BioEssays最新文献

Formyl peptides, exemplified by the synthetic tripeptide formyl-Met-Leu-Phe (fMLF), are well-established ligands for formyl peptide receptors (FPRs), central to neutrophil chemotaxis, and innate immune signaling. Traditionally attributed to bacterial and mitochondrial origins, these peptides are now proposed to arise from an additional, stress-inducible source within the eukaryotic cytosol. Recent findings suggest that under specific stress conditions, eukaryotic translation can initiate with formylmethionine (fMet), producing fMet-bearing nascent chains that are processed by the fMet/N-degron and fMet-mediated ribosome quality control (fMet-RQC) pathways. These proteostatic mechanisms may generate short, structurally diverse formyl peptides with the potential to function as endogenous FPR ligands. By introducing cytosolic proteostasis as a hypothetical source of formyl peptides, this perspective expands the landscape of formyl peptide biology and opens new directions for investigating their roles in immune regulation under stress and disease.

Cancer cells exhibit reprogrammed metabolic pathways to sustain aggressive phenotypes, including continuous cell division, stemness, invasion, and metastasis. Emerging evidence suggests that these metabolic adaptations profoundly impact DNA repair pathways, which contribute to the responses to therapy and influence overall outcomes. Metabolic processes such as the Warburg effect, nicotinamide adenine dinucleotide (NAD) metabolism, glutamine metabolism, and one-carbon metabolism support DNA repair by expanding the metabolite pool and facilitating post-translational modifications. Conversely, oncometabolites impair DNA repair pathways through epigenetic reprogramming, thereby promoting genomic instability. This review highlights recent discoveries that elucidate the intricate connections between metabolic hallmarks in cancer cells and DNA repair mechanisms, offering insights into potential therapeutic targets for future cancer treatments.

Advanced biosensing technologies, such as Förster resonance energy transfer (FRET) and bioluminescence resonance energy transfer (BRET), have enabled real-time, high-resolution tracking of Rho GTPase activity, surpassing traditional methods like pull-down assays. However, current biosensors mainly detect the GTP-bound active state through effector interactions, without directly measuring Rho GTPase expression or identifying related biomarkers of abnormal activation. Small Rho GTPases are essential molecular switches that regulate key cellular processes such as cytoskeletal organization, cell movement, polarity, vesicle trafficking, and the cell cycle. Their precise activation and deactivation are critical for cellular balance, and disruptions in their signaling pathways are linked to diseases like cancer and immune disorders. Monitoring their activity is vital for understanding these processes and developing treatments. This study highlights the need for next-generation biosensors capable of directly monitoring expression levels and novel biomarkers, offering new avenues for research and therapeutic development targeting small Rho GTPases.

Neutrophil extracellular traps (NETs)—web-like DNA structures extruded by neutrophils in response to various stimuli, including pathogens, sterile inflammation, and mechanical stress—play a dual role in immunity and disease. While NETs serve to trap and neutralize pathogens during host defense, excessive or dysregulated NET formation, known as NETosis, can amplify inflammation and contribute to thrombotic complications such as atherosclerosis and valve disease. Increasing evidence supports that NETosis is a regulated, signaling-driven process, and that mechanical forces—including shear stress, tensile force, and matrix stiffness—can act as noncanonical danger signals capable of inducing NETosis. Mechanosensitive ion channels such as Piezo1, have emerged as key transducers of these biophysical cues, enabling cells to convert changes in shear stress levels into intracellular calcium flux, cytoskeletal remodeling, and ultimately NET release. Furthermore, exposure to pathologically high levels of shear stress may improve the sensitivity of neutrophils to secondary stimuli, lowering their activation threshold and amplifying inflammatory and thrombotic cascades. This mechanosensitive framework highlights shear-induced NETosis as a critical pathway by which neutrophils contribute to inflammation and thrombosis in mechanically stressed vascular environments.