Synaptic pruning mediated by glia in Alzheimer's disease / 药学学报

Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory loss and cognitive impairment. To date, however, no disease-modifying strategies to prevent or cure AD exist. Synapses are involved in the connection of neurons and present as the key component for the memory and other neural activities. Synapse loss is a critical hallmark of AD pathology. In brain, glia cells, including microglia and astrocytes, are a group of highly specific cell types other than neurons. Microglia and astrocytes play a key role in maintaining the healthy neural circuit and regulating synaptic plasticity. Under development and physiological conditions, glial cells contribute to construct and maintain mature central neural networks via synaptic pruning. However, during AD pathogenesis, glial cells engulf synapses excessively, which leads to synapse loss, neuronal dysfunction, and cognitive impairment. Here, we review recent advances in our understanding of the underlying mechanisms for glia-mediated synaptic pruning in AD, and provide a novel strategy for the development of AD drugs.

Clinical, Neuroimaging, and Pathological Analyses of 13 Chinese Leigh Syndrome Patients with Mitochondrial DNA Mutations / 中华医学杂志(英文版)

Background@#Leigh syndrome (LS) is a rare disease caused by mitochondrial defects and has high phenotypic and genotypic heterogeneity. We analyzed the clinical symptoms, neuroimaging, muscular histopathology, and genotypes of 13 Chinese LS patients with mitochondrial DNA (mtDNA) mutations.@*Methods@#Mutations in mtDNA were identified by targeted sequencing. The brain imaging features on magnetic resonance imaging (MRI) were analyzed. The levels of lactate in fasting blood and cerebrospinal fluid (CSF) were routinely tested. The levels of urinary organic acids, plasma amino acids, and acylcarnitines were examined with gas chromatography-mass spectrometry and tandem mass spectrometry. The histopathological traits of skeletal muscles were analyzed under microscope.@*Results@#Among 13 patients, mutations of MT-NDs (n = 8) and MT-ATP6 (n = 4) genes were most common. Strabismus (8/13), muscle weakness (8/13), and ataxia (5/13) were also common, especially for the patients with late-onset age after 2 years old. However, respiratory distress was common in patients with early-onset age before 2 years old. The most frequently affected brain area in these patients was the brain stem (12/13), particularly the dorsal part of midbrain, followed by basal ganglia (6/13), thalamus (6/13), cerebellum (5/13), and supratentorial white matter (2/13). Besides, the elevated lactate levels in CSF (6/6) were more common than those in serum (7/13). However, the analysis of abnormal plasma amino acid and urinary organic acid showed limited results (0/3 and 1/4, respectively). Muscular histopathology showed mitochondrial myopathy in the three late-onset patients but not in the early-onset ones.@*Conclusions@#Noninvasive genetic screening is recommended for mtDNA mutations in MT-NDs and MT-ATP6 genes in patients with ophthalmoplegia, muscle weakness, ataxia, and respiratory disorder. Furthermore, the lactate detection in CSF and the brain MRI scanning are suggested as the diagnosis methods for LS patients with mtDNA mutations.

Primary angiitis of the central nervous system: a case report / 中华医学杂志(英文版)

Primary angiitis of the central nervous system is a rare and difficult entity. Here we represented the clinical and pathological features of a patient with little response to steroid before definite diagnosis. The 50-year-old male had a fluctuating disease course for more than 3 years. He presented visual disorders, seizure, cognitive impairment, hypersomnia, unsteady gait, dysphasia, dysphagia, and incontinence. Magnetic resonance imaging showed multiple, supratentorial and infratentorial abnormal signals, while cerebrospinal fluid and cerebral angiography were normal. Magnetic resonance spectrum showed a decrease of N-acetyl-aspartate. Brain biopsy revealed nongranulomatous lymphatic vasculitis with reactive gliosis, cicatrization, demyelination and focal hemorrhages.

Analysis of scalp potential activity and heart rate variability during volitional control of heart beat / 中国医疗器械杂志

In the study the changes of scalp potential and cardiac autonomic nervous system during volitional control of heart beat are explored with the wavelet packet parameters and approximate entropy (ApEn) of Electroencephalogram (EEG) and heart rate variability. The results show that volition can control heart beat and the changes of brain activity are earlier than that of autonomic activity. But its control of heart beat is very different from the motor nervous system because different cortical positions are respectively concerned during the quick and slow control of heart beat. The pre-central areas of brain are correlated with parasympathetic activity by which HR is controlled to slow down. The post-central areas of brain are correlated with sympathetic activity by which HR is controlled to accelerate.

Changes of gene expression profile in homoharringtonine-induced leukemia multi-drug resistant cell line K562/HHT / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the resistant related molecules of human leukemia drug resistant K562 cells (K562/HHT) induced by homoharringtonine (HHT).</p><p><b>METHODS</b>Gene expression profiles on K562/HHT, K562 and K562/HHT/RU486 (K562/HHT reversed by RU486) cells were detected by DNA microarray. The bone marrow tyrosine kinase gene in chromosome X (BMX) which changed dynamically among the three cells was confirmed by RT-PCR and Western blot. Then, BMX was transfected into K562 and K562/HHT cells, and the changes of daunorubicin (DNR) concentrations in these two cells were observed for BMX overexpression.</p><p><b>RESULTS</b>As compared with K562, there were changes in 117 gene expressions in K562/HHT, 57 of which were up-regulated and 60 down-regulated. The mdrl gene was significantly up-regulated. When compared with K562/HHT, 50 significantly differently expressed genes were screened out in the K562/HHT/RU486 cells, of which up- and down-regulated genes were 13 and 37 respectively. These genes involved in drug resistance, cell signaling, cell differentiation, cell proliferation, transcription regulator, ion transport and so on. Four genes [NM-001721 (BMX), NM-031459 (SESN2), NM-033642 (FGF13) and AL-049309 (SFRS12)] expressed significantly differently in the two group cells, BMX gene expression was higher in K562/HHT, than in K562, but lower than in K562/HHT/RU486 as confirmed by RT-PCR and Western blot. After the plasmid pCI-neo-BMX was transfected into K562 and K562/HHT cells, DNR concentration was significantly lower (79.28 +/- 4.04, 29.84 +/- 2.67) than those before transfection (158.52 +/- 8.08, 58.58 +/- 6.53).</p><p><b>CONCLUSION</b>BMX is associated with multi-drug resistance of K562/HHT cell line.</p>

Synthesis and anti-inflammatory analgesic activities of phenylfuroxan-coupled diclofenac / 药学学报

<p><b>AIM</b>To search for new derivatives of diclofenac (DC) having higher potency than the parent drug and lacking its undesirable effects.</p><p><b>METHODS</b>Coupling DC with NO donor 3-hydroxymethyl-4-phenylfuroxan and its isomer through esterification, evaluating anti-inflammatory and analgesic activities, observing side effects in the rat gastrointestinal (GI) tract and assessing NO releasing ability both in vitro and in vivo.</p><p><b>RESULTS</b>Fifteen new compounds including nine target ones (II1-9) were synthesized, and their structures were determined by IR, 1HNMR, MS and elemental analysis. Compounds II3 and II9 showed anti-inflammatory activity comparable to DC. Compound II2 showed stronger anti-inflammatory and analgesic activities and less GI side effect than DC, and released NO in vivo.</p><p><b>CONCLUSION</b>Compound II2 is worthy to be intensively studied.</p>