ARX
Homeobox protein ARX (Aristaless-related homeobox)
PublicationsПравить
Insulin-producing pancreatic β cells in mice can slowly regenerate from glucagon-producing α cells in settings like β cell loss, but the basis of this conversion is unknown. Moreover, it remains unclear if this intra-islet cell conversion is relevant to diseases like type 1 diabetes (T1D). We show that the α cell regulators Aristaless-related homeobox (Arx) and DNA methyltransferase 1 (Dnmt1) maintain α cell identity in mice. Within 3 months of Dnmt1 and Arx loss, lineage tracing and single-cell RNA sequencing revealed extensive α cell conversion into progeny resembling native β cells. Physiological studies demonstrated that converted α cells acquire hallmark β cell electrophysiology and show glucose-stimulated insulin secretion. In T1D patients, subsets of glucagon-expressing cells show loss of DNMT1 and ARX and produce insulin and other β cell factors, suggesting that DNMT1 and ARX maintain α cell identity in humans. Our work reveals pathways regulated by Arx and Dnmt1 that are sufficient for achieving targeted generation of β cells from adult pancreatic α cells.
MeSH Terms
- Adult
- Aging
- Calcium Signaling
- Cell Lineage
- Child
- Child, Preschool
- DNA (Cytosine-5-)-Methyltransferase 1
- DNA (Cytosine-5-)-Methyltransferases
- Diabetes Mellitus, Type 1
- Electrophysiological Phenomena
- Female
- Gene Deletion
- Gene Expression Regulation
- Glucagon
- Glucagon-Secreting Cells
- Glucose
- Homeodomain Proteins
- Humans
- Insulin
- Insulin Secretion
- Insulin-Secreting Cells
- Male
- Sequence Analysis, RNA
- Single-Cell Analysis
- Transcription Factors
- Young Adult
The advancements in the field of gerontology have unraveled the signaling pathways that regulate life span, suggesting that it might be feasible to modulate aging. To this end, we isolated a novel phytomolecule Acacetin 7-O-α-l-rhamnopyranosyl (1-2) β-D-xylopyranoside (ARX) from Premna integrifolia and evaluated its antiaging effects in Caenorhabditis elegans The spectral data analysis revealed the occurrence of a new compound ARX. Out of the three tested pharmacological doses of ARX, viz. 5, 25, and 50 µM, the 25-µM dose was able to extend life span in C. elegans by more than 39%. The present study suggests that ARX affects bacterial metabolism, which in turn leads to dietary restriction (DR)-like effects in the worms. The effect of ARX on worms with mutations (mev-1, eat-2, sir-2.1, skn-1, daf-16, and hsf-1) indicates that ARX-mediated life-span extension involves mechanisms associated with DR and maintenance of cellular redox homeostasis. This study is the first time report on longevity-promoting activity of ARX in C. elegans mediated by stress and DR-regulating genes. This novel phytomolecule can contribute in designing therapeutics for managing aging and age-related diseases.
MeSH Terms
- Aging
- Animals
- Animals, Genetically Modified
- Body Size
- Caenorhabditis elegans
- Caenorhabditis elegans Proteins
- Feeding Behavior
- Flavones
- Gene Expression Regulation
- Longevity
- Oxidative Stress
Keywords
- Aging
- Caenorhabditis elegans
- Longevity.
- Oxidative stress
- Phytomolecule
There are several commercially available electroencephalogram-derived devices for monitoring anaesthesia depth. This article reviews all published studies describing their use in children; first assessing studies of performance in measuring anaesthesia depth in observational, physiological studies and then describing relevant outcome studies. There is also a brief discussion of why they might be useful, what physiological problems may arise and what the reader should be wary of in the methodology of these studies. The subject is approached from a clinical perspective. There are several physiological studies suggesting that for older children the bispectral index, entropy, Narcotrend index, cerebral state index and A-line ARX index all change with induction of anaesthesia, and have reasonable correlations with doses of anaesthetic agent. There is consistent evidence that the performances are substantially poorer in infants. Some of these devices have been demonstrated to reduce anaesthesia drug consumption and hasten recovery in older children. The bispectral index is the most widely studied, but at this stage there is no evidence to suggest any one device is substantially superior to any other. There may be a role emerging for their use in older children, but their use in infants cannot be supported.
MeSH Terms
- Adolescent
- Aging
- Anesthesia
- Child
- Child, Preschool
- Electroencephalography
- Entropy
- Humans
- Infant
- Monitoring, Intraoperative
- Reproducibility of Results
- Treatment Outcome