Effectiveness of Magnolol,a Lignan from Magnolia Bark,in Diabetes,Its Complications and Comorbidities—A Review

Diabetes mellitus is a chronic metabolic disease characterized by disturbances in carbohydrate, protein, and lipid metabolism, often accompanied by oxidative stress. Diabetes treatment is a complicated process in which, in addition to the standard pharmacological action, it is necessary to append a comprehensive approach. Introducing the aspect of non-pharmacological treatment of diabetes allows one to alleviate its many adverse complications. Therefore, it seems important to look for substances that, when included in the daily diet, can improve diabetic parameters. Magnolol, a polyphenolic compound found in magnolia bark, is known for its health-promoting activities and multidirectional beneficial effects on the body. Accordingly, the goal of this review is to systematize the available scientific literature on its beneficial effects on type 2 diabetes and its complications. Taking the above into consideration, the article collects data on the favorable effects of magnolol on parameters related to glycemia, lipid metabolism, or oxidative stress in the course of diabetes. After careful analysis of many scientific articles, it can be concluded that this lignan is a promising agent supporting the conventional therapies with antidiabetic drugs in order to manage diabetes and diabetes-related diseases.     

Nonalcoholic Fatty Liver: A Possible New Target for Type 2 Diabetes Prevention and Treatment

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide. Several lines of evidence have indicated a pathogenic role of insulin resistance, and a strong association with type 2 diabetes (T2MD) and metabolic syndrome. Importantly, NAFLD appears to enhance the risk for T2MD, as well as worsen glycemic control and cardiovascular disease in diabetic patients. In turn, T2MD may promote NAFLD progression. The opportunity to take into account NAFLD in T2MD prevention and care has stimulated several clinical studies in which antidiabetic drugs, such as metformin, thiazolidinediones, GLP-1 analogues and DPP-4 inhibitors have been evaluated in NAFLD patients. In this review, we provide an overview of preclinical and clinical evidences on the possible efficacy of antidiabetic drugs in NAFLD treatment. Overall, available data suggest that metformin has beneficial effects on body weight reduction and metabolic parameters, with uncertain effects on liver histology, while pioglitazone may improve liver histology. Few data, mostly preclinical, are available on DPP4 inhibitors and GLP-1 analogues. The heterogeneity of these studies and the small number of patients do not allow for firm conclusions about treatment guidelines, and further randomized, controlled studies are needed.     

Bioactive Peptides as Potential Nutraceuticals for Diabetes Therapy: A Comprehensive Review

Diabetes mellitus is a major public health concern associated with high mortality and reduced life expectancy. The alarming rise in the prevalence of diabetes is linked to several factors including sedentary lifestyle and unhealthy diet. Nutritional intervention and increased physical activity could significantly contribute to bringing this under control. Food-derived bioactive peptides and protein hydrolysates have been associated with a number health benefits. Several peptides with antidiabetic potential have been identified that could decrease blood glucose level, improve insulin uptake and inhibit key enzymes involved in the development and progression of diabetes. Dietary proteins, from a wide range of food, are rich sources of antidiabetic peptides. Thus, there are a number of benefits in studying peptides obtained from food sources to develop nutraceuticals. A deeper understanding of the underlying molecular mechanisms of these peptides will assist in the development of new peptide-based therapeutics. Despite this, a comprehensive analysis of the antidiabetic properties of bioactive peptides derived from various food sources is still lacking. Here, we review the recent literature on food-derived bioactive peptides possessing antidiabetic activity. The focus is on the effectiveness of these peptides as evidenced by in vitro and in vivo studies. Finally, we discuss future prospects of peptide-based drugs for the treatment of diabetes.     

