Substrate stiffness dictates unique doxorubicin-induced senescence-associated secretory phenotypes and transcriptomic signatures in human pulmonary fibroblasts.

Cells are subjected to dynamic mechanical environments which impart forces and induce cellular responses. In age-related conditions like pulmonary fibrosis, there is both an increase in tissue stiffness and an accumulation of senescent cells. While senescent cells produce a senescence-associated secretory phenotype (SASP), the impact of physical stimuli on both cellular senescence and the SASP is not well understood.

Quantitative Glycan-Protein Cross-Linking Mass Spectrometry Using Enrichable Linkers Reveals Extensive Glycan-Mediated Protein Interaction Networks.

Protein-protein interactions in the cell membrane are typically mediated by glycans, with terminal sialic acid often involved in these interactions. To probe the nature of the interactions, we developed quantitative cross-linking methods involving the glycans of the glycoproteins and the polypeptide moieties of proteins. We designed and synthesized biotinylated enrichable cross-linkers that were click-tagged to metabolically incorporate azido-sialic acid on cell surface glycans to allow cross-linking of the azido-glycans with lysine residues on proximal polypeptides.

Non-Genetic Biomarkers in Merkel Cell Carcinoma: Prognostic Implications and Predictive Utility for Response to Anti-PD-(L)1 Immune Checkpoint Inhibitors.

Merkel cell carcinoma (MCC) is a skin cancer that arises due to either Merkel cell polyomavirus infection (MCPyV) or ultraviolet (UV) radiation exposure, presenting primarily in the head and neck region of fair-skinned males. The recent success of PD-(L)1 immune checkpoint inhibitors (ICIs) in locally advanced/metastatic MCC, with an objective response rate (ORR) around 50% and improved survival, as a first-line treatment has moved ICIs to the forefront of therapy for MCC and generated interest in identifying biomarkers to predict clinical response. The MCC tumour microenvironment (TME) contains various components of the adaptive and innate immune system.

Estimated exposure to endotoxin and circulating immunological markers among male farmers in the Biomarkers of Exposure and Effect in Agriculture study.

Background: Occupational exposure to endotoxin has been associated with reduced lung cancer risk. The mechanisms underlying this association are unclear, though immunological alterations likely play a role. Farmers who perform certain tasks (eg, raising hogs) can be highly exposed to endotoxin.