• CD8+ T cells
• inflammatory bowel disease
• microbiomes
• perforin
• β-hydroxybutyrate

• the National Natural Science Foundation of China
• R&D Program of Beijing Municipal Education Commission
• Beijing Municipal Administration of Hospitals’ Ascent Plan
• the Youth Beijing Scholar
• the National Key Technologies R&D Program
• Beijing Natural Science Foundation
• Distinguished Young Scholars from Beijing Friendship Hospital

• Humans
• Proteome
• Proteomics
• Drug Development
• Healthy Lifestyle
• Mendelian Randomization Analysis
• Neoplasms/drug therapy
• Neoplasms/epidemiology
• Neoplasms/genetics
• Blood Proteins
• Genome-Wide Association Study
• Polymorphism, Single Nucleotide
• Calcium-Binding Proteins
• Membrane Proteins

• LR22H260001 Natural Science Fund for Distinguished Young Scholars of Zhejiang Province
• 82204019 National Nature Science Foundation of China
• K-20230085 Healthy Zhejiang One Million People Cohort
• 82073641 National Natural Science Foundation of China
• GZY-ZJ-KJ-24077 Key Project of Traditional Chinese Medicine Science and Technology Plan of Zhejiang Province
• 82001673 National Natural Science Foundation of China

We develop scSTEM, single-cell STEM, a method for clustering dynamic profiles of genes in trajectories inferred from pseudotime ordering of single-cell RNA-seq (scRNA-seq) data. scSTEM uses one of several metrics to summarize the expression of genes and assigns a p-value to clusters enabling the identification of significant profiles and comparison of profiles across different paths. Application of scSTEM to several scRNA-seq datasets demonstrates its usefulness and ability to improve downstream analysis of biological processes. scSTEM is available at https://github.com/alexQiSong/scSTEM.

• Gene clustering
• Genomics
• Single cell
• Visualization

Colorectal cancer (CRC) is among the most common malignancies worldwide. CRC is considered a heterogeneous disease due to various clinical symptoms, biological behaviours, and a variety of mutations. A number of studies demonstrate that as many as 50% of CRC patients have distant metastases at the time of diagnosis. However, despite the fact that social and medical awareness of CRC has increased in recent years and screening programmes have expanded, there is still an urgent need to find new diagnostic tools for early detection of CRC. The effectiveness of the currently used classical tumour markers in CRC diagnostics is very limited. Therefore, new proteins that play an important role in the formation and progression of CRC are being sought. A number of recent studies show the potential significance of granzymes (GZMs) in carcinogenesis. These proteins are released by cytotoxic lymphocytes, which protect the body against viral infection as well specific signalling pathways that ultimately lead to cell death. Some studies suggest a link between GZMs, particularly the expression of Granzyme A, and inflammation. This paper summarises the role of GZMs in CRC pathogenesis through their involvement in the inflammatory process. Therefore, it seems that GZMs could become the focus of research into new CRC biomarkers.

• biomarkers
• cancer
• colorectal cancer
• granzymes
• serin proteases

• Biomarkers, Tumor
• Carcinogenesis/genetics
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/pathology
• Granzymes/metabolism
• Humans
• Virus Diseases

• Bioinformatic analysis
• Diagnosis
• Differently expressed genes
• Logistic regression
• Ulcerative colitis

• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/genetics
• Computational Biology/methods
• Gene Expression/genetics
• Genetic Association Studies/methods
• Humans
• Lithostathine
• Logistic Models
• Machine Learning
• Pancreatitis-Associated Proteins
• alpha-Defensins

• 2017D01C112 natural science foundation of xinjiang uygur autonomous region

Nowadays, new advances in society and health have brought an increased life expectancy. However, at the same time, aging comes with complications that impact the development of autoimmunity, neurodegenerative diseases and cancer. These complications affect the quality of life and impact the public health system. Specifically, with aging, a low-grade chronic sterile systemic inflammation with self-reactivity in the absence of acute infection occurs termed inflammaging. Inflammaging is related to an imbalanced immune response that can be either naturally acquired with aging or accelerated due to external triggers. Different molecules, metabolites and inflammatory forms of cell death are highly involved in these processes. Importantly, adoptive cellular immunotherapy is a modality of treatment for cancer patients that administers ex vivo expanded immune cells in the patient. The manipulation of these cells confers them enhanced proinflammatory properties. A general consequence of proinflammatory events is the development of autoimmune diseases and cancer. Herein, we review subsets of immune cells with a pertinent role in inflammaging, relevant proteins involved in these inflammatory events and external triggers that enhance and accelerate these processes. Moreover, we mention relevant preclinical studies that demonstrate associations of chronic inflammation with cancer development.

