Regulation of Microglia and Macrophage Polarization via Apoptosis Signal-Regulating Kinase 1 Silencing after Ischemic/Hypoxic Injury

Inflammation is implicated in ischemic stroke and is involved in abnormal homeostasis. Activation of the immune system leads to breakdown of the blood–brain barrier and, thereby, infiltration of immune cells into the brain. Upon cerebral ischemia, infiltrated macrophages and microglia (resident CNS immune cell) are activated, change their phenotype to M1 or M2 based on the microenvironment, migrate toward damaged tissue, and are involved in repair or damage. Those of M1 phenotype release pro-inflammatory mediators, which are associated with tissue damage, while those of M2 phenotype release anti-inflammatory mediators, which are related to tissue recovery. Moreover, late inflammation continually stimulates immune cell infiltration and leads to brain infarction. Therefore, regulation of M1/M2 phenotypes under persistent inflammatory conditions after cerebral ischemia is important for brain repair. Herein, we focus on apoptosis signal-regulating kinase 1 (ASK1), which is involved in apoptotic cell death, brain infarction, and production of inflammatory mediators after cerebral ischemia. We hypothesized that ASK1 is involved in the polarization of M1/M2 phenotype and the function of microglia and macrophage during the late stage of ischemia/hypoxia. We investigated the effects of ASK1 in mice subjected to middle cerebral artery occlusion and on BV2 microglia and RAW264.7 macrophage cell lines subjected to oxygen-glucose deprivation. Our results showed that ASK1 silencing effectively reduced Iba-1 or CD11b-positive cells in ischemic areas, suppressed pro-inflammatory cytokines, and increased anti-inflammatory mediator levels at 7 days after cerebral ischemia. In cultured microglia and macrophages, ASK1 inhibition, induced by NQDI-1 drug, decreased the expression and release of M1-associated factors and increased those of M2-associated factors after hypoxia/reperfusion (H/R). At the gene level, ASK1 inhibition suppressed M1-associated genes and augmented M2-associated genes. In gap closure assay, ASK1 inhibition reduced the migration rate of microglia and macrophages after H/R. Taken together, our results provide new information that suggests ASK1 controls the polarization of M1/M2 and the function of microglia and macrophage under sustained-inflammatory conditions. Regulation of persistent inflammation via M1/M2 polarization by ASK1 is a novel strategy for repair after ischemic stroke

Post-mortem re-cloning of a transgenic red fluorescent protein dog

Recently, the world's first transgenic dogs were produced by somatic cell nuclear transfer. However, cellular senescence is a major limiting factor for producing more advanced transgenic dogs. To overcome this obstacle, we rejuvenated transgenic cells using a re-cloning technique. Fibroblasts from post-mortem red fluorescent protein (RFP) dog were reconstructed with in vivo matured oocytes and transferred into 10 surrogate dogs. One puppy was produced and confirmed as a re-cloned dog. Although the puppy was lost during birth, we successfully established a rejuvenated fibroblast cell line from this animal. The cell line was found to stably express RFP and is ready for additional genetic modification

Provisional drug-coated balloon treatment guided by physiology on de novo coronary lesion

Although drug-eluting stents (DES) have become the mainstay of percutaneous coronary intervention, late and very late stent thrombosis remains a concern. Drug-coated balloons (DCB) have the advantage of preserving the anti-restenotic benefits of DES while minimizing potential long-term safety concerns. Currently the two methods to ensure successful DCB treatment of a stenotic lesion are angiography or physiology-guided DCB application. This review will evaluate these two methods based on previous evidence and make suggestions on how to perform DCB treatment more efficiently and safely

Assessment of organic acid and sugar composition in apricot, plumcot, plum, and peach during fruit development

Variation in content of organic acids and soluble sugars, and in physical characteristics was evaluated in apricot (P. armeniaca L. cv. Harcot), plumcot (plum-apricot hybrid, P. salicina ⅹ P. armeniaca L. cv. Harmony), plum (P. salicina Lindl. cv. Formosa), and peach (P. persica L. Batsch cv. Jinmi). The content of organic acids and sugars, as well as parameters of fruit quality (weight, dimensions, firmness, total soluble solids, and total acidity) in Prunus fruits during fruit development were determined. Organic acids, including oxalic acid, quinic acid, malic acid, shikimic acid, citric acid, and quinic acid, sugars, including sucrose, fructose, glucose, and sugar alcohol (sorbitol), were identified and quantified using HPLC. Organic acid mostly increased during the early stages of fruit growth (30 - 60 days after full bloom) and decreased until fruits were fully ripened. In general, plum was the highest in most organic acids compared with the other fruits, while apricot contained the lowest acid content except for citric acid. Sucrose, fructose, and glucose content increased with fruit development, unlike content of sorbitol. Plumcot contained the highest fructose, and peach showed the maximum content of sucrose at full maturation stages. Total soluble solids averaged 17.5, 14.8, 11.9, and 10.6 ºBrix in apricot, plumcot, plum, and peach, respectively, whereas total acidity was 0.9, 1.4, 0.5, and 0.3% in four Prunus cultivars at ripened stages. Shikimic acid was significantly correlated with oxalic acid in apricot, plumcot, and plum, but not in peach. Fructose and glucose were highly correlated in plumcot, plum, and peach.