Peptidyl arginine deiminase 4 and its potential role in Alzheimer's disease.

Alzheimer's disease (AD) is the main cause of dementia, and its pathogenesis is still not clear. Peptidyl arginine deiminases 4(PAD4) as one of the important members of PAD family, is the only protein with nuclear transfer function, it can regulate the expression of many proteins through citrullinating histone. PAD4 can also interact with many transcription factors, involved in regulating gene expression. PAD4 expression is closely related to the inflammatory factors secreted, cell autophagy, tumorigenesis and other neurodegenerative diseases. More importantly, PAD4 and its citrullinated protein were found in cortical and hippocampal neurons of AD patients. To study the expression and regulatory pathway of PAD4 in vivo and in vitro experiments on AD may be of helpful to elucidate the pathogenesis of AD. Meanwhile, detection of anti-citrullinated antibody will have potential value as novel biomarkers of AD.

FABP4 alleviates endoplasmic reticulum stress-mediated ischemia-reperfusion injury in PC12 cells via regulation of PPARγ.

Ischemic stroke is a life-threatening complication with a high rate of morbidity. Circulating fatty acid binding protein 4 (FABP4) has been reported to be associated with the outcome of acute ischemic stroke. The present study aimed to illustrate the function of FABP4 in ischemic stroke. PC12 cells exposed to oxygen glucose deprivation/reoxygenation (OGD/R) were used to mimic ischemia-reperfusion (I/R) injury in ischemic stroke. Cell viability was estimated using a Cell Counting Kit-8 assay. The expression of FABP4 in PC12 cells under OGD/R was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). PC12 cells were transfected with FABP4 small interfering RNA (siRNA), inflammatory cytokines and reactive oxygen species (ROS) were determined via RT-qPCR and ROS assay kit. Western blotting was performed to detect endoplasmic reticulum stress (ERS)-related proteins and peroxisome proliferator-activated receptor γ (PPARγ). Flow cytometry was used to evaluate the cell apoptotic rate. The expression of FABP4 increased gradually with the prolongation of reoxygenation within 8 h. FABP4-knockdown inhibited the transcription of inflammatory cytokines, the production of ROS and decreased cell apoptosis. Furthermore, decreased ERS-related proteins and increased PPARγ were estimated in PC12 cells transfected with FABP4 siRNA. PPARγ inhibitor GW9662 weakened the anti-apoptotic effect of FABP4-knockdown. Taken together, these results indicated that FABP4-knockdown suppressed cell apoptosis via relieving ERS; this effect was reversed by treatment of GW9662.

Brief screening for mild cognitive impairment in subcortical ischemic vascular disease: a comparison study of the Montreal Cognitive Assessment with the Mini-Mental State Examination.

BACKGROUND AND PURPOSE: To assess the validity of the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) in the detection of vascular mild cognitive impairment (VaMCI) in patients with subcortical ischemic vascular disease (SIVD). METHODS: Among 102 SIVD patients, both cutoff scores of the MMSE and MoCA for differentiating VaMCI from no cognitive impairment (NCI) or differentiating VaMCI from vascular dementia (VaD) were determined by the receiver operator characteristic (ROC) analysis. Optimal sensitivity with specificity of cutoff scores was obtained after the raw scores were adjusted for education. RESULTS: After adjusting for education, the MoCA cutoff score for differentiating VaMCI from NCI was at 24/25 and that for differentiating VaMCI from VaD was at 18/19. After applying the adjusted MoCA scores from 19 to 24 to identify VaMCI in all SIVD patients, sensitivity was at 76.7% and specificity was at 81.4% (κ = 0.579). The adjusted cutoff score of the MMSE for differentiating VaMCI from NCI was at 28/29 and that for differentiating VaMCI from VaD was at 25/26. The sensitivity and specificity of the adjusted MMSE was at 58.1 and 71.2%, respectively, when using the score from 26 to 28 to identify VaMCI in SIVD patients (κ = 0.294). CONCLUSIONS: The MoCA detected subcortical VaMCI better than the MMSE.

[A survey on the attitudes and confidence of general practitioners in handling dementia and its related problems].

OBJECTIVE: To investigate general practitioners (GPs)' attitudes and confidence in handling dementia and its related problems. METHOD: A questionnaire survey was conducted in GPs from Shanghai on 25th Sep, 2012. The questionnaire included the basic information of the GPs and their attitudes toward and confidence in handling dementia and its related problems. RESULTS: A total of 287 GPs from 73 hospitals participated in the survey.78.4% of them responded that they met fewer demented patients during their clinical practice and only 24.7% of them had attended some kinds of dementia-related knowledge training courses.Senior GPs were less enthusiastic than junior GPs in handling dementia and its related problems as they were more likely to think that dementia should be diagnosed by specialist (87.1% vs. 74.8%, OR = 2.28, 95%CI:1.14~4.57, P = 0.02), less likely to actively referral patients (22.0% vs. 10.1%, OR = 2.52, 95%CI:1.24~5.14, P = 0.01), and more likely to think about that GPs have very limited role in care of demented patients (9.7% vs. 0.7%, OR = 15.59, 95%CI:1.96~123.81, P = 0.00). CONCLUSION: The GPs in Shanghai are lack of trainings about the dementia and its' related knowledge and their attitudes toward the care of dementia are pessimistic. Thus, it is necessary to train the GPs more to enhance their confidence and enthusiasm in care of dementia.