Previous studies have demonstrated that chronic brain hypoperfusion (CBH) causes A aggregation by upregulating expression of amyloid precursor protein (APP) and -site APP cleaving enzyme 1 (BACE1) protein, which is accompanied by cognitive impairment, but the mechanisms are not fully understood. In this study, we evaluated the effect of microRNA on memory impairment in rats induced by CBH. We show here that CBH generated by bilateral common carotid artery occlusion (2VO) significantly decreased the learning and memory ability in rats, as assessed by Morris water maze, and upregulated expression of APP and BACE1 proteins in the hippocampus and cortex of rats, as evaluated by Western blot and immunofluorescence. In reciprocal, qRT-PCR analysis showed that microRNA-195 (miR-195) was downregulated in both the hippocampus and cortex of rats following CBH, and in the plasma of dementia patients. APP and BACE1 proteins were downregulated by miR-195 overexpression, upregulated by miR-195 inhibition, and unchanged by binding-site mutation or miR-masks, indicating that APP and BACE1 are two potential targets for miR-195. Knockdown of endogenous miR-195 by lentiviral vector-mediated overexpression of its antisense molecule (lenti-pre-AMO-miR-195) elicited dementia in rats, whereas overexpression of miR-195 using lenti-pre-miR-195 reduced dementia vulnerability triggered by 2VO. Additionally, chromatin immunoprecipitation analysis showed that NFB was bound to the promoter region of miR-195 and inhibited its expression. We conclude that miR-195 may play a key role in determining dementia susceptibility in 2VO rats by regulating APP and BACE1 expression at the post-transcriptional level, and exogenous complement of miR-195 may be a potentially valuable anti-dementia approach.
Chronic brain hypoperfusion (CBH) is a common clinical feature of Alzheimer's disease and vascular dementia, but the underlying molecular mechanism is unclear. Our previous study reported that the down-regulation of promotes amyloidogenesis via regulation of amyloid precursor protein and b-site amyloid precursor protein cleaving enzyme 1 (BACE1) expression at the post-transcriptional level in CBH rats with bilateral common carotid artery occlusion (2VO). CBH owing to unilateral common carotid artery occlusion (UCCAO) increases tau phosphorylation levels at multiple phosphorylation sites in the brain, but the molecular mechanism is poorly understood. The purpose of this study was to investigate whether miR-195 could both deregulate amyloid metabolism and indirectly deregulate tau phosphorylation in CBH. We observed that 2VO leads to tau hyperphosphorylation at Ser202/Thr205, Ser262, Thr231, and Ser422 and to the conversion from cyclin-dependent kinase 5 (Cdk5)/ p35 to Cdk5/p25 in rat hippocampi. Endogenous miR-195 was knocked down using over-expression of its antisense molecule (pre-AMO-miR-195) via a lentivirus (lenti-pre-AMO-miR-195); this knockdown increased the tau phosphorylation at Ser202/ Thr205, Ser262, Thr231, Ser422, and the Cdk5/p25 activation, but over-expression of miR-195 using lenti-pre-miR-195 decreased the tau phosphorylation and Cdk5/p25 activation. Further in vitro studies demonstrated that miR-195 overexpression prevented tau hyperphosphorylation and Cdk5/p35 activity, which were increased by miR-195 inhibition. A dual luciferase reporter assay showed that miR-195 bound to the Cdk5r1 gene, which encodes p35 protein, in the 3 0 UTR and inhibited p35 expression. We concluded that tau hyperphosphorylation involves the down-regulation of miR-195, which is mediated by Cdk5/p25 activation in 2VO rats. Our findings demonstrated that down-regulation of miR-195 led to increased vulnerability via the regulation of multiple targets.
With the development of the wireless communication technology and intelligent mobile phone, the positioning services based on Wi-Fi and mobile phone are increasingly demanded. In this paper, a Wi-Fi fingerprint localization method is proposed on the basis of important access points (IAP). For the Wi-Fi fingerprint, Wi-Fi access point with the highest received signal strength (RSS) is denoted as the important access point. At the localization stage, the fingerprints are chosen with the same IAP as the estimated fingerprint from the database. Then, the distance and the AP repetition of the fingerprints are used to calculate the similarity degree. The location of the fingerprint which matches the estimated fingerprint well can be regarded as the estimated location. Experimental results show that the proposed algorithm can achieve high accuracy in indoor environment.
