Covalently linking poly(lactic-co-glycolic acid) nanoparticles to microbubbles before intravenous injection improves their ultrasound-targeted delivery to skeletal muscle

Intravenously injected nanoparticles can be delivered to skeletal muscle through capillary pores created by the activation of microbubbles with ultrasound; however, strategies that utilize coinjections of free microbubbles and nanoparticles are limited by nanoparticle dilution in the bloodstream. Here, improvement in the delivery of fluorescently labeled ≈150 nm poly(lactic-co-glycolic acid) nanoparticles to skeletal muscle is attempted by covalently linking them to albumin-shelled microbubbles in a composite agent formulation. Studies are performed using an experimental model of peripheral arterial disease, wherein the right and left femoral arteries of BalbC mice are surgically ligated. Four days after arterial ligation, composite agents, coinjected microbubbles and nanoparticles, or nanoparticles alone are administered intravenously and 1 MHz pulsed ultrasound was applied to the left hindlimb. Nanoparticle delivery was assessed at 0, 1, 4, and 24 h post-treatment by fluorescence-mediated tomography. Within the coinjection group, both microbubbles and ultrasound are found to be required for nanoparticle delivery to skeletal muscle. Within the composite agent group, nanoparticle delivery is found to be enhanced 8- to 18-fold over 'no ultrasound' controls, depending on the time of measurement. A maximum of 7.2% of the initial nanoparticle dose per gram of tissue was delivered at 1 hr in the composite agent group, which was significantly greater than in the coinjection group (3.6%). It is concluded that covalently linking 150 nm-diameter poly(lactic-co-glycolic acid) nanoparticles to microbubbles before intravenous injection does improve their delivery to skeletal muscle.     

牛宰后肌肉生物电阻抗值变化及其影响因素的研究

本试验用四电极法在多频(5-200KHz)条件下对宰后牛骨骼肌肉的电阻抗特性进行了初步的研究。发现牛骨骼肌生物电阻抗与肌肉纤维方向,电流信号频率和宰后肌肉所经历的阶段有关。横向电阻(沿垂直于骨骼肌纤维方向)大于纵向电阻(沿骨骼肌纤维方向),而且受电流信号频率的影响较明显,尤其是在5KHz～100KHz范围内。牛宰后生物电阻抗的变化与pH值的变化有一定的相关性。     

Effect of Hibiscus anthocyanins-rich extract induces apoptosis of proliferating smooth muscle cell via activation of P38 MAPK and p53 pathway

Hibiscus sabdariffa L. (Malvaceae), an attractive plant believed to be native to Africa, is cultivated in Sudan and in eastern Taiwan. It has been reported to contain a number of protocatechuic acid and anthocyanins. In vitro experimental studies have shown that anthocyanins administration of the extract produces anti-inflammation and chemoprevention effects. In spite of the wide use of Hibiscus sabdariffa L. in folk medicine for treating various diseases, our previous study indicated a potency of Hibiscus sabdariffa extract (HSE) in anti-atherosclerosis. The mechanisms of anthocyanins administration of the extract produce from Hibiscus sabdariffa L. to attenuate atherosclerosis were not clarified. In this study, we found that Hibiscus anthocyanins (HAs) could inhibit the serum-stimulated proliferation of smooth muscle cell (SMC) and result in cell apoptosis. The HAs inducing cell apoptosis was dose dependent. We further used SB203580 (p38 inhibitor) to block cellular apoptosis and evaluate its effect on the HAs-inducing SMC death via some apoptosis criteria including DNA fragmentation and flow cytometry. We suggested that the mechanisms of the inhibitory effect of HAs on atherosclerosis could be via inhibiting the proliferation of SMC. HAs induces apoptosis via (i) activating p38 MAP kinase that subsequently phosphorylates target protein c-Jun and transduces the signal to further activate the apoptotic protein cascades that contain Fas-mediated signaling (Fas/caspase-8 signaling module) and (ii) activating p53 and inducing bax expression. As an outcome of the events, cytochrome c releases from the mitochondria, leading to cell apoptosis. In these experiments, HAs showed strong potential to induce SMC cell apoptosis via p38 and p53 pathway. In consequence, the rate of atherosclerotic formation is slowed down, and the progress is suppressed.     

Aging and Processing Affect Color, Metmyoglobin Reductase and Oxygen Consumption of Beef Muscles

Color stability and various biochemical properties were determined in bovine longissimus dorsi and psoas major at different times postmortem (8 hr to 21 days) and during retail display. Surface metmyoglobin accumulation, metmyoglobin reductase activity and oxygen consumption rate were affected by muscle type, postmortem aging, and fabrication method (p < 0.01). Psoas steaks had greater metmyoglobin accumulation, lower metmyoglobin reductase activity, and greater oxygen consumption than longissimus steaks. However, color stability of muscles was similar after grinding, which increased oxygen consumption. Color was most stable in steaks fabricated at 4 or 7 days postmortem. The order of color stability was knife-cut steaks > saw-cut steaks > ground muscle.     