Effects of Sodium-Glucose Co-Transporter 2 Inhibitors on Vascular Cell Function and Arterial Remodeling

Cardiovascular disease is the leading cause of morbidity and mortality in diabetes. Recent clinical studies indicate that sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in patients with diabetes. The mechanism underlying the beneficial effect of SGLT2 inhibitors is not completely clear but may involve direct actions on vascular cells. SGLT2 inhibitors increase the bioavailability of endothelium-derived nitric oxide and thereby restore endothelium-dependent vasodilation in diabetes. In addition, SGLT2 inhibitors favorably regulate the proliferation, migration, differentiation, survival, and senescence of endothelial cells (ECs). Moreover, they exert potent antioxidant and anti-inflammatory effects in ECs. SGLT2 inhibitors also inhibit the contraction of vascular smooth muscle cells and block the proliferation and migration of these cells. Furthermore, studies demonstrate that SGLT2 inhibitors prevent postangioplasty restenosis, maladaptive remodeling of the vasculature in pulmonary arterial hypertension, the formation of abdominal aortic aneurysms, and the acceleration of arterial stiffness in diabetes. However, the role of SGLT2 in mediating the vascular actions of these drugs remains to be established as important off-target effects of SGLT2 inhibitors have been identified. Future studies distinguishing drug- versus class-specific effects may optimize the selection of specific SGLT2 inhibitors in patients with distinct cardiovascular pathologies.     

Activation of Insulin Signaling by Botanical Products

Type 2 diabetes (T2D) is a worldwide health problem, ranked as one of the leading causes for severe morbidity and premature mortality in modern society. Management of blood glucose is of major importance in order to limit the severe outcomes of the disease. However, despite the impressive success in the development of new antidiabetic drugs, almost no progress has been achieved with regard to the development of novel insulin-sensitizing agents. As insulin resistance is the most eminent factor in the patho-etiology of T2D, it is not surprising that an alarming number of patients still fail to meet glycemic goals. Owing to its wealth of chemical structures, the plant kingdom is considered as an inventory of compounds exerting various bioactivities, which might be used as a basis for the development of novel medications for various pathologies. Antidiabetic activity is found in over 400 plant species, and is attributable to varying mechanisms of action. Nevertheless, relatively limited evidence exists regarding phytochemicals directly activating insulin signaling, which is the focus of this review. Here, we will list plants and phytochemicals that have been found to improve insulin sensitivity by activation of the insulin signaling cascade, and will describe the active constituents and their mechanism of action.     

The PPARβ/δ-AMPK Connection in the Treatment of Insulin Resistance

The current treatment options for type 2 diabetes mellitus do not adequately control the disease in many patients. Consequently, there is a need for new drugs to prevent and treat type 2 diabetes mellitus. Among the new potential pharmacological strategies, activators of peroxisome proliferator-activated receptor (PPAR)β/δ show promise. Remarkably, most of the antidiabetic effects of PPARβ/δ agonists involve AMP-activated protein kinase (AMPK) activation. This review summarizes the recent mechanistic insights into the antidiabetic effects of the PPARβ/δ-AMPK pathway, including the upregulation of glucose uptake, muscle remodeling, enhanced fatty acid oxidation, and autophagy, as well as the inhibition of endoplasmic reticulum stress and inflammation. A better understanding of the mechanisms underlying the effects resulting from the PPARβ/δ-AMPK pathway may provide the basis for the development of new therapies in the prevention and treatment of insulin resistance and type 2 diabetes mellitus.     

