Publications

Aging is a major risk factor for both cardiovascular and neurodegenerative diseases. The bidirectional communication between the heart and brain, commonly referred to as heart-brain crosstalk, is increasingly disrupted with age. In this review, we summarize current evidence linking cardiovascular and neurodegenerative disorders, particularly in the context of aging. We also discuss the underlying mechanisms responsible for the heart-brain crosstalk, including blood-brain barrier breakdown, vascular dysfunction, nervous system alterations, inflammation, and endocrine dysregulation, which may explain the frequent co-occurrence of dysfunction in both organs during aging. Understanding these interconnections provides critical insights into the pathophysiology of age-related diseases and highlights potential therapeutic targets to preserve both heart and brain health in the aging population.

Pericytes, which share markers with smooth muscle cells (SMCs), are heterogenous cells. Pericytes in the brain and skeletal muscle have different embryonic origins, representing distinct subpopulations. One challenge in the field is that there are no subpopulation-specific pericyte markers. Here, we compared the transcriptomes of muscle pericytes and SMCs, and identified 741 muscle pericyte-enriched genes and 564 muscle SMC-enriched genes. Gene ontology analysis uncovered distinct biological processes and molecular functions in muscle pericytes and SMCs. Interestingly, the Venn diagram revealed only one gene shared by brain and muscle pericytes, suggesting that they are indeed distinct subpopulations with different transcriptional profiles. We further validated that GSN co-localized with PDGFRβ⁺SMA⁻ cells in small and large blood vessels but not PDGFRβ⁺SMA⁺ cells, indicating that GSN predominantly marks pericytes and fibroblasts rather than SMCs in skeletal muscle. Negligible levels of GSN were detected in the brain. These findings indicate that GSN may serve as a selective marker for muscle pericytes.

Laminin exerts a variety of important functions via binding to its receptors, including integrins and dystroglycan. With the advance in gene-targeting technology, many integrin/dystroglycan knockout/mutant mice were generated in the past 3 decades. These mutants enable loss-of-function studies and have substantially enriched our knowledge of integrin/dystroglycan functions. In this review, we summarize the functions of laminin receptors during embryonic development and in the central nervous system and vasculature. First, the biochemical properties of integrins and dystroglycan are briefly introduced. Next, we discuss loss-of-function studies on laminin receptors, including integrin-α3, integrin-α6, integrin-α7, integrin-β1, integrin-β4, and dystroglycan, focusing on embryonic development, the central nervous system, and vasculature. The phenotypes of compound knockout mice are described and compared with that of single mutants. Last, important questions and challenges in the field as well as potential future directions are discussed. Our goal is to provide a synthetic review on loss-of-function studies of laminin receptors in the central nervous system and vasculature, which could serve as a reference for future research, encourage the formation of new hypotheses, and stimulate new research in this field.

The blood-brain barrier (BBB) is a dynamic structure that maintains brain homeostasis. BBB breakdown is a key pathological hallmark of almost all neurological diseases. Although the regulation of BBB integrity by different cells has been extensively studied, the function of its non-cellular component-the basal lamina in BBB regulation remains largely unknown. Laminin, a trimeric protein with multiple isoforms, is one of the most important constituents of the basal lamina. In the CNS, different cells synthesize distinct laminin isoforms, which differentially regulate BBB integrity in both physiological and pathological conditions. A thorough understanding of laminin expression and function in BBB integrity could lead to the identification of novel therapeutic targets and potentially result in effective treatments for neurological disorders involving BBB disruption. Here in this review, we first briefly introduce the BBB and basal lamina with a focus on laminin. Next, we elucidate laminin expression and its function in BBB maintenance/repair in a cell-specific manner. Potential functional compensation among laminin isoforms is also discussed. Last, current challenges in the field and future directions are summarized. Our goal is to provide a synthetic review to encourage novel ideas and stimulate new research in the field.

Intracerebral hemorrhage (ICH), the deadliest form of stroke, is characterized by bleeding into brain parenchyma and formation of hematoma. Currently, there is no treatment available for ICH. Inflammatory response is a key pathology of ICH and plays a dual role in ICH---contributing to both secondary brain injury and recovery processes. This review discusses different types (both brain-resident and infiltrated) of immune cells and their functions during inflammation processes following ICH. Specifically, the temporal dynamics, polarization, and function of microglia/macrophages, neutrophils, lymphocytes, and astrocytes in ICH are summarized in a cell-specific manner. In addition, we also discuss key challenges and unanswered questions that need to be addressed in the future. A thorough understanding of the functions of different immune cells in ICH will provide a strong foundation for future studies and lead to the identification of novel cellular/molecular targets for therapeutic development.

Background: Pericytes, a type of mural cells, exert important functions in the CNS. One major challenge in pericyte research is the lack of pericyte-specific and subpopulation-specific markers.

Methods: To address this knowledge gap, we first generated a novel transgenic mouse line in which vascular smooth muscle cells (vSMCs) are permanently labeled with tdTomato. Next, we isolated PDGFRβ⁺tdTomato^- pericytes and PDGFRβ⁺tdTomato⁺ vSMCs from the brains of these mice and subsequently performed RNAseq analysis to identify pericyte-enriched genes.

Results: Using this approach, we successfully identified 40 pericyte-enriched genes and 158 vSMC-enriched genes, which are involved in different biological processes and molecular functions. Using ISH/IHC analysis, we found that Pla1a and Cox4i2 were predominantly enriched in subpopulations of brain pericytes, although they also marked some non-vascular parenchymal cells.

Conclusions: These findings suggest that Pla1a and Cox4i2 preferably label subpopulations of pericytes in the brain compared to vSMCs, and thus, they may be useful in distinguishing these populations.

[This corrects the article on p. 1922 in vol. 9, PMID: 31598395.].

Head and neck cancers represent a critical global health issue, contributing to substantial morbidity and mortality. Recent research has explored the role of microRNAs (miRNAs) in these cancers by constructing miRNA-associated disease networks using bipartite graphs. Graph attention networks (GATs) have emerged as a powerful tool for predicting disease associations within such biological networks, offering enhanced accuracy in identifying potential miRNA-disease relationships. This study employs GATs to uncover and predict potential miRNA contributors to head and neck cancers. Data on miRNA-disease associations were sourced from the HMDD v4.0 database, a platform based on SQLite and Django. The head and neck neoplasms dataset included miRNA, disease, causality, category, and PubMed ID (PMID). GATs were applied to analyze the network, leveraging their ability to capture the significance and interdependencies of nodes and edges. The model used a learnable weight matrix to compute attention coefficients, normalize them, and aggregate information from neighboring nodes for edge prediction. The GAT model, integrating graph neural networks with attention mechanisms, achieved an accuracy of 83% in predicting miRNA-disease associations for head and neck neoplasms. This study highlights the potential of graph-based deep learning models, particularly GATs, in accurately predicting miRNA-disease associations. A functional enrichment analysis revealed significant involvement of miRNAs in oral cancer pathways, notably highlighting the critical roles of the TGF-beta and PI3K-Akt signaling pathways in tumor progression and cell survival. These findings offer a pathway to better understanding the molecular mechanisms underlying head and neck cancers. Future improvements in dataset size, model evaluation, and interpretability could further enhance prediction accuracy, potentially advancing diagnostic and therapeutic strategies for these cancers.

[This corrects the article on p. 350 in vol. 18, PMID: 39822678.].

[This corrects the article on p. 1835 in vol. 7, PMID: 28979807.].