High levels circulating saturated fatty acids are associated with diabetes, obesity and hyperlipidemia. In heart, the accumulation of saturated fatty acids has been determined to play a role in the development of heart failure and diabetic cardiomyopathy. High-density lipoprotein (HDL) has been reported to possess key atheroprotective biological properties, including cellular cholesterol efflux capacity, anti-oxidative and anti-inflammatory activities. However, the underlying mechanisms are still largely unknown. Therefore, the aim of the present study is to test whether HDL could protect palmitic acid (PA)-induced cardiomyocyte injury and explore the possible mechanisms. H9c2 cells were pretreated with HDL (50–100 μg/ml) for 2 h followed by PA (0.5 mM) for indicated time period. Our results showed that HDL inhibited PA-induced cell death in a dose-dependent manner. Moreover, HDL rescued PA-induced ROS generation and the phosphorylation of JNK which in turn activated NF-κB-mediated inflammatory proteins expressions. We also found that PA impaired the balance of BCL2 family proteins, destabilized mitochondrial membrane potential, and triggered subsequent cytochrome c release into the cytosol and activation of caspase 3. These detrimental effects were ameliorated by HDL treatment. PA-induced ROS accumulation and results in cardiomyocyte apoptosis and inflammation. However, HDL attenuated PA-induced lipotoxicity and oxidative dysfunction via ROS suppression. These results may provide insight into a possible molecular mechanism underlying HDL suppression of the free fatty acid-induced cardiomyocyte apoptosis.

Objective: The effects of pre-treatments from s-methyl cysteine (SMC) alone, syringic acid (SA) alone and SMC plus SA against kainic acid (KA) induced injury in nerve growth factor (NGF) differentiated PC12 cells were investigated. Methods: NGF-differentiated PC12 cells were treated with 1 mu M SMC, 1 mu M SA or 0.5 mu M SMC plus 0.5 mu M SA for 2 days. Subsequently, cells were further treated by 150 mu M KA. Results: KA suppressed Bcl-2 mRNA expression, enhanced Bax mRNA expression and casued cell death. SMC was greater than SA, and similar as SMC+SA in increasing Bcl-2 mRNA expression. SMC+SA led to greater increase in mitochondrial membrane potential and cell survival than SMC or SA alone. SMC+SA resulted in more reduction in reactive oxygen species and tumor necrosis factor-alpha generation, more increase in glutathione content and glutathione reductase activity than SMC or SA alone. KA up-regulated protein expression of nuclear factor kappa B (NF-kappa B) p65 and phosphorylated p38 (p-p38). SMC or SA pre-treatments alone limited protein expression of both factors. SMC+SA resulted in more suppression in NF-kappa B p65 and p-p38 expression. KA decreased glutamine level, increased glutamate level and stimulated calcium release. SMC pre-treatments alone reversed these alterations. SMC alone elevated glutamine synthetase (GS) activity and mRNA expression. SMC+SA led to greater GS activity and mRNA expression than SMC pre-treatments alone. Conclusion: These findings suggested that this combination, SMC+SA, might provide greater protective potent for neuronal cells.

Background: The health benefits of coixol, an active compound of adlay seed, have attracted certain attention. Adlay seed is often adopted in traditional Chinese medicine for the treatment of various inflammatory disorders. Thus, it is hypothesized that coixol could protect neuronal cells. Objectives: The preventive effects of coixol against Abeta _25-35 -induced damage in nerve growth factor-differentiated PC12 cells were explored. Methods: Differentiated PC12 cells were treated with coixol at 0.125 μM, 0.25 μM, 0.5 μM, 1 μM, and 2 μM for 48 h. Then, cells were further exposed to Abeta _25-35 at 20 μM for 24 h. Results: Coixol treatments at 0.25–2 μM exhibited antiapoptotic effect via increasing Bcl-2 mRNA expression, mitochondrial membrane potential, and Na ⁺ -K ⁺ ATPase activity as well as decreasing Bax mRNA expression, caspase-3 activity, and intracellular Ca ²⁺ release. In addition, coixol treatments at 0.25–2 μM alleviated oxidative and inflammatory responses via lowering reactive oxygen species level, increasing glutathione content, promoting the activity of glutathione peroxidase, glutathione reductase, and catalase, decreasing the generation of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and prostaglandin E ₂ . Furthermore, coixol treatments at 0.25–2 μM diminished intracellular Ca ²⁺ release, and restricted nuclear factor kappa B-binding activity and phosphorylation of p65 and p38. Coixol treatments at 0.5–2 μM increased protein generation of nuclear factor E2-related factor 2, and limited protein production of inducible nitric oxide synthase and receptor of advanced glycation end product. Conclusion: Our novel findings suggested that coixol was a compelling agent against beta-amyloid peptide-induced neurotoxicity.

Background/Aim: The tissue inhibitor of metalloproteinase-2 (TIMP-2) is a critical inhibitor of matrix metalloproteinases (MMPs). Along with MMPs, TIMP-2 regulates the breakdown and remodeling of the extracellular matrix (ECM) and basement membranes. This study investigated the role of genotypes of the TIMP-2 -418G/C (rs8179090) single nucleotide polymorphism on lung risk. Materials and Methods: A total of 358 lung cancer patients and 716 healthy subjects were recruited in this study. Genotypes were identified via the polymerase chain reaction-restriction fragment length polymorphism methodology. Results: The distribution of alleles and genotype frequencies of TIMP-2 -418G/C genotypes between the two groups were compared and no statistically significant difference (p>0.05) was found. The heterozygous and homozygous variant genotypes showed no differential distribution between the control and case groups (p>0.05). Conclusion: TIMP-2 -418G/C variants might not be associated with lung cancer susceptibility and could not serve as predictors.

By Ya-chen Yang, Zhi-hong Wang, and Mei-chin Yin, Published on