The Mechanism of Nano-Particles Intervening Invasion and Metastasis of Lymphoma Based on Autophagy Targeted with miR-36b and Orienteering Analysis on Apoptosis Gene

Whether the expression of gene P53 related with autophagy and apoptosis and action was regulated by miR-36b was discussed in our study. And the action of orienteering nano-particles on intervening invasion and metastasis of lymphoma was analyzed. The normal lymphoid tissue collected from the patients with simple lymphatic hyperplasia was set as control. The lymphoma samples from patients with early indolent lymphoma were collected. The level of mRNA in miR-36b and P53 was detected by PCR. The level of P53 protein and level of mRNA in miR-36b and P53 among normal lymphoid cell, cell strain of low metastatic lymphoma and cell strain of high metastatic lymphoma was compared. They were divided into four groups: miR-NC group, orienteering nano-particles’ group, siRNA-NC group and siRNA-P53 group. The cell proliferative capacity was detected by FCM. The quantity of cell invasion and metastasis was detected by transwell. The expression quantity of P53 mRNA in lymphoma tissue was increased obviously compared with control group. The expression of miR-36b was lower while the expression of P53 was higher along with the later staging of TNM. And the express was related with the staging of TNM. The expression quantity of P53 mRNA in lymphoma cell was higher in normal cell notably. But expression quantity of miR-36b in lymphoma cell was lower in normal cell notably. The decreased of expression of miR-36b and increased of expression of P53 was related with enhancing the ability of invasion and metastasis of lymphoma cells.

Cell strain-derived induced pluripotent stem cell as a genetically controlled approach to investigating aging mechanisms and viral pathogenesis

The expansion of the geographic footprint of dengue viruses (DENVs) and their mosquito vectors have affected more than half of the global population, including older adults who appear to show elevated risk of severe dengue. Despite this epidemiological trend, how age and senescence impact virus-host interactions involved in dengue pathogenesis to increase the risk of severe dengue is poorly understood. Herein, we show that conversion of diploid cells with finite lifespan into iPSCs followed by differentiation back into cell strain can be an approach to derive genetically identical cells at different stages of senescence to study virus and aging host interactions. Our findings show that cellular senescence impact the host response to infection and the ensuing outcome. We suggest iPSC-derive cell strains as a potentially useful technical approach to genetically controlled host-virus interaction studies to understand how aging impact viral pathogenesis.

Non-Random Sister Chromatid Segregation in Human Tissue Stem Cells

The loss of genetic fidelity in tissue stem cells is considered a significant cause of human aging and carcinogenesis. Many cellular mechanisms are well accepted for limiting mutations caused by replication errors and DNA damage. However, one mechanism, non-random sister chromatid segregation, remains controversial. This atypical pattern of chromosome segregation is restricted to asymmetrically self-renewing cells. Though first confirmed in murine cells, non-random segregation was originally proposed by Cairns as an important genetic fidelity mechanism in human tissues. We investigated human hepatic stem cells expanded by suppression of asymmetric cell kinetics (SACK) for evidence of non-random sister chromatid segregation. Cell kinetics and time-lapse microscopy analyses established that an ex vivo expanded human hepatic stem cell strain possessed SACK agent-suppressible asymmetric cell kinetics. Complementary DNA strand-labeling experiments revealed that cells in hepatic stem cell cultures segregated sister chromatids non-randomly. The number of cells cosegregating sister chromatids with the oldest “immortal DNA strands” was greater under conditions that increased asymmetric self-renewal kinetics. Detection of this mechanism in a human tissue stem cell strain increases support for Cairns’ proposal that non-random sister chromatid segregation operates in human tissue stem cells to limit carcinogenesis.

Cell focal adhesion clustering leads to decreased and homogenized basal strains

The subendothelial matrix of the artery is a complex mechanical environment where endothelial cells respond to and affect changes upon the underlying substrate. Our recent work has demonstrated that endothelial cell strain heterogeneity increases on a more heterogeneous underlying subendothelial matrix, and these cells display increased focal adhesion presence on stiffer substrate areas. However, the impact of these grouped focal adhesions on endothelial cell strains has not been explored. Here, we use finite element modeling to investigate the effects of micro-scale stiffness heterogeneities and focal adhesion location and stiffness on endothelial cell strains. Shear stress applied to the apical cell layer demonstrated a minimal effect on cell strain values while substrate stretch had a greater effect on cell strain in the cell-substrate model. The addition of focal adhesions into the computational model (cell-FA-substrate model) predicted a decrease and homogenization of the cell strains. For simulations including focal adhesions, stiffer and more distributed adhesions caused increased and more heterogeneous endothelial cell strains. Overall, our data indicate that cells may group focal adhesions to minimize and homogenize their basal strains.