Novel Development and Prospects in Pathogenesis, Diagnosis, and Therapy of Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease with cognitive decline and behavioral dysfunction. AD will become a global public health concern due to its increasing prevalence brought on by the severity of global aging. It is critical to understand the pathogenic mechanisms of AD and investigate or pursue a viable therapy strategy in clinic. Amyloid-ß (Aß) accumulation and abnormally hyperphosphorylated tau protein are the main regulating variables in the pathological phase of AD. And neuroinflammation brought on by activated microglia was found to be one risk factor contributing to changes in Aß and tau pathology. It is important to investigate the unique biomarkers of early diagnosis and advanced stage, which may help to elucidate the specific pathological process of AD and provide potential novel therapeutic targets or preventative measures.

Cardiac commitment driven by MyoD expression in pericardial stem cells.

Cellular therapy holds immense promise to remuscularize the damaged myocardium but is practically hindered by limited allogeneic sources of cardiac-committed cells that engraft stably in the recipient heart after transplantation. Here, we demonstrate that the pericardial tissue harbors myogenic stem cells (pSCs) that are activated in response to inflammatory signaling after myocardial infarction (MI). The pSCs derived from the MI rats (MI-pSCs) show in vivo and in vitro cardiac commitment characterized by cardiac-specific Tnnt2 expression and formation of rhythmic contraction in culture. Bulk RNA-seq analysis reveals significant upregulation of a panel of genes related to cardiac/myogenic differentiation, paracrine factors, and extracellular matrix in the activated pSCs compared to the control pSCs (Sham-pSCs). Notably, we define MyoD as a key factor that governs the process of cardiac commitment, as siRNA-mediated MyoD gene silencing results in a significant reduction of myogenic potential. Injection of the cardiac-committed cells into the infarcted rat heart leads to long-term survival and stable engraftment in the recipient myocardium. Therefore, these findings point to pericardial myogenic progenitors as an attractive candidate for cardiac cell-based therapy to remuscularize the damaged myocardium.