Background: High-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (L-DLPFC) is the most widely applied treatment protocol for major depressive disorder (MDD), while low-frequency (LF) rTMS over the right DLPFC (R-DLPFC) also exhibits similar, if not better, efficacy for MDD. Therefore, a meta-analysis is warranted to compare the efficacy of the two protocols for MDD.Method: We searched the literature from 1990 through to August 1, 2017 using MEDLINE, and the literature from 1995 through to August 1, 2017 using EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), SCOPUS, and ProQuest Dissertations and Theses (PQDT). We included randomized controlled trials (RCT) comparing the efficacy of HF rTMS over the L-DLPFC and LF rTMS over the R-DLPFC for MDD, which used response and/or remission rates as the primary endpoints, with and without sham-controlled.Results: (1) The meta-analysis of the response rates was based on 12 studies, including 361 patients with MDD (175 for HF (> 5 Hz) over the L-DLPFC, and 186 for LF (<5 Hz) over the R-DLPFC; odds ratio = 1.08; 95%, confidence interval = 0.88–1.34). (2) The meta-analysis of the remission rate was based on 5 studies, including 131 MDD patients (64 for HF over the L-DLPFC and 67 for LF over the R-DLPFC; odds ratio = 1.29; 95% confidence interval = 0.54–3.10).Conclusion: Both HF rTMS over the L-DLPFC and LF over the R-DLPFC demonstrated similar therapeutic efficacy for the treatment of patients with MDD. The results suggested that further investigation on treatment efficacy indicators before/during treatment is necessary and helpful for optimizing a personalized protocol for patients.
Lung cancer is a malignant tumor characterized by a rapid proliferation rate, less survivability, high mortality, and metastatic potential. This review focuses on updated research about the clinical application of traditional Chinese medicine (TCM) as an adjuvant therapy to lung cancer treatment and the mechanisms of TCM effect on lung cancer in vitro and in vivo. We summarized the recent 5 years of different research progress on clinical applications and antitumor mechanisms of TCM in the treatment of lung cancer. As a potent adjuvant therapy, TCM could enhance conventional treatments (chemotherapy, radiation therapy, and epidermal growth factor receptors [EGFRs] tyrosine kinase inhibitors [TKIs]) effects as well as provide synergistic effects, enhance chemotherapy drugs chemosensitivity, reverse drug resistance, reduce adverse reactions and toxicity, relieve patients’ pain and improve quality of life (QOL). After treating with TCM, lung cancer cells will induce apoptosis and/or autophagy, suppress metastasis, impact immune reaction, and therapeutic effect of EGFR-TKIs. Therefore, TCM is a promisingly potent adjuvant therapy in the treatment of lung cancer and its multiple mechanisms are worthy of an in-depth study.
A remote mobile health monitoring system with mobile phone and web service capabilities is proposed in this paper. It provides an end-to-end solution; specifically, (1) physiologic parameters, including respiration rate and heart rate, are measured by wearable sensors and recorded by a mobile phone which presents the graphical interface for the user to observe his/her health status more easily; (2) it provides doctors and family members with necessary data through a web interface and enables authorized personnel to monitor the patient's condition and to facilitate remote diagnosis; and (3) it supports real-time alarming and positioning services during an urgent situation, such as a tumble or a heart attack, so that unexpected events can be handled in a timely manner. Experimental results show that the proposed system can reliably monitor the physiologic parameters and conveniently report the user's position.
Radix angelicae pubescentis (RAP) has been used in Chinese traditional medicine to treat painful diseases such as rheumatism and headache. A previous study has reported that columbianadin (CBN), a major coumarin in RAP inhibits acute and inflammatory pain behaviors. However, the effects of CBN on neuropathic pain behaviors, and the potential underlying mechanism have not been reported. In the present study, the effects of CBN, compared to another major coumarin of RAP osthole (OST), on oxaliplatin-induced neuropathic pain behaviors and on the voltage-gated calcium currents in small dorsal root ganglion (DRG) neurons were studied in mice. It was found that CBN and OST inhibited both mechanical and cold hypersensitivity induced by oxaliplatin. Moreover, CBN and OST might preferentially inhibit T-and L-type calcium currents (Ica). The inhibitory effects of CBN and OST on the oxaliplatin-induced mechanical allodynia were prevented by gabapentin. These results suggest that CBN, as well as OST might inhibit neuropathic pain behaviors through an inhibition of T-and L-type calcium currents in nociceptive DRG neurons.
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