Autophagy in osteoarthritis

Osteoarthritis is characterized by continuous degeneration of articular cartilage resulting in disability. The death of chondrocytes and the loss of the extracellular matrix are the central peculiarities in cartilage degeneration during osteoarthritis pathogenesis. Autophagy is an essential cellular homeostasis mechanism whereby cellular organelles and macromolecules are recycled to maintain cellular metabolism. Autophagy is reported to be cytoprotective effects for articular cartilage, and osteoarthritis is associated with decreased autophagy. While autophagy is known to be cytoprotective to chondrocytes, its role may vary with differing stages and models of osteoarthritis. Therefore, more in-depth studies on autophagy are needed to determine its impact on cell survival and death in articular cartilage under various in vitro and in vivo conditions. Application of autophagy on osteoarthritis therapeutics will be possible after a profound understanding is established on the role of autophagy in osteoarthritis pathogenesis.     

Quantitative assessment of global cerebral metabolic rate of oxygen (CMRO2) in neonates using MRI

The cerebral metabolic rate of oxygen (CMRO₂) is the rate of oxygen consumption by the brain, and is thought to be a direct index of energy homeostasis and brain health. However, in vivo measurement of CMRO₂ is challenging, in particular for the neonatal population, in whom conventional radiotracer methods are not applicable because of safety concerns. In this study, we propose a method to quantify global CMRO₂ in neonates based on arteriovenous differences in oxygen content, and employ separate measurements of oxygenation and cerebral blood flow (CBF) parameters. Specifically, arterial and venous oxygenation levels were determined with pulse oximetry and the novel T₂ relaxation under spin tagging (TRUST) MRI, respectively. Global CBF was measured with phase contrast (PC) flow velocity MRI. The proposed method was implemented on a standard 3‐T MRI scanner without the need for any exogenous tracers, and the total scan duration was less than 5 min. We demonstrated the feasibility of this method in 12 healthy neonates within an age range of 35–42 gestational weeks. CMRO₂ values were successfully obtained from 10 neonates. It was found that the average CMRO₂ in this age range was 38.3 ± 17.7 µmol/100 g/min and was positively correlated with age (p = 0.007; slope, 5.2 µmol/100 g/min per week), although the highest CMRO₂ value in this age range was still less than half of the adult level. Test–retest studies showed a coefficient of variation of 5.8 ± 2.2% between repeated CMRO₂ measurements. In addition, given the highly variable blood flow velocity within this age range, it is recommended that the TRUST labeling thickness and position should be determined on a subject‐by‐subject basis, and an automatic algorithm was developed for this purpose. Although this method provides a global CMRO₂ measure only, the clinical significance of an energy consumption marker and the convenience of this technique may make it a useful tool in the functional assessment of the neonatal population. Copyright © 2014 John Wiley & Sons, Ltd.     

Melatonin regulates lipid metabolism in porcine oocytes

It is being increasingly recognized that the processes of lipogenesis and lipolysis are important for providing an essential energy source during oocyte maturation and embryo development. Recent studies demonstrated that melatonin has a role in lipid metabolism regulation, including lipogenesis, lipolysis, and mitochondrial biogenesis. In this study, we attempted to investigate the effects of melatonin on lipid metabolism during porcine oocyte in vitro maturation. Melatonin treatment significantly enhanced the number of lipid droplets (LDs) and upregulated gene expression related to lipogenesis (ACACA, FASN, PPARγ, and SREBF1). Oocytes treated with melatonin formed smaller LDs and abundantly expressed several genes associated with lipolysis, including ATGL, CGI‐58, HSL, and PLIN2. Moreover, melatonin significantly increased the content of fatty acids, mitochondria, and ATP, as indicated by fluorescent staining. Concomitantly, melatonin treatment upregulated gene expression related to fatty acid β‐oxidation (CPT1a, CPT1b, CPT2, and ACADS) and mitochondrial biogenesis (PGC‐1α, TFAM, and PRDX2). Overall, melatonin treatment not only altered both the morphology and amount of LDs, but also increased the content of fatty acids, mitochondria, and ATP. In addition, melatonin upregulated mRNA expression levels of lipogenesis, lipolysis, β‐oxidation, and mitochondrial biogenesis‐related genes in porcine oocytes. These results indicated that melatonin promoted lipid metabolism and thereby provided an essential energy source for oocyte maturation and subsequent embryonic development.     

Silymarin Inhibits Morphological Changes in LPS-Stimulated Macrophages by Blocking NF-κB Pathway

The present study showed that silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), inhibited lipopolysaccharide (LPS)-induced morphological changes in the mouse RAW264.7 macrophage cell line. We also showed that silymarin inhibited the nuclear translocation and transactivation activities of nuclear factor-kappa B (NF-κB), which is important for macrophage activation-associated changes in cell morphology and gene expression of inflammatory cytokines. BAY-11-7085, an NF-κB inhibitor, abrogated LPS-induced morphological changes and NO production, similar to silymarin. Treatment of RAW264.7 cells with silymarin also inhibited LPS-stimulated activation of mitogen-activated protein kinases (MAPKs). Collectively, these experiments demonstrated that silymarin inhibited LPS-induced morphological changes in the RAW264.7 mouse macrophage cell line. Our findings indicated that the most likely mechanism underlying this biological effect involved inhibition of the MAPK pathway and NF-κB activity. Inhibition of these activities by silymarin is a potentially useful strategy for the treatment of inflammation because of the critical roles played by MAPK and NF-κB in mediating inflammatory responses in macrophages.