NOX Inhibitors - A Promising Avenue for Ischemic Stroke.

NADPH-oxidase (NOX) mediated superoxide originally found on leukocytes, but now recognized in several types of cells in the brain. It has been shown to play an important role in the progression of stroke and related cerebrovascular disease. NOX is a multisubunit complex consisting of 2 membrane-associated and 4 cytosolic subunits. NOX activation occurs when cytosolic subunits translocate to the membrane, leading to transport electrons to oxygen, thus producing superoxide. Superoxide produced by NOX is thought to function in long-term potentiation and intercellular signaling, but excessive production is damaging and has been implicated to play an important role in the progression of ischemic brain. Thus, inhibition of NOX activity may prove to be a promising treatment for ischemic brain as well as an adjunctive agent to prevent its secondary complications. There is mounting evidence that NOX inhibition in the ischemic brain is neuroprotective, and targeting NOX in circulating immune cells will also improve outcome. This review will focus on therapeutic effects of NOX assembly inhibitors in brain ischemia and stroke. However, the lack of specificity and toxicities of existing inhibitors are clear hurdles that will need to be overcome before this class of compounds could be translated clinically

Real-time delay-multiply-and-sum beamforming with coherence factor for in vivo clinical photoacoustic imaging of humans

In the clinical photoacoustic (PA) imaging, ultrasound (US) array transducers are typically used to provide B-mode images in real-time. To form a B-mode image, delay-and-sum (DAS) beamforming algorithm is the most commonly used algorithm because of its ease of implementation. However, this algorithm suffers from low image resolution and low contrast drawbacks. To address this issue, delay-multiply-and-sum (DMAS) beamforming algorithm has been developed to provide enhanced image quality with higher contrast, and narrower main lobe compared but has limitations on the imaging speed for clinical applications. In this paper, we present an enhanced real-time DMAS algorithm with modified coherence factor (CF) for clinical PA imaging of humans in vivo. Our algorithm improves the lateral resolution and signal-to-noise ratio (SNR) of original DMAS beam-former by suppressing the background noise and side lobes using the coherence of received signals. We optimized the computations of the proposed DMAS with CF (DMAS-CF) to achieve real-time frame rate imaging on a graphics processing unit (GPU). To evaluate the proposed algorithm, we implemented DAS and DMAS with/without CF on a clinical US/PA imaging system and quantitatively assessed their processing speed and image quality. The processing time to reconstruct one B-mode image using DAS, DAS with CF (DAS-CF), DMAS, and DMAS-CF algorithms was 7.5, 7.6, 11.1, and 11.3 ms, respectively, all achieving the real-time imaging frame rate. In terms of the image quality, the proposed DMAS-CF algorithm improved the lateral resolution and SNR by 55.4% and 93.6 dB, respectively, compared to the DAS algorithm in the phantom imaging experiments. We believe the proposed DMAS-CF algorithm and its real-time implementation contributes significantly to the improvement of imaging quality of clinical US/PA imaging system.11Ysciescopu

PARN and TOE1 constitute a 3 ' end maturation module for nuclear non-coding RNAs

Poly(A)-specific ribonuclease (PARN) and target of EGR1 protein 1 (TOE1) are nuclear granule-associated deadenylases, whose mutations are linked to multiple human diseases. Here, we applied mTAIL-seq and RNA sequencing (RNA-seq) to systematically identify the substrates of PARN and TOE1 and elucidate their molecular functions. We found that PARN and TOE1 do not modulate the length of mRNA poly(A) tails. Rather, they promote the maturation of nuclear small non-coding RNAs (ncRNAs). PARN and TOE1 act redundantly on some ncRNAs, most prominently small Cajal body-specific RNAs (scaRNAs). scaRNAs are strongly downregulated when PARN and TOE1 are compromised together, leading to defects in small nuclear RNA (snRNA) pseudouridylation. They also function redundantly in the biogenesis of telomerase RNA component (TERC), which shares sequence motifs found in H/ACA box scaRNAs. Our findings extend the knowledge of nuclear ncRNA biogenesis, and they provide insights into the pathology of PARN/TOE1-associated genetic disorders whose therapeutic treatments are currently unavailable.

