Myokines in skeletal muscle physiology and metabolism: Recent advances and future perspectives

Myokines are molecules produced and secreted by skeletal muscle to act in an auto‐, para‐ and endocrine manner to alter physiological function of target tissues. The growing number of effects of myokines on metabolism of distant tissues provides a compelling case for crosstalk between skeletal muscle and other tissues and organs to regulate metabolic homoeostasis. In this review, we summarize and discuss the current knowledge regarding the impact on metabolism of several canonical and recently identified myokines. We focus specifically on myostatin, β‐aminoisobutyric acid, interleukin‐15, meteorin‐like and myonectin, and discuss how these myokines are induced and regulated as well as their overall function. We also review how these myokines may serve as potential prognostic biomarkers that reflect whole‐body metabolism and how they may be attractive therapeutic targets for treating muscle and metabolic diseases.     

右美托咪定对七氟醚吸入麻醉诱导行颅脑手术围术期脑保护作用的影响：随机对照试验

文题释义：右美托咪定：是高选择性α2-肾上腺素受体激动剂,通过作用于中枢神经系统和外周神经系统的α2受体产生相应的药理作用。右美托咪定还有抗焦虑、降低应激反应、稳定血流动力学、镇痛、抑制唾液腺分泌、抗寒战和利尿等作用。此外,右美托咪定与其他镇静镇痛药物联合使用时具有良好的协同效应,能显著减少其他镇静镇痛药物的使用量。七氟醚：诱导迅速,刺激性小,血流动力学稳定,是临床广泛应用的吸入麻醉药之一。背景：颅脑手术中常使用的吸入麻醉剂是七氟醚,其具有起效速度快、循环稳定性好,且安全性高、不良反应少等优势,但是其还存在血压和心率异常以及躁动、疼痛等不良反应,因而需要一种辅助麻醉剂帮助改善不良反应。右美托咪定作为一种高效高选择性α2-肾上腺素受体激动剂,具有抗焦虑、催眠、镇痛、镇静及解交感作用,既往研究显示其可减轻七氟醚麻醉诱导后患者的躁动程度,减少围术期患者血流动力学波动,但尚缺乏在颅脑手术中进行验证。 目的：观察右美托咪定对七氟醚吸入麻醉诱导行颅脑手术患者的效果。方法：此次前瞻性、单中心、随机对照试验将在中国十堰市太和医院进行,拟纳入1 308例患者,以随机数字表法分为观察组和对照组,各654例。2组均以七氟醚行麻醉诱导下进行颅脑手术。观察组麻醉诱导前15 min予负荷剂量右美托咪定1 μg/kg静脉泵注10 min,继之以0.3 μg/(kg•h)持续泵注,手术前0.5 h停药;对照组以相同方式、同等速率输注同等剂量0.9%氯化钠注射液。试验于2015-12-08经十堰市太和医院伦理审查委员会批准(批准号2015GJJ-087)。参与者对试验方案和过程均知情同意,并签署知情同意书。试验已于2020-03-02在中国临床试验注册中心进行注册(注册号：ChiCTR2000030459),注册方案版本号1.0。结果与结论：①试验的主要观察指标为患者苏醒时间;②试验的次要观察指标为麻醉与恢复情况以及给予负荷剂量右美托咪定前、给予负荷剂量右美托咪定后、麻醉诱导期、开颅时、颅内操作期、关颅时、苏醒时的生命体征、应激指标、脑氧代谢指标以及不良事件;③2016年3月至2017年2月进行了190例的小样本前期试验,患者随机分为对照组和观察组,各95例,分别接受七氟醚麻醉诱导以及右美托咪定辅助麻醉+七氟醚麻醉诱导,结果显示2组麻醉时间、术中出血量、术中输液量、苏醒时间、拔管时间接近(P > 0.05),但与对照组相比,观察组血管活性药物麻黄碱以及艾司洛尔的用量较低(P < 0.05),给予负荷剂量右美托咪定后、麻醉诱导期、开颅时、颅内操作期、关颅时以及苏醒时心率与脑电双频指数较高(P < 0.05),开颅时、颅内操作期、关颅时与苏醒时平均动脉压较高(P < 0.05),给予负荷剂量右美托咪定后、麻醉诱导期、开颅时、颅内操作期、关颅时以及苏醒时血糖水平较高(P < 0.05),给予负荷剂量右美托咪定后、麻醉诱导期与开颅时皮质醇浓度较低(P < 0.05),颅内操作期、关颅时以及苏醒时静脉球部血氧饱和度、动脉-静脉球部血氧含量差以及脑氧摄取率较高(P < 0.05)。试验旨在验证右美托咪定可减少七氟醚吸入麻醉诱导颅脑患者血流动力学波动,降低应激指标,以及肯定的脑保护作用,这将为右美托咪定联合七氟醚吸入麻醉诱导应用于颅脑手术提供有力支持。ORCID: 0000-0002-2524-9449(刘勇攀) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Bilirubin as a signaling molecule

