Journal: PLOS One

Article Title: Multi-cohort transcriptomics and donor-aware single-cell analyses prioritize S100A8 within an emergency-myeloid, HLA-DR-low state in sepsis

doi: 10.1371/journal.pone.0359578

Figure Lengend Snippet: (A) Limma volcano plot using log2 RMA expression; red and blue indicate upregulated and downregulated genes at FDR < 0.05 and |log2 fold change| > 1. S100A8 is labeled. (B) Correlations of all module eigengenes with sepsis status; raw correlations and BH-adjusted FDR values are shown. (C) Black-module eigengene distribution in 42 normal-control and 760 sepsis samples; the displayed Wilcoxon P value is descriptive. (D) Intersection of 713 black-module genes and 1,508 corrected DEGs: 448 module-only, 265 overlapping, and 1,243 DEG-only genes. (E) Representative FDR-significant GO terms among the 265 genes. (F) Highest-ranked nominal KEGG terms; none of 241 tested pathways passed FDR < 0.05.

Article Snippet: Initial-experiment antibodies included S100A8 (Proteintech, 15792–1-AP), NF-κB p65 (CST, 8242S), and phospho-NF-κB p65 (CST, 3033S); their batch-specific dilutions were not recoverable from the archive.

Techniques: Expressing, Labeling, Control, Protein Binding

Journal: PLOS One

Article Title: Multi-cohort transcriptomics and donor-aware single-cell analyses prioritize S100A8 within an emergency-myeloid, HLA-DR-low state in sepsis

doi: 10.1371/journal.pone.0359578

Figure Lengend Snippet: (A-C) Performance across class-weighted, unweighted, and training-fold-downsampled repeated nested cross-validation. (D) S100A8 feature-selection frequency by model under sensitivity strategies. (E) Distribution of S100A8 AUC across 1,000 balanced 1:1 samples. (F) Calibration and selection-stability summary. Preprocessing and balancing were restricted to training folds; outer folds were used only for validation.

Article Snippet: Initial-experiment antibodies included S100A8 (Proteintech, 15792–1-AP), NF-κB p65 (CST, 8242S), and phospho-NF-κB p65 (CST, 3033S); their batch-specific dilutions were not recoverable from the archive.

Techniques: Biomarker Discovery, Selection, Sensitivity, Stability

Journal: PLOS One

Article Title: Multi-cohort transcriptomics and donor-aware single-cell analyses prioritize S100A8 within an emergency-myeloid, HLA-DR-low state in sepsis

doi: 10.1371/journal.pone.0359578

Figure Lengend Snippet: (A) ROC curves in the prespecified sepsis-versus-healthy external cohorts. (B) S100A8 distributions in clinically similar comparator cohorts. (C) Standardized effect sizes across healthy and clinically similar comparisons. (D) ROC curves for non-infectious ICU, cardiogenic shock, postoperative sterile inflammation, and uninfected chronic-disease controls. For the postoperative comparison, expression was higher in sepsis than in sterile inflammation; the ROC direction was fixed toward higher S100A8 in sepsis, so AUC = 0.927 was not produced by automatic orientation reversal. (E) Decision-curve analysis; thresholds are cohort specific and exploratory. (F) Associations with 30-day mortality, septic shock, and mortality in available cohorts. AUC, area under the curve; CI, confidence interval.

Article Snippet: Initial-experiment antibodies included S100A8 (Proteintech, 15792–1-AP), NF-κB p65 (CST, 8242S), and phospho-NF-κB p65 (CST, 3033S); their batch-specific dilutions were not recoverable from the archive.

Techniques: Sterility, Comparison, Expressing, Produced, Automatic, Analysis

Journal: PLOS One

Article Title: Multi-cohort transcriptomics and donor-aware single-cell analyses prioritize S100A8 within an emergency-myeloid, HLA-DR-low state in sepsis

doi: 10.1371/journal.pone.0359578

Figure Lengend Snippet: (A) UMAP of major cell classes. (B) S100A8 expression in UMAP space. (C) Canonical-marker dot plot across clusters C0-C11. (D) Unsupervised monocyte clusters C0-C2. (E) State-program scores showing an emergency-myeloid/immature-neutrophil-like, inflammatory, HLA-DR-low C0 state; a VCAN-positive classical C1 state; and a lymphoid-like C2 contamination profile. Cell-level plots are descriptive; formal differential expression used donor-level pseudo-bulk profiles.

