Figure 5.

CyC production is dynamically regulated in disease states

(A and B) Significant (p < 0.05) changes in paired (A) CST3 gene expression (reverse transcription PCR) and (B) extracellular CyC concentration in PMA-treated human THP-1 cells (macrophage-like) normalized to cellular protein content during 0- to 18-h DEX (100 nM) treatment. There are 6 biological replicates per group.

(C) Change in normalized extracellular CyC concentration in macrophage-like THP-1 cells after 18-h treatment with DEX (100 nM) or VEH control.

(D and E) Creatinine-normalized plasma CyC (C2 ratio) at specific time points with sufficient data in hospitalized COVID-19 patients treated with DEX or standard of care (control [CTRL]) as part of cohorts based in (D) Calgary, Canada, and (E) Charité Hospital, Germany. Day 1 in the Calgary, Canada, cohort refers to a time window of 72 h after admission to the ICU. Error bars indicate standard error of the mean.

(F) Single-cell CST3 gene expression in each cell cluster in melanoma tumors (n = 12) from Jerby-Anon et al.⁶⁴ Clusters defined by correlation to reference PBMC data,⁶⁰ with unclassified cells that exhibit detectable clonal copy-number variation classified as tumors.

(G) Plasma CyC concentration in BALBc mice after inoculation with colon-26 (C26) tumor cells. Cachexia is defined by >15% body weight loss, and pre-cachexia refers to 14 days after tumor inoculation; tumor bearing refers to day 7 after tumor inoculation.

(H) Significant positive correlation between plasma corticosterone and plasma CyC during tumor progression in C26 model.

(I) Extracellular CyC concentrations in C26 cells normalized to cellular protein content after 0-, 6-, 12-, 18-, or 24-h treatment with 100 nM DEX. Each time point comprises at least 4 biological replicates. p values refer to two-sided t tests. VEH, vehicle; DEX, dexamethasone.