For long time bilirubin was only considered as a potentially dangerous sign of liver diseases, but it now appears clear that it is also a powerful signaling molecule. Together with potent antioxidant activities that were only reported in the last few decades, many other biological effects have now been clearly described. These include especially profound inhibitory effects on almost all effectors of the immune system, with their clinical consequences in the bilirubin-mediated protection against autoimmune and inflammatory diseases. Separate from these, bilirubin activates various nuclear and cytoplasmic receptors, resembling the endocrine activities of actual hormonal substances. This is true for the “classical” hepatic nuclear receptors, including the aryl hydrocarbon receptor, or the constitutive androstane receptor; and also for some lesser-explored receptors such as peroxisome proliferator-activated receptors α and γ; Mas-related G protein-coupled receptor; or other signaling molecules including fatty acid binding protein 1, apolipoprotein D, or reactive oxygen species. All of these targets have broad metabolic effects, which in turn may offer protection against obesity, diabetes mellitus, and other metabolic diseases. The (mostly experimental) data are also supported by clinical evidence. In fact, data from the last three decades have convincingly demonstrated the protective effects of mildly elevated serum bilirubin concentrations against various “diseases of civilization.” Additionally, even tiny, micromolar changes of serum bilirubin concentrations have been associated with substantial alteration in the risks of these diseases. It is highly likely that all of the biological activities of bilirubin have yet to be exhaustively explored, and thus we can expect further clinical discoveries about this evolutionarily old molecule into the future.     

Metabolic abnormalities and hypoleptinemia in α-synuclein A53T mutant mice

Parkinson's disease (PD) patients frequently display loss of body fat mass and increased energy expenditure, and several studies have outlined a relationship between these metabolic abnormalities and disease severity, yet energy metabolism is largely unstudied in mouse models of PD. Here we characterize metabolic and physiologic responses to a high calorie diet (HCD) in mice expressing in neurons a mutant form of human α-synuclein (A53T) that causes dominantly inherited familial forms of the disease. A53T (SNCA) and wild type (WT) littermate mice were placed on a HCD for 12 weeks and evaluated for weight gain, food intake, body fat, blood plasma leptin, hunger, glucose tolerance, and energy expenditure. Results were compared with both SNCA and WT mice on a control diet. Despite consuming similar amounts of food, WT mice gained up to 66% of their original body weight on a HCD, whereas SNCA mice gained only 17%. Further, after 12 weeks on a HCD, magnetic resonance imaging analysis revealed that WT mice had significantly greater total and visceral body fat compared with SNCA mice (p < 0.007). At the age of 24 weeks SNCA mice displayed significantly increased hunger compared with WT (p < 0.03). At the age of 36 weeks, SNCA mice displayed significant hypoleptinemia compared with WT, both on a normal diet and a HCD (p < 0.03). The HCD induced insulin insensitivity in WT, but not SNCA mice, as indicated by an oral glucose tolerance test. Finally, SNCA mice displayed greater energy expenditure compared with WT, as measured in a Comprehensive Laboratory Animal Monitoring System, after 12 weeks on a HCD. Thus, SNCA mice are resistant to HCD-induced obesity and insulin resistance and display reduced body fat, increased hunger, hypoleptinemia and increased energy expenditure. Our findings reveal a profile of metabolic dysfunction in a mouse model of PD that is similar to that of human PD patients, thus providing evidence that α-synuclein pathology is sufficient to drive such metabolic abnormalities and providing an animal model for discovery of the underlying mechanisms and potential therapeutic interventions.     

