WNT信号通路及其与唇腭裂发生

WNT信号通路作为调控胚胎发生的四大信号转导途径之一,主要参与细胞的增殖、分化和极化以及程序性细胞死亡和抗程序性细胞死亡等,近年来其研究逐渐成为热点。唇腭裂作为最常见的先天性畸形,其发病机制至今尚无定论。研究显示,WNT信号通路与唇腭裂发生关系密切,本文就WNT信号通路及其与唇腭裂发生的研究进展作一综述。     

Eritoran attenuates tissue damage and inflammation in hemorrhagic shock/trauma

Background

Severe injury and associated hemorrhagic shock lead to an inflammatory response and subsequent increased tissue damage. Numerous reports have shown that injury-induced inflammation and the associated end-organ damage is driven by Toll-like receptor 4 (TLR4) activation via damage-associated molecular patterns. We examined the effectiveness of Eritoran tetrasodium (E5564), an inhibitor of TLR4 function, in reducing inflammation induced during hemorrhagic shock with resuscitation (HS/R) or after peripheral tissue injury (bilateral femur fracture, BFF).

Material and methods

Mice underwent HS/R or BFF with or without injection of Eritoran (5 mg/kg body weight) or vehicle control given before, both before and after, or only after HS/R or BFF. Mice were sacrificed after 6 h and plasma and tissue cytokines, liver damage (histology; aspartate aminotransferase/alanine aminotransferase), and inflammation (NF-κB) and gut permeability were assessed.

Results

In HS/R Eritoran significantly reduced liver damage (values ± SEM: alanine aminotransferase 9910 ± 3680 U/L versus 1239 ± 327 U/L and aspartate aminotransferase 5863 ± 2000 U/L versus 1246 ± 243 U/L, P < 0.01) at 6 h compared with control when given just before HS and again just prior to resuscitation. Eritoran administration also led to lower IL-6 levels in plasma and liver and less NF-κB activation in liver. Increases in gut barrier permeability induced by HS/R were also prevented with Eritoran. Eritoran similarly diminished BFF-mediated systemic inflammatory responses.

Conclusion

These data suggest Eritoran can inhibit tissue damage and inflammation induced via TLR4/myeloid differentiation factor 2 signaling from damage-associated molecular patterns released during HS/R or BFF. Eritoran may represent a promising therapeutic for trauma patients to prevent multiple organ failure.     

Skeletal Muscle Triacylglycerol Hydrolysis Does Not Influence Metabolic Complications of Obesity

Intramyocellular triacylglycerol (IMTG) accumulation is highly associated with insulin resistance and metabolic complications of obesity (lipotoxicity), whereas comparable IMTG accumulation in endurance-trained athletes is associated with insulin sensitivity (the athlete’s paradox). Despite these findings, it remains unclear whether changes in IMTG accumulation and metabolism per se influence muscle-specific and systemic metabolic homeostasis and insulin responsiveness. By mediating the rate-limiting step in triacylglycerol hydrolysis, adipose triglyceride lipase (ATGL) has been proposed to influence the storage/production of deleterious as well as essential lipid metabolites. However, the physiological relevance of ATGL-mediated triacylglycerol hydrolysis in skeletal muscle remains unknown. To determine the contribution of IMTG hydrolysis to tissue-specific and systemic metabolic phenotypes in the context of obesity, we generated mice with targeted deletion or transgenic overexpression of ATGL exclusively in skeletal muscle. Despite dramatic changes in IMTG content on both chow and high-fat diets, modulation of ATGL-mediated IMTG hydrolysis did not significantly influence systemic energy, lipid, or glucose homeostasis, nor did it influence insulin responsiveness or mitochondrial function. These data argue against a role for altered IMTG accumulation and lipolysis in muscle insulin resistance and metabolic complications of obesity.Obesity is a global public health problem and a major risk factor for insulin resistance and type 2 diabetes. These disorders are characterized by excess lipid accumulation in multiple tissues, primarily as triacylglycerols (TAGs). The lipotoxicity hypothesis suggests that this lipid excess promotes cellular dysfunction and cell death, which ultimately contribute to insulin resistance and metabolic disease (1). However, intracellular TAG accumulation is not always associated with adverse metabolic outcomes, suggesting that TAGs themselves are not pathogenic (2). In contrast, other non-TAG lipid metabolites such as fatty acids (FAs), diacylglycerols (DAGs), and ceramides have been shown to influence glucose homeostasis and insulin action by interfering with insulin signaling and glucose transport, promoting endoplasmic reticulum stress and mitochondrial dysfunction, and activating inflammatory and apoptotic pathways (reviewed in ref. 3). Nevertheless, the precise identities and sources of these bioactive lipid intermediates remain elusive (4,5). Furthermore, whether intracellular TAGs serve as a protective sink or a toxic source of deleterious lipid metabolites that contribute to insulin resistance remains unclear (6).Since skeletal muscle is the major contributor to insulin-mediated glucose disposal, lipid excess in this tissue could have serious implications for systemic glucose homeostasis and insulin responsiveness (7). Indeed, numerous studies have demonstrated a strong association between intramyocellular triacylglycerol (IMTG) accumulation and insulin resistance (reviewed in ref. 8). In contrast, endurance exercise training is characterized by IMTG accumulation and insulin sensitivity (the athlete’s paradox) (2). This variable association between IMTG accumulation and insulin responsiveness has largely been attributed to differences in the balance between lipid delivery and muscle oxidative capacity (8–10). Not surprisingly then, most studies have focused on the impact of muscle FA uptake and/or oxidation on glucose homeostasis and insulin action (11). However, experimental manipulations of these parameters cannot distinguish among the effects of IMTGs, IMTG metabolism, and other lipid intermediates. Furthermore, accumulating evidence suggests that muscle oxidative capacity cannot entirely explain differences in IMTGs or insulin responsiveness (12). These findings have led to speculation that dynamic IMTG metabolism (i.e., TAG synthesis or hydrolysis) may be critically involved in lipid-induced insulin resistance (6). However, few studies have specifically addressed the contribution of IMTG metabolism per se to this process.The regulated storage and release of IMTGs remain poorly understood, but require the coordinated action of synthetic enzymes (i.e., diacylglycerol acyltransferases [DGATs]), hydrolytic enzymes (i.e., adipose triglyceride lipase [ATGL] and hormone sensitive lipase [HSL]), and other lipid droplet proteins (6). Specifically, modulating IMTG synthesis in murine skeletal muscle alters IMTG content and systemic glucose homeostasis, supporting a role for IMTG metabolism in metabolic disease (13–15). However, the metabolic impact of modulating IMTG hydrolysis in vivo remains unclear. Global deletion of either ATGL (16–19) or HSL (20) has produced variable results. The former, but not the latter, results in massive IMTG accumulation with improvement in systemic glucose homeostasis, suggesting that inhibition of ATGL-mediated TAG hydrolysis protects against insulin resistance. In contrast, recent studies in cardiac muscle (21) and other tissues (22,23) indicate that ATGL-mediated TAG hydrolysis is required for mitochondrial function such that enhancing, rather than inhibiting, ATGL action may improve metabolic outcomes. Nevertheless, the autonomous role of skeletal muscle TAG catabolism in influencing muscle-specific and systemic metabolic phenotypes remains unknown.The goal of the current study was to understand the contribution of IMTG hydrolysis to tissue-specific and systemic metabolic phenotypes, particularly glucose homeostasis and insulin action, in the context of obesity. We therefore generated animal models with decreased (skeletal muscle-specific ATGL knockout [SMAKO] mice) and increased (muscle creatine kinase [Ckm]-ATGL transgenic [Tg] mice) ATGL action exclusively in skeletal muscle, and assessed the metabolic consequences at baseline and in response to chronic high-fat feeding. Interestingly, modulation of IMTG hydrolysis via ATGL action did not significantly influence glucose homeostasis, insulin action, or other metabolic phenotypes in the context of obesity despite dramatic changes in IMTG content.     

