综合护理干预对老年住院糖尿病患者影响的临床观察

目的:观察综合护理干预对老年住院糖尿病患者的临床影响,探讨改善老年住院糖尿病患者临床表现及预后的护理方式。方法:选择老年住院糖尿病患者160例,随机均分为对照组和观察组,对照组采取常规专科护理,观察组加行综合护理干预,治疗2周后比较两组患者焦虑自评量表(SAS)和抑郁自评量表(SDS)评分;出院3个月后比较两组患者自我管理和生活质量(GQOL-100)评分结果:治疗2周和出院3个月后,两组患者在上述方面比较,差异具有统计学意义(P<0.01,P<0.05),观察组优于对照组。结论:对老年住院DM患者施行综合护理干预措施,具有积极的临床意义。     

视黄醇结合蛋白4与2型糖尿病微血管病变的研究进展

视黄醇结合蛋白4(Retinolbindingprotein4,RBP4)是一种分泌型视黄醇结合蛋白,主要由肝脏合成,在协助视黄醇发挥生理功能中起着重要的作用。近年研究发现,RBP4是一种新的循环性脂肪因子,亦能由脂肪组织特异性分泌,它不仅能够抑制肌肉组织中的胰岛素信号通路,而且能够促进糖异生,增加肝糖输出,从而导致胰岛素抵抗的发生,增加糖尿病的发病风险。目前RBP4与2型糖尿病(Type2diabetes mellitus,T2DM)关系逐渐受到人们的重视,本文就RBP4的生理功能、RBP4与T2DM微血管病变的研究进展作一综述。     

Endothelial cell senescence in aging-related vascular dysfunction

Increased cardiovascular disease in aging is partly a consequence of the vascular endothelial cell (EC) senescence and associated vascular dysfunction. In this contest, EC senescence is a pathophysiological process of structural and functional changes including dysregulation of vascular tone, increased endothelium permeability, arterial stiffness, impairment of angiogenesis and vascular repair, and a reduction of EC mitochondrial biogenesis. Dysregulation of cell cycle, oxidative stress, altered calcium signaling, hyperuricemia, and vascular inflammation have been implicated in the development and progression of EC senescence and vascular disease in aging. A number of abnormal molecular pathways are associated with these underlying pathophysiological changes including Sirtuin 1, Klotho, fibroblast growth factor 21, and activation of the renin angiotensin-aldosterone system. However, the molecular mechanisms of EC senescence and associated vascular impairment in aging are not completely understood. This review provides a contemporary update on molecular mechanisms, pathophysiological events, as well functional changes in EC senescence and age-associated cardiovascular disease. This article is part of a Special Issue entitled: Genetic and epigenetic regulation of aging and longevity edited by Jun Ren & Megan Yingmei Zhang.     

Vascular smooth muscle cell senescence and age-related diseases: State of the art

Aging is a worldwide challenge, and it is accompanied by the accumulation of senescent cells. Cellular senescence is traditionally defined as permanent cell growth arrest and currently includes the senescence-associated secretory phenotype (SASP). There are two main types of cellular senescence, including telomere-dependent replicative senescence and stress-induced premature senescence. The process of cellular senescence is mainly controlled by two effector pathways, namely, the p53-p21 and p16-retinoblastoma protein (pRB) pathways. Vascular smooth muscle cells (VSMCs) are integral parts of arteries and play an important role in vascular structure and function. VSMC senescence may be triggered by many factors, such as angiotensin II, oxidative stress, inflammation, DNA damage, and small molecule compounds. These inducers are able to genetically and epigenetically regulate VSMC senescence. The senescence of VSMCs together with the SASP contributes to chronic vascular inflammation, the loss of arterial function, and the development of age-related diseases. Current evidence suggests that the senescence of VSMCs might be harmful to individual health, whereas its influence on the lifespan is not clear. The purpose of this paper was to review the current knowledge regarding VSMC senescence and its relevance to hypertension, atherosclerosis, and diabetes, as well as the potential mechanisms responsible for VSMC senescence in these age-related diseases.     

