Association between remnant cholesterol and subclinical carotid atherosclerosis among Chinese general population in health examination.

OBJECTIVE: Remnant cholesterol (RC) was associated with carotid atherosclerosis in patients with clinical settings. But the value of RC as a risk management indicator for subclinical carotid atherosclerosis in health examination has not been fully determined. METHODS: This was a real-world, cross-sectional study including 12317 Chinese general population. Carotid intima-media thickness (CIMT) and carotid atherosclerotic plaque (CAP) were assessed by ultrasound. RC was calculated by total cholesterol minus low density lipoprotein-cholesterol (LDL-C) minus high density lipoprotein-cholesterol (HDL-C).Carotid atherosclerosis (CAS) was defined as a composite of increased CIMT and CAP. Multivariable logistic regression models were used to investigate the association of RC and CAS, increased CIMT and CAP. RESULTS: Among 12317 participants (mean age: 51.21±13.76 years; 8303 men and 4014 women), the prevalence of CAS and increased CIMT was higher in participants with higher RC levels (P for trend<0.01). After multivariable adjustment, the highest quartile of RC was significantly associated with higher risk of CAS (OR: 1.45 95%CI: 1.26-1.67) and increased CIMT (OR: 1.48 95%CI: 1.29-1.71) with the lowest quartile of RC as reference. And the relationships remained significant even after adjustment of LDL-C and HDL-C. Every 1-SD increase of RC level was positively associated with 17% risk increment for CAS (6-30%) and 20% risk increment for increased CIMT (8-34%). CONCLUSION: Elevated serum RC levels were significantly associated with CAS and increased CIMT among Chinese general population, independent of LDL-C and HDL-C. RC evaluation could be applied for the risk management of early stage of subclinical carotid atherosclerosis in health examination.

LncRNA-MIAT regulates the growth of SHSY5Y cells by regulating the miR-34-5p-SYT1 axis and exerts a neuroprotective effect in a mouse model of Parkinson's disease.

To examine the neuroprotective roles of lncRNA-MIAT in Parkinson's disease (PD). RNA sequencing expression profiles were utilized to screen the dysregulated lncRNAs in patients with PD and to explore the underlying molecular mechanisms by which the lncRNAs regulate the pathogenesis of PD. 6-hydroxydopamine-induced SH-SY5Y cell lines and a PD mouse model were used to prove how the overexpressing or knocking-down of MIAT produce a marked effect in both in vitro and in vivo experiments. Subsequently, the subcellular localization of MIAT was detected via RNA fluorescence in situ hybridization (FISH) assays. Quantitative PCR, as well as western blotting, were used to determine the expression levels of the associated genes and proteins. We utilized Cell Counting Kit-8 (CCK8) assays to measure the viability of the cells, and the apoptotic rate was determined using Annexin V-FITC/PI double staining. The expressions of tyrosine hydroxylase (TH) and Parkin were quantified in the substantia nigra using immunohistochemical staining. Also, TUNEL staining was performed to visualize the apoptotic cells in the substantia nigra. Compared with the normal rats, the downregulation of MIAT was observed in the cortex, hippocampus, substantia nigra, and striatum of the PD rats. Overexpression of MIAT exhibited a neuroprotective effect on the SH-SY5Y cells. Through RNA-sequencing of the PD mice treated with an overexpression of MIAT and through a differentially expressed genes analysis, it was hypothesized that MIAT could upregulate the expression of synaptotagmin-1 (SYT1) through sponging of miR-34-5p. Interactions between MIAT, miR-34-5p, and SYT1 were confirmed using RIP and dual-luciferase reporter assays. At the same time, the MIAT overexpression group exhibited elevated Parkin and TH protein levels, increased cell viability but a decreased apoptosis rate of the SH-SY5Y cells in contrast with the negative control (NC) group. In vivo, compared with the NC group, the overexpression of MIAT resulted in an increase in the positive rates of Parkin and TH, and the apoptosis was decreased in the PD mice. The behavioral test results showed that the motor coordination and autonomous activity of the mice were enhanced in the MIAT overexpression group compared with the NC group. LncRNA-MIAT regulates the growth of SHSY5Y cells by sponging miR-34-5p which targets SYT1 and exerts a neuroprotective effect in a mouse model of PD.

lncRNA PART1 mitigates MPP+-induced neuronal injury in SH-SY5Y cells via micRNA-106b-5p/MCL1 axis.

