Evaluation of a Selective Chemical Probe Validates That CK2 Mediates Neuroinflammation in a Human Induced Pluripotent Stem Cell-Derived Mircroglial Model

Novel treatments for neurodegenerative disorders are in high demand. It is imperative that new protein targets be identified to address this need. Characterization and validation of nascent targets can be accomplished very effectively using highly specific and potent chemical probes. Human induced pluripotent stem cells (hiPSCs) provide a relevant platform for testing new compounds in disease relevant cell types. However, many recent studies utilizing this platform have focused on neuronal cells. In this study, we used hiPSC-derived microglia-like cells (MGLs) to perform side-by-side testing of a selective chemical probe, SGC-CK2-1, compared with an advanced clinical candidate, CX-4945, both targeting casein kinase 2 (CK2), one of the first kinases shown to be dysregulated in Alzheimer’s disease (AD). CK2 can mediate neuroinflammation in AD, however, its role in microglia, the innate immune cells of the central nervous system (CNS), has not been defined. We analyzed available RNA-seq data to determine the microglial expression of kinases inhibited by SGC-CK2-1 and CX-4945 with a reported role in mediating inflammation in glial cells. As proof-of-concept for using hiPSC-MGLs as a potential screening platform, we used both wild-type (WT) MGLs and MGLs harboring a mutation in presenilin-1 (PSEN1), which is causative for early-onset, familial AD (FAD). We stimulated these MGLs with pro-inflammatory lipopolysaccharides (LPS) derived from E. coli and observed strong inhibition of the expression and secretion of proinflammatory cytokines by simultaneous treatment with SGC-CK2-1. A direct comparison shows that SGC-CK2-1 was more effective at suppression of proinflammatory cytokines than CX-4945. Together, these results validate a selective chemical probe, SGC-CK2-1, in human microglia as a tool to reduce neuroinflammation

Family Centered Care in NICU

NICUにおけるFamily Centered Care(以下FCC)は重要である.しかし日本では,FCCという用語そのものの検討は十分なされていない.そこで文献をもとにFCCという用語を検討した.結果,FCCとは,出生した子どもを含めた家族をひとつのユニットとして,ケアの対象と捉え,新たなメンバーとしての子どもを受け入れ,家族が発展することを支えることを重視する.これは専門職と家族との開かれた信頼しあえる関係を基盤に,両者の協動によって展開される.専門職は,権威者としてではなく.親のよきパートナー,ファシリテ一夕ーとして,家族の力を信じエンパワーメントとし,needsにそった個別的で継続的なsupportを提供する.それによって両親が自らの力を信じ.最大限に発揮し,子どもに関するあらゆる医学的問題やケアの意思決定,子どものケア全般に.主体的に快く参加することが可能となるような統合的なケアシステムであると捉えられた.またFCCを困雉にする要素として.スタッフの態度(考え)特に両親への力への疑い/両親の心理的な混乱/医療施設の環境(理念、物理的環境等を含む)等があげられた.しかし,日本ではFCCケア実践の重要性の認識と.現状には欧米以上のずれがあることが示唆され,FCCの捉え方や,現在どのような実践がなされているか.等を家族や専門職両者の視点から探り,そこから,日本なりのFCCのありかたを明確にしていくことが重要であると考えられた.The concept of the family centered care (FCC) in NICU and major elements related to this concept were examined through a literature review. From this literature review, i t was clarified that the FCC was an integrated care system based on a trusting relationship between family and health-care profession. It was essential for this concept that nurses should focus on not only the baby but also its whole family as one unit, believe in power of the family, and empower the family. Furthermore, nurses should make the family members to be involved their baby's care and decision making process comfortably and independently. Since there were few Japanese articles on the concept of the FCC, it is necessary to examine this concept in Japan