Direct Stimulation of Adult Neural Stem/Progenitor Cells In Vitro and Neurogenesis In Vivo by Salvianolic Acid B

Background: Small molecules have been shown to modulate the neurogenesis processes. In search for new therapeutic drugs, the herbs used in traditional medicines for neurogenesis are promising candidates. Methodology and Principal Findings: We selected a total of 45 natural compounds from Traditional Chinese herbal medicines which are extensively used in China to treat stroke clinically, and tested their proliferation-inducing activities on neural stem/progenitor cells (NSPCs). The screening results showed that salvianolic acid B (Sal B) displayed marked effects on the induction of proliferation of NSPCs. We further demonstrated that Sal B promoted NSPCs proliferation in dose- and time-dependent manners. To explore the molecular mechanism, PI3K/Akt, MEK/ERK and Notch signaling pathways were investigated. Cell proliferation assay demonstrated that Ly294002 (PI3K/Akt inhibitor), but neither U0126 (ERK inhibitor) nor DAPT (Notch inhibitor) inhibited the Sal B-induced proliferation of cells. Western Blotting results showed that stimulation of NSPCs with Sal B enhanced the phosphorylation of Akt, and Ly294002 abolished this effect, confirming the role of Akt in Sal B mediated proliferation of NSPCs. Rats exposed to transient cerebral ischemia were treated for 4 weeks with Sal B from the 7th day after stroke. BrdU incorporation assay results showed that exposure Sal B could maintain the proliferation of NSPCs after cerebral ischemia. Morris water maze test showed that delayed post-ischemic treatment with Sal B improved cognitive impairment after stroke in rats

Autophagy–physiology and pathophysiology

“Autophagy” is a highly conserved pathway for degradation, by which wasted intracellular macromolecules are delivered to lysosomes, where they are degraded into biologically active monomers such as amino acids that are subsequently re-used to maintain cellular metabolic turnover and homeostasis. Recent genetic studies have shown that mice lacking an autophagy-related gene (Atg5 or Atg7) cannot survive longer than 12 h after birth because of nutrient shortage. Moreover, tissue-specific impairment of autophagy in central nervous system tissue causes massive loss of neurons, resulting in neurodegeneration, while impaired autophagy in liver tissue causes accumulation of wasted organelles, leading to hepatomegaly. Although autophagy generally prevents cell death, our recent study using conditional Atg7-deficient mice in CNS tissue has demonstrated the presence of autophagic neuron death in the hippocampus after neonatal hypoxic/ischemic brain injury. Thus, recent genetic studies have shown that autophagy is involved in various cellular functions. In this review, we introduce physiological and pathophysiological roles of autophagy

Supplementary Material for: Kidney Volume Estimations with Ellipsoid Equations by Magnetic Resonance Imaging in Autosomal Dominant Polycystic Kidney Disease

<b><i>Background:</i></b> Kidney volume (KV) becomes clinically relevant in autosomal dominant polycystic kidney disease (ADPKD) management. KV can be conveniently estimated (ceKV) using ellipsoid volume equations with three axes measurements; however, the accuracy and reliability are unknown. <b><i>Methods:</i></b> KVs of 347 kidneys in 177 consecutive ADPKD patients were determined with a volumetric method (standard-KV), and ceKV was calculated using six different ellipsoid equations with three axes measurements using magnetic resonance imaging. The inter- and intraobserver reliabilities were analyzed using intraclass correlation coefficients (ICCs). Ellipsoid-KVs were obtained by linear regression analysis between standard-KV and ceKVs, and six ellipsoid-KVs were validated with a bootstrap model. <b><i>Results:</i></b> The ICCs of intra- and interobserver reliabilities in standard-KV and axes measurements were highly reliable. All ceKVs underestimated standard-KV and % differences between ceKV and standard-KV were reduced by ellipsoid-KVs. Bootstrap analyses suggested that six ellipsoid-KVs reliably simulated standard-KV. <b><i>Conclusion:</i></b> Among six ellipsoid-KVs, ellipsoid-KV₃ = 84 + 1.01 x π/24 × Length × (sum of two width measurements)² relatively accurately simulated the standard-KV. Kidney volume estimation using ellipsoid equations is reliably applied to clinical management of ADPKD while recognizing wide scattering in the difference between estimated and volumetrically measured kidney volume