Identification of immunological characteristics and cuproptosis-related molecular clusters in primary Sjogren's syndrome

Article Plant Sciences

Protein lipoylation in mitochondria requires Fe-S cluster assembly factors NFU4 and NFU5

Jonathan Przybyla-Toscano et al.

Summary: NFU4 and NFU5 proteins in plants have a housekeeping function and are involved in the lipoylation process of mitochondrial dehydrogenases, providing Fe-S clusters to lipoyl synthase.

PLANT PHYSIOLOGY (2022)

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Review Medicine, Research & Experimental

Sjogren's syndrome: a systemic autoimmune disease

Simone Negrini et al.

Summary: Sjogren's syndrome is a chronic autoimmune disease characterized by dryness in the eyes and mouth, with systemic manifestations and unclear pathogenesis. Diagnosis is based on clinical symptoms and specific tests, while treatment ranges from local to systemic medications. New classification criteria and disease activity scores have been developed for research and clinical practice.

CLINICAL AND EXPERIMENTAL MEDICINE (2022)

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Editorial Material Multidisciplinary Sciences

Copper-induced cell death Excess copper causes mitochondrial protein aggregation and triggers a distinct form of cell death

Martha A. Kahison et al.

SCIENCE (2022)

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Article Multidisciplinary Sciences

Copper induces cell death by targeting lipoylated TCA cycle proteins

Peter Tsvetkov et al.

Summary: Copper is an essential cofactor for all organisms, but excessive copper can lead to cell death. We found that copper-dependent cell death mechanism is different from known mechanisms, and it is related to mitochondrial respiration. Copper directly binds to lipoylated components of the tricarboxylic acid cycle, causing protein aggregation and loss of iron-sulfur cluster proteins, ultimately leading to cell death.

SCIENCE (2022)

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Article Genetics & Heredity

A Novel Cuproptosis-Related Prognostic Gene Signature and Validation of Differential Expression in Clear Cell Renal Cell Carcinoma

Zilong Bian et al.

Summary: This study systematically evaluated the genetic alterations of cuproptosis-related genes in clear cell renal cell carcinoma (ccRCC) and constructed a prognostic signature of these genes. The results suggest that the cuproptosis-related gene signature may serve as a potential prognostic predictor for ccRCC patients and is associated with immune infiltration levels and PD-1 expression.

GENES (2022)

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Article Oncology

SGOL2 is a novel prognostic marker and fosters disease progression via a MAD2-mediated pathway in hepatocellular carcinoma

Qingqing Hu et al.

Summary: This study reveals that SGOL2 acts as an oncogene in hepatocellular carcinoma (HCC) by regulating MAD2 and dysregulating the cell cycle, providing a potential therapeutic target for HCC.

BIOMARKER RESEARCH (2022)

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Review Biochemistry & Molecular Biology

Copper homeostasis and cuproptosis in health and disease

Liyun Chen et al.

Summary: Copper is an essential micronutrient that is required for various physiological processes in almost all cell types, and its homeostasis is tightly regulated to avoid oxidative stress and cellular dysfunction. Recent studies have identified a novel form of cell death called cuproptosis, which is induced by copper binding to lipoylated enzymes in the tricarboxylic acid cycle and ultimately leads to protein aggregation, proteotoxic stress, and cell death. This article summarizes current knowledge on copper metabolism, copper-related diseases, the characteristics of cuproptosis, and the regulatory mechanisms involved. The implications of cuproptosis in the pathogenesis of diseases such as Wilson's disease, neurodegenerative diseases, and cancer are also discussed, along with the therapeutic potential of targeting cuproptosis.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2022)

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Article Multidisciplinary Sciences

Indispensable epigenetic control of thymic epithelial cell development and function by polycomb repressive complex 2

Thomas Barthlott et al.

Summary: Thymic T cell development and T cell receptor repertoire selection rely on molecular signals from thymic epithelial cells (TEC), whose development and function are epigenetically regulated. Disruption of PRC2 activity alters H3K27me3 configuration, impairs TEC functions, and affects T cell development.

NATURE COMMUNICATIONS (2021)

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Article Immunology

Ubiquitin Ligases CBL and CBL-B Maintain the Homeostasis and Immune Quiescence of Dendritic Cells

Haijun Tong et al.

Summary: DC-specific ablation of CBL and CBL-B leads to spontaneous liver inflammation and fibrosis in mice, associated with an increase in cDC1s and abnormal activation of the FLT3-mTOR signaling pathway. This study highlights the critical role of CBLs in maintaining DC homeostasis and immune quiescence, and suggests their relevance to liver inflammatory diseases and fibrosis in humans.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Rheumatology

Parsing multiomics landscape of activated synovial fibroblasts highlights drug targets linked to genetic risk of rheumatoid arthritis

Haruka Tsuchiya et al.

Summary: Objectives: Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation in the synovium, where synovial fibroblasts (SFs) play a major role. This study aimed to understand the genetic contribution to molecular regulatory networks in SFs under inflammatory conditions. Methods: SFs from RA and osteoarthritis (OA) patients were stimulated with various cytokines and immune cell subsets were analyzed. Integrative analyses including mRNA expression, histone modifications, 3D genome architecture, and genetic variations were performed. Results: Unstimulated SFs from RA patients showed differences in transcriptome and epigenome compared to OA SFs. Most responses to stimulations were shared between the diseases. SFs expressed pathogenic genes and chromatin remodeling in activated SFs revealed enrichment of RA risk loci in clusters of enhancers induced by proinflammatory cytokines. A RA risk SNP formed 3D contact with the promoter of a gene related to arthritis, and inhibition of this gene suppressed cytokine and chemokine production in SFs. Conclusions: This study identified potential therapeutic targets associated with genetic risk of RA and established a dynamic landscape of activated SFs.

ANNALS OF THE RHEUMATIC DISEASES (2021)

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Review Cell Biology