Xanthones from Swertia mussotii as Multitarget‐Directed Antidiabetic Agents

Oxidative stress has been suggested to play a causative role in the development of obesity‐induced insulin resistance and type 2 diabetes. Given the antioxidant potency of previously reported xanthones isolated from Swertia mussotii. These natural products were further evaluated against other targets in diabetes, aldose reductase and α‐glucosidase, in order to identify novel multitarget‐directed antidiabetic agents. Among the 14 xanthones screened, 1,3,7,8‐tetrahydroxyxanthone ( 6 ), 1,3,5,8‐tetrahydroxyxanthone ( 7 ), and 2,3,6,8‐tetrahydroxyxanthone‐7C‐(β‐D ‐glucoside) ( 12 ) were confirmed as good antioxidants and α‐glucosidase inhibitors. Xanthone 7 was also confirmed as a potent inhibitor of aldose reductase (ALR2). Xanthone 7 was the most active α‐glucosidase and ALR2 inhibitor, with IC₅₀ values of 5.2±0.3 μM and 88.6±1.6 nM , respectively, while compound 12 was shown to be the most active antioxidant. Given the overall profile, xanthone 7 is considered to be the most promising multitarget antidiabetic agent, and may have potential for the treatment of both diabetes and diabetic complications.     

几种塑料在吐鲁番与广州的户外老化试验

几种塑料试件在我国新疆吐鲁番和广州地区户外老化试验结果,说明塑料在严酷干热气候条件下受户外日光照射后会加速老化;自然环境试验能真实反映塑料制品、制件以及它们的改性材料或产品的光氧老化特征与规律。     

Do the Effects of Secondary Prevention of Cardiovascular Events in PAD Patients Differ from Other Atherosclerotic Disease?

Atherosclerosis is considered a generalized disease. Similar or identical etiopathogenetic mechanisms and risk factors are involved in various atherosclerotic diseases, and the positive effects of preventive measures on atherogenesis in different parts of the arterial system were shown. However, until know, great emphasis has been placed on the aggressive pharmacological management of coronary artery disease (CHD), while less attention has been devoted to the management of peripheral arterial disease (PAD), despite its significant morbidity and mortality. Data on the efficacy of preventive measures in PAD patients have mostly been gained from subgroup analyses from studies devoted primarily to the management of coronary patients. These data have shown that treatment of risk factors for atherosclerosis with drugs can reduce cardiovascular events also in patients with PAD. The effects of some preventive procedures in PAD patients differ from coronary patients. Aspirin as a basic antiplatelet drug has been shown to be less effective in PAD patients than in coronary patients. The latest Antithrombotic Trialists’ Collaboration (ATC) meta-analysis demonstrates no benefit of aspirin in reducing cardiovascular events in PAD. Statins reduce cardiovascular events in all three of the most frequently presented cardiovascular diseases, including PAD to a comparable extent. Recent studies indicate that in PAD patients, in addition to a reduction in cardiovascular events, statins may have some hemodynamic effects. They prolong walking distance and improve quality of life. Similarly, angiotensin enzyme inhibitors are also effective in the prevention of cardiovascular events in coronary, cerebrovascular, as well as PAD patients and show positive effects on the walking capacity of patients with intermittent claudication. In PAD patients, the treatment of hypertension and diabetes also effectively prevents cardiovascular morbidity and mortality. As PAD patients are at a highest risk of cardiovascular complications, the risk factors of atherosclerosis should be treated intensively in this group of patients. Most of the preventive measures, including the drugs used for prevention of CHD, are also effective in PAD patients.     

Plasma Lipoprotein-Associated Phospholipase A2 Levels Correlated with the Cardio-Ankle Vascular Index in Long-Term Type 2 Diabetes Mellitus Patients

The circulating levels of lipoprotein-associated phospholipase A₂ (Lp-PLA₂) can be a simple, but practical and useful marker of cardiovascular disease (CVD). As limited studies are available in patients with diabetes mellitus (DM), further studies are needed to establish the clinical application of Lp-PLA₂ in DM practice. The present study investigated the correlation between Lp-PLA₂ and the cardio-ankle vascular index (CAVI), a recent marker of arterial stiffness, in DM patients according to their diabetes duration. Clinical data, including the plasma Lp-PLA₂ mass and CAVI values, were collected from CVD-free type 2 DM female patients (n = 65, mean age 62 years, mean hemoglobin A1c 7.0%). The Lp-PLA₂ level of patients with a diabetes duration of <10 years (n = 40:20.2 IU/mL) was not significantly different from that of patients with a diabetes duration of ≥10 years (n = 25:20.5 IU/mL), while the CAVI level was significantly higher in patients with ≥10 years (9.0) than in those with <10 years (8.1; p < 0.05). A stepwise multiple regression analysis found a positive correlation between the Lp-PLA₂ and CAVI levels (β = 0.43, p < 0.01) in patients with a diabetes duration of ≥10 years. This correlation between Lp-PLA₂ and CVAI suggests the possible use of Lp-PLA₂ in DM patients with long-term disease. Further studies on Lp-PLA₂ are warranted in DM practice in relation to the disease duration.     

