Project description:In this study, we explore the role of melatonin, abundantly secreted by enteroendocrine cells (EECs) yet overlooked beyond its circadian regulation, in promoting intestinal regeneration. Our findings demonstrate that melatonin can be integrated into the PGE2-EP4-YAP signaling axis to facilitate injury-responsive reprogramming and RSC induction in the intestinal epithelium both in vitro and in vivo. This work uncovers a novel function of melatonin, opening new therapeutic possibilities in regenerative medicine.
Project description:total RNA from mouse (male c57BL/6) spleen labeled with Cy3 vs total RNA from mouse (male c57BL/6) B cells treated with Prostaglandin E2 labeled with Cy5- time course with repeats Keywords: ordered
Project description:Melatonin is a well-known agent that plays multiple roles in animals. Its possible function in plants is less clear. In the present study, we tested the effect of melatonin (N-acetyl-5-methoxytryptamine) on soybean growth and development. Both spraying of leaves and seed-coating with melatonin significantly promoted soybean growth as judged from leaf size and plant height. This enhancement was also observed in soybean production and their fatty acid content. Melatonin increased pod number, seed number and seed weight. However, the 100-seed weight was not influenced by melatonin application. Melatonin also improved soybean tolerance to salt and drought stresses. Transcriptome analysis revealed that melatonin up-regulated the expression of many genes and alleviated the inhibitory effects of salt stress on gene expressions. Further detailed analysis of the affected pathways documents that melatonin likely achieved its promotional roles in soybean through enhancement of genes involved in cell division, photosynthesis, carbohydrate metabolism, fatty acid biosynthesis and ascorbate metabolism. Our results demonstrate that melatonin has significant potential for improving of soybean growth and seed production. Further study should uncover more about the molecular mechanisms of melatoninM-bM-^@M-^Ys function in soybeans and other crops. Four different treatments were chosen, water, salt, 100M-BM-5M melatonin and salt plus 100M-BM-5M melatonin. The comparison of salt/melatonin-treated sample versus water-treated sample reveals salt or melatonin induced transcriptome changes. The comparison of melatonin plus salt treated sample versus salt-treated sample reveals melatonin induced changes when salt exists.
Project description:Direct cardiac reprogramming from fibroblasts can be a promising approach for disease modeling, drug screening, and cardiac regeneration in pediatric and adult patients. However, postnatal and adult fibroblasts are less efficient for reprogramming compared with embryonic fibroblasts, and barriers to cardiac reprogramming associated with aging remain undetermined. In this study, we screened 8,400 chemical compounds, and found that diclofenac sodium (diclofenac), a non-steroidal anti-inflammatory drug, greatly enhanced cardiac reprogramming in combination with Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Hand2. Intriguingly, diclofenac promoted cardiac reprogramming in mouse postnatal and adult tail-tip fibroblasts (TTFs), but not in mouse embryonic fibroblasts (MEFs). Mechanistically, diclofenac enhanced cardiac reprogramming by inhibiting cyclooxygenase-2, prostaglandin E2/prostaglandin E receptor 4, cyclic AMP/protein kinase A, and interleukin 1b pathway, silencing inflammatory and fibroblast programs, which were activated in postnatal and adult TTFs. Thus, anti-inflammation can be a new target for cardiac reprogramming associated with aging.
Project description:Assessment of openly accessible chromatin regions in young and aged muscle stem cells and short term epigenetic response to prostaglandin E2 treatment.
Project description:Prostaglandins are involved in maintaining tissue integrity under homeostatic conditions. However, in chronic inflammation and cancer prostaglandins have been linked to immune deviation including strong suppression of effector T-cell function. Yet, the molecular mechanisms underlyingimmunosuppression and the cell types involved are only purely understood. Here, we show for the first time that Treg cells are the critical cellular component exerting immunosuppressive effects in prostaglandin E2 (PGE2)-rich environments. Hydroxyprostaglandin dehydrogenase (HPGD), which catabolizes PGE2 into immunosuppressive metabolites, is the critical molecular link between prostaglandin accumulation, increased Treg-cell function and avoidance of tissue destruction.
Project description:Tumour immune escape is a major factor contributing to cancer progression and unresponsiveness to cancer therapies. Tumours can produce prostaglandin E2 (PGE2), an inflammatory mediator that directly acts on NK cells to inhibit anti-tumour immunity. However, it is unclear precisely how PGE2 influences NK cell tumour-restraining functions. Here, we investigated how treatment with PGE2 over 24 hours affects gene expression in human NK cells.
Project description:Objective: Melatonin and auxin are both tryptophan-derived indole molecules. Much attention has been given to proposed auxin-like activities of melatonin (regulating growth concentration-dependently). However, it still largely remains unclear whether melatonin and auxin regulate signalling pathways in a similar fashion. The purpose of this study is to directly compare the transcriptome response of Arabidopsis with melatonin or auxin. Method: mRNA profiles of 12-day old rosettes treated for a further of 3 days with +/- melatonin (5µM, 1005µM) or NAA(4.5µM) were generated by RNA-sequencing in triplicates (three independent biological experiments), using Illumina NextSeq 550 technology. Results: Comparative global transcriptome analysis conducted on Arabidopsis rosette treated with melatonin or NAA under exact same set of experimental conditions revealed differential number of genes and type of pathways. While auxin (4.5µM) regulated a large number of genes and elicited a diverse response, melatonin (100µM) showed a modest effect on transcriptome with only few genes significantly regulated whereas none regulated at approximately equimolar concentration with NAA (5µM) as compared to untreated solvent control (0.1% EtOH). Interestingly, the most prominent category of genes regulated by melatonin trended towards biotic stress defense pathways. Conclusions: These findings indicate that melatonin and auxin act quite differently toward signaling pathways in Arabidopsis. Melatonin has its own set of mechanisms to exert its functions, with strong inclination toward biotic defense pathways.