Relationship Between Thermal Denaturation of Porcine Muscle Proteins and Water-holding Capacity

ABSTRACT: Differential scanning calorimetry was used to investigate denaturation characteristics of pork muscle proteins from carriers and noncarriers of the RN-gene. Pork from RN-carriers deviated from noncarriers in maximum denaturation temperatures and denaturation enthalpy, with proteins of RN-carriers being the most heat-labile. Correlation studies on the results showed that water-holding capacity was significantly correlated to changes in enthalpy of the population mainly representing myosin tails and sarcoplasmic proteins (p < 0.001). Finally, the influence of ultimate pH and preheating on thermal characteristics of porcine muscle proteins was studied. Myosin tails and sarcoplasmic proteins were most sensitive to pH changes, while myosin heads were most sensitive to preheating simulating stress-induced temperature increases.     

Production of dialysable iron by in vitro digestion of chicken muscle protein fractions: the size of the dialysable iron

Muscle foods enhance the absorption of non‐haem iron. We studied the size of the dialysable iron species produced following in vitro digestion of soluble and insoluble chicken muscle proteins and compared the results with those for egg white and whey protein. Digestion of chicken muscle proteins caused a four‐ to fivefold increase in dialysable iron, whereas egg white showed only a slight increase and whey protein caused a reduction, as compared with the control. All the dialysable iron species produced by egg white and whey were smaller than 1 kDa. In contrast, chicken muscle proteins produced dialysable iron species of all sizes up to 10 kDa, but the majority were in the range 2–3.5 kDa for both soluble and insoluble muscle proteins. Copyright © 2005 Society of Chemical Industry     

萝卜硫素通过抑制PINK1/Parkin信号通路介导的线粒体自噬减轻力竭运动诱导的骨骼肌损伤和疲劳

目的 评价萝卜硫素（SFN）对力竭运动所致小鼠骨骼肌损伤和疲劳的影响。方法 将60只雄性昆明小鼠随机分成对照组（Control）、力竭运动组（EE）、SFN低剂量组（SFN-L,20 mg/kg/d）、SFN中剂量组（SFN-M,40 mg/kg/d）和SFN高剂量组（SFN-H,60 mg/kg/d）,每组12只。共给药4周,然后进行力竭运动。测定各组小鼠肌酸激酶（CK）、乳酸（LA）、乳酸脱氢酶（LDH）、丙二醛（MDA）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）水平。苏木精-伊红染色观察组织病理学改变。透射电镜观察线粒体超微结构。通过测定柠檬酸合成酶（CS）、琥珀酸脱氢酶（SDH）及肝脏和股四头肌糖原含量来评估能量水平。用RT-qPCR和Western blot检测骨骼肌中与线粒体自噬相关的mRNA和蛋白表达水平。结果 与EE组相比,SFN-L组、SFN-M组和SFN-H组的CK、LA、LDH和MDA水平显著降低,而SOD和CAT活性显著升高（P<0.05）。SFN明显减轻了EE小鼠的骨骼肌损伤并改善了线粒体形态。与EE组相比,SFN-L组、SFN-M组和SFN-H组的肝糖原和肌糖原含量、CS表达和SDH活性显著升高（P<0.05）。与EE组相比,SFN-L组、SFN-M组和SFN-H组小鼠股四头肌组织中PINK1、Parkin、Lc3-Ⅱ、p62和ubiquitin的蛋白表达水平显著降低（P<0.05）。与EE组相比,SFN-L组、SFN-M组和SFN-H组小鼠股四头肌组织中PINK1和Parkin的mRNA表达水平显著降低（P<0.05）。结论 SFN通过抑制PINK1/Parkin信号通路介导的线粒体自噬来发挥抗疲劳作用。     

The mechanism of formation of gels from myosin molecules

Heat-set myosin gels form the basis of the adhesive that binds particles of meat together in meat products. The manner in which a gel network is formed from myosin has been investigated by studying the aggregates produced when dilute solutions of rabbit skeletal myosin molecules in 0.6 M KCI, 20 mM potassium phosphate, pH 6.5, were heated at a single temperature between 30 and 60°C. The aggregates have been examined by transmission electron microscopy after either negative staining or rotary shadowing. After heating at 30°C for 30 min. no change in structure is detected. After heating at 35°C for 30 min, the two heads of some myosin molecules coalesce and some dimers are formed by aggregation through the heads. After heating at 40°C for 30 min. up to about 13 myosin molecules aggregate through their heads to form a globular mass up to 60 nm across with the tails radiating outwards. At higher temperatures such head-linked oligomers aggregate further. At 48°C oligomers coexist with aggregates formed by the coalescence of two or more oligomers. In such aggregates the globular masses are in close proximity and tails radiate from them. After heating myosin at 50°C, aggregates are formed by the coalescence of more oligomers and the tails are seen only indistinctly. At 60°C the particles formed contain a large number of globular masses and are typically 100 to 200 nm across, occasionally up to 1 μm. It is possible that the globules making up the strands of the gel networks in scanning electron micrographs are composed of similar particles. It is suggested that these globules are formed by head-head interactions but that tail-tail interactions may be important in forming the strands and cross-links of the gel network. When a heat-set myosin gel is compacted by centrifugation, the supernate contains essentially all the LC1 and LC3 light chains of the parent molecule but only a small fraction of the LC2 light chains. We suppose that dissociation of the LC1 and LC3 chains from the heads creates hydrophobic patches which cause intramolecular and intermolecular head association.