The complexities of cell death mechanisms: a new perspective in systemic sclerosis therapy.

Systemic sclerosis, also termed scleroderma, is a severe and debilitating autoimmune disease characterized by fibrosis, an aberrant immune response, and vascular dysfunction. Cell death is essential to the body's continued normal development as it removes old or damaged cells. This process is governed by several mechanisms, including programmed cell death through apoptosis, necrosis, and pyroptosis, as well as metabolic processes, such as ferroptosis and cuproptosis.

[Expression and significance of ferroptosis marker 4-HNE in model of systemic sclerosis].

Objective: To investigate the expression and physiological significance of the ferroptosis marker 4-hydroxynonenal (4-HNE) in myofibroblasts induced by transforming growth factor-β1 (TGF-β1), providing theoretical evidence for its potential role in the diagnosis and treatment of fibrosis in systemic sclerosis (SSc).

Methods: Mouse embryonic fibroblasts (NIH3t3) were cultured and divided into two groups after 12 h of starvation: the control group (cultured in 1% serum-containing medium) and the TGF-β1 group (cultured in 10 μg/L TGF-β1 with 1% serum-containing medium). Cell morphology changes in both groups were observed under a microscope.

Age-related epithelial defects limit thymic function and regeneration.

The thymus is essential for establishing adaptive immunity yet undergoes age-related involution that leads to compromised immune responsiveness. The thymus is also extremely sensitive to acute insult and although capable of regeneration, this capacity declines with age for unknown reasons. We applied single-cell and spatial transcriptomics, lineage-tracing and advanced imaging to define age-related changes in nonhematopoietic stromal cells and discovered the emergence of two atypical thymic epithelial cell (TEC) states.

The bidirectional relationship between periodontitis and diabetes: New prospects for stem cell-derived exosomes.

Periodontitis and diabetes have a bidirectional link, making therapeutic treatment of periodontitis and diabetes challenging. Numerous factors, including microbes, inflammatory cytokines, immune cell activity, glucose levels, and metabolic disorders, contribute to the bidirectional relationship of periodontitis and diabetes. Basic periodontal treatment, medication, surgical treatment, and combined treatment are the most widely used treatments, but their efficacy are limited.

Potential angiogenic, immunomodulatory, and antifibrotic effects of mesenchymal stem cell-derived extracellular vesicles in systemic sclerosis.

Systemic sclerosis (SSc) is an intricate systemic autoimmune disease with pathological features such as vascular injury, immune dysregulation, and extensive fibrosis of the skin and multiple organs. Treatment options are limited; however, recently, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been acknowledged in preclinical and clinical trials as being useful in treating autoimmune diseases and are likely superior to MSCs alone. Recent research has also shown that MSC-EVs can ameliorate SSc and the pathological changes in vasculopathy, immune dysfunction, and fibrosis.

The acetyltransferase KAT7 is required for thymic epithelial cell expansion, expression of AIRE target genes, and thymic tolerance.

The autoimmune regulator (AIRE) induces the transcription of thousands of peripheral tissue genes (PTGs) in thymic epithelial cells (TECs) to mediate immunological tolerance. The chromatin state required for optimal AIRE function in TECs and how this state is induced remains unclear. We tested the role of the histone acetyltransferase, KAT7 (also known as HBO1 or MYST2), which is essential for acetylation of histone 3 lysine 14, in TEC differentiation, AIRE-mediated PTG expression, and thymic tolerance.