Single-cell transcriptomics reveals gene signatures and alterations associated with aging in distinct neural stem/progenitor cell subpopulations

Aging associated cognitive decline has been linked to dampened neural stem/progenitor cells (NSC/NPCs) activities manifested by decreased proliferation, reduced propensity to produce neurons, and increased differentiation into astrocytes. While gene transcription changes objectively reveal molecular alterations of cells undergoing various biological processes, the search for molecular mechanisms underlying aging of NSC/NPCs has been confronted by the enormous heterogeneity in cellular compositions of the brain and the complex cellular microenvironment where NSC/NPCs reside. Moreover, brain NSC/NPCs themselves are not a homogenous population, making it even more difficult to uncover NSC/NPC sub-type specific aging mechanisms. Here, using both population-based and single cell transcriptome analyses of young and aged mouse forebrain ependymal and subependymal regions and comprehensive "big-data" processing, we report that NSC/NPCs reside in a rather inflammatory environment in aged brain, which likely contributes to the differentiation bias towards astrocytes versus neurons. Moreover, single cell transcriptome analyses revealed that different aged NSC/NPC subpopulations, while all have reduced cell proliferation, use different gene transcription programs to regulate age-dependent decline in cell cycle. Interestingly, changes in cell proliferation capacity are not influenced by inflammatory cytokines, but likely result from cell intrinsic mechanisms. The Erk/Mapk pathway appears to be critically involved in regulating age-dependent changes in the capacity for NSC/NPCs to undergo clonal expansion. Together this study is the first example of using population and single cell based transcriptome analyses to unveil the molecular interplay between different NSC/NPCs and their microenvironment in the context of the aging brain.

Using Prescription Sequence Symmetry Analysis to Analyze Adverse Drug Reactions of Traditional Chinese Medicine Injection / 世界科学技术-中医药现代化

Traditional Chinese medicine (TCM) injections are very useful in the treatment of acute and severe diseases due to their rapid onset. While, adverse drug reactions (ADRs) of TCM injections is an important problem, how to quickly detect ADRs signal of TCM injections is a key and difficult issue to make sure the safely application of TCM injections.Prescription sequence symmetry analysis (PSSA) is an effective surveillance tool for drug associated ADRs, through examining the distribution of marker drugs (potentially used for managing ADRs), before and after initiation of index drugs, PSSA can evaluate the causal association of index drugs and ADRs. PSSA can quickly detect ADRs signal based on medical electronic databases or prescription databases, which is suitable for the rapid emergence of ADRs for TCM injections. We described the basic principle and worldwide researches of PSSA, then we introduced the research methods when using PSSA to analyze the three aspects of ADRs for TCM injections. At present, when we use PSSA to detect ADRs signals in electronic prescription databases in China, we still need to think about the number of patients, structure and combination of data. With the development of medical electronic databases in China, PSSA can be more used to detect ADRs signal.

Effect of Ganoderma lucidum polysaccharides on the insu lin releasing function of pancreatic islets in rats / 中国临床药理学与治疗学

AIM: To investigate the effect of (Ganoderma lucidum ) polysaccharides (Gl-PS) on the insulin-releasing function of pancreati c islets. METHODS: Pancreatic islets were isolated and incubated with 5.6 or 16.7 mmol?L -1 glucose and different concentratio ns of Gl-PS for 1 h. Then the insulin was examined. Verapamil, and verapamil co mbined EGTA were used to testify whether the insulin-releasing effect of Gl-PS was inhibited by these inhibitors. The effects of Gl-PS on protein expression of the glucose transporter 2(GLUT2) under 5.6 and 16.7 mmol?L -1 glucose were also investigated. RESULTS: Gl-PS stimulated th e insulin release when incubated with the glucose of 5.6 or 16.7 mmol ?L -1 . The insulin releasing effect of Gl-PS was partly inhibited by ve rapamil and completely inhibited by verapamil+EGTA. Gl-PS could promote the GLU T2 protein expression of pancreatic islets under glucose of 5.6 and 16.7 mmol?L -1 . CONCLUSION: Gl-PS possesses insulin-rele asing effect under the glucose of 5.6 and 16.7 mmol?L -1 due t o the promotion of the GLUT2 protein expression and the subsequent facilitation of Ca 2+ inflow into the pancreatic B cells.

Studies of protective effect of FTY720 on immunological liver injury / 中国药理学通报

AIM This study was undertaken to investigate the protective effect against ConcanavalinA (ConA) or BCG+LPS induced liver injury in mice by FTY720 and possible mechanisms. METHODS The serum ALT and its AST level changes were measured in two kinds of immunological liver injury models. The serum IFN ? and IL 4 changes were determined by ELISA and tested the effect of FTY720 on lymphocyte proliferation. RESULTS FTY720 dose dependently reduced serum ALT, AST levels in ConA or BCG+LPS induced liver injury in mice. It was also found that FTY720 decreases serum IFN ? and IL 4 levels during liver injury. The results also proved that FTY720 was able to inhibit lymphocyte proliferation. CONCLUSION Pretreatment with FTY720 could protect the mice from immunological liver injury. The possible mechanisms of its action are related to inhibiting lymphocyte proliferation and cytokines production.