Bioinformatic identification and experiment validation reveal 6 hub genes, promising diagnostic and therapeutic targets for Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease that can cause dementia. We aim to screen out the hub genes involved in AD based on microarray datasets. METHODS: Gene expression profiles GSE5281 and GSE28146 were retrieved from Gene Expression Omnibus database to acquire differentially expressed genes (DEGs). Gene Ontology and pathway enrichment were conducted using DAVID online tool. The STRING database and Cytoscape tools were employed to analyze protein-protein interactions and identify hub genes. The predictive value of hub genes was assessed by principal component analysis and receiver operating characteristic curves. AD mice model was constructed, and histology was then observed by hematoxylin-eosin staining. Gene expression levels were finally determined by real-time quantitative PCR. RESULTS: We obtained 197 overlapping DEGs from GSE5281 and GSE28146 datasets. After constructing protein-protein interaction network, three highly interconnected clusters were identified and 6 hub genes (RBL1, BUB1, HDAC7, KAT5, SIRT2, and ITGB1) were selected. The hub genes could be used as basis to predict AD. Histological abnormalities of brain were observed, suggesting successful AD model was constructed. Compared with the control group, the mRNA expression levels of RBL1, BUB1, HDAC7, KAT5 and SIRT2 were significantly increased, while the mRNA expression level of ITGB1 was significantly decreased in AD groups. CONCLUSION: RBL1, BUB1, HDAC7, KAT5, SIRT2 and ITGB1 are promising gene signatures for diagnosis and therapy of AD.

Early diagnosis, treatment, and outcomes of five patients with acute thallium poisoning.

BACKGROUND: Thallium poisoning is rare and difficult to recognize. Early diagnosis and treatment of thallium-poisoned patients are essential to prevent morbidity and mortality. AIM: To evaluate the efficacy of treatments and outcomes of five patients with early diagnosis of acute thallium poisoning. METHODS: Five patients who consumed a thallium-contaminated meal were hospitalized in succession, and underwent clinical examinations such as blood tests and electromyography tests. Urine and blood tests confirmed the diagnosis of thallotoxicosis, revealing the occurrence of food poisoning. All patients underwent detoxification treatment, including hemoperfusion (HP) and treatment with Prussian blue (PB). A 24-mo follow-up was performed to evaluate the long-term outcomes on the patients after discharge. RESULTS: Initially, the patients presented with symptoms of acute thallium poisoning including hyperalgesia of the limbs and abdominalgia, which may differ from common peripheral neuropathy. Accompanying symptoms such as hepatic damage and alopecia were observed in all the patients, which further confirmed the diagnosis of poisoning. Treatment with chelating agents was ineffective, while HP and treatment with PB drastically decreased the thallium concentration in the urine and blood. With early diagnosis and intervention, four patients had a good prognosis and no permanent sequelae. One patient developed blindness and disability during the 24-mo follow-up period. CONCLUSION: Identification of incident cluster and characteristic symptoms is extremely important for early diagnosis of acute thallium poisoning. HP plus PB is essential to improve the prognosis of thallium-poisoned patients.

Downregulation of miR­146a promotes proliferation and migration of AOB­treated embryoid body via PDGFRA induction.

Antioxidant of bamboo leaves (AOB) has been proven to have antioxidant activity and an inhibitory effect on free radicals that induce deterioration of macromolecules. The multi­target regulation of microRNAs (miRs) in the complicated process of vasculogenesis and angiogenesis lead to the use of miRNA therapy in vascular development. In the present study, the role of miRNAs on early embryo vascular development upon AOB stimulation was investigated. For this purpose, mouse embryonic stem cells were spontaneously differentiated as embryoid bodies (EBs) and were examined by phase contrast microscopy. miR­146a mimic and scramble control were transfected into EBs and potential targets of miR­146a were predicted. Cell proliferation and migration were detected by cell viability and wound­healing and migration assays, respectively. Angiogenesis was determined by the Spheroid sprouting assay. It was demonstrated that EBs transfected with miR­146a mimic had an increased growth rate compared with the control cells. miR­146a­transfected cells were very susceptible to AOB treatment. Furthermore, among the predicted miR­146a targets, platelet­derived growth factor receptor alpha (PDGFRA) was identified as a bona fide target of miR­146a. In conclusion, PDGFRA was demonstrated to participate in the modulation of cell migration and proliferation of mouse EBs. The present study expanded the current understanding of AOB biology and elucidated the mechanisms underlying early embryo vascular development upon AOB stimulation.

Macrophage related cytokine expressions in depression mouse model induced by chronic unpredictable mild stress.

Depression is characterized by mental retardation, interest blank, hypoactivity, anxiety, appetite loss, sexual dysfunction, sleep disorders and other symptoms. The incidence of depressed patients has demonstrated an upward trend in recent years. Antidepressant drugs are commonly used in modern medicine, but they have the side effect of drug resistance. This study aims to explore the effect of acupuncture stimulation on expressions of macrophage-related cytokines in mice with depression induced by chronic unpredictable mild stress (CUMS), and to explore the underlying immunological mechanism. The CUMS model was successfully developed. The secretion of nuclear transcription factor-kB (NF-kB) and interleukin (IL)-8 increased significantly in the modeling group compared with the blank control group (P<0.05). However, no significant difference of tumor necrosis factor-α (TNF-α) concentration was found (P>0.05). After acupuncture treatment, the behavior indicator was improved and meanwhile, the levels of TNF-α, NF-κB, IL-8 decreased significantly compared with the sham group (P<0.05). Depression mice were given treatment of acupuncture, and the effect of behavior change was observed and the content of macrophage cytokine production was measured, respectively. These findings suggested that inflammatory cytokines secreted by peritoneal macrophages increased significantly in mild depression mice, which can be improved by stimulation with acupuncture.