支气管动脉灌注化疗药治疗原发性肺癌85例疗效分析

目的探讨支气管动脉灌注化疗药物治疗原发性肺癌的疗效。方法对85例原发性肺癌病人采用改良式Seldinger穿刺技术,行选择性和(或)超选择性支气管动脉插管。首先注入其它化疗药物,后注入超液态碘化油5～20mL和吡柔比星10mg的混悬液,支气管动脉主干保持通畅。结果鳞癌的近期疗效明显优于其他病理类型;中心型肺癌的近期疗效优于周围型肺癌;多次灌注行BAI治疗的近期疗效优于单次灌注者;临床分期的近期疗效与治疗效果无关。结论支气管动脉灌注化疗是治疗原发性肺癌的有效方法之一。肺癌的病理类型、生长部位和血供类型等是影响疗效的主要因素。     

Incretin-Based Therapies for Diabetic Complications: Basic Mechanisms and Clinical Evidence

An increase in the rates of morbidity and mortality associated with diabetic complications is a global concern. Glycemic control is important to prevent the development and progression of diabetic complications. Various classes of anti-diabetic agents are currently available, and their pleiotropic effects on diabetic complications have been investigated. Incretin-based therapies such as dipeptidyl peptidase (DPP)-4 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA) are now widely used in the treatment of patients with type 2 diabetes. A series of experimental studies showed that incretin-based therapies have beneficial effects on diabetic complications, independent of their glucose-lowering abilities, which are mediated by anti-inflammatory and anti-oxidative stress properties. Based on these findings, clinical studies to assess the effects of DPP-4 inhibitors and GLP-1RA on diabetic microvascular and macrovascular complications have been performed. Several but not all studies have provided evidence to support the beneficial effects of incretin-based therapies on diabetic complications in patients with type 2 diabetes. We herein discuss the experimental and clinical evidence of incretin-based therapy for diabetic complications.     

Effect of Superfine Grinding on Antidiabetic Activity of Bitter Melon Powder

The antidiabetic activities of bitter melon powders produced with lyophilization/superfine grinding and hot air drying/normal grinding were investigated in vivo for selecting a suitable bitter melon processing procedure. After a five-week treatment, bitter melon lyophilized superfine grinding powder (BLSP) had a higher antidiabetic activity with reducing fasting blood glucose levels from 21.40 to 12.54 mmol/L, the serum insulin levels from 40.93 to 30.74 mIU/L, and restoring activities of SOD compared with those in the bitter melon hot air drying powder (BAP) treated group. Furthermore, BLSP protected pancreatic tissues including islet beta cells and reduced the loss of islet cells. Combined with the difference of compositions in BLSP and BAP, it could be concluded that superfine grinding and lyophilization processes were beneficial for presenting the antidiabetic activity, which will provide a reference for direct utilization of bitter melon as a suitable functional food to relieve symptoms of diabetes.     

