Chromatin accessibility of circulating CD8(+) T cells predicts treatment response to PD-1 blockade in patients with gastric cancer

Although tumor genomic profiling has identified small subsets of gastric cancer (GC) patients with clinical benefit from anti-PD-1 treatment, not all responses can be explained by tumor sequencing alone. We investigate epigenetic elements responsible for the differential response to anti-PD-1 therapy by quantitatively assessing the genome-wide chromatin accessibility of circulating CD8(+) T cells in patients' peripheral blood. Using an assay for transposase-accessible chromatin using sequencing (ATAC-seq), we identify unique open regions of chromatin that significantly distinguish anti-PD-1 therapy responders from non-responders. GC patients with high chromatin openness of circulating CD8(+) T cells are significantly enriched in the responder group. Concordantly, patients with high chromatin openness at specific genomic positions of their circulating CD8(+) T cells demonstrate significantly better survival than those with closed chromatin. Here we reveal that epigenetic characteristics of baseline CD8(+) T cells can be used to identify metastatic GC patients who may benefit from anti-PD-1 therapy. Anti-PD-1 therapy could induce a durable response in patients with gastric cancer, however biomarkers to predict response to immunotherapy are generally lacking. Here the authors report that openness of chromatin in circulating CD8(+) T cells predicts treatment outcome in patients with metastatic gastric cancer treated with pembrolizumab

In Situ Preconditioning of Human Mesenchymal Stem Cells Elicits Comprehensive Cardiac Repair Following Myocardial Infarction

Human bone marrow-derived mesenchymal stem cells (BM-MSCs), represented as a population of adult stem cells, have long been considered as one of the most promising sources for cell-based cardiac regenerative therapy. However, their clinical use has been significantly hampered by low survival and poor retention following administration into failing hearts. Here, to improve the therapeutic effectiveness of BM-MSCs, we examined a novel therapeutic platform named in situ preconditioning in a rat myocardial infarction (MI) model. In situ preconditioning was induced by a combinatory treatment of BM-MSCs with genetically engineered hepatocyte growth factor-expressing MSCs (HGF-eMSCs) and heart-derived extracellular matrix (hdECM) hydrogel. Subsequently, our results demonstrated that in situ preconditioning with cell mixture substantially improved the survival/retention of BM-MSCs in the MI-induced rat hearts. Enhanced retention of BM-MSCs ultimately led to a significant cardiac function improvement, which was derived from the protection of myocardium and enhancement of vessel formation in the MI hearts. The results provide compelling evidence that in situ preconditioning devised to improve the therapeutic potential of BM-MSCs can be an effective strategy to achieve cardiac repair of MI hearts

In Situ Preconditioning of Human Mesenchymal Stem Cells Elicits Comprehensive Cardiac Repair Following Myocardial Infarction

Human bone marrow-derived mesenchymal stem cells (BM-MSCs), represented as a population of adult stem cells, have long been considered as one of the most promising sources for cell-based cardiac regenerative therapy. However, their clinical use has been significantly hampered by low survival and poor retention following administration into failing hearts. Here, to improve the therapeutic effectiveness of BM-MSCs, we examined a novel therapeutic platform named in situ preconditioning in a rat myocardial infarction (MI) model. In situ preconditioning was induced by a combinatory treatment of BM-MSCs with genetically engineered hepatocyte growth factor-expressing MSCs (HGF-eMSCs) and heart-derived extracellular matrix (hdECM) hydrogel. Subsequently, our results demonstrated that in situ preconditioning with cell mixture substantially improved the survival/retention of BM-MSCs in the MI-induced rat hearts. Enhanced retention of BM-MSCs ultimately led to a significant cardiac function improvement, which was derived from the protection of myocardium and enhancement of vessel formation in the MI hearts. The results provide compelling evidence that in situ preconditioning devised to improve the therapeutic potential of BM-MSCs can be an effective strategy to achieve cardiac repair of MI hearts

The Earth-Moon Transfer Trajectory Design and Analysis using Intermediate Loop Orbits

Various Earth-Moon transfer trajectories are designed and analyzed to prepare the future Korea's Lunar missions. Minimum fuel trajectory solutions are obtained for the departure year of 2017, 2020, 2022, and every required mission phases are analyzed from Earth departure to the final lunar mission orbit. N-body equations of motion are formulated which include the gravitational effect of the Sun, Earth and Moon. In addition, accelerations due to geopotential harmonics, Lunar J2 and solar radiation pressures are considered. Impulsive high thrust is assumed as the main thrusting method of spacecraft with launcher capability of KSLV-2 which is planned to be developed. For the method of injecting a spacecraft into a trans Lunar trajectory, both direct shooting from circular parking orbit and shooting from the multiple elliptical intermediate orbits are adapted, and their design results are compared and analyzed. In addition, spacecraft's visibility from Deajeon ground station are constrained to see how they affect the magnitude of TLI (Trans Lunar Injection) maneuver. The results presented in this paper includes launch opportunities, required optimal maneuver characteristics for each mission phase as well as the trajectory characteristics and numerous related parameters. It is confirmed that the final mass of Korean lunar explorer strongly depends onto the initial parking orbit's altitude and launcher's capability, rather than mission start time

