Regulation of Amyloidogenesis and Clearance of p-Amyloid in Alzheimer' s Disease / 中国生物化学与分子生物学报

Alzheimer ' s disease (AD ) , an age-associated chronic progressive neurodegeneration disorder, is characterized by progressive loss of memory, cognitive impairment and behavioral changes.The pathological hallmarks of AD are (3-amyloid (A(3) deposition, neurofibrillary tangles induced by phosphorylation of tau protein, upregulation of inflammation and neuronal apoptosis.Amyloid is a polypeptide consisting of 39-42 amino acids which is produced by a series of enzymatic hydrolysis of amyloid precursor protein in neurons.Studying the regulation of the production and clearance of Ais of great importance which may help in finding potential intervention to effectively delay or even reverse the process of Alzheimer's disease.As the key enzyme of A(3 production, (3-secretase ((3-site APP cleaving enzyme 1, BACE'l) plays an essential role in the development of AD.The aggregation of inflammatory cells around senile plaques suggests that A(3 is highly associated with neuroinflammation.Neuroinflammation-related cells participate in the clearance of A(3 and multiple cytokines regulate the level of A0.In addition, although non-coding UNA is rarely involved in the production, deposition and clearance of A(3 directly, it can regulate the production of A(3 through other pathways.In this article, we will focus on the important role of BACE1, neuroinflammation and non-coding RNA in the regulation of A(3 and review the mechanism of production and clearance of A(3 in AD.

MicroRNA-135a in ABCA1-labeled Exosome is a Serum Biomarker Candidate for Alzheimer's Disease / 生物医学与环境科学（英文）

Objective@#In the present study, the ABCA1 was used as a label to capture specific exosomes, the level of ABCA1-labeled exosomal microRNA-135a (miR-135a) was evaluated for the diagnosis of Alzheimer's disease (AD), especially in patients with early stages of AD.@*Methods@#This is a preliminary research focused on the levels of ABCA1 in WBCs, RBCs, HT-22 cells, and neuron cells. The diagnostic value of ABCA1-labeled exosomal miR-135a was examined using the CSF and serum of APP/PS1 double transgenic mice, and 152 patients with SCD, 131 patients with MCI, 198 patients with DAT, and 30 control subjects.@*Results@#The level of ABCA1 exosomes harvested from HT-22 cells and neuron culture medium was significantly higher compared to that of RBCs and WBCs ( @*Conclusion@#This study outlines a method to capture specific exosomes and detect them using immunological methods, which is more efficient for early diagnosis of AD.

The Serum Exosome Derived MicroRNA-135a, -193b, and -384 Were Potential Alzheimer's Disease Biomarkers / 生物医学与环境科学（英文）

OBJECTIVE@#MicroRNAs (miRs) are attractive molecules to be considered as one of the blood-based biomarkers for neurodegenerative disorders such as Alzheimer's disease (AD). The goal of this study was to explore their potential value as biomarkers for the diagnosis of AD.@*METHODS@#The expression levels of exosomal miR-135a, -193b, and -384 in the serum from mild cognitive impairment (MCI), dementia of Alzheimer-type (DAT), Parkinson's disease with dementia (PDD), and vascular dementia (VaD) patients were measured with a real-time quantitative reverse transcriptase PCR (qRT-PCR) method.@*RESULTS@#Both serum exosome miR-135a and miR-384 were up-regulated while miR-193b was down-regulated in serum of AD patients compared with that of normal controls. Exosome miR-384 was the best among the three miRs to discriminate AD, VaD, and PDD. Using the cut-off value could better interpret these laboratory test results than reference intervals in the AD diagnosis. ROC curve showed that the combination of miR-135a, -193b, and -384 was proved to be better than a particular one for early AD diagnosis.@*CONCLUSION@#Our results indicated that the exosomal miRs in the serum were not only potential biomarker of AD early diagnosis, but might also provide novel insights into the screen and prevention of the disease.

Evaluation of detection performance of urinary vanilmandelic acid on automatic biochemical analyzer / 医疗卫生装备

Objective To evaluate the automatic biochemical analyzer when used to detect urinary vanilmandelic acid (VMA), and to compare it with manual method. Methods The automatic biochemical analyzer using homogenous enzyme immunoassay technology was compared with the manual method on accuracy, precision, linear range, recovery rate, anti-interference capability and etc when used to detect VMA.The comparison was also carried out on positive rate and etc when the two methods were used to test the urine specimens of the healthy subjects and suspected patients of hypertension, hyperthyroidism and hypothyroidism. Results The two methods both had the results on accuracy, precision, linear range, recovery rate, anti-interference capability meet the requirements described in the instruction of reagent kit, while the analyzer gained advantages over the manual method.The positive rates by the two methods for testing urine specimens were similar,while the analyzer behaved better in diagnosing the patient with critical value.Conclusion The analyzer proves better than the manual method when used to detect VMA,and thus is worthy promoting in clinical trial.

