(1) Background: Information regarding gene expression profiles and the prognosis of community-acquired pneumonia (CAP) is scarce. We aimed to examine the differences in the gene expression profiles in peripheral blood at hospital admission between patients with CAP who died during hospitalization and those who survived. (2) Methods: This is a multicenter study of nonimmunosuppressed adult patients who required hospitalization for CAP. Whole blood samples were obtained within 24 h of admission for genome-expression-profile analysis. Gene expression profiling identified both differentially expressed genes and enriched gene sets. (3) Results: A total of 198 samples from adult patients who required hospitalization for CAP were processed, of which 13 were from patients who died. Comparison of gene expression between patients who died and those who survived yielded 49 differentially expressed genes, 36 of which were upregulated and 13 downregulated. Gene set enrichment analysis (GSEA) identified four positively enriched gene sets in survivors, mainly associated with the interferon-alpha response, apoptosis, and sex hormone pathways. Similarly, GSEA identified seven positively enriched gene sets, associated with the oxidative stress, endoplasmic reticulum stress, oxidative phosphorylation, and angiogenesis pathways, in the patients who died. Protein–protein-interaction-network analysis identified FOS, CDC42, SLC26A10, EIF4G2, CCND3, ASXL1, UBE2S, and AURKA as the main gene hubs. (4) Conclusions: We found differences in gene expression profiles at hospital admission between CAP patients who died and those who survived. Our findings may help to identify novel candidate pathways and targets for potential intervention and biomarkers for risk stratification.

The clinical manifestations of SARS-CoV-2 infection vary widely, from asymptomatic infection to the development of acute respiratory distress syndrome (ARDS) and death. The host response elicited by SARS-CoV-2 plays a key role in determining the clinical outcome. We hypothesized that determining the dynamic whole blood transcriptomic profile of hospitalized adult COVID-19 patients and characterizing the subgroup that develops severe disease and ARDS would broaden our understanding of the heterogeneity in clinical outcomes. We recruited 60 hospitalized patients with RT-PCR-confirmed SARS-CoV-2 infection, among whom 19 developed ARDS. Peripheral blood was collected using PAXGene RNA tubes within 24 h of admission and on day 7. There were 2572 differently expressed genes in patients with ARDS at baseline and 1149 at day 7. We found a dysregulated inflammatory response in COVID-19 ARDS patients, with an increased expression of genes related to pro-inflammatory molecules and neutrophil and macrophage activation at admission, in addition to an immune regulation loss. This led, in turn, to a higher expression of genes related to reactive oxygen species, protein polyubiquitination, and metalloproteinases in the latter stages. Some of the most significant differences in gene expression found between patients with and without ARDS corresponded to long non-coding RNA involved in epigenetic control.

Background: Immune mechanisms underlying elicitation in allergic contact dermatitis (ACD) have yet to be fully elucidated. Previous studies have shown a double‐faceted nature of ACD with both common biomarkers among different allergens and allergen‐specific imprinting, albeit with discordance in terms of relevant pathways involved. Several factors, including co‐existing atopic dermatitis, may influence immune reactions. We aim to characterize molecular signatures and their immune mechanisms of different relevant allergens (nickel, 2‐hydroxyethylmethacrylate [2‐HEMA], methylisothiazolinone [MIT], formaldehyde) in strong and extreme positive (2/3+) patch test reactions of patients without atopic dermatitis. Methods: A transcriptomic analysis of 40 skin biopsies of ACD reactions (11 nickel, 10 MIT, 10 2‐HEMA, 9 formaldehyde) and 19 controls (petrolatum‐occluded skin) was performed using RNA sequencing. Differentially expressed genes (DEG) were assessed, and enriched functional pathways were obtained with an over‐representation analysis for allergens. Results: ACD molecular profiling revealed a strong, common imprinting of DEG among allergens versus controls ( n = 814), with further partially shared DEG among allergens ( n = 664) and allergen‐specific DEG ( n = 430). The most relevant shared pathways were associated with immune adaptive and innate responses. All allergens exhibited mixed effector immune responses, mainly type 1 and 3 immunity, and, to a lesser extent, type 2 immunity. Furthermore, partially shared and unique DEG were associated with further inflammatory pathways, particularly for nickel and 2‐HEMA. Conclusions: This study confirms shared ACD imprinting among different allergens and shared pathways' predominant role in ACD elicitation in patients without atopic dermatitis, alongside allergen‐specific immune processes and mixed effector responses (type 1, 3 and 2).

The initial dissemination of cancer cells from many primary tumors implies intravasation to lymphatic nodes or blood vessels. To investigate the mechanisms involved, we analyzed the expression of small non-coding RNAs in cutaneous squamous cell carcinoma (cSCC), a prevalent tumor that mainly spreads to lymph nodes. We report the reduced expression of small nucleolar RNAs in primary cSCCs that metastasized when compared to non-metastasizing cSCCs, and the progressive loss of DKC1 (dyskerin, which stabilizes the small nucleolar RNAs) along the metastasis. DKC1 depletion in cSCC cells triggered lipid metabolism by altering the mevalonate pathway and the acquisition of metastatic traits. Treatment of DKC1-depleted cells with simvastatin, an inhibitor of the mevalonate pathway, blocked the expression of proteins involved in the epithelial-to-mesenchymal transition. Consistently, the expression of the enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 1 was associated with pathological features of high metastatic risk in cSCC patients. Our data underpin the relevance of the mevalonate metabolism in metastatic dissemination and pave the possible incorporation of therapeutic approaches among the antineoplastic drugs used in routine patient care.