2023年 · 第06卷第01期

Acute ischemic stroke (AIS), a neurological injury resulting from blood clots, is the second most common cause of death worldwide. Novel therapeutics are urgently needed. Rapid developments in instrumentation and bioinformatics have resulted in increased use of mass spectrometry-based proteomics as an effective tool for the in-depth study of AIS. This review focuses on proteomics investigations of AIS in animal models. We highlight the study findings in system-wide protein abundance changes and molecular mechanisms underlying AIS with or without therapeutic intervention, as well as prestroke prognosis investigations. This review reveals that common molecular pathways related to ischemic injury and spontaneous recovery have been uncovered and part of AIS-changed proteins have been repeatedly identified, indicating the promise of proteomics in generating novel therapeutic targets and biomarker candidates. We also discuss challenges, alleviating strategies, and perspectives of mass spectrometry-based proteomics in AIS research and call for a broad application of systems-level investigations on preclinical AIS molecular mechanism elucidation, target discovery and validation, and therapeutics development.

Aging research has shifted from studying phenotypes to studying in-depth mechanisms in recent decades. However, extrapolating cellular and molecular bases of aging from studying traditional model systems to humans has been challenging. The advent of organoids holds promise for overcoming the limitations of monolayer cell culture and bridging the gap between animal models and humans. Here, we mainly discuss recent paradigms for using organoid models in studying organ aging. Pluripotent stem cells-derived organoid provides a promising platform for simulating the pathophysiology of several aging-related diseases, especially neurodegenerative diseases, and adult stem cells organoids derived from different age groups have been applied to detect aging-related functional changes. We also assess the value of organoid model systems in understanding human aging and aging-related diseases, and identify challenges to be addressed in the future, such as the immaturity of organoids, and effective methods of inducing aging.

To the editor:

Although the neurological and olfactory symptoms of coronavirus disease 2019 have been identified, the neurotropic properties of the causative virus, severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2), remain unknown. We sought to identify the susceptible cell types and potential routes of SARS-CoV-2 entry into the central nervous system, olfactory system, and respiratory system.

We collected single-cell RNA data from normal brain and nasal epithelium specimens, along with bronchial, tracheal, and lung specimens in public datasets. The susceptible cell types that express SARS-CoV-2 entry genes were identified using single-cell RNA sequencing and the expression of the key genes at protein levels was verified by immunohistochemistry. We compared the coexpression patterns of the entry receptor angiotensin-converting enzyme 2 (ACE2) and the spike protein priming enzyme transmembrane serine protease (TMPRSS)/cathepsin L among the specimens.

The SARS-CoV-2 entry receptor ACE2 and the spike protein priming enzyme TMPRSS/cathepsin L were coexpressed by pericytes in brain tissue; this coexpression was confirmed by immunohistochemistry. In the nasal epithelium, ciliated cells and sustentacular cells exhibited strong coexpression of ACE2 and TMPRSS. Neurons and glia in the brain and nasal epithelium did not exhibit coexpression of ACE2 and TMPRSS. However, coexpression was present in ciliated cells, vascular smooth muscle cells, and fibroblasts in tracheal tissue; ciliated cells and goblet cells in bronchial tissue; and alveolar epithelium type 1 cells, AT2 cells, and ciliated cells in lung tissue.

Neurological symptoms in patients with coronavirus disease 2019 could be associated with SARS-CoV-2 invasion across the blood-brain barrier via pericytes. Additionally, SARS-CoV-2-induced olfactory disorders could be the result of localized cell damage in the nasal epithelium.