药物性牙龈增生与胶原代谢失衡的相关性研究进展

药物性牙龈增生(drug-induced gingival overgrowth,DIGO)是指长期服用某些特定药物而引起的牙龈纤维性增生和体积增大,其发病机制尚不清楚。目前研究表明,胶原的合成和降解失衡与药物性牙龈增生有密切关系。本文就药物性牙龈增生与胶原代谢失衡的相关研究进展作一综述。     

Impact of Mild versus Moderate Intensity Aerobic Walking Exercise Training on Markers of Bone Metabolism and Hand Grip Strength in Moderate Hemophilic A Patients

Background

Patients with hemophilia A have low bone density than healthy controls. It is now widely recognized that physical activity and sports are beneficial for patients with hemophilia.

Objective

To compare the effects of mild and moderate intensity treadmill walking exercises on markers of bone metabolism and hand grip strength in male patients with moderate hemophilia A.

Material and Methods

Fifty male patients with moderate hemophilia, and age range from 25 to 45 years. The subjects were randomly assigned into 2 equal groups; the first group (A) received moderate intensity aerobic exercise training. The second group (B) received mild intensity aerobic exercise training.

Results

There was a 32.1% and 24.8% increase in mean values of serum calcium and hand grip strength respectively and 22.7 % reduction in mean values of parathyroid hormone in moderate exercise training group (A). While there was a 15.1 % and 15 % increase in mean values of Serum Calcium and Hand grip strength respectively and 10.3 % reduction in mean values of parathyroid hormone in mild exercise training group(B). The mean values of serum calcium and hand grip strength were significantly increased, while the mean values of parathyroid hormone were significantly decreased in both groups . There were significant differences between mean levels of the investigated parameters in group (A) and group (B) after treatment.

Conclusion

Moderate intensity aerobic exercise training on treadmill is appropriate to improve markers of bone metabolism and hand grip strength in male patients with hemophilia A.     

Expression of sarcosine metabolism-related proteins according to metastatic site in breast cancer

We aimed to evaluate the expression of sarcosine metabolism-related proteins according to site of metastatic breast cancer, and the clinical implications. Immunohistochemical staining for glycine N-methyltransferase (GNMT), sarcosine dehydrogenase (SARDH), and l-pipecolic acid oxidase (PIPOX) was performed on tissue microarrays from 162 metastatic breast cancer (bone metastases = 47, brain metastases = 39, liver metastases = 24, and lung metastases = 52). Sarcosine metabolism-related proteins showed variable expression with regard to metastatic sites. GNMT was expressed in brain and lung metastases, but not in bone and liver metastases (P = 0.016). In view of the sarcosine metabolic phenotype, high sarcosine and intermediate type were only found in the brain and lung metastases, and low sarcosine type was observed more frequently in bone and lung metastases (P = 0.047). By univariate analysis, PIPOX positivity was correlated with shorter overall survival (OS) (P = 0.031). In lung metastases, PIPOX positivity (P = 0.019) and stromal PIPOX positivity (P = 0.001) were associated with shorter OS. In conclusion, in metastatic breast cancer, sarcosine metabolism-related proteins are differently expressed according to the metastatic site. Expression of GNMT and high sarcosine type are predominantly observed in brain and lung metastases.