OBJECTIVE: Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons. Here, we aimed to explore the function of LncRNA PART1 in PD and its underlying mechanisms. METHODS: An in vivo MPTP-induced mouse model of PD was generated and the SH-SY5Y cells were treated with MPP+ to induce neuronal damage in vitro. The expressions of LncRNA PART1 and microRNA-106b-5p were assessed by RT-qPCR. The level of caspase 3 protein was detected by western blot. CCK8 assay and Annexin V/PI staining were used for detecting cell viability and survival rate, respectively. The interactions between microRNA-106b-5p and LncRNA PART1 or MCL1 were determined by RNA pull-down assay, RIP assay and DLR assay. The levels of inflammatory cytokines were assessed by ELISA, and the levels of LDH, ROS or SOD were verified using the appropriate assay kits. RESULTS: The expression of LncRNA PART1 was decreased in PD model in vivo and in vitro (all P<0.05). In SH-SY5Y cells treated with MPP+, the overexpression of LncRNA PART1 increased cell viability and reduced cell apoptosis, the secretion of inflammatory cytokines and oxidative stress reaction (all P<0.05). Furthermore, LncRNA PART1 sponged microRNA-106b-5p which directly targeted MCL1 and thus regulated the expression of MCL1. LncRNA PART1 attenuated the injury of SH-SY5Y cells induced by MPP+ via targeting microRNA-106b-5p and enhancing MCL1 expression. CONCLUSION: LncRNA PART1 could alleviate the damage effects of MPP+ on SH-SY5Y cells by regulating microRNA-106b-5p/MCL1 axis, suggesting the potential therapeutic value of LncRNA PART1 as a target in PD.

Concomitant memantine and Lactobacillus plantarum treatment attenuates cognitive impairments in APP/PS1 mice.

Trimethylamine-N-oxide (TMAO) is a gut microbial metabolite that promotes Alzheimer's disease (AD) progression. Given that probiotics can alleviate AD symptoms by inhibiting the synthesis of TMAO, here we investigated the correlation between TMAO and cognitive deterioration by measuring TMAO levels in the plasma of choline-treated APP/PS1 mice (an AD mouse model) with and without probiotic treatments. We found that declines in L.plantarum in the gut were associated with cognitive impairment. Moreover, 12-weeks of treatment with memantine plus L. plantarum ameliorated cognitive deterioration, decreased Αß levels in the hippocampus, and protected neuronal integrity and plasticity. These effects were accompanied by reductions in TMAO synthesis and neuroinflammation. These experiments demonstrate that L. plantarum augments the beneficial therapeutic effects of memantine treatment in APP/PS1 mice by remodeling the intestinal microbiota, inhibiting the synthesis of TMAO, and reducing clusterin levels. Our results thus highlight intestinal microbiota as a potential therapeutic target to decrease the risk of AD.

Effects of edaravone on amyloid-ß precursor protein processing in SY5Y-APP695 cells.

Previous reports have revealed that reactive oxygen species (ROS) is involved in the development of Alzheimer's disease (AD), and recent studies indicate that free radical-generating systems can regulate amyloid-ß precursor protein (APP) processing. Edaravone is a novel free radical scavenger currently used to reduce cerebral damages after acute cerebral infarction. In the present study, we used SH-SY5Y cells stably transfected with the human "Swedish" APP mutation APP695 (SY5Y-APP695swe) as an in vitro model to investigate the effect of edaravone on APP processing. The result showed that edaravone treatment for 24 h down-regulated ß-amyloid (Aß) production in a dose-dependent manner. Moreover, edaravone modulated APP processing by increasing α-secretase-derived APP fragments and decreasing ß-secretase-derived APP fragments. In addition, the mRNA and protein levels of insulin degrading enzyme (IDE) and neprilysin (NEP), two key Aß degrading enzymes, were not changed after edaravone administration. Taken together, our data suggested that edaravone played an important role in regulating Aß production by enhancing the non-amyloidogenic pathway and inhibiting the amyloidogenic pathway. Thus, edaravone may be potentially useful for treating Alzheimer's disease (AD).