Higher serum lipocalin 2 is associated with post-stroke depression at discharge.

BACKGROUND AND AIMS: Post-stroke depression (PSD), as one of the common complications after stroke, seriously affects the physical and mental health and functional prognosis of patients. Previous studies have shown that the increase of inflammatory mediators is associated with the occurrence of PSD. Lipocalin 2 (LCN2), as an acute phase protein, is involved in the development of acute ischemic stroke (AIS), and its expression is up-regulated in patients with depression, suggesting that there is a potential correlation between serum LCN2 and depression. The aim of this study was to explore the relationship between serum LCN2 at admission and PSD at discharge. METHODS: A total of 358 AIS patients were retrospectively included. All patients had fasting venous blood taken within 24 h of admission to detect serum LCN2. The patients were evaluated by 17-item Hamilton Depression Scale (HAMD) before discharge. Patients with HAMD score > 7 were diagnosed with PSD. The correlation between serum LCN2 and PSD was tested using binary logistic regression analysis. RESULTS: In our study, 92 (25.7%) patients were diagnosed with PSD at discharge. According to the serum LCN2 value, the patients were divided into three layers (Tertile1 ≤ 105.24ng/ml; Tertile2: 105.24-140.12ng/ml; Tertile3 ≥ 140.12ng/ml), with T1 layer (the lowest levels) as a reference, after adjusting for multiple potential confounding factors, T3 layer (the highest levels) was independently associated with the occurrence of PSD (odds ratio [OR] = 2.639, 95% confidence interval [CI]: 1.317-5.287, P = 0.006). Similar results were found when the serum LCN2 was analyzed as a continuous variable. The optimal cut-off value of serum LCN2 at admission to predict PSD at discharge was 117.60ng/ml, at this threshold, the sensitivity was 77.2%, and the specificity was 53.4%. CONCLUSIONS: High serum LCN2 levels at admission are an independent risk factor for PSD in patients with AIS at discharge.

Effects of cerebral artery thrombectomy on efficacy, safety, cognitive function and peripheral blood Aß, IL-6 and TNF-α levels in patients with acute cerebral infarction.

OBJECTIVE: Acute cerebral infarction (ACI) can lead to death or disability, posing a serious threat to human health. This study aimed to investigate the effects of cerebral artery thrombectomy on the efficacy, safety, cognitive function and peripheral blood amyloid-ß (Aß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in patients with ACI. METHODS: The clinical data of 169 patients with ACI admitted to our hospital from April 2019 to September 2020 were analyzed retrospectively. Among them, 100 patients were treated with cerebral artery thrombectomy and assigned to the research group, and the other 69 patients were intervened by conventional treatment and assigned to the control group. The clinical effects in the two groups were observed and compared. The cognitive function was evaluated by the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment Scale (MoCA), the neurological dysfunction was assessed by the National Institutes of Health Stroke Scale (NIHSS), and the prognosis was determined by the Modified Rankin Scale (mRS). Peripheral blood Aß1-40, Aß1-42, IL-6 and TNF-α levels were determined using the enzyme-linked immunosorbent assay (ELISA). The incidence of adverse reactions and complications was statistically analyzed. RESULTS: The overall response rate (ORR) was notably higher in the research group compared with the control group. Aß1-40, Aß1-42, IL-6 and TNF-α levels showed no significant difference between the two groups before treatment (P>0.05). After treatment, serum Aß1-40 level was lower and Aß1-42 was higher in the research group compared with the control group at each time point. Serum IL-6 level was markedly higher within 24 h while it was dramatically lower 24 h after treatment in the research group as compared with the control group. At 24 h, 7 d and 14 d after treatment, serum TNF-α level in the research group was lower than that in the control group (P<0.05). The MMSE and MoCA scores showed no significant differences between the two groups before treatment; however, the two scores in the research group were statistically higher than those in the control group after treatment. In addition, lower NIHSS and mRS scores were determined in the research group compared with the control group after treatment. Moreover, except for the statistically significant difference in the number of cases with cognitive dysfunction (P<0.05), there was no significant difference in the incidence of other adverse reactions between the research group and the control group (P>0.05). CONCLUSIONS: Cerebral artery thrombectomy is effective in the treatment of ACI, which can improve the cognitive function of patients and alleviate the high Aß accumulation and inflammation in the central nervous system, with a high safety profile.

Simvastatin ameliorate memory deficits and inflammation in clinical and mouse model of Alzheimer's disease via modulating the expression of miR-106b.

BACKGROUND: Alzheimer's disease (AD) as a neurodegenerative brain disorder is a devastating pathology leading to disastrous cognitive impairments and dementia, and several studies have shown that AD is closely related to the inflammation, so anti-inflammatory treatment may provide therapeutic benefits. In this study, the effect of simvastatin on inflammation was investigated and the underlying mechanisms were explored. METHODS: First, we tested the effect of simvastatin on AD in clinical research. The fasting venous blood was collected in order to evaluate the levels of interleukin-6 (IL-6), interleukine-1 beta (IL-1ß), antichymotrypsin (ACT) and human tumor necrosis factor α (TNF-α), which were measured with the enzyme-linked immunosorbent assay (ELISA) kits. Amyloid-ß (Aß), amyloid-ß precursor protein (APP) and ß-site APP-cleaving enzyme 1(BACE1) were tested by western blotting. Second, we used an APPswe/PS1E9 (APP/PS1) double transgenic mice to evaluate the amelioration ability of simvastatin against the memory impairment in vivo. Spatial learning and memory of mice were investigated by the Morris water maze test (MWM). The mRNA of inflammatory cytokines were measured using real-time PCR. Third, the phospho-proteome profile of SH-SY5Y human neuroblastoma cells treated with simvastatin was used to investigate the possible mechanisms. RESULTS: The results showed that simvastatin ameliorated the memory deficits both in clinical AD patients and animal model of AD. Simvastatin could reduce the mRNA expression of inflammatory cytokines and mediators, suppress the apoptosis of neural stem cells and improve the survival rate of neurons. Moreover, long non-coding RNA (lnc RNA) n336694 and miR-106b was overexpressed in APP/PS1 mice brain tissues, the relationship between lnc RNA n336694 and miR-106b was explored using the method of Target Scan bioinformatics predictions, the results revealed that miR-106b might be a potential target of lnc RNA n336694. Furthermore, miR-106b mediated apoptosis in SH-SY5Y cell and simvastatin could suppressed this process. CONCLUSION: Our results suggested that simvastatin could be of benefit in preventing the progression of AD and expected to be potentially used as a lead drug for further anti-AD treatment.

Atorvastatin May Correct Dyslipidemia in Adult Patients at Risk for Alzheimer's Disease Through an Anti-Inflammatory Pathway.

BACKGROUND: Dyslipidemia is a risk factor for the pathogenesis of Alzheimer's disease. Although, atorvastatin is a well-accepted lipid-lowering agent, the benefits of atorvastatin treatment through an anti-inflammatory mechanism are still unclear. OBJECTIVE: The present study was designed to examine changes in inflammatory markers following administration of atorvastatin in dyslipidemic patients with a parental history of Alzheimer's disease. METHODS: Dyslipidemic adults with a parental history of Alzheimer's disease were administered either 40 mg of atorvastatin or placebo for 18 months. Before and after the study, lpid levels, blood pressure, body weight and body mass index, and the inflammatory markers hs-Creactive protein, serum monocyte chemoattractant protien-1, interleukin-1ß, interleukin-6, and tumor necrosis factor-α were tested. RESULTS: Baseline levels of lipids, body mass index, hs-Creactive protein, monocyte chemoattractant protien-1, interleukin- 1ß, interleukin-6 and tumor necrosis factor-α did not show any difference between the two groups. However, after 18 months of atorvastatin treatment, all inflammatory markers significantly decreased in association with a reduction of lipid profiles, body mass index, bodyweight, and blood pressure, compared with those patients treated with placebo. CONCLUSION: Administration of atorvastatin corrected dyslipidemia in association with a reduction in inflammatory markers. Our results suggest that the therapeutic benefits of atorvastatin possibly involve an anti-inflammatory pathway.

The Effects of the Recombinant CCR5 T4 Lysozyme Fusion Protein on HIV-1 Infection.

BACKGROUND: Insertion of T4 lysozyme (T4L) into the GPCR successfully enhanced GPCR protein stability and solubilization. However, the biological functions of the recombinant GPCR protein have not been analyzed. METHODS: We engineered the CCR5-T4L mutant and expressed and purified the soluble recombinant protein using an E.coli expression system. The antiviral effects of this recombinant protein in THP-1 cell lines, primary human macrophages, and PBMCs from different donors were investigated. We also explored the possible mechanisms underlying the observed antiviral effects. RESULTS: Our data showed the biphasic inhibitory and promotion effects of different concentrations of soluble recombinant CCR5-T4L protein on R5 tropic human immunodeficiency virus-1 (HIV-1) infection in THP-1 cell lines, human macrophages, and PBMCs from clinical isolates. We demonstrated that soluble recombinant CCR5-T4L acts as a HIV-1 co-receptor, interacts with wild type CCR5, down-regulates the surface CCR5 expression in human macrophages, and interacts with CCL5 to inhibit macrophage migration. Using binding assays, we further determined that recombinant CCR5-T4L and [125I]-CCL5 compete for the same binding site on wild type CCR5. CONCLUSIONS: Our results suggest that recombinant CCR5-T4L protein marginally promotes HIV-1 infection at low concentrations and markedly inhibits infection at higher concentrations. This recombinant protein may be helpful in the future development of anti-HIV-1 therapeutic agents.