Article Snippet: Initial-experiment antibodies included S100A8 (Proteintech, 15792–1-AP), NF-κB p65 (CST, 8242S), and phospho-NF-κB p65 (CST, 3033S); their batch-specific dilutions were not recoverable from the archive.

Techniques: Expressing, Marker, Quantitative Proteomics

Journal: PLOS One

Article Title: Multi-cohort transcriptomics and donor-aware single-cell analyses prioritize S100A8 within an emergency-myeloid, HLA-DR-low state in sepsis

doi: 10.1371/journal.pone.0359578

Figure Lengend Snippet: (A) SCP548 donor pseudo-bulk S100A8 across clinical groups. (B) Donor distribution of the MS1-like monocyte fraction. (C) Median antigen-presentation score difference from control by SCP548 group. (D,E) GSE205672 donor S100A8 and antigen-presentation scores. (F) Cross-dataset Spearman correlations of S100A8 with emergency-myeloid and antigen-presentation programs. State signatures exclude S100A8 ; the stricter sensitivity signature also excludes S100A9 .

Article Snippet: Initial-experiment antibodies included S100A8 (Proteintech, 15792–1-AP), NF-κB p65 (CST, 8242S), and phospho-NF-κB p65 (CST, 3033S); their batch-specific dilutions were not recoverable from the archive.

Techniques: Immunopeptidomics, Control, Sensitivity

Journal: PLOS One

Article Title: Multi-cohort transcriptomics and donor-aware single-cell analyses prioritize S100A8 within an emergency-myeloid, HLA-DR-low state in sepsis

doi: 10.1371/journal.pone.0359578

Figure Lengend Snippet: (A) L1000CDS2 candidate screen highlighting 16-hydroxytriptolide. (B) Structures of triptolide and 16-hydroxytriptolide. (C,D) Representative triptolide docking pose and interface contacts in the S100A8 homodimer (PDB 5HLO). (E) Matched score differences between compounds across A/C and B/D receptors and Vina/Vinardo scoring. Scores from different functions are not directly comparable. (F) Contact-set Jaccard indices. (G) Complex and apo backbone RMSD across three 100-ns replicates. (H) Triptolide displacement from the original pocket, showing retention in replicate 2 and migration in replicates 1 and 3. Docking and dynamics do not establish direct binding.

Article Snippet: Initial-experiment antibodies included S100A8 (Proteintech, 15792–1-AP), NF-κB p65 (CST, 8242S), and phospho-NF-κB p65 (CST, 3033S); their batch-specific dilutions were not recoverable from the archive.

Techniques: Docking Assay, Migration, Binding Assay

Journal: PLOS One

Article Title: Multi-cohort transcriptomics and donor-aware single-cell analyses prioritize S100A8 within an emergency-myeloid, HLA-DR-low state in sepsis

doi: 10.1371/journal.pone.0359578

Figure Lengend Snippet: (A) IL6, TNF, IL1B, and S100A8 RT-qPCR in Control, LPS, and LPS + TPL groups. (B) Representative immunoblots. (C) S100A8/β-actin, total NF-κB/β-actin, and p-NF-κB/total NF-κB quantification. (D) CETSA soluble-S100A8 curves across 40-70°C. (E) Representative CETSA blots. Points denote independent experiments as specified in the source data; bars show means with the displayed uncertainty. CETSA is compatible with target engagement or indirect stabilization and does not prove direct binding.

Article Snippet: Initial-experiment antibodies included S100A8 (Proteintech, 15792–1-AP), NF-κB p65 (CST, 8242S), and phospho-NF-κB p65 (CST, 3033S); their batch-specific dilutions were not recoverable from the archive.

Techniques: Quantitative RT-PCR, Control, Western Blot, Drug discovery, Binding Assay

Journal: PLOS One

Article Title: Multi-cohort transcriptomics and donor-aware single-cell analyses prioritize S100A8 within an emergency-myeloid, HLA-DR-low state in sepsis

doi: 10.1371/journal.pone.0359578

Figure Lengend Snippet: (A) Eight-condition siNC/siS100A8×Control/TPL/LPS/LPS + TPL immunoblots. (B,C) p-NF-κB/total NF-κB and S100A8/β-actin across three independent experiments. (D) Four-condition siRNA × LPS immunoblots. (E-G) CD74/β-actin, HLA-DRα/β-actin, and S100A8/β-actin. (H) TPL effects under LPS and the dependency contrast. The p-NF-κB dependency contrast was −0.011 (95% CI −0.249 to 0.226; P = 0.857); the three-way interaction was P = 0.848.

