Cell signaling最新文献

Aging contributes significantly to the deterioration of cardiac function and increases the prevalence of heart failure, including those with reduced or preserved ejection fraction. Heart failure with preserved ejection fraction (HFpEF) is highly prevalent in the elderly population and it has become a leading cause of morbidity and mortality in this group. This commentary discusses the important findings and broader implications of the study by Daneshgar et al. on the role of the anti-aging hormone α-Klotho in alleviating diastolic dysfunction in the aged heart via Sirtuin1 (Sirt1)-mediated pathways. Using aged and Klotho-deficient mouse models, they demonstrated that soluble Klotho (sKL) supplementation improved cardiac diastolic function, reduced left ventricular hypertrophy and fibrosis, and increased capillary density. Mechanistically, the cardioprotective effects of sKL were found to rely on Sirt1-mediated regulation of DNA damage pathways and cardiac protein acetylation. These findings provide new insights into the therapeutic potential of targeting the Klotho-Sirt1 axis for HFpEF and other age-related cardiovascular diseases.

The comprehensive changes and shared dysregulated signaling pathways in early stage acne remains largely unexplored. In our recently published paper entitled "Analysis of Intracellular Communication Reveals Consistent Gene Changes Associated with Early-Stage Acne Skin," we utilized single-cell RNA sequencing and spatial transcriptomics datasets from acne patients to analyze cell communication. We identified dysregulated genes linked to inflammatory responses and hyperkeratinization. This commentary discusses potential new markers across major skin cell types, including endothelial cells, fibroblasts, lymphocytes, myeloid cells, keratinocytes, and smooth muscle cells. Additionally, we discuss key dysregulated genes in acne lesions, focusing on the intricate interplay between inflammation and hyperkeratinization. Based on our findings, we explore potential FDA-approved treatments targeting two key pathways involved in acne pathogenesis. These insights provide new therapeutic targets for acne treatment.

Sample multiplexing significantly enhanced the depth of single-cell proteomic analysis in CyTOF (Cytometry by Time-Of-Flight). New polymer-based chelators have broadened the utility of metal isotopes, enabling improved tagging and simultaneous analysis of multiple samples. These approaches minimize batch effects, streamline experiments, conserve valuable samples, reduce costs, enhance throughput, and increase the accuracy of biological data, thereby facilitating novel discoveries.

MCL1 is an anti-apoptotic member of the BCL2 protein family, and its overexpression is associated with poor prognosis across various cancers. Small molecule inhibitors targeting MCL1 are currently in clinical trials for TNBC and other malignancies. However, one major challenge in the clinical application of MCL1 inhibitors is the inherent or acquired resistance to these drugs. Additionally, there is a lack of predictive biomarkers to identify which tumors will respond to MCL1 inhibition. We identified a four-gene functional signature that promotes MCL1 inhibitor resistance in TNBC cells. This gene signature (GS) can distinguish resistant from sensitive TNBC cell lines. Factors encoded by these four genes promote MCL1 inhibitor resistance at least in part through regulation of the ERK signaling pathway. This mechanism involves the upregulation of BCL2 and the downregulation of BIM, which contribute to the inhibitor resistance. Thus, we have discovered a functional GS that drives MCL1 inhibitor resistance. Currently, the MCL1 inhibitor GS-9716 is in clinical trials for TNBC therapy. If validated in clinical samples, this GS could potentially serve as a predictive biomarker for therapy response and help guide the selection of combination therapies to enhance the effectiveness of MCL1 inhibitors.