Improving bread quality using Deinococcus geothermalis glycogen branching enzyme

Glycogen branching enzyme(GBE) catalyzes transglycosylation reaction producing α-1,6-glucosidic linkages by cleaving an α-1,4-glucosidic linkage. Deinococcus geothermalis GBE (DgGBE) has the unique activity to form a large number of short oligosaccharide side chains(degree of polymerization 3~5) from the reaction with amylose. To observe the influence of DgGBE on bread quaility, we added 100 unit of the enzyme per kg of the flour at the step of mixing dough. During the fermentation, DgGBE treated dough showed 50~100% larger volume than control. After baking, the total volume and the specific volume of DgGBE treated loaf showed about 10% larger than those of control. The baked breads were sliced to 2cm of depth and stored in 25 degrees celcius, and then the texture was evaluated by texture analyzer during storage time. Hardness and Chewiness of DgGBE treadted bread increased slowly to compared with those of the control. DgGBE treated bread showed a significant effect on antistaling. 1. Shupeng Wua, Yu Liu , Qiaojuan Yan , Zhengqiang Jiang (2014) Gene cloning, functional expression and characterisation of a novel glycogen branching enzyme from Rhizomucor miehei and its application in wheat breadmaking. Food Chemistry 159 (2014) 85-94 2. José Manuel Amigo , Arantxa del Olmo Alvarez , Merete Møller Engelsen , Henrik Lundkvist , Søren Balling Engelsen (2016) Staling of white bread crumb and effect of maltogenic α-amylases. Part 1 : Spatial distribution and kinetic modeling of hardness and resilience. Food Chemistry 208 (2016) 318-32

Development of screening method for the selection of mutants to improve the substrate specificity of Pyrococcus furiosus thermostable amylase

Pyrococcus furiosus thermostable amylase (PFTA) shows the activities of both a cyclodextrin hydrolyzing enzyme and an α-amylase. To improve the substrate affinity and hydrolyzing activity against cyclodextrins, the saturation mutagenesis on the residue of PFTA active site was carried out. After the mutagenesis, the new screening method was needed to select appropriate mutants efficiently from various mutants. Among the α-, β-, γ-cyclodextrins, only β-cyclodextrin makes the complex with phenolphthalein. When added the β-cyclodextrin into phenolphthalein reagent, the color of the solution was changed red to colorless under alkaline condition. In this study, we developed screening method by using 24-well plate and phenolphthalein to compare the activity of PFTA mutants. Escherichia coli MC1061 was used as a host for the expression of various recombinant plasmids and cultured in 24-well plate with Luria-Bertani broth containing kanamycin. After cell lysis by heat treatment, each cell extracts were reacted with β-cyclodextrin at 70℃. Reacted mixtures were put into 96-well plate with NaOH solution and then add the phenolphthalein reagent respectively. Lastly, the absorbance of the mixture was measured at 550 nm. The substrate specificity of PFTA mutants was compared from the difference of absorbance. References 1. Sung-Jae Yang, Hee-Seob Lee, Cheon-Seok Park, Yong-Ro Kim, Tae-Wha Moon, and Kwan-Hwa Park. 2004. Enzymatic Analysis of an Amylolytic Enzyme from the Hyperthermophilic Archaeon Pyrococcus furiosus Reveals Its Novel Catalytic Properties as both an α-Amylase and a Cyclodextrin-Hydrolyzing Enzyme. APPL. ENVIRON. MICROBIOL. 70:5988-5995 2. Anuj Goel, Sanjay N. Nene. 1995. Modifications in the Phenolphthalein Method for Spectrophotometric Estimation of Beta Cyclodextrin. Starch/Starke. 47:399-40

Benign metastasizing leiomyoma of the lung

Benign leiomyomas of the uterus are uncommonly found in association with benign smooth muscle tumors beyond the confines of the uterus. Benign metastasizing leiomyoma (BML) is a rare disease in which the lung is described to be the most afflicted extrauterine organ. We present a brief review of the literature, along with case reports for four patients who were followed up after resection of a pulmonary lesion or after pathological confirmation by biopsy. The clinical course of BML varies from chronic asymptomatic appearance to rapid progression, leading to respiratory failure and death. Our BML patients did not complain of pulmonary symptoms, such as cough, dyspnea, or chest tightness. Pathology revealed benign leiomyomas with no atypia and mitotic activity <5 per 10 high-power field. Immunohistochemical staining was positive for actin and desmin. A standard treatment for BML has not yet been established. Because of the hormone-sensitive characteristics of BML, treatments are based on hormonal manipulation along with either surgical or medical oophorectomy. Benign metastasizing leiomyoma can be observed in postmenopausal women. We observed four patients who did not receive adjuvant hormonal therapy because they were postmenopausal or perimenopausal. All patients are still healthy and show no evidence of recurrence or progression of the disease

Soybeans Ameliolate Diabetic Nephropathy in Rats

Diabetic nephropathy is one of the most frequent and serious complications of diabetes mellitus. Soybeans have been shown to reduce urinary albumin excretion and total cholesterol in non-diabetic patients with nephrotic syndrome. However, reports focusing specifically on diabetic nephropathy are scarce and the available results are inconsistent. It was reported that soybean consumption reduced urinary protein excretion in type 1 diabetic patients with diabetic nephropathy, whereas it was found to elicit an increase in urinary protein excretion when soybeans were consumed by type 2 diabetic patients. This study aims to investigate the effects of soybean in diabetic nephropathy, particularly the effects of consuming soybeans on the histopathology of diabetic nephropathy, using aquaporin (AQP) and osteopontin (OPN) expression as diagnostic markers. Male Sprague-Dawley rats were assigned to one of three groups: control, diabetic with red chow diet and diabetic with soybean diet. For histological examination, the expression of OPN and AQP, renal function and hemoglobin A1c were evaluated at the end of the study. Improvements in glomerular and tubulointerstitial lesions were demonstrated in the diabetic rat group given a soybean diet. OPN and AQP expression were suppressed in the kidney specimens of diabetic rats with the soybean diet. In conclusion, soybeans may prevent the weight loss and morphological disruption of the kidney associated with diabetes mellitus. Soybeans also may improve glycemic control. It seems likely that long-term control of blood glucose levels using a soybean diet could prevent the progression of diabetes mellitus, and therefore, nephropathy could be prevented

Regulation of endothelial nitric oxide synthase by agmatine after transient global cerebral ischemia in rat brain

Nitric oxide (NO) production by endothelial nitric oxide synthase (eNOS) plays a protective role in cerebral ischemia by maintaining vascular permeability, whereas NO derived from neuronal and inducible NOS is neurotoxic and can participate in neuronal damage occurring in ischemia. Matrix metalloproteinases (MMPs) are up-regulated by ischemic injury and degrade the basement membrane if brain vessels to promote cell death and tissue injury. We previously reported that agmatine, synthesized from L-arginine by arginine decarboxylase (ADC) which is expressed in endothelial cells, has shown a direct increased eNOS expression and decreased MMPs expression in bEnd3 cells. But, there are few reports about the regulation of eNOS by agmatine in ischemic animal model. In the present study, we examined the expression of eNOS and MMPs by agmatine treatment after transient global ischemia in vivo. Global ischemia was induced with four vessel occlusion (4-VO) and agmatine (100 mg/kg) was administered intraperitoneally at the onset of reperfusion. The animals were euthanized at 6 and 24 hours after global ischemia and prepared for other analysis. Global ischemia led severe neuronal damage in the rat hippocampus and cerebral cortex, but agmatine treatment protected neurons from ischemic injury. Moreover, the level and expression of eNOS was increased by agmatine treatment, whereas inducible NOS (iNOS) and MMP-9 protein expressions were decreased in the brain. These results suggest that agmatine protects microvessels in the brain by activation eNOS as well as reduces extracellular matrix degradation during the early phase of ischemic insult