Article Snippet: Initial-experiment antibodies included S100A8 (Proteintech, 15792–1-AP), NF-κB p65 (CST, 8242S), and phospho-NF-κB p65 (CST, 3033S); their batch-specific dilutions were not recoverable from the archive.

Techniques: Western Blot

Journal: Journal of Inflammation Research

Article Title: S100A8/A9 Inhibition Reduces Neutrophil Extracellular Trap Formation and Mitigates Sepsis-Related Liver Injury

doi: 10.2147/JIR.S609689

Figure Lengend Snippet: Baseline Characteristics of Healthy Controls (HCs), Patients Without Sepsis-Related Liver Injury (SRLI), or Patients Without Sepsis-Related Liver Injury (Non-SRLI)

Article Snippet: To investigate the effect of S100A8/A9 on SRLI, wild-type mice were intraperitoneally injected with the S100A8/A9 inhibitor paquinimod (MedChemExpress, Monmouth Junction, NJ, USA) at a dose of 10 mg/kg 24 h before CLP or sham surgery.

Techniques:

Journal: Journal of Inflammation Research

Article Title: S100A8/A9 Inhibition Reduces Neutrophil Extracellular Trap Formation and Mitigates Sepsis-Related Liver Injury

doi: 10.2147/JIR.S609689

Figure Lengend Snippet: Receiver Operating Characteristic (ROC) Curve Analysis Results of S100A8/A9 on Patients Without Sepsis-Related Liver Injury (SRLI)

Article Snippet: To investigate the effect of S100A8/A9 on SRLI, wild-type mice were intraperitoneally injected with the S100A8/A9 inhibitor paquinimod (MedChemExpress, Monmouth Junction, NJ, USA) at a dose of 10 mg/kg 24 h before CLP or sham surgery.

Techniques:

Journal: Frontiers in Immunology

Article Title: Endothelial cell, but not neutrophil, programmed cell death receptor-ligand 1 loss has a morbid impact on experimental murine shock/sepsis-induced lung injury

doi: 10.3389/fimmu.2026.1816915

Figure Lengend Snippet: Description (A) and characterization of endothelial cell ( ec PD-L1 −/− ) (B, D) or neutrophil ( pmn PD-L1 −/− ) (C, E) restricted constitutive PD-L1 gene-deficient mice. Taconic Knockout Repository [mouse TF0103 (MGI:1926446); Taconic Biosciences Inc., Germantown, NY], CD274/PD-L1 conditional knockout mouse. PD-L1 gene exons 1 to 4 are shown as green boxes and loxP sites flanking exon 2 are depicted as red triangles (A) . Homozygous PD-L1 flox/flox were subsequently crossed to either VE-Cadherin‐Cre (B6.FVB-Tg[Cdh5-cre]7Mlia/J; Strain #:006137; RRID: IMSR_JAX:006137) or the S100a8-Cre (B6.Cg-Tg[S100a8-cre,-EGFP]1IIw/J; Strain #:021614; RRID: IMSR_JAX:021614) mice, obtained from Jackson Labs, to produce either mice homozygous for both the flox PD-L1 and specific cell-lineage Cre promoter genes or mice that were heterozygous for one or both genes that served as “Controls”. Gating strategy and typical flow cytogram/dot plot of select cell-lineage restricted PD-L1 expression [either CD31 and PD-L1 (B) or Ly6G and PD-L1 (C) ] for various breeding outcomes from respective Cre-Lox matings for PD-L1 flox/flox animals with VE-Cadherin‐Cre (B) or PD-L1 flox/flox animals with S100a8-Cre (C) . Summary data for the change in percentage PD-L1 + endothelial cells (CD31 + ) (D) and percentage PD-L1 + neutrophils (Ly6G + ) (E) . A dotted line is provided to indicate median frequency of non-specific antibody binding typically detected using gating strategy during analysis, which was 2.75% ± 1.77% CD31 + PD-L1 + (D) and 2.29 ± 0.50% Ly6G + PD-L1 + (E) , respectively. The presence of a significant difference between groups was established at * p < 0.05 with a Mann–Whittney U test.

Article Snippet: The VE-Cadherin‐Cre (Strain #:006137; RRID: IMSR_JAX:006137) and the S100a8-Cre (Strain #:021614; RRID: IMSR_JAX:021614) breeder mouse strains were also obtained from The Jackson Laboratory (see ).