Sphk2−/− mice are protected from obesity and insulin resistance

Sphingosine kinases phosphorylate sphingosine to sphingosine 1?phosphate (S1P), which functions as a signaling molecule. We have previously shown that sphingosine kinase 2 (Sphk2) is important for insulin secretion. To obtain a better understanding of the role of Sphk2 in glucose and lipid metabolism, we have characterized 20- and 52-week old Sphk2^?/? mice using glucose and insulin tolerance tests and by analyzing metabolic gene expression in adipose tissue. A detailed metabolic characterization of these mice revealed that aging Sphk2^?/? mice are protected from metabolic decline and obesity compared to WT mice. Specifically, we found that 52-week old male Sphk2^?/? mice had decreased weight and fat mass, and increased glucose tolerance and insulin sensitivity compared to control mice. Indirect calorimetry studies demonstrated an increased energy expenditure and food intake in 52-week old male Sphk2^?/? versus control mice. Furthermore, expression of adiponectin gene in adipose tissue was increased and the plasma levels of adiponectin elevated in aged Sphk2^?/? mice compared to WT. Analysis of lipid metabolic gene expression in adipose tissue showed increased expression of the Atgl gene, which was associated with increased Atgl protein levels. Atgl encodes for the adipocyte triglyceride lipase, which catalyzes the rate-limiting step of lipolysis. In summary, these data suggest that mice lacking the Sphk2 gene are protected from obesity and insulin resistance during aging. The beneficial metabolic effects observed in aged Sphk2^?/? mice may be in part due to enhanced lipolysis by Atgl and increased levels of adiponectin, which has lipid- and glucose-lowering effects.     

孕晚期孕妇肠道菌群与孕期体重增长的相关性

【背景】孕妇体重过度增长在全球范围内呈现上升趋势,对母亲和子代健康均会造成不良影响。肠道菌群与人体众多疾病相关,其有可能作为重要的调节因素影响母婴健康。【目的】研究孕晚期孕妇肠道菌群的多样性和群落组成,探讨孕期体重增长对肠道菌群的影响。【方法】收集62位孕晚期(36.82±2.19孕周)孕妇粪便样本,利用MiSeq高通量测序技术对样品中16SrRNA基因V3-V4区序列进行测序,分析不同孕期体重增长水平的孕妇肠道菌群的多样性、群落结构和物种丰度,探讨孕期体重增长对孕妇肠道菌群的影响。【结果】与正常孕妇相比,孕期体重增长过度孕妇肠道菌群多样性显著降低,群落结构变化不大;在菌群组成上,筛选出5个与孕期体重增长最为相关的菌群,分别为Alistipes spp.、Eubacterium-nodatum group spp.、Oxalobacter spp.、Raoultella spp.和Odoribacter spp.,其中Alistipesspp.不仅是相关程度最高也是丰度最高的菌群,与孕期体重增长密切相关。【结论】孕期体重增长对孕晚期孕妇肠道菌群群落结构影响显著,在孕期保持肠道菌群稳态能够促进母婴健康。     

Bis-coumarins; non-cytotoxic selective urease inhibitors and antiglycation agents

