L-carnitine ameliorated fatty liver in high-calorie diet/STZ-induced type 2 diabetic mice by improving mitochondrial function

<p>Abstract</p> <p>Background</p> <p>There are an increasing number of patients suffering from fatty liver caused by type 2 diabetes. We intended to study the preventive and therapeutic effect of L-carnitine (LC) on nonalcoholic fatty liver disease (NAFLD) in streptozotocin (STZ)-induced type 2 diabetic mice and to explore its possible mechanism.</p> <p>Methods</p> <p>Thirty male Kungming mice were randomly divided into five groups: control group, diabetic group, pre-treatment group (125 mg/kg BW), low-dose (125 mg/kg BW) therapeutic group and high-dose (250 mg/kg BW) therapeutic group. The morphology of hepatocytes was observed by light and electron microscopy. LC and ALC (acetyl L-carnitine) concentrations in the liver were determined by high-performance liquid chromatography (HPLC). Moreover, liver weight, insulin levels and free fatty acid (FFA) and triglyceride (TG) levels in the liver and plasma were measured.</p> <p>Results</p> <p>Average liver LC and ALC levels were 33.7% and 20% lower, respectively, in diabetic mice compared to control mice (P < 0.05). After preventive and therapeutic treatment with LC, less hepatocyte steatosis, clearer crista and fewer glycogen granules in the mitochondria were observed. Decreased liver weight, TG levels, and FFA concentrations (P < 0.05) in the liver were also observed after treatment with LC in diabetic mice. Moreover, liver LC and ALC levels increased upon treatment with LC, whereas the ratio of LC and ALC decreased significantly (P < 0.01).</p> <p>Conclusion</p> <p>LC supplements ameliorated fatty liver in type 2 diabetic mice by increasing fatty acid oxidation and decreasing the LC/ALC ratio in the liver. Therefore, oral administration of LC protected mitochondrial function in liver.</p

Potential role of cyanidin 3-glucoside (C3G) in diabetic cardiomyopathy in diabetic rats: An in vivo approach

AbstractThe present study aimed to evaluate the importance of cyanidin 3-glucoside (C3G) of diabetic cardiomyopathy in diabetic rats. The rats were induced with diabetic using streptozotocin and total triglyceride (TG) and total cholesterol (TC) were determined. The range of myocardial enzymes such as aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LD) were also estimated, further, the Immuno histochemical analysis and western blot investigation were determined for the actual activity of C3G. Results indicated that the marker enzymes such as CK, LD and AST were significantly (P<0.05) increased in STZ administered rats (DM group), while the levels of these elevated marker enzymes of cardiac injury significantly (P<0.05) declined in the DM+C3G group, as compared to the diabetic group of rats. Additionally, a decrease in the level of TNF-alpha and interleukin-6, was noticed in the C3G treated group as compared to diabetic group. Finally, blotting analysis clearly confirmed that theC3G treatment resulted to higher level response of Bcl-2 and lower level response of caspase-3 and BAX. In conclusion, C3G a natural antioxidant may prevent cardiovascular complications by ameliorating oxidative damage, inflammation, metabolic dysfunctions and apoptosis pathways in type 2 diabetes

Neuropeptide Y-Positive Neurons in the Dorsomedial Hypothalamus Are Involved in the Anorexic Effect of Angptl8

Angiopoietin-like protein 8 (Angptl8), a recently identified member of the angiopoietin-like protein family (ANGPTLs), is a 22-kDa peptide synthesized in the liver. It participates in lipid metabolism by inhibiting lipoprotein lipase (LPL) activity, consequently increasing the triglyceride levels. Despite evidence that Angptl8 is involved in feeding control, the underlying mechanisms are unclear. Central and peripheral injections of Angptl8 significantly decreased food intake. Angptl8 was widely expressed in appetite-related nuclei, including the paraventricular nucleus (PVN), the dorsomedial hypothalamus (DMH), the ventromedial hypothalamus, and the arcuate nucleus (ARC) in the hypothalamus. Peripheral Angptl8 administration decreased c-Fos-positive neurons in the DMH. Central Angptl8 administration decreased c-Fos-positive neurons in the DMH and PVN but increased these neurons in the ARC. Angptl8 inhibited appetite via neuropeptide Y (NPY) neurons in the DMH. Furthermore, the chronic administration of Angptl8 decreased body weight gain and altered adipose tissue deposits. Nevertheless, neither peripheral nor central Angptl8 influenced the brown adipose tissue (BAT) morphology or uncoupling protein 1 (Ucp-1) expression in BAT. Taken together, these data suggested that Angptl8 modulates appetite and energy homeostasis

Effects of cerium addition on the microstructure, mechanical properties and strain hardening behaviour of TWIP steel Fe-18Mn-0.6c