Nash equilibrium solutions of tracking game for bilinear systems with exponential reference signals

In this paper, we consider the problem of Nash equilibrium solutions of two players tracking game for bilinear systems. A successive approximation approach is modified to design optimal controllers for bilinear systems. More specifically, a sequence of extended Sylvester differential equations are solved by this modified approach. A simulation example is given to demonstrate the validity of this approach. Copyright © 2012 John Wiley & Sons, Ltd.     

Decontamination of dental implant surfaces by means of photodynamic therapy

Several implant surface debridement methods have been reported for the treatment of peri-implantitis, however, some of them can damage the implant surface or promote bacterial resistance. Photodynamic therapy (PDT) is a new treatment option for peri-implantitis. The aim of this in vitro study was to analyze implant surface decontamination by means of PDT. Sixty implants were equally distributed (n?=?10) into four groups and two subgroups. In group G1 there was no decontamination, while in G2 decontamination was performed with chlorhexidine. G3 (PDT???laser?+?dye) and G4 (laser, without dye) were divided into two subgroups each; with PDT performed for 3 min in G3a and G4a, and for 5 min in G3b and G4b. After 5 min in contact with methylene blue dye (G3), the implants were irradiated (G3 and G4) with a low-level laser (GaAlAs, 660 nm, 30 mW) for 3 or 5 min (7.2 and 12 J). After the dilutions, culture media were kept in an anaerobic atmosphere for 1 week, and then colony forming units were counted. There was a significant difference (p?<?0.001) between G1 and the other groups, and between G4 in comparison with G2 and G3. Better decontamination was obtained in G2 and G3, with no statistically significant difference between them. The results of this study suggest that photodynamic therapy can be considered an efficient method for reducing bacteria on implant surfaces, whereas laser irradiation without dye was less efficient than PDT.     

Condom use with various types of sex partners by money boys in China

Money boys (MBs) who typically sell sex to males have not yet been extensively studied in China. In this 2009 study, 28 venue-based MBs were interviewed. We analyzed their condom use behaviors with various partners, including male and female clients, male and female casual partners, other MBs and female sex workers, and boyfriends and girlfriends. All participants were aware of the need for using condoms; however, usage with different partner types varied. The longer a relationship with a partner, the less frequent was condom use. A major reason for not using condoms was that they or their partners did not like the loss of sensation due to condom use. Other factors included sexual orientation, age, duration in commercial sex, concerns about HIV/AIDS, attractiveness of partners, and support of "mommies" (brothel supervisors). Both individual- and venue-level interventions are needed to promote condom use, and mommies need to be included in intervention strategies.