Periodical Opinion Toward Rendering of 4D Circulation MRI in Specialized medical Workflow

As the original compound of many podophyllotoxin derivatives, podophyllotoxin has a beneficial antitumor effect. The mechanism of podophyllotoxin activity in triple-negative breast cancer still needs to be explored.
We used cell proliferation assay, scratch and transwell experiments, and cell cycle and apoptosis analyses to observe the intervention effect of podophyllotoxin on breast cancer. Furthermore, we analyzed the differences between GSE31448, GSE65194, and GSE45827 in the Gene Expression Omnibus database (GEO) and explored the differential genes using a STRING database. Centiscape2.2, MCODE cluster analysis and KEGG pathway analysis were used to identify the most significant gene differences. Next, we utilized BATMAN-TCM and TCMSP databases for further screening to identify key genes. Finally, quantitative RT-PCR (qRT-PCR) and Western blotting were performed to detect the expression of key targets.
Our research confirmed that podophyllotoxin could not only inhibit the migration and invasion of tr PLK1, CDC20, and CDK1 in the cell cycle pathway is inhibited by regulating P53. Our research shows that natural drugs inhibit tumor activity by regulating the expression of cyclins, and the combination of natural drugs and modern extensive database analysis has a wide range of potential applications in the development of antitumor therapies.
Podophyllotoxin has an intervention effect on the development of triple-negative breast cancer. The expression of PLK1, CDC20, and CDK1 in the cell cycle pathway is inhibited by regulating P53. Our research shows that natural drugs inhibit tumor activity by regulating the expression of cyclins, and the combination of natural drugs and modern extensive database analysis has a wide range of potential applications in the development of antitumor therapies.Chronic long-term glucocorticoids (GC) use is associated with glucocorticoid-induced osteoporosis (GIOP) by inhibiting the survival and impairing the functions of osteoblasts. Autophagy and mitophagy play key roles in osteoblast differentiation, mineralization and survival, and mounting evidence have implicated osteoblast autophagy and mitophagy as a novel mechanism in the pathogenesis of GIOP. Vitamin K2 (VK2) is an essential nutrient supplement that have been shown to exert protective effects against osteoporotic bone loss including GIOP. In this study, we showed that the glucocorticoid dexamethasone (Dex) deregulated osteoblast autophagy and mitophagy by downregulating the expression of autophagic and mitophagic markers LC3-II, PINK1, Parkin. This consequently led to inhibition of osteoblast differentiation and mineralization function in vitro. Interestingly, co-treatment with VK2 significantly attenuated the Dex-induced downregulation of LC3-II, PINK1, Parkin, thereby restoring autophagic and mitophagic processes and normal osteoblastic activity. In addition, using an established rat model of GIOP, we showed that VK2 administration can protect rats against the deleterious effects of Dex on bone by reinstating autophagic and mitophagic activities in bone tissues. Collectively, our results provide new insights into the role of osteoblast autophagy and mitophagy in GIOP. Additionally, the use of VK2 supplementation to augment osteoblast autophagy/mitophagy may significantly improve clinical outcomes of GIOP patients.
The NLRP3 inflammasome produces interleukin (IL)-1β and IL-18, which when chronically activated by transforming growth factor (TGF)-β1, contribute to fibrosis. The recombinant form of the anti-fibrotic hormone, relaxin (RLX), suppresses the pro-fibrotic influence of TGF-β1 and toll-like receptor (TLR)-4 on NLRP3 inflammasome priming and activity in human cardiac myofibroblasts and mice with cardiomyopathy. However, whether RLX also modulates components of the myofibroblast NLRP3 inflammasome remains unknown.
Stimulation of a human dermal fibroblast (HDF) cell line with TGF-β1 [5 ng/ml; to promote myofibroblast (HDMF) differentiation], LPS (100 ng/ml; to prime the NLRP3 inflammasome) and ATP (5 mM; to activate the NLPR3 inflammasome) (T+L+A) significantly increased NLRP3 inflammasome priming and activity after 8 and 72h; and α-SMA expression (myofibroblast differentiation) and collagen-I deposition after 72h. Selleckchem GSK3 inhibitor siRNA-induced knock-down of NLRP3 inflammasome priming components (NLRP3, ASC, caspase-1) in T+L+A-stimulated HDMFs for 24h, completely knocked-down each component after 72h. RLX (100 ng/ml) administration to T+L+A-stimulated HDMFs after control, NLRP3 or ASC siRNA transfection, equivalently suppressed IL-1β, pro-IL-18, α-SMA, and collagen-I protein levels (by 40%-50%; all p<0.05 vs. T+L+A) after 72h, as determined by Western blotting. These RLX-induced effects were abrogated by siRNA knock-down of caspase-1.
The anti-fibrotic actions of RLX appear to require modulation of caspase-1 within the myofibroblast NLRP3 inflammasome.
The anti-fibrotic actions of RLX appear to require modulation of caspase-1 within the myofibroblast NLRP3 inflammasome.We previously have revealed that 1-trifluoromethoxyphenyl-3-(1- propionylpiperidin-4-yl) urea (TPPU), as a soluble epoxide hydrolase (sEH) inhibitor can reduce infarct volume, protect blood-brain barrier (BBB) and brain against ischemic injury in rats. Here, we investigated the potential mechanisms of TPPU on BBB integrity in both in permanent middle cerebral artery occlusion (pMCAO) rat model and in oxygen-glucose deprivation/reperfusion (OGD/R)-induced human brain microvascular endothelial cells (HBMVECs) model. In pMCAO rat, TPPU administration decreased brain edema and Evans blue content, increased tight junction proteins (TJs) expression of claudin-5, occludin, and zonula occludens-1 (ZO-1). In OGD/R model, OGD/R significantly increased permeability and cell apoptosis, downregulated the expression of claudin-5, ZO-1, occludin, and lymphoma (Bcl)-2. Notably, TPPU pretreatment effectively protected the BBB integrity by reducing the permeability, promoting expression of claudin-5, ZO-1, occluding and Bcl-2, mitigating reactive oxygen species (ROS) injury and release of interleukin-1β (IL-1β), IL-6β, and tumor necrosis factor-α (TNF-α), downregulating expression of matrix metalloproteinase-9 (MMP-9), MMP-2, bcl-2-associated X protein (Bax), IL-1β, IL-6β, and TNF-α. Moreover, OGD/R induced the up-regulation of p-p65, p-IκB, and p-p38, which were effectively decreased after TPPU pretreatment in comparison with that of the OGD/R group. Furthermore, pyrrolidinedithiocarbamate (PDTC, a selective inhibitor of NF-κB p65) not only alleviated the OGD/R-induced HBMVECs injury and permeability, but also reduced the expression of TNF-α, IL-6, IL-1β, p-p65, and p-IκB, and the protective effect of PDTC was equivalent to that of TPPU. These results indicate that TPPU protects BBB integrity against ischemic injury by multiple protective mechanisms