The effects of cerium (Ce) on the microstructure, mechanical properties and strain hardening behavior of Fe-18Mn-0.6C twin-induced plasticity (TWIP) steel were investigated by electron backscatter diffraction, X-ray diffraction and transmission electron microscopy. Compared with the addition of Al, the addition of Ce significantly reduced the stacking fault probability of TWIP steel, which promotes the formation of deformation and annealing twins. The dynamic strain aging behavior of TWIP steel was inhibited by Al and Ce atoms during ambient deformation. The optimal mechanical properties were obtained when 0.015 wt.% of Ce was added, resulting in a tensile strength of 1023MPa; and an elongation was 92%. The interaction of twin variants in the Ce-containing alloys exhibited an X shape, which was significantly different from the T shape in the non-Ce containing alloy. This is mainly attributed to the fact that Ce promotes dislocations near grain boundaries, where for the nucleation of deformation twins at grain boundaries is favored. Compared with the T-shaped twin variants, the dynamic Hall-Petch effect caused by the X-shaped staggered twin variants was stronger, which improved the strain hardening ability of TWIP steel

Reliability modeling and prediction of passive controlled structures through Random Forest

Reliability prediction plays a significant role in risk assessment of engineering structures. Mathematically, the prediction task can be seen as a classification (regression) procedure. In this aspect, machine learning methods have recently shown their superior performance over others in various research domains. Random forest (RF) is distinguished for its robustness and high accuracy in modeling and prediction work. However, its application in the area of structural reliability has not been widely explored. This study aims to explore the feasibility of RF as well as examine its performance in modeling and prediction of structure reliability in passive control mode. A numerical example is introduced in the simulation part to evaluate performance of the proposed method in different perspectives

Reliability modeling and prediction of passive controlled structures through Random Forest

Reliability prediction plays a significant role in risk assessment of engineering structures. Mathematically, the prediction task can be seen as a classification (regression) procedure. In this aspect, machine learning methods have recently shown their superior performance over others in various research domains. Random forest (RF) is distinguished for its robustness and high accuracy in modeling and prediction work. However, its application in the area of structural reliability has not been widely explored. This study aims to explore the feasibility of RF as well as examine its performance in modeling and prediction of structure reliability in passive control mode. A numerical example is introduced in the simulation part to evaluate performance of the proposed method in different perspectives

Potential role of cyanidin 3-glucoside (C3G) in diabetic cardiomyopathy in diabetic rats: An in vivo approach

The present study aimed to evaluate the importance of cyanidin 3-glucoside (C3G) of diabetic cardiomyopathy in diabetic rats. The rats were induced with diabetic using streptozotocin and total triglyceride (TG) and total cholesterol (TC) were determined. The range of myocardial enzymes such as aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LD) were also estimated, further, the Immuno histochemical analysis and western blot investigation were determined for the actual activity of C3G. Results indicated that the marker enzymes such as CK, LD and AST were significantly (P < 0.05) increased in STZ administered rats (DM group), while the levels of these elevated marker enzymes of cardiac injury significantly (P < 0.05) declined in the DM + C3G group, as compared to the diabetic group of rats. Additionally, a decrease in the level of TNF-alpha and interleukin-6, was noticed in the C3G treated group as compared to diabetic group. Finally, blotting analysis clearly confirmed that theC3G treatment resulted to higher level response of Bcl-2 and lower level response of caspase-3 and BAX. In conclusion, C3G a natural antioxidant may prevent cardiovascular complications by ameliorating oxidative damage, inflammation, metabolic dysfunctions and apoptosis pathways in type 2 diabetes. Keywords: Cyanidin 3-glucoside, Cardiomyopathy, Immuno histochemistry, Western blo

Hydrophilic Excipient-Independent Drug Release from SLA-Printed Pellets

Three-dimensional (3D) printing technology, specifically stereolithography (SLA) technology, has recently created exciting possibilities for the design and fabrication of sophisticated dosages for oral administration, paving a practical way to precisely manufacture customized pharmaceutical dosages with both personalized properties and sustained drug release behavior. However, the sustained drug release achieved in prior studies largely relies on the presence of hydrophilic excipients in the printing formulation, which unfortunately impedes the printability and formability of the corresponding printing formulations. The current study developed and prepared mini-sized oral pellets using the SLA technique and successfully accomplished a hydrophilic excipient-independent drug release behavior. With ibuprofen as the model drug, the customized photopolymerizable printing formulation included polyethylene glycol diacrylate (PEGDA) as a monomer and diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (TPO) as a photoinitiator. The produced mini-sized pellets were thoroughly investigated for various factors, including their printability, physical properties, microscopic features, drug content, and drug-release profiles. The drug release profiles from the printed pellets that were larger size (3 mm and 6 mm) followed the Ritger–Peppas model, demonstrating that the release was influenced by both the diffusion of the dissolved drug and by the erosion of the hydrophilic excipients (PEG400). The profiles from the smaller printed pellets (1 mm and 2 mm) followed first release kinetics, not only illustrating that the release was impacted only by drug diffusion, but also indicating that there is a size boundary between the dependent and independent hydrophilic excipients. These results could create practical benefits to the pharmaceutical industry in terms of the design and development personalized dosages using the SLA printing technique with controllable drug release by manipulating size alone