• NK cells
• SASP
• T cells
• immunosenescence
• immunotherapy
• inflammaging

• Animals
• Anti-Inflammatory Agents/administration & dosage
• CD4-Positive T-Lymphocytes/immunology
• CD4-Positive T-Lymphocytes/transplantation
• Colitis, Ulcerative/drug therapy
• Colitis, Ulcerative/immunology
• Colitis, Ulcerative/prevention & control
• Disease Models, Animal
• Female
• Helminth Proteins/administration & dosage
• Helminth Proteins/chemistry
• Helminth Proteins/genetics
• Hookworm Infections/metabolism
• Humans
• Male
• Matrix Metalloproteinase Inhibitors/chemistry
• Mice, Inbred C57BL
• Mice, Knockout
• Necator americanus/chemistry
• Netrins/administration & dosage
• Netrins/analysis
• Recombinant Proteins/administration & dosage
• Mice

• IL6
• STAT3
• colorectal cancer
• extracellular
• granzyme
• gut
• inflammation
• macrophage

• Acute Disease
• Animals
• Azoxymethane
• Carcinogenesis/genetics
• Carcinogenesis/pathology
• Chronic Disease
• Colon/pathology
• Colorectal Neoplasms/enzymology
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/pathology
• Cyclooxygenase 2/metabolism
• Cytokines/metabolism
• Dextran Sulfate
• Disease Progression
• Extracellular Space/enzymology
• Granzymes/antagonists & inhibitors
• Granzymes/genetics
• Granzymes/metabolism
• Humans
• Inflammasomes/metabolism
• Inflammation/pathology
• Inflammation Mediators/metabolism
• Interleukin-6/biosynthesis
• Mice, Knockout
• NF-kappa B/metabolism
• RNA, Messenger/genetics
• RNA, Messenger/metabolism

Granzyme A (GzmA), together with perforin, are well-known for their cytotoxic activity against tumor or virus-infected cells. In addition to this cytotoxic function, GzmA stimulates several immune cell types and induces inflammation in the absence of perforin, however, its effect on the dendritic cell (DC) is unknown. In the current study, we showed that recombinant GzmA induced the phenotypic maturation of plasmacytoid DCs (pDCs) and conventional DCs (cDCs), but not their apoptosis. Particularly, GzmA made pDCs more functional, thus leading to production of type I interferon (IFN) via the TLR9-MyD88 pathway. We also demonstrated that GzmA binds TLR9 and co-localizes with it in endosomes. When co-administered with antigen, GzmA acted as a powerful adjuvant for eliciting antigen-specific cytotoxic CD8⁺ T lymphocytes (CTLs) that protected mice from tumor challenge. The induction of CTL was completely abolished in XCR1⁺ DC-depleted mice, whereas it was reduced to less than half in pDC-depleted or IFN-α/β receptor knockout mice. Thus, CTL cross-priming was dependent on XCR1⁺cDC and also type I IFN, which was produced by GzmA-activated pDCs. These results indicate that GzmA -stimulated pDCs enhance the cross-priming activity of cDCs in situ. We also showed that the adjuvant effect of GzmA is superior to CpG-ODN and LPS. Our findings highlight the ability of GzmA to bridge innate and adaptive immune responses via pDC help and suggest that GzmA may be useful as a vaccine adjuvant.

• TLR9
• adaptive immunity
• adjuvant
• anti-tumor effect
• dendritic cell
• granzyme A
• innate immunity
• type I IFN

The current study analyzed gene expression profiles of the endolymphatic sac (ES) in rats and identified expressed genes, present in the human and rat ES, to reveal key hubs for inflammatory responses. Microarray data (accession no. E-MEXP-3022) were obtained from the European Bioinformatics Institute database, including three biological replicates of ES plus dura tissues and three replicates of pure dura tissues form rats. Differentially expressed genes (DEGs) were screened using the Linear Model for Microarray data method and a protein-protein interaction (PPI) network was constructed using data from the Search Tool for the Retrieval of Interacting Genes/Proteins database followed by a module analysis via Clustering with Overlapping Neighborhood Expansion. Function enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery online tool. A total of 612 DEGs were identified, including 396 upregulated and 216 downregulated genes. Gene ontology term enrichment analysis indicated DEGs were associated with cell adhesion, including α5-integrin (Itga1) and secreted phosphoprotein 1 (Spp1); T cell co-stimulation, including C-C chemokine ligand (Ccl)21 and Ccl19; and the toll-like receptor signaling pathway, including toll-like receptor (Tlr)2, Tlr7 and Tlr8. These conclusions were supported by Kyoto Encyclopedia of Genes and Genomes pathway analyses revealing extracellular matrix-receptor interaction, including Itga1 and Spp1; leukocyte transendothelial migration, includingclaudin-4 (Cldn4); and malaria, including Tlr2. The hub roles of Itga1, Cd24 and Spp1 were revealed by calculating three topological properties of the PPI network. Ccl21, Ccl19 and Cldn4 were demonstrated to be crucial following significant module analysis according to the corresponding threshold, which revealed they were enriched in inflammation pathways. Tlr7, Tlr2, granzyme m and Tlr8 were common genes associated with inflammatory responses in rat and human ES. In conclusion, abnormal expression of the aforementioned inflammation-associated genes may be associated with the development of autoimmune inner ear diseases.

• cell adhesion
• endolymphatic sac
• hearing loss
• inflammation

• cancer progression
• extracellular matrix
• granzymes
• inflammation

• Antiproteases
• Intestinal barrier
• Intestinal permeability
• Paracellular permeability
• Protease inhibitor
• Proteases
• Proteinase-activated receptor
• Tight junction

• Animals
• Diabetes Mellitus, Type 1/physiopathology
• Electrolytes
• Epithelial Cells/metabolism
• Humans
• Inflammation/physiopathology
• Inflammatory Bowel Diseases/physiopathology
• Intestines/pathology
• Matrix Metalloproteinase Inhibitors/chemistry
• Mice
• Peptide Hydrolases/metabolism
• Permeability
• Protease Inhibitors/chemistry
• Serine Proteinase Inhibitors/chemistry
• Tight Junctions
• Treatment Outcome