Prevalence and subtype distribution of HPV infection among women in Beijing urban area and their correlation with age / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the prevalence and subtype distribution of human papillomavirus (HPV) infection and its correlation with age among women in Beijing urban area, and provide some epidemiological evidence for the clinical application of HPV vaccines.</p><p><b>METHODS</b>We collected cervical specimens from 1999 women in the Outpatient Department of our hospital, performed genetyping of HPV-DNA, and analyzed the incidence of HPV infection in different age groups.</p><p><b>RESULTS</b>HPV infection was detected in 502 (25.2%) of the 1999 women patients, with 391 (19.6%) cases of high-risk HPV, which included 326 (83.4%, 326/391) cases of single infection. HPV-16 was the most common type (21.2%, 69/326), followed by HPV-52 (19.3%, 63/326) and HPV-58 (16.0%, 52/326). The prevalence of HPV infection was the highest among the women aged 41 -50 years and the lowest among those over 60 years.</p><p><b>CONCLUSION</b>The subtype- and age-specific distribution of HPV infection among women in Beijing urban area shows an obvious heterogeneity, which deserves due consideration in the clinical application of HPV vaccines.</p>

Two isomers of HDTIC isolated from Astragali Radix decrease the expression of p16 in 2BS cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Astragali Radix, the root of Astragalus membranceus (Fish) Bunge Var. mongholicus (Bge), is a crude drug considered as one of the effective traditional Chinese anti-ageing material. The two isomers of 4-hydroxy-5-hydroxymethyl-[1, 3] dioxolan-2, 6'-spirane-5', 6', 7', 8'-tetrahydro-indolizine-3'-carbaldehyde (HDTIC), HDTIC-1 and HDTIC-2, were first extracted from the herb in 2002. We demonstrated previously that 0.1 micromol/L HDTIC-1 or 1.0 micromol/L HDTIC-2 strongly delay replicative senescence of human fetal lung diploid fibroblasts (2BS). In this study, we chose them to investigate their effects on the expression of senescence-associated genes to explore the mechanism of how HDTIC delays replicative senescence.</p><p><b>METHODS</b>The effects of HDTIC-1 and HDTIC-2 on the expression of p16 and p21 were observed in vitro by RT-PCR and Western blot. The anti-oxidative activities of the compounds were also observed by phenotype alteration after treatment with antioxidants.</p><p><b>RESULTS</b>There was an obvious expression of p16 in the control senescent cells. However, in the 2BS cells, after 56 population doublings (PDs) grown from PD28 in 0.1 micromol/L HDTIC-1 or 1.0 micromol/L HDTIC-2, there was a weak mRNA expression of p16 and no protein expression of p16 was observed. The expression level of p21 increased with cell ageing. Moreover, there was no difference between the expression level of p21 in the control cells and that in the same PD cells cultured with HDTIC compounds. The results also showed that 2BS cells exposed to 100 micromol/L H2O2 for 5 minutes return to their non-senescent phenotype and continue to be confluent after incubating the damaged cells with HDTIC-1 (1.0 micromol/L ) or HDTIC-2 (10 micromol/L ) for 1 hour.</p><p><b>CONCLUSIONS</b>Expression of p16 by 2BS cells was strongly inhibited by HDTIC compounds, which could contribute to their delayed replicative senescence by the way of p16(INK4a)/Rb/MAPK. The anti-oxidative activities of HDTIC-1 and HDTIC-2, described in this study for the first time, might be indirectly related to their inhibition of p16 expression.</p>

Aminoguanidine delays the replicative senescence of human diploid fibroblasts / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The accumulation of free radicals and advanced glycation end products (AGEs) in cell plays a very important role in replicative senescence. Aminoguanidine (AG) has potential antioxidant effects and decreases AGE levels. This study aimed to investigate its effect on replicative senescence in vitro.</p><p><b>METHODS</b>The effects of aminoguanidine on morphology, replicative lifespan, cell growth and proliferation, AGEs, DNA damage, DNA repair ability and telomere length were observed in human fetal lung diploid fibroblasts (2BS).</p><p><b>RESULTS</b>Aminoguanidine maintained the non-senescent phenotype of 2BS cells even at late population doubling (PD) and increased cumulative population doublings by at least 17 - 21 PDs. Aminoguanidine also improved the potentials of growth and proliferation of 2BS cells as detected by the MTT assay. The AGE levels of late PD cells grown from early PD in DMEM containing aminiguanidine decreased significantly compared with those of late PD control cells and were similar to those of young control cells. In addition, the cells pretreated with aminoguanidine had a significant reduction in DNA strand breaks when they were exposed to 200 micromol/L H(2)O(2) for 5 minutes which indicated that the compound had a strong potential to protect genomic DNA against oxidative stress. And most of the cells exposed to 100 micromol/L H(2)O(2) had much shorter comet tails and smaller tail areas after incubation with aminoguanidine-supplemented DMEM, which indicated that the compound strongly improved the DNA repair abilities of 2BS cells. Moreover, PD55 cells grown from PD28 in 2 mmol/L or 4 mmol/L aminoguanidine retain telomere lengths of 7.94 kb or 8.12 kb, which was 0.83 kb or 1.11 kb longer than that of the control cells.</p><p><b>CONCLUSION</b>Aminoguanidine delays replicative senescence of 2BS cells and the senescence-delaying effect of aminoguanidine appear to be due to its many biological properties including its potential for proliferation improvement, its inhibitory effect of AGE formation, antioxidant effect, improvement of DNA repair ability and the slowdown of telomere shortening.</p>