Techniques: Knock-Out, Expressing, Binding Assay

Journal: JID Innovations

Article Title: A neuroimmune axis linking S100A8/9 to itch sensitization in both bullous pemphigoid and atopic dermatitis

doi: 10.1016/j.xjidi.2026.100470

Figure Lengend Snippet: Increased S100A8/9 expression in the skin and serum of patients with BP and AD. ( a ) Immunohistochemical analysis with anti-S100A8/9 antibody showing the expression of S100A8/9 in keratinocytes and infiltrating inflammatory cells of lesional skin of patients with BP and AD. S100A8/9 expression was not observed in the healthy skin. Scale bar: 100 μm. (b) Quantification of the expression level of S100A8/9. (control, n = 2; BP, n = 5; AD n = 2). Inter-patient heterogeneity of the expression level of S100A8/9 was observed in the BP skin samples, and representative images of both low and high S100A8/9 expression were shown in A. (c) ELISA analysis showing increased S100A8/9 concentrations in the serum of patients with BP. (control, n = 8; BP, n = 16; P = .0087, Mann-Whitney test). Data are reported as mean ± SD. AD, atopic dermatitis; BP, bullous pemphigoid.

Article Snippet: Chemicals used are listed as follows: S100A8, S100A9, and S100A8/9 (100 ng/ml, R&D Systems, 9877-S8, 2065-S9, 8916-S8), Bam8-22 (1 μM, custom synthesized by Genscript), and capsaicin (Sigma M2028, 1 μM).

Techniques: Expressing, Immunohistochemical staining, Control, Enzyme-linked Immunosorbent Assay, MANN-WHITNEY

Journal: JID Innovations

Article Title: A neuroimmune axis linking S100A8/9 to itch sensitization in both bullous pemphigoid and atopic dermatitis

doi: 10.1016/j.xjidi.2026.100470

Figure Lengend Snippet: S100A8/9 directly activates small-diameter, nociceptive DRG sensory neurons. ( a ) Representative fluorescent images of cultured DRG sensory neurons isolated from Pirt GCaMP3/+ mice before and after S100A8/9 (100 ng/ml) application. Arrows point to sensory neurons showing increased GCaMP3 fluorescence levels after S100A8/9 application. (b) Histogram showing size distribution of S100A8/9-responsive neurons. (c–e) Representative traces of DRG neurons evoked by indicated chemicals, including S100A8/9 (100 ng/ml), S100A8 (100 ng/ml), S100A9 (100 ng/ml), capsaicin (1 μM), and KCl (75 mM) in a calcium imaging assay. All S100A8/9-sensitive neurons responded to capsaicin and KCl. The majority of S100A8- and S100A9-responsive neurons also responded to S100A8/9. The three different colors (Red, Green, and Blue) represent individual cells in C-E. (f) TAK-242 inhibited S100A8/9-induced calcium responses in sensory neurons. (n = 3 for both groups P = .018, Welch’s t -test). Data are reported as mean ± SD. AD, atopic dermatitis; BP, bullous pemphigoid; DRG, dorsal root ganglia.

Article Snippet: Chemicals used are listed as follows: S100A8, S100A9, and S100A8/9 (100 ng/ml, R&D Systems, 9877-S8, 2065-S9, 8916-S8), Bam8-22 (1 μM, custom synthesized by Genscript), and capsaicin (Sigma M2028, 1 μM).

Techniques: Cell Culture, Isolation, Fluorescence, Imaging

Journal: JID Innovations

Article Title: A neuroimmune axis linking S100A8/9 to itch sensitization in both bullous pemphigoid and atopic dermatitis

doi: 10.1016/j.xjidi.2026.100470

Figure Lengend Snippet: S100A8/9 potentiate histamine-induced itch. ( a ) Subcutaneous injection of S100A8/9 (20 μg/ml) into the nape of the neck of wild-type mice does not induce scratching behavior. (n = 7 for both groups, P = .97, Welch’s t test). (b) Co-injection of S100A8/9 increased histamine (20 mM)-induced scratching behavior. (n = 11 for both groups, P = .038, Welch’s t test). Data are reported as mean ± SD.

Article Snippet: Chemicals used are listed as follows: S100A8, S100A9, and S100A8/9 (100 ng/ml, R&D Systems, 9877-S8, 2065-S9, 8916-S8), Bam8-22 (1 μM, custom synthesized by Genscript), and capsaicin (Sigma M2028, 1 μM).

Techniques: Injection