An Earth-Moon Transfer Trajectory Design and Analysis Considering Spacecraft’s Visibility from Daejeon Ground Station at TLI and LOI Maneuvers

The optimal Earth-Moon transfer trajectory considering spacecraft’s visibility from the Daejeon ground station visibility at both the trans lunar injection (TLI) and lunar orbit insertion (LOI) maneuvers is designed. Both the TLI and LOI maneuvers are assumed to be impulsive thrust. As the successful execution of the TLI and LOI maneuvers are crucial factors among the various lunar mission parameters, it is necessary to design an optimal lunar transfer trajectory which guarantees the visibility from a specified ground station while executing these maneuvers. The optimal Earth-Moon transfer trajectory is simulated by modifying the Korean Lunar Mission Design Software using Impulsive high Thrust Engine (KLMDS-ITE) which is developed in previous studies. Four different mission scenarios are established and simulated to analyze the effects of the spacecraft’s visibility considerations at the TLI and LOI maneuvers. As a result, it is found that the optimal Earth-Moon transfer trajectory, guaranteeing the spacecraft’s visibility from Daejeon ground station at both the TLI and LOI maneuvers, can be designed with slight changes in total amount of delta-Vs. About 1% difference is observed with the optimal trajectory when none of the visibility condition is guaranteed, and about 0.04% with the visibility condition is only guaranteed at the time of TLI maneuver. The spacecraft’s mass which can delivered to the Moon, when both visibility conditions are secured is shown to be about 534 kg with assumptions of KSLV-2’s on-orbit mass about 2.6 tons. To minimize total mission delta-Vs, it is strongly recommended that visibility conditions at both the TLI and LOI maneuvers should be simultaneously implemented to the trajectory optimization algorithm

Structural Elucidation and Immune-Enhancing Effects of Novel Polysaccharide from Grifola frondosa

Beta-glucan (β-glucan) is a macromolecule structure where glucose unit has bonded through β-glycosidic bond at 1 and 3 positions. It is well known as a natural immunomodulator without exhibiting any side effects via enhancing immunity. Mushroom contains a large amount of β-glucan and it has anticancerous and antioxidant efficacy. Structure and physical properties of β-glucan are highly influenced by the types of mushroom. In particular, Grifola frondosa has β-1, 3 and β-1, 6 bonds in their structure. It has been noted that β-glucan content also depends upon the size of mushroom particles. The exact content of β-glucan and their immunological activity by a particle size of G. frondosa have yet to be fully elucidated. Herein, β-glucan contents were analyzed according to the particle size of leaf mushroom followed by cell activation and immunoactivity analysis. The highest β-glucan content was observed at a particle size of 20-30 μm (27.65 ± 0.30 w/w). All samples showed ~ 103% cell activation compared to the control and greater cell activity was observed at higher concentration. The significant increase in cytokines secretion was observed in the presence of 20-30 μm particle size of G. frondosa compared to the control. This study suggested that 20-30 μm size is the suitable size of G. frondosa that can be used as a health supplement and food additive to act as an immune booster, hypotensive agent, and hypoglycemic agent

Sutureless transplantation ofin vivopriming human mesenchymal stem cell sheet promotes the therapeutic potential for cardiac repair

© 2022 IOP Publishing Ltd.The heart, contrary to its small size, vigorously pumps oxygen and nutrients to our entire body indeterminably; and thus, its dysfunction could be devastating. Until now, there ave been several major obstacles to applying a cardiac patch for the treatment for myocardial infarction, including poor integration and low engraftment rates, due to the highly-curved surface of the heart and its dynamic nature. Here, we demonstrate a novel way for a comprehensive cardiac repair achieved by the sutureless transplantation of a highly integrablein vivopriming bone marrow mesenchymal stem cell (BMSC) sheet based on the utilization of a highly aligned thermoresponsive nanofiber membrane. Moreover, we developed a BMSC sheet specialized for vascular regeneration through 'in-vivopriming' using human umbilical vein endothelial cells. A prolonged secretion of multiple angiogenic cytokines, such as vascular endothelial growth factor, angiopoietin-1, insulin-like growth factor-1, which was observedin vitrofrom the specialized BMSC sheet seemed to lead a significant improvement in the cardiac function, including intrinsic contractibility and remodeling. In this study, we provide strong evidence thatin vivopriming of a human BMSC sheet develops the therapeutic potential for cardiac repair.11Nsciescopu