Vasodilatory Effect of a Novel Rho-Kinase Inhibitor,DL0805-2, on the rat Mesenteric Artery and its Potential Mechanisms

Purpose

In the present study, we investigated the vasodilatory effect of a novel scaffold Rho-kinase inhibitor, DL0805-2, on isolated rat arterial rings including mesenteric, ventral tail, and renal arteries. We also examined the potential mechanisms of its vasodilatory action using mesenteric artery rings.

Methods

A DMT multiwire myograph system was used to test the tension of isolated small arteries. Several drugs were employed to verify the underlying mechanisms.

Results

DL0805-2 (10^?7–10^?4 M) inhibited KCl (60 mM)-induced vasoconstriction in three types of small artery rings (pEC₅₀: 5.84?±?0.03, 5.39?±?0.03, and 5.67?±?0.02 for mesenteric, renal, and ventral tail artery rings, respectively). Pre-incubation with DL0805-2 (1, 3, or 10 μM) attenuated KCl (10–60 mM) and angiotensin II (AngII; 10^?6 M)-induced vasoconstriction in mesenteric artery rings. The relaxant effect on the rat mesenteric artery was partially endothelium-dependent (pEC₅₀: 6.02?±?0.05 for endothelium-intact and 5.72?±?0.06 for endothelium-denuded). The influx and release of Ca²⁺ were inhibited by DL0805-2. In addition, the increased phosphorylation levels of myosin light chain (MLC) and myosin-binding subunit of myosin phosphatase (MYPT1) induced by AngII were blocked by DL0805-2. However, DL0805-2 had little effect on K⁺ channels.

Conclusions

The present results demonstrate that DL0805-2 has a vasorelaxant effect on isolated rat small arteries and may exert its action through the endothelium, Ca²⁺ channels, and the Rho/ROCK pathway.     

Hemoglobin A1c as a marker for identifying diabetes and cardiovascular risk factors: the China Health and Nutrition Survey 2009

Hemoglobin A_1c (HbA_1c) has been recommended as an optional method for diagnosing diabetes. The impact of HbA_1c on the diagnosis of diabetes has not been evaluated in China, a country with the greatest number of people with diabetes in the world. Hence, we aim to examine how well HbA_1c performs as compared with fasting plasma glucose (FPG) for diagnosing diabetes in Chinese population. We conducted a cross-sectional analysis of 7,641 Chinese men and women aged ≥18 years using data from the China Health and Nutrition Survey 2009 in which FPG and standardized HbA_1c were measured. HbA_1c was measured with high-performance liquid chromatography system. Diabetes is defined as having FPG ≥7 mmol/l or HbA_1c ≥6.5 %. Overall, 5.0 and 5.8 % had undiagnosed diabetes by FPG ≥7 mmol/l and HbA_1c ≥6.5 %, respectively. Overlap between HbA_1c- and FPG-based diagnosis of diabetes was limited (n = 214, 34.9 %). Similar trends were noted in both genders, all age groups, urban/rural settings, regions, body mass index (BMI) categories, waist circumference (WC) groups, and blood pressure status. Solely HbA_1c-defined individuals exhibited higher levels of BMI, WC, total cholesterol, and hypersensitive C-reactive protein and lower levels of homeostasis model assessment of insulin resistance. We note limited overlap between FPG- and HbA_1c-based diagnosis of diabetes. The limited overlap between FPG- and HbA_1c-based diagnosis of diabetes persisted in each evaluated subgroup. HbA_1c criterion for the diagnosis of diabetes identifies individuals with a worse cardiovascular risk profile compared with FPG.     

Magnetic resonance imaging and risk factors for progression of lacunar infarct lesions in Chinese patients

Neuroradiology - The proportion of acute symptomatic lacunar infarction lesions that undergo cavitation and the factors influencing cavity formation are yet unclear, particularly in the Chinese...     

江苏省乳腺X射线摄影频度调查及乳腺癌风险评估

目的 调查估算江苏省乳腺X射线摄影的频度,进而估算乳腺摄影对江苏省女性人口的剂量负担,并评估乳腺摄影对江苏省各年龄组女性人口诱发乳腺癌的风险。方法 采用分层随机抽样调查的方法,通过调查30台乳腺摄影设备年检查人数和受检者年龄分布,估算全省乳腺摄影的频度,并计算乳腺摄影对女性人口的剂量负担。使用美国科学院电离辐射生物效应报告BEIR-Ⅶ中的超额归因风险（EAR）模型估算乳腺摄影检查对3个年龄组诱发乳腺癌的风险。结果 江苏省乳腺摄影检查的频度为3.77次/千人口;乳腺摄影对江苏省女性人口剂量负担为0.02 mGy/人。每次乳腺摄影检查对0~15岁组、16~40岁和>40岁3个年龄组的乳腺癌终生归因风险（LAR）分别为138/10万人、14.7/10万人和1.0/10万人。结论 乳腺摄影对人群乳腺癌诱发风险较小,但低年龄组的风险较大,提示针对低年龄乳腺摄影检查仍应慎重。     

Effects of acid and phosphate on arsenic solidification in a phosphogypsum-based cement backfill process

Phosphogypsum (PG) produced during phosphoric acid production contains significant amounts of arsenic and can potentially cause adverse environmental and health effects. Cement backfill technology is an effective management technique that is used to store PG to prevent such problems. The goal of this paper is to study the influencing factors and mechanism of arsenic stabilization in a PG-based cement backfill process. First, a leaching toxicity test was conducted, which showed that the arsenic concentration in PG batches ranged from 129.1 μg L⁻¹ to 407.1 μg L⁻¹, which were all far above the standard limit (10 μg L⁻¹) set by GB/T 14848-93. In addition, the arsenic content was higher in samples with larger PG particles. Secondly, hydrogen and phosphate ions were added to the backfill to investigate how they influenced arsenic solidification, and the results indicated that phosphate ions, rather than hydrogen ions, delayed the arsenic solidification process. This suggests that controlling the soluble phosphate in PG will help reduce arsenic pollution during backfilling. A toxicity leaching test was carried out after backfill samples were cured for 28 d. All arsenic concentrations were below the standard limit, indicating that the cement backfill technology ensured the long-term solidification and stabilization of arsenic.

Phosphogypsum (PG) produced during phosphoric acid production contains significant amounts of arsenic and can potentially cause adverse environmental and health effects.     

Simple,rapid, sensitive,selective and label-free lincomycin detection by using HAuCl4 and NaOH

A simple, rapid, sensitive, selective and label-free method is presented for the colorimetric determination of lincomycin (Lin) by using HAuCl₄ and NaOH. Upon the addition of Lin, the mixture of HAuCl₄ and NaOH shows a color change from colorless to blue (or dark blue). The limit of colorimetric detection is as low as 1 μM, observed both in Milli-Q water and real samples. The selectivity of Lin detection is excellent compared with 9 other common antibiotics. On the basis of the “three-color” principle of Thomas Young, we extracted the red, green and blue (RGB) alterations of the sensor in the absence and presence of different concentrations of Lin. The color changes are quantitatively illustrated by the total Euclidean distances (EDs = [ΔR² + ΔG² + ΔB²]^1/2). The good linear relationship between the EDs and Lin concentration is used for the quantitative assay of Lin. The developed method demonstrates great potential for the detection of Lin in environmental water and milk.

A simple, rapid, sensitive, selective and label-free method is presented for the colorimetric determination of lincomycin (Lin) by using HAuCl₄ and NaOH.     

LncRNA NEXN-AS1 attenuates proliferation and migration of vascular smooth muscle cells through sponging miR-33a/b

Non-protein-coding RNAs (lncRNAs) are emerging as important regulators in disease pathogenesis, including atherosclerosis (AS). Here, we investigated the role and underlying mechanisms of nexilin F-actin binding protein antisense RNA 1 (NEXN-AS1) on the proliferation and migration of vascular smooth muscle cells (VSMCs). Our data revealed that ox-LDL treatment resulted in decreased NEXN-AS1 expression and increased miR-33a/b levels in human aorta VSMCs (HA-VSMCs) in dose- and time-dependent manners. Overexpression of NEXN-AS1 mitigated the proliferation and migration of HA-VSMCs under ox-LDL stimulation using CCK-8 and wound-healing assays. Moreover, dual-luciferase reporter and RNA immunoprecipitation assays verified that NEXN-AS1 acted as molecular sponges of miR-33a and miR-33b in HA-VSMCs. MiR-33a or miR-33b silencing attenuated the proliferation and migration of ox-LDL-treated HA-VSMCs. Furthermore, miR-33a or miR-33b mediated the inhibitory effects of NEXN-AS1 overexpression on the proliferation and migration of ox-LDL-treated HA-VSMCs. Our study suggested that high level of NEXN-AS1 mitigated VSMC proliferation and migration under ox-LDL stimulation at least partly through sponging miR-33a and miR-33b, illuminating NEXN-AS1 as a novel therapeutic approach for AS treatment.

Non-protein-coding RNAs (lncRNAs) are emerging as important regulators in disease pathogenesis, including atherosclerosis (AS).