The current study is concerned with the identification of lead molecules based on the bis-coumarin scaffold having selective urease inhibitory and antiglycation activities. For that purpose, bis-coumarins (1-44) were synthesized and structurally characterized by different spectroscopic techniques. Eight derivatives 4, 8-10, 14, 17, 34, and 40 demonstrated urease inhibition in the range of IC₅₀ = 4.4 ± 0.21–115.6 ± 2.13 μM, as compared to standard thiourea (IC₅₀ = 21.3 ± 1.3 μM). Especially, compound 17 (IC₅₀ = 4.4 ± 0.21 μM) was found to be five-fold more potent than the standard. Kinetic studies were also performed on compound 17 in order to identify the mechanism of inhibition. Kinetic studies revealed that compound 17 is a competitive inhibitor. Antiglycation activity was evaluated using glycation of bovine serum albumin by methylglyoxal in vitro. Compounds 2, 11-13, 16, 17, 19–22, 35, 37, and 42 showed good to moderate antiglycation activities with IC₅₀ values of 333.63–919.72 μM, as compared to the standard rutin (IC₅₀ = 294.46 ± 1.5 μM). Results of both assays showed that the compounds with urease inhibitory activity did not show any antiglycation potential, and vice versa. Only compound 17 showed dual inhibition potential. All compounds were also evaluated for cytotoxicity. Compounds 17, 19, and 37 showed a weak toxicity towards 3 T3 mouse fibroblast cell line. All other compounds were found to be non-cytotoxic. Urease inhibition is an approach to treat infections caused by ureolytic bacteria whereas inhibition of glycation of proteins is a strategy to avoid late diabetic complications. Therefore, these compounds may serve as leads for further research.     

Discovery of HWL-088: A highly potent FFA1/GPR40 agonist bearing a phenoxyacetic acid scaffold

Based on a previously reported phenoxyacetic acid scaffold, compound 7 (HWL-088) has been identified as a superior free fatty acid receptor 1 (FFA1) agonist by comprehensive structure-activity relationship study. Our results indicated that the introduction of ortho-fluoro greatly increased the activity of phenoxyacetic acid series, and the unique structure-activity relationship in biphenyl moiety is different from previously reported FFA1 agonists. Moreover, the modeling study was also performed to better understand the binding mode of present series. Compound 7 significantly improved glucose tolerance both in normal and diabetic models, and even exerted greater potential on glucose control than that of TAK-875. These findings provided a novel candidate HWL-088, which is currently in preclinical study to evaluate its potential for the treatment of diabetes.     

Role of the PI3K/AKT (mTOR and GSK3β) signalling pathway and photobiomodulation in diabetic wound healing

Activated phosphatidylinositol 3 kinase/Protein kinase B (PI3K/AKT) signalling with increased or reduced mTOR and GSK3β activity influences the wound repair process. Diabetic wounds, usually ulcerated, are characterised by reduced growth factors and cellular performance. The occurrence of diabetic ulcers is linked to peripheral arterial disease, neuropathy, and wound contamination. Lasers or light emitting diodes (LEDs) provide photon energy with therapeutic benefits (Photobiomodulation-PBM), and has been broadly commended to quicken diabetic wound healing. PBM is efficient in the visible red and near-infrared electromagnetic spectrum, and fluencies ranging from 2 to 6 J/cm². However, cellular and molecular mechanisms induced by PBM are not fully understood. In this review we discuss PBM and the PI3K/AKT pathway with specific focus on the mTOR and GSK3β downstream activity in diabetic wound healing.     

Interfering PLD1-PED/PEA15 interaction using self-inhibitory peptides: An in silico study to discover novel therapeutic candidates against type 2 diabetes

Diabetes type 2 (T2D) is a very complex disorder with a large number of cases reported worldwide. There are several reported molecular targets which are being used towards drug design. In spite of extensive research efforts, there is no sure shot treatment available. One of the major reasons for this failure or restricted success in T2D research is the identification of a major/breakthrough therapeutic target responsible for the progression of T2D. It has been well documented that one of the major causes mediating the insulin resistance is the interaction of PLD1 with PED/PEA15. Herein, we have performed in silico experiments to investigate the interaction between PLD1 with PED/PEA15. Furthermore, this study has explored pertinent molecular interactions involving the self-derived peptides. The peptides identified in this study are found to be capable of restricting the interaction of these two proteins. Accordingly, the study suggests that the “self-derived peptides” could be used as promising therapeutic candidate(s) against T2D.