Wen Jia

The epithelial-mesenchymal transition (EMT) often plays a critical role in cancer metastasis and chemoresistance, and decoding its dynamics is crucial to design effective therapeutics. EMT is regulated at multiple levels-transcriptional, translational, protein stability and epigenetics; the mechanisms by which epigenetic regulation can alter the dynamics of EMT remain elusive. Here, to identify the possible effects of epigenetic regulation in EMT, we incorporate a feedback term in our previously proposed model of EMT regulation of the miR-200/ZEB/miR-34/SNAIL circuit. This epigenetic feedback that stabilizes long-term transcriptional activity can alter the relative stability and distribution of states in a given cell population, particularly when incorporated in the inhibitory effect on miR-200 from ZEB. This feedback can stabilize the mesenchymal state, thus making transitions out of that state difficult. Conversely, epigenetic regulation of the self-activation of ZEB has only minor effects. Our model predicts that this effect could be seen in experiments, when epithelial cells are treated with an external EMT-inducing signal for a sufficiently long period of time and then allowed to recover. Our preliminary experimental data indicates that a chronic TGF-β exposure gives rise to irreveversible EMT state; i.e. unable to reverse back to the epithelial state. Thus, this integrated theoretical-experimental approach yields insights into how an epigenetic feedback may alter the dynamics of EMT.

The outer membrane vesicle ( OMV ) derived from Porphyromonas gingivalis plays an essential role in causing inflammation which, in turn, plays an important part in the pathogenesis of cardiovascular diseases such as atherosclerosis and thromboembolism. However, the contribution of oral bacteria to vascular calcification is yet to be determined. Here, we evaluated the effect of OMV on vascular smooth muscle cell ( VSMC ) calcification both in vitro and ex vivo . We established a reproducible P. gingivalis OMV ‐induced differentiation and calcification model of VSMC s in vitro . The results indicate that OMV promotes VSMC calcification in a concentration‐dependent manner, modulating the expression of bone markers and SMC markers both on genes and proteins that are important for osteoblastic differentiation and mineralization of VSMC s. We also showed that the key osteogenic transcription factor, runt‐related transcription factor 2 (Runx2), which is affected by upstream extracellular‐regulated kinase ( ERK ) signaling, is a key regulator of OMV ‐induced VSMC differentiation and calcification. Taken together, our research demonstrates that Runx2 is a crucial component of OMV ‐induced calcification of VSMC s, and ERK signaling plays a vital role in mediating Runx2 up‐regulation and VSMC calcification.

BACKGROUND: Dietary fiber plays a potential role in regulating energy intake and stabilizing postprandial blood glucose levels. Soluble dietary fiber has become an important entry point for nutritional research on the regulation of satiety. METHODS: this was a double-blind, randomized cross-over trial enrolling 12 healthy subjects to compare the effects of RPG (R+PolyGly) dietary fiber products (bread, powder, and capsule) and pectin administered with a standard meal on satiety, blood glucose, and serum insulin level. RESULTS: Adding 3.8% RPG dietary fiber to bread significantly increased the volume, water content, hardness, and chewiness of bread compared to 3.8% pectin bread and white bread and significantly improved the sensory quality of bread. RPG bread had better appetite suppression effects at some time points than the other two groups and the best postprandial blood glucose lowering effects among the three groups. Administration of RPG capsules containing 5.6 g of RPG dietary fiber with meals improved satiety and reduced hunger compared to 6 g of RPG powder and 6 g of pectin, which had the greatest effect on suppressing appetite and reducing prospective food consumption. The peak level of serum glucagon-like peptide-1 (GLP-1) in the RPG capsule group (578.17 ± 19.93 pg/mL) was significantly higher than that in other groups at 0 min and 30 min after eating. RPG powder had the best effect in reducing postprandial blood glucose and increasing serum insulin levels; the total area under the curve (AUC) of serum insulin with RPG powder was higher than other groups (5960 ± 252.46 μU min/mL). CONCLUSION: RPG dietary fiber products can improve the sensory properties of food, reduce postprandial blood glucose, and enhance satiety, especially in capsule and powder forms. Further research on the physiological effects of RPG dietary fiber is required to facilitate its use as a functional ingredient in food products.

// Wen Jia 1 , 2 , Shubham Tripathi 1 , 3 , 4 , Priyanka Chakraborty 5 , Adithya Chedere 6 , Annapoorni Rangarajan 5 , 6 , Herbert Levine 1 , 4 and Mohit Kumar Jolly 5 1 Center for Theoretical Biological Physics, Rice University, Houston, TX, USA 2 Department of Physics and Astronomy, Rice University, Houston, TX, USA 3 PhD Program in Systems, Synthetic, and Physical Biology, Rice University, Houston, TX, USA 4 Department of Physics, Northeastern University, Boston, MA, USA 5 Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore, India 6 Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India Correspondence to: Herbert Levine, email: h.levine@northeastern.edu Mohit Kumar Jolly, email: mkjolly@iisc.ac.in Keywords: epithelial-mesenchymal transition; mesenchymal-epithelial transition; GRHL2; epigenetics; asymmetric cell division Received: May 02, 2020     Accepted: June 01, 2020     Published: July 07, 2020 ABSTRACT Epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET) are central to metastatic aggressiveness and therapy resistance in solid tumors. While molecular determinants of both processes have been extensively characterized, the heterogeneity in the response of tumor cells to EMT and MET inducers has come into focus recently, and has been implicated in the failure of anti-cancer therapies. Recent experimental studies have shown that some cells can undergo an irreversible EMT depending on the duration of exposure to EMT-inducing signals. While the irreversibility of MET, or equivalently, resistance to EMT, has not been studied in as much detail, evidence supporting such behavior is slowly emerging. Here, we identify two possible mechanisms that can underlie resistance of cells to undergo EMT: epigenetic feedback in ZEB1/GRHL2 feedback loop and stochastic partitioning of biomolecules during cell division. Identifying the ZEB1/GRHL2 axis as a key determinant of epithelial-mesenchymal plasticity across many cancer types, we use mechanistic mathematical models to show how GRHL2 can be involved in both the abovementioned processes, thus driving an irreversible MET. Our study highlights how an isogenic population may contain subpopulation with varying degrees of susceptibility or resistance to EMT, and proposes a next set of questions for detailed experimental studies characterizing the irreversibility of MET/resistance to EMT.

207-27 administration in healthy adults resulted in improvements in gut microbiota community and sleep duration. The mechanisms might involve modulation of the gut microbiota structure to regulate the function of the gut-brain axis, including increases in SCFA levels and decreases in hypothalamic-pituitary-adrenal axis activity. The Chinese clinical trial registry number is ChiCTR2300069453 (https://www.chictr.org.cn/showproj.html?proj=191193, registered 16 May 2023 - retrospectively registered).