AI Article Synopsis
- Kidney stones are primarily made of calcium oxalate and can cause inflammation and damage in kidney cells, leading to a condition known as CaOx nephrocalcinosis.
- The study tested a new drug, MDL-800, which acts as an allosteric agonist for Sirtuin 6 (SIRT6), showing it can reduce kidney cell damage and inflammation caused by calcium oxalate crystals in both cell cultures and animal models.
- MDL-800 works by decreasing levels of inflammatory proteins and enhancing SIRT6's function, offering a potential new treatment approach for kidney damage linked to calcium oxalate stones.
Article Abstract
Kidney stones consist largely of calcium oxalate (CaOx), and induce inflammation and damage to renal tubular epithelial (RTE) cells, leading to CaOx nephrocalcinosis. Sirtuin 6 (SIRT6), a sirtuin family member, is an NAD-dependent deacetylase that has been associated with cell damage and inflammation in various diseases. This study evaluated the efficacy of the novel SIRT6 allosteric agonist MDL-800 in treating CaOx nephrocalcinosis. The data revealed that MDL-800 preconditioning alleviated CaOx crystal-mediated damage in RTE cells by suppressing inflammation, as shown in both cell and animal studies. Furthermore, MDL-800 enhanced SIRT6 deacetylation at H3K9AC. However, MDL-800 pretreatment of SIRT6-knockdown (KD) RTE cells did not protect against CaOx crystal-induced cell damage and inflammation. Mechanistically, MDL-800 markedly downregulated the expression of IL-1β, TNF-α, MCP-1, and IL-6 in mouse kidneys via the TRL4/NF-κB pathway. These data indicated that MDL-800 reduces inflammation and inhibits the TLR4/NF-κB axis by increasing SIRT6-modulated histone deacetylation, thus inhibiting and protecting against inflammatory responses. In summary, MDL-800 modulation of SIRT6-mediated inflammation and renal damage represents a novel strategy for treating CaOx-mediated nephrocalcinosis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.intimp.2024.113864 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The SIRT6 allosteric activator MDL-800 suppresses calcium oxalate nephrocalcinosis by alleviating inflammatory and renal damage.
Int Immunopharmacol
December 2024
Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China; Institute of Urology, Anhui Medical University, Hefei, China; Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, Hefei, China. Electronic address:
Article Synopsis
- Kidney stones are primarily made of calcium oxalate and can cause inflammation and damage in kidney cells, leading to a condition known as CaOx nephrocalcinosis.
- The study tested a new drug, MDL-800, which acts as an allosteric agonist for Sirtuin 6 (SIRT6), showing it can reduce kidney cell damage and inflammation caused by calcium oxalate crystals in both cell cultures and animal models.
- MDL-800 works by decreasing levels of inflammatory proteins and enhancing SIRT6's function, offering a potential new treatment approach for kidney damage linked to calcium oxalate stones.
Internal regulation between constitutively expressed T cell co-inhibitory receptors BTLA and CD5 and tolerance in recent thymic emigrants.
Open Biol
October 2024
Department of Surgery, University of Alberta, Edmonton, AB, Canada.
Immunologic self-tolerance involves signals from co-inhibitory receptors. Several T cell co-inhibitors, including PD-1, are expressed upon activation, whereas CD5 and BTLA are expressed constitutively. The relationship between constitutively expressed co-inhibitors and when they are needed is unknown.
View Article and Find Full Text PDFVariable clinical presentation of hypomorphic DCLRE1C deficiency from childhood to adulthood.
Pediatr Allergy Immunol
October 2024
Division of Pediatric Immunology and Allergy, Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey.
Article Synopsis
- The study focuses on long-term follow-up of 18 pediatric and adult patients with hypomorphic DCLRE1C mutations diagnosed with leaky severe combined immunodeficiency (SCID).
- Common clinical manifestations included recurrent infections, skin issues, autoimmune diseases, and malignancy, with a significant number of patients showing low immunoglobulin levels and T/B-cell lymphopenia.
- Findings suggested a dominant Th1 immune response, with elevated IFN-γ and T cells contributing to chronic inflammation and autoimmunity, emphasizing the need for ongoing patient monitoring post-hematopoietic stem cell transplantation (HSCT).
Dynamic dysregulation of retrotransposons in neurodegenerative diseases at the single-cell level.
Genome Res
October 2024
Center for Precision Health, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, Texas 77030, USA;
Retrotransposable elements (RTEs) are common mobile genetic elements comprising ∼42% of the human genome. RTEs play critical roles in gene regulation and function, but how they are specifically involved in complex diseases is largely unknown. Here, we investigate the cellular heterogeneity of RTEs using 12 single-cell transcriptome profiles covering three neurodegenerative diseases, Alzheimer's disease (AD), Parkinson's disease, and multiple sclerosis.
View Article and Find Full Text PDFExpression of most retrotransposons in human blood correlates with biological aging.
Elife
October 2024
Comprehensive Cancer Centre, School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, King's College London, London, United Kingdom.
Retrotransposons (RTEs) have been postulated to reactivate with age and contribute to aging through activated innate immune response and inflammation. Here, we analyzed the relationship between RTE expression and aging using published transcriptomic and methylomic datasets of human blood. Despite no observed correlation between RTE activity and chronological age, the expression of most RTE classes and families except short interspersed nuclear elements (SINEs) correlated with biological age-associated gene signature scores.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!