Oxidative Stress and Epigenetic Regulation in Ageing and Age-Related Diseases

Recent statistics indicate that the human population is ageing rapidly. Healthy, but also diseased, elderly people are increasing. This trend is particularly evident in Western countries, where healthier living conditions and better cures are available. To understand the process leading to age-associated alterations is, therefore, of the highest relevance for the development of new treatments for age-associated diseases, such as cancer, diabetes, Alzheimer and cardiovascular accidents. Mechanistically, it is well accepted that the accumulation of intracellular damage determined by reactive oxygen species (ROS) might orchestrate the progressive loss of control over biological homeostasis and the functional impairment typical of aged tissues. Here, we review how epigenetics takes part in the control of stress stimuli and the mechanisms of ageing physiology and physiopathology. Alteration of epigenetic enzyme activity, histone modifications and DNA-methylation is, in fact, typically associated with the ageing process. Specifically, ageing presents peculiar epigenetic markers that, taken altogether, form the still ill-defined “ageing epigenome”. The comprehension of mechanisms and pathways leading to epigenetic modifications associated with ageing may help the development of anti-ageing therapies.     

新型光致发光塑料及装饰应用技术研究

介绍光致发光塑料的配方和注塑成型条件，研究了产品加速老化和自然老化性能。结果表明助剂的品种和用量对亮度的影响显著，经加速老化5000h和自然老化12－22月后，各项技术指标同进口产品比较，结果基本接近，产品的寿命在广州地区为2－3a，在其他地区为3－5a，在室内可达6－10a。     

核用O型圈的加速老化试验与存储寿命预测与分析

针对核电站库存O型圈进行了基于热应力的加速老化试验与存储寿命预测。结合O型圈的特点,选取断裂伸长率作为关键指标,根据多温度条件下的断裂伸长率随时间的变化趋势,计算材料的活化能,进而预测O型圈的存储寿命。最后对三种O型圈进行了实例分析与对比,说明了方法的有效性。     

Liraglutide-Loaded Milk Exosomes Lower Blood Glucose When Given by Sublingual Route

Bovine milk is rich in extracellular vesicles (mEVs) which have been suggested as a possible drug delivery vehicle with oral bioavailability. As the digestive fluids contain many lipid- and protein-degrading enzymes, we explored whether mEVs given sublingually could be taken up systemically. mEVs were isolated using three different protocols, which were 120 nm in diameter and carried bovine CD81. Fluorescently stained mEVs given by sublingual route were detected in the circulation, whereas mEVs given by gavage were detected at 2-Log lower concentrations. As proof of the concept, we loaded mEVs with the antidiabetic drug Liraglutide (LRT-EV), which reduced blood glucose levels when given by the sublingual route but showed no efficacy via gavage. This study suggests that mEV may be an efficient delivery vehicle for drugs that are not orally bioavailable, and LRT-loaded EVs have the potential as the next-generation drug delivery platform for the treatment of chronic diseases, including diabetes.     

LDPE农用耐候棚膜专用料的配方研究及工业化生产

研究了LDPE农用聚乙烯耐候棚膜专用料的配方及老化问题,介绍了选用母粒掺混法制备专用料的工艺路线。经人工加速老化和扣棚自然老化试验证明,用该专用料吹制的棚膜,其使用寿命可达1.5～2年,比普通膜寿命长3～4倍。     

Der Einfluß von Emulgatoren auf das Verhalten von Fett im Eismix während des Reifens

Effect of Emulsifiers on the Behaviour of Fat in Ice Cream Mix During Ageing Ageing of ice cream mix takes up most of the time in the production of ice cream. This is due to the fat crystallisation which is important for the processing of the mix in the freezer. The influence of emulsifiers is investigated with regard to their degree of saturation and their hydrophilic-lipophilic balance using simple laboratory methods such as the determination of the free extractable fat and the emulsion stability. Saturated emulsifiers do not show any remarkable changes of the extractable fat and the emulsion stability during the ageing time. Saturated emulsifiers cause an increase of the extractable fat and a deterioration of the emulsion stability. These changes are especially obvious during the first three to six hours of ageing. The definite orientation of the protein-emulsifier membrane around the fat globules is only finished after twelve to twenty-four hours of ageing. This might explain the fact that in practice three hours of ageing are considered as absolutely necessary and that a longer ageing time causes a further improve of ice cream quality.