cognitive Assessment (MoCA), clinical dementia rating (CDR), and activities of daily living scale (ADL) were used to assess neuropsychological functions. Clinical periodontal examinations were conducted, the periodontal inflamed surface area (PISA) was calculated, and the periodontitis stage was determined in accordance with the 2018 classification. Fasting elbow venous blood samples were collected in the morning, and blood biochemical indicators were measured. Plasma p-tau217 levels were detected using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using t-test, Mann-Whitney U test, chi-square test, partial correlation analysis, multivariate Logistic regression analysis, multiple linear regression analysis, restricted cubic spline (RCS) regression analysis, and mediation effect analysis. RESULTS: Among the 192 participants, 96 belong to the MCI group and 96 to the CN group. The prevalence of periodontitis was 63.5% in the MCI group and 43.8% in the CN group, with a statistically significant difference (χ²=7.561, P=0.006). The plasma p-tau217 levels in the MCI group were significantly higher than those in the CN group [7.00 (4.27-9.65) ng/mL versus 2.02 (0.80-3.81) ng/mL, Z=-8.108, P<0.001]. Partial correlation analysis revealed that plasma p-tau217 levels were positively correlated with all the clinical periodontal indices (all P<0.001). After adjustments for baseline covariates, multivariate Logistic regression indicated that periodontitis was an independent risk factor for MCI. Patients with periodontitis had a 1.977-fold higher MCI risk than those without periodontitis (OR=1.977, 95%CI: 1.088-3.594, P=0.025). Moreover, the MCI risk for stage Ⅰ/Ⅱ periodontitis and stage Ⅲ/Ⅳ periodontitis was 1.878 times (OR=1.878, 95%CI: 1.029-3.425, P=0.040) and 2.625 times (OR=2.625, 95%CI: 1.073-6.246, P=0.035) higher than that for patients without periodontitis, respectively. Trend test showed that the MCI risk increased with periodontitis severity (P_trend=0.016). After adjustments for baseline covariates, multiple linear regression analysis showed that periodontitis was an independent risk factor for increased plasma p-tau217 levels (β=3.309, 95%CI: 2.363-4.254, P<0.001). Compared with patients without periodontitis, those with stage Ⅰ/Ⅱ periodontitis (β=1.838, 95%CI: 0.869-2.806, P<0.001) and stage Ⅲ/Ⅳ periodontitis (β=5.539, 95%CI: 4.442-6.636, P<0.001) had significantly higher plasma p-tau217 levels. In addition, trend test indicated that plasma p-tau217 levels increased with periodontitis severity (P_trend<0.001). After adjustments for baseline covariates, RCS regression analysis further revealed that PISA had a positive linear dose-response relationship with MCI risk (P_overall=0.002, P_nonlinear=0.344) and plasma p-tau217 levels (P_overall<0.001, P_nonlinear=0.140). After adjustments for baseline covariates, mediation analysis showed that plasma p-tau217 mediated the association between periodontitis and MCI, with a mediation proportion of 13.99% (95% Bootstrap CI: 0.38%-49.39%, P=0.038). CONCLUSIONS Periodontitis was independently positively associated with MCI risk, and plasma p-tau217 plays a mediating role in this association.
Humans ; Cognitive Dysfunction/complications* ; tau Proteins/blood* ; Periodontitis/complications* ; Case-Control Studies ; Male ; Female ; Phosphorylation ; Aged ; Middle Aged ; Activities of Daily Living

Objective:To investigate the improvement effects of duodenal-jejunal bypass (DJB)on the blood glucose homeostasis,insulin resistance and inflammation of the obese type 2 diabetic (T2DM)ZDF rats,and to discuss its possible mechanism.Methods:A total of 20 ZDF rats were randomly divided into DJB operation group and sham operation group (n = 10).There were 8 rats survived in each group after operation.The level of blood glucose (FBG)was detected by Roche glucose meter at 1 week before operation,2 weeks,4 weeks and 6 weeks after operation;the fasting serum insulin level of the rats was measured by ELISA kit;the insulin sensitivity index (HOMA-ISI)and insulin resistance index (HOMA-IR)were calculated.The rats were executed 6 weeks after operation.HE staining was used to observe the morphology of the inflammatory cells in BP limb of the rats;the expression levels of AMPK and pAMPK in BP lamb of the rats were observed by immunohistochemical staining;the expression levels of interleukin 1β(IL-1β),interleukin 6 (IL-6),tumor necrosis factorα(TNF-α),nuclear factorκB (NF-κB),and interleukin 10 (IL-10)mRNA of the rats were detected by QRT-PCR method.Results:From the 2nd week after operation,compared with before operation,the FBG levels of the rats in DJB operation group were decreased (t=3.798,P <0.05);compared with sham operation group,the FBG level of the rats in DJB operation group was decreased (t=3.205,P <0.05).Six weeks after operation,compared with sham operation group,the HOMA-IR of the rats in DJB operation group was significantly decreased (t=4.441,P <0.05)and the HOMA-ISI was significantly increased (t=-8.65,P < 0.05).The HE staining results showed that compared with sham operation group,the morphology of the inflammatory cells in BP limb of the rats in DJB operation group was significantly improved.The QRT-PCR results showed that the expression levels of IL-1β,IL-6,TNF-αand NF-κB of the rats in DJB operation group was significantly decreased compared with sham operation group (P < 0.05), while the expression level of IL-10 was significantly increased (P < 0.05).The immunohistochemical test results showed that the expression levels of AMPK and pAMPK in BP lamb of the rats in DJB operation group were increased compared with sham operation group.Conclusion:DJB can significantly improve the blood glucose homeostasis and insulin resistance in the T2DM rats,and its mechanism may be related to the decreased expressions of inflammatory factors and the activation of AMPK molecules in BP lamb of the T2DM rats.

OBJECTIVE:To investigate the effects of the antihypertensive protein from Pheretima on blood pressure, angiotensinⅡ and angiotensin Ⅱ AT1 receptor in spontaneously hypertensive rats (SHR).METHODS: The dynamic change of blood pressure in SHR after singel intravenous injection of antihypertensive protein from Pheretima was observed. After intervention with antihypertensive protein from earthworm for 28 d,the levels of blood pressure, angiotensinⅡ and expression of angiotensin Ⅱ AT1 receptor in SHR were detected. RESULTS: Either single intravenous injecion or multiple dosing of the antihypertensive protein from Pheretima could significantly reduce the blood pressure in SHR (P0.05).The expression of angiotensin Ⅱ AT1 receptor in kidney of SHR model increased significanlty compared the normal control (wistar rats), but decreased after the intervention of the antihypertensive protein from Pheretima.CONCLUSION: The antihypertensive protein from Pheretima has antihypertensive effect on SHR. The mechanism may be related to the reduction of angiotensinⅡ level and lowering of the expression of a angiotensin Ⅱ AT1 receptor in kidney.

Aim To probe the mechanism of the therapeutic effect of APS against DM rats by measuring the level of TNF-?,as well as observing the change of caspase-3 protein in pancreatic beta cells.Methods Thirty DM rats induced by STZ were randomly divided into three groups:DM group,APS low dosage group,APS high dosage group,and another 10 normal rats were taken as the control group.The drug was given for 6 weeks.The research included measuring the level of TNF-? in serum and the expression of caspase-3 protein in pancreatic beta cells.Results ① The level of TNF-? was higher in model group than that of the normal group(P