AGK2 Alleviates Lipopolysaccharide Induced Neuroinflammation through Regulation of Mitogen-Activated Protein Kinase Phosphatase-1

Journal of Neuroimmune Pharmacology - Neuroinflammation is associated with the progression of multiple neurological diseases. Many studies show that SIRT2 involves in multiple inflammatory...     

Rapid Changes in Serum Testosterone in Men With Newly Diagnosed Type 2 Diabetes With Intensive Insulin and Metformin

OBJECTIVETo investigate the effect of metformin on testosterone levels in men with type 2 diabetes mellitus (T2DM).RESEARCH DESIGN AND METHODSSeventy men with newly diagnosed drug-naive T2DM and HbA_1c >9.0% (75 mmol/mol) were treated with intensive insulin pump therapy for 5 days to achieve glucose normalization. They were randomized to control (continued on intensive insulin only) and metformin (plus metformin) groups (1:1) for 1 month. Testosterone was measured at baseline, randomization, and after 1-month treatment.RESULTSTotal, free, and bioavailable testosterone increased significantly within 5 days (all P < 0.001). After 1 month, compared with the control group, the metformin group had lower total (12.7 vs. 15.3 nmol/L), free (0.20 vs. 0.24 nmol/L), and bioavailable (4.56 vs. 5.31 nmol/L) testosterone (all P < 0.05).CONCLUSIONSIn men with T2DM, 1-month oral metformin may decrease serum testosterone levels independent of blood glucose control. The effects of long-term metformin on testosterone in men need further study.     

Harnessing hyperuricemia to atherosclerosis and understanding its mechanistic dependence

Atherosclerosis is regarded as the disease of the arterial vasculature. The main characteristics of atherosclerosis are the abnormal accumulation of lipids, increased inflammatory cells, matrix deposits, and proliferation of smooth muscle cells. Diabetes mellitus, obesity, and hyperlipidemia are the most studied risk factors of atherosclerosis. One least studied risk factor is the uric acid (UA), a high UA in circulation is interlinked with many pathological processes. Several epidemiological studies suggest elevated UA levels as an essential biomarker in the forecast of several cardiovascular diseases. Available evidence claims that UA upholds the atherosclerosis process via disturbing lipid metabolism, reducing the nitric oxide synthesis in endothelial cells, promoting the proliferation of vascular smooth muscle cells, and overwhelms inflammation. In endothelial dysfunction and coronary artery lesions, UA is considered as an independent predictor. The updated studies on the involvement of hyperuricemia in atherosclerosis prove that treatment with xanthine oxidase (XO) inhibitors not just benefits the treatment of hyperuricemia but also reduces the burden of atherosclerosis to a greater extent. In this review, we highlight how the hyperuricemia affects vascular integrity, causes atherosclerosis, and the mechanism of action of XO inhibitors on atherosclerosis.     

Retrieval of fractured dialysis catheter through phlebotomy of internal jugular vein: a case report

A central venous catheter is the most common access for initiating hemodialysis. Prolonged access through a central venous catheter increases the risk of infection and dysfunction of the catheter with potential development of catheter-induced thrombosis and embolism. However, fracture and dislodgement of the catheter with subsequent embolization is an unexpected complication. Endovascular treatment is a promising method to remove intravascular foreign bodies. We herein report a case of a 58-year-old woman undergoing prolonged hemodialysis who required central venous catheter removal because of mechanical fracture of the tunneled cuffed catheter and its migration in the internal jugular vein. An urgent chest X-ray showed that the two free ends of the fractured tunneled cuffed catheter were located in the right atrium and right internal jugular vein. Phlebotomy of the internal jugular vein was successfully performed to retrieve the fractured tunneled cuffed catheter and the associated thrombi. In this case, phlebotomy for retrieval of the embolized catheter fragment extending into the right atrium was a safe alternative to an endovascular technique of catheter fragment retrieval. Phlebotomy preserved the integrity of the catheter fragment and its associated thrombus and was both cost-effective and safe.     

Effects of Ethanol Extract of Radix Sophorae Flavescentis on Activity of Colon Cancer HT29 Cells

This paper mainly studied the inhibitory effect of total ethanol extract of Radix Sophorae Flavescentis on proliferation of colon cancer HT29 cells. By reflux extraction method and with ethanol as extraction solvent, different extracts were obtained at different ethanol concentrations, different solid-liquid ratios, and at different times. And their inhibitory activities against HT29 cells were compared using MTT assay. The experimental results showed that the extraction processes under three conditions can all draw relatively high inhibition rates. The optimum ethanol extraction process conditions were as follows: a solid-liquid ratio of 1:9, 80 min of heat reflux extraction with 95% ethanol.     

Research of fetal ECG extraction using wavelet analysis and adaptive filtering

Extracting clean fetal electrocardiogram (ECG) signals is very important in fetal monitoring. In this paper, we proposed a new method for fetal ECG extraction based on wavelet analysis, the least mean square (LMS) adaptive filtering algorithm, and the spatially selective noise filtration (SSNF) algorithm. First, abdominal signals and thoracic signals were processed by stationary wavelet transform (SWT), and the wavelet coefficients at each scale were obtained. For each scale, the detail coefficients were processed by the LMS algorithm. The coefficient of the abdominal signal was taken as the original input of the LMS adaptive filtering system, and the coefficient of the thoracic signal as the reference input. Then, correlations of the processed wavelet coefficients were computed. The threshold was set and noise components were removed with the SSNF algorithm. Finally, the processed wavelet coefficients were reconstructed by inverse SWT to obtain fetal ECG. Twenty cases of simulated data and 12 cases of clinical data were used. Experimental results showed that the proposed method outperforms the LMS algorithm: (1) it shows improvement in case of superposition R-peaks of fetal ECG and maternal ECG; (2) noise disturbance is eliminated by incorporating the SSNF algorithm and the extracted waveform is more stable; and (3) the performance is proven quantitatively by SNR calculation. The results indicated that the proposed algorithm can be used for extracting fetal ECG from abdominal signals.     

Brain-targeting delivery for RNAi neuroprotection against cerebral ischemia reperfusion injury

Nanoparticles (NPs) with modification of brain-targeting molecules have been extensively exploited for therapeutic gene delivery across the blood–brain barrier (BBB). As one of the effective RNA interference (RNAi) approaches, short hairpin RNA (shRNA) has been proved to be promising in the field of gene therapy. Apoptosis signal-regulating kinase 1 (Ask1) has been reported to be an important target for gene therapy against cerebral ischemia reperfusion injury. In this study, dendrigraft poly-l-lysine (DGL) was decorated by dermorphin (a μ-opiate receptor agonist) through PEG for efficient brain-targeting, then complexed with anti-Ask1 shRNA plasmid DNA, yielding the DGL-PEG-dermorphin/shRNA NPs. The DGL-PEG-dermorphin/shRNA NPs were characterized and estimated the brain-targeting ability. In vitro, increased cellular uptake and transfection efficiency were explored; in vivo, preferable accumulation and gene transfection in brain were showed in images. The DGL-PEG-dermorphin/shRNA NPs also revealed high efficiency of neuroprotection. As a result of RNAi, corresponding mRNA was distinctly degraded, expression of Ask1 protein was obviously suppressed, apoptotic cell death was apparently decreased and cerebral infarct area was significantly reduced. Above all, DGL-PEG-dermorphin/shRNA NPs were proved to be efficient and safe for brain-targeting RNAi neuroprotection against cerebral ischemia reperfusion injury.