Impact of glucocorticoid on neurogenesis

Neurogenesis is currently an area of great interest in neuroscience.It is closely linked to brain diseases,including mental disorders and neurodevelopmental disease.Both embryonic and adult neurogeneses are influenced by glucocorticoids secreted from the adrenal glands in response to a variety of stressors.Moreover,proliferation/differentiation of the neural stem/progenitor cells（NSPCs）is affected by glucocorticoids through intracellular signaling pathways such as phosphoinositide 3-kinase（PI3K）/Akt,hedgehog,and Wnt.Our review presents recent evidence of the impact of glucocorticoids on NSPC behaviors and the underlying molecular mechanisms;this provides important information for understanding the pathological role of glucocorticoids on neurogenesis-associated brain diseases.

Feasibility study of cyclodextrins as active pharmaceutical ingredients for the treatment of GM1-gangliosidosis

GM1-gangliosidosis is a rare lysosomal storage disorder characterized clinically by a wide range of variable neurovisceral,ophthalmological and dysmorphic features. Without enough functionalβ-galactosidase, GM1-gangliosides cannot be degraded in lysosomes, and accumulate to toxic levels in many tissues and organs, particularly in the brain. In spite of several approaches for the treatment of GM1-gangliosidosis.

Generation of insulin-producing β-like cells from human iPS cells in a defined and completely xeno-free culture system

Human induced pluripotent stem （hiPS） cells are considered a potential source for the generation of insulin-producing pancreatic β-ceUs because of their differentiation capacity. In this study, we have developed a five-step xeno-free culture system to efficiently dif- ferentiate hiPS cells into insulin-producing cells in vitro. We found that a high NOGGIN concentration is crucial for specifically inducing the differentiation first into pancreatic and duodenal homeobox-1 （PDX1）-positive pancreatic progenitors and then into neurogenin 3 （NGN3）-expressing pancreatic endocrine progenitors, while suppressing the differentiation into hepatic or intestinal cells. We also found that a combination of 3-isobutyl-l-methylxanthine （IBMX）, exendin-4, and nicotinamide was important for the differentiation into insulin single-positive cells that expressed various pancreatic β-cell markers. Most notably, the differentiated cells contained en- dogenous C-peptide pools that were released in response to various insulin secretagogues and high levels of glucose. Therefore, our results demonstrate the feasibility of generating hiPS-derived pancreatic β-ceUs under xeno-free conditions and highlight their poten- tial to treat patients with type I diabetes.

Expression of leukotriene B4 receptor 1 defines functionally distinct DCs that control allergic skin inflammation

Leukotriene B4(LTB4)receptor 1(BLT1)is a chemotactic G protein-coupled receptor expressed by leukocytes,such as granulocytes,macrophages,and activated T cells.Although there is growing evidence that BLT1 plays crucial roles in immune responses,its role in dendritic cells remains largely unknown.Here,we identified novel DC subsets defined by the expression of BLT1,namely,BLT1hi and BLT1lo DCs.We also found that BLT1hi and BLT1lo DCs differentially migrated toward LTB4 and CCL21,a lymph node-homing chemoattractant,respectively.By generating LTB4-producing enzyme LTA4H knockout mice and CD11c promoter-driven Cre recombinase-expressing BLT1 conditional knockout(BLT1 cKO)mice,we showed that the migration of BLT1hi DCs exacerbated allergic contact dermatitis.Comprehensive transcriptome analysis revealed that BLT1hi DCs preferentially induced Th1 differentiation by upregulating IL-12p35 expression,whereas BLT1lo DCs accelerated T cell proliferation by producing IL-2.Collectively,the data reveal an unexpected role for BLT1 as a novel DC subset marker and provide novel insights into the role of the LTB4-BLT1 axis in the spatiotemporal regulation of distinct DC subsets.