Asthma is a heterogeneous disease that varies in clinical presentation, severity, and underlying biology but consistently involves airway remodeling (AR) and airway hyperresponsiveness (AHR), which is characterized by excessive airway narrowing in response to various stimuli. Airway smooth muscle (ASM) cells are primary contributors to airway hyperresponsiveness and bronchoconstriction. This review focuses on ASM cells and their role in asthma. We discuss the mechanisms by which ASM mediates AHR, increases airway thickness, and contributes to AR. Signaling through G protein-coupled receptors (GPCRs) regulates many ASM functions, including contraction, growth, and the synthetic activities that drive airway inflammation and remodeling. GPCR-dependent calcium flux serves as a key signaling axis controlling the contractile responses of ASM. Here we provide a comprehensive summary of the major GPCRs as well as other non-GPCRs identified in ASM cells. GPCR-induced calcium mobilization, downstream signaling and how it has been linked to specific ASM functions are also discussed. Furthermore, we highlight the clinical significance of targeting GPCRs in asthma therapy as well as recent development of novel therapeutics in the management of asthma. Thus, this review provides a comprehensive overview of airway smooth muscle in the context of asthma pathophysiology.

The B Cell Lymphoma-2 (BCL-2) family proteins are central regulators of apoptosis, and their dysregulation is frequently associated with cancer progression and resistance to therapy. While small molecules like venetoclax have shown promise, nucleic acid-based therapeutics targeting BCL-2 remain underexplored. Here, we report a novel in vitro evolution strategy to generate trans-acting RNA-cleaving DNAzymes targeting natural BCL-2 mRNA without requiring covalent substrate-linking. Using a 50-base region of BCL-2 mRNA as a selection target, we evolved several DNAzymes that demonstrate significant RNA cleavage activity. These DNAzymes downregulated BCL-2 expression, induced apoptosis, and reduced cell viability in HepG2 and MCF-7 cancer cells. In vivo, our novel DNAzymes significantly suppressed tumor growth in a syngeneic mouse breast cancer model, with efficacy comparable to 5-Fluorouracil. This study presents a proof of concept for a novel strategy to evolve functional DNAzymes against native mRNA sequences and highlights their potential as gene-silencing tools in cancer therapy. Future studies will explore the therapeutic potential of these findings in cancer patients. Additionally, investigating the underlying molecular mechanisms in more complex cancer models will further validate the observed effects.