Melatonin Ameliorates the Progression of Alzheimer's Disease by Inducing TFEB Nuclear Translocation, Promoting Mitophagy, and Regulating NLRP3 Inflammasome Activity.

Background: The NLRP3 inflammasome is overactivated in the brains of APP/PS1 transgenic mice and AD patients, and mitophagy has an obvious negative regulatory role on NLRP3 inflammasome activation. The protective effect of melatonin in AD may be related to the regulation of mitophagy and NLRP3 inflammasome activity. TFEB plays a critical role in maintaining autophagy/mitophagy. Studies have found that TFEB plays a protective role in AD. Methods: APP/PS1 transgenic mice were given melatonin in their drinking water for 3 months. Compared with mice without melatonin treatment, the mice given melatonin showed changes in the following features: (1) cognitive function, (2) mitophagy-related proteins in the brain, (3) ROS, (4) NLRP3 inflammasome and related proteins and the concentrations of inflammatory cytokines, and (5) Aß deposition. In in vitro experiments, effects of melatonin on mitophagy, NLRP3 inflammasome activity, and TFEB in SH-SY5Y cells with Aß 25-35 were observed. TFEB knockdown was implemented in combination with Aß 25-35 and melatonin treatment, and the expressions of TFEB, Parkin, p62, IL-1ß, caspase-1, ROS, and IL-18 were explored. Results: Melatonin improved cognitive function in APP/PS1 transgenic mice and decreased ROS and senile plaques. Melatonin promoted mitophagy in SH-SY5Y cells with Aß 25-35 and APP/PS1 transgenic mice. NLRP3 inflammasome activity was inhibited, and the concentrations of IL-18 and IL-1ßwere clearly reduced. Compared with C57/BL6J mice, the amount of TFEB in the brain nucleus of APP/PS1 transgenic mice was decreased. Melatonin treatment increased the nuclear translocation of TFEB in SH-SY5Y cells. TFEB knockout was implemented in combination with Aß 25-35 and MT treatment; the expressions of Parkin, p62, caspase-1, IL-1ß, IL-18, and ROS were accelerated. Conclusions: Melatonin promotes mitophagy by inducing TFEB nuclear translocation, downregulates NLRP3 inflammasome activation, and exerts protective effects in SH-SY5Y cells and APP/PS1 transgenic mice.

Design of Detection Module in Coagulometers Based on Dual-magnetic Circuit Beads Method / 中国医疗器械杂志

Coagulometer, known as blood coagulation analyzer, is a product that can provide accurate test results for medical diagnosis and treatment analysis by detecting a series of items closely related to thrombosis and hemostasis in coagulation reaction. On the basis of previous traditional methods, and with our deep understanding about the principles of hemagglutination detection, we propose a hemagglutination detection method by using the dual-magnetic circuit beads method. Then, the corresponding hemagglutination detection module is designed. The coagulation time of plasma can be measured by detecting the movement of the magnetic beads when the magnetic field intensity is appropriate. The activated partial thromboplastin time(APTT) of plasma is tested when the most suitable magnetic field intensity is found. The results preliminarily show that this blood coagulation test method is valid and the corresponding test module has a potential value in business.

Association of extracellular superoxide dismutase gene methylation with cerebral infarction / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of extracellular superoxide dismutase (EC-SOD) gene methylation with cerebral infarction.</p><p><b>METHODS</b>Eighty-three patients with cerebral infarction and 94 healthy controls were enrolled. Based on cerebral MR findings, the size of infarction, extent of intracranial atherosclerosis, the National Institutes of Health Stroke Scale (NIHSS) score, and Barthel index were calculated. Methylation-specific PCR was used to analyze the methylation status of the EC-SOD gene in peripheral blood samples and its correlation with cerebral infarction.</p><p><b>RESULTS</b>The rate of EC-SOD gene promoter region methylation of the cerebral infarction group was lower than that of the control group (30.1% vs. 53.2%, P < 0.05). Patients with larger area of cerebral infarction (>4 cm in diameter) showed a lower methylation rate than those with a smaller cerebral infarction (0 vs. 39.1%, P < 0.05). Based on their cerebral MRA, 57 patients were divided into none, mild, moderate, and severe cerebral arteriosclerosis groups. The rate of EC-SOD gene methylation of the four groups showed a downward trend (at 45.5%, 42.9%, 23.8%, and 14.3%, respectively), though no statistical significance was found (P > 0.05). For the cerebral infarction group, those with higher rate of methylation had lower NIHSS scores (P < 0.05) but insignificantly higher Barthel index (P > 0.05).</p><p><b>CONCLUSION</b>The EC-SOD methylation frequency of case group was lower than the control group. The methylation status is associated with the size of cerebral infarction, degree of cerebral arteriosclerosis and severity of neurological impairment.</p>

Granulocyte colony-stimulating factor induces neurogenesis and improves cognition in amyloid precursor protein transgenic mouse model of Alzheimer's disease / 中华老年医学杂志

Objective To investigate the effect of granulocyte colony-stimulating factor(G-CSF)and its effect on the cognation in the PDGF hAPPV717I transgenic mice of Alzheimer's disease model.Methods Totally 36 PDGF hAPPV717I transgenic mice were randomly divided into two groups:G-CSF group and control group.The G CSF group was subcutaneously injected with 50 μg · kg-1 · d-1 of G-CSF for 7 days.The control group was injected subcutaneously with an equal volume of PBS in parallel.The animals were tested in Morris water maze on the 7th,14th,and 28th days after the last day of the injection,and the escape latency was recorded.Once the test was completed,the peripheral blood was taken to evaluate the effect of G-CSF to induce hematopoietic stem cells (HSCs) via flow cytometry.Then the mice were killed,their brains were quickly removed and frozen on dry ice.With the immunohistochemical staining and double immunofluorescence staining,the neurogenesis could be observed in the model mice.Results We found that G-CSF significantly shortened the escape latencies in PDGF-hAPPV717I transgenic mice compared to controls on the 7th,14th,and 28th day after G-CSF treatment [7 d:(27.19±4.07) s and (46.07±7.21) s,P＜0.000; 14 d:(26.48±5.29) sand (42.99±11.70) s,P＜0.010; 28 d:(24.97±3.61) s and (45.54±9.55) s,P＜0.002)].At the same time,we found that the percentage of CD34+/CD45+ cells in the peripheral blood was 0.358±0.161,0.223±0.038,0.168±0.049 on the 7th,14th,and 28th day after G-CSF treatment,respectively.Compared with the control group (0.073±0.026,0.067±0.034,0.072± 0.037),the percentage of CD34′ /CD45+ cells in the peripheral blood were increased (P＜0.001).BrdU+ cells were found in dentate gyrus (DG) of hippocampus and the cortex of the G-CSF group,where the BrdU+ /Ncstin- and BrdU-/MAP-2+ cells were also detected positively.Conclusions Subcutaneous administration of G- CSF may improve the cognition in APP transgenic mouse model of AD.G-CSF may mediate the proliferation,differentiation of hcmatopoietic stem cells (HSCs).and may induce the neural stem cells into the brain.