Apocynum Tablet Protects against Cardiac Hypertrophy via Inhibiting AKT and ERK1/2 Phosphorylation after Pressure Overload

Background. Cardiac hypertrophy occurs in many cardiovascular diseases. Apocynum tablet (AT), a traditional Chinese medicine, has been widely used in China to treat patients with hypertension. However, the underlying molecular mechanisms of AT on the hypertension-induced cardiac hypertrophy remain elusive. The current study evaluated the effect and mechanisms of AT on cardiac hypertrophy. Methods. We created a mouse model of cardiac hypertrophy by inducing pressure overload with surgery of transverse aortic constriction (TAC) and then explored the effect of AT on the development of cardiac hypertrophy using 46 mice in 4 study groups (combinations of AT and TAC). In addition, we evaluated the signaling pathway of phosphorylation of ERK1/2, AKT, and protein expression of GATA4 in the cardioprotective effects of AT using Western blot. Results. AT inhibited the phosphorylation of Thr202/Tyr204 sites of ERK1/2, Ser473 site of AKT, and protein expression of GATA4 and significantly inhibited cardiac hypertrophy and cardiac fibrosis at 2 weeks after TAC surgery (P<0.05). Conclusions. We experimentally demonstrated that AT inhibits cardiac hypertrophy via suppressing phosphorylation of ERK1/2 and AKT

O-GlcNAc Modification of NFκB p65 Inhibits TNF-α-Induced Inflammatory Mediator Expression in Rat Aortic Smooth Muscle Cells

BACKGROUND: We have shown that glucosamine (GlcN) or O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc) treatment augments O-linked-N-acetylglucosamine (O-GlcNAc) protein modification and attenuates inflammatory mediator expression, leukocyte infiltration and neointima formation in balloon injured rat carotid arteries and have identified the arterial smooth muscle cell (SMC) as the target cell in the injury response. NFκB signaling has been shown to mediate the expression of inflammatory genes and neointima formation in injured arteries. Phosphorylation of the p65 subunit of NFκB is required for the transcriptional activation of NFκB. This study tested the hypothesis that GlcN or PUGNAc treatment protects vascular SMCs against tumor necrosis factor (TNF)-α induced inflammatory stress by enhancing O-GlcNAcylation and inhibiting TNF-α induced phosphorylation of NFκB p65, thus inhibiting NFκB signaling. METHODOLOGY/PRINCIPAL FINDINGS: Quiescent rat aortic SMCs were pretreated with GlcN (5 mM), PUGNAc (10(-4) M) or vehicle and then stimulated with TNF-α (10 ng/ml). Both treatments inhibited TNF-α-induced expression of chemokines [cytokine-induced neutrophil chemoattractant (CINC)-2β and monocyte chemotactic protein (MCP)-1] and adhesion molecules [vascular cell adhesion molecule (VCAM)-1 and P-Selectin]. Both treatments inhibited TNF-α induced NFκB p65 activation and promoter activity, increased NFκB p65 O-GlcNAcylation and inhibited NFκB p65 phosphorylation at Serine 536, thus promoting IκBα binding to NFκB p65. CONCLUSIONS: There is a reciprocal relationship between O-GlcNAcylation and phosphorylation of NFκB p65, such that increased NFκB p65 O-GlcNAc modification inhibits TNF-α-Induced expression of inflammatory mediators through inhibition of NFκB p65 signaling. These findings provide a mechanistic basis for our previous observations that GlcN and PUGNAc treatments inhibit inflammation and remodeling induced by acute endoluminal arterial injury

Dexmedetomidine in combination with sufentanil for postoperative analgesia after partial laryngectomy

Abstract Background Dexmedetomidine as an adjunct with opioids has been confirmed to spare opioids usage and improve analgesia for postoperative pain treatment. Furthermore, dexmedetomidine can attenuate the airway reflex. The aim of this study is to assess the safety and efficacy of dexmedetomidine combined with sufentanil for postoperative analgesia after partial laryngectomy. Methods A total of 60 adult male patients were recruited and randomly allocated to receive sufentanil 1.0 μg ml−1 (Group S) or sufentanil 1.0 μg ml−1 plus dexmedetomidine 4 μg ml−1 (Group SD) for postoperative analgesia. The IV patient controlled analgesia (PCA) device was programmed to deliver 1.5 ml per demand with a 10 min lockout interval and 1.5 ml per hour background infusion. Cumulative consumption of sufentanil and pain intensity during 24 hour (h) after surgery were recorded. Coughing episodes per day, sleep quality, hemodynamic and respiratory profiles were measured. Results Compared with Group S, patients in Group SD required less sufentanil during the 0–24 h postoperative period (p < 0.0001) and reported significant lower pain intensity from the second postoperative hour to the end of the study (P < 0.0001). Daily coughing episodes, sleep disturbance was lower and patients’ satisfaction was higher in Group SD (P < 0.05). Decrease in heart rate and mean blood pressure from baseline at 1 h, 2 h, 3 h, 12 h, and 24 h after operation were significantly greater in Group SD (P = 0.00). The incidence of PCA related adverse events were comparable between the two groups. Conclusion Dexmedetomidine/sufentanil combination for postoperatjve analgesia in partial laryngectomized patients resulted in significant sufentanil sparing, better analgesia, reduced frequency coughing episodes, and better sleep quality. Trial registration Chinese Clinical Registry (ChiCTR): ChiCTR-TRC-14004618 , date of registration: 08 May 2014

An End-To-End View Of Iot Security And Privacy

In this paper, we present an end-to-end view of IoT security and privacy and a case study. Our contribution is twofold. First, we present our end-to-end view of an IoT system and this view can guide risk assessment and design of an IoT system. We identify 10 basic IoT functionalities that are related to security and privacy. Based on this view, we systematically present security and privacy requirements in terms of IoT system, software, networking and big data analytics in the cloud. Second, using the end-to-end view of IoT security and privacy, we present a vulnerability analysis of the Edimax IP camera system. We are the first to exploit this system and have identified various attacks that can fully control all the cameras from the manufacturer. Our real- world experiments demonstrate the effectiveness of the discovered attacks and raise the alarms again for the IoT manufacturers

Synthetic extracellular matrices with nonlinear elasticity regulate cellular organization

One of the promises of synthetic materials in cell culturing is that control over their molecular structures may ultimately be used to control their biological processes. Synthetic polymer hydrogels from polyisocyanides (PIC) are a new class of minimal synthetic biomaterials for three-dimensional cell culturing. The macromolecular lengths and densities of biofunctional groups that decorate the polymer can be readily manipulated while preserving the intrinsic nonlinear mechanics, a feature commonly displayed by fibrous biological networks. In this work, we propose the use of PIC gels as cell culture platforms with decoupled mechanical inputs and biological cues. For this purpose, different types of cells were encapsulated in PIC gels of tailored compositions that systematically vary in adhesive peptide (GRGDS) density, polymer length, and concentration; with the last two parameters controlling the gel mechanics. Both cancer and smooth muscle cells grew into multicellular spheroids with proliferation rates that depend on the adhesive GRGDS density, regardless of the polymer length, suggesting that for these cells, the biological input prevails over the mechanical cues. In contrast, human adipose-derived stem cells do not form spheroids but rather spread out. We find that the morphological changes strongly depend on the adhesive ligand density and the network mechanics; gels with the highest GRGDS densities and the strongest stiffening response to stress show the strongest spreading. Our results highlight the role of the nonlinear mechanics of the extracellular matrix and its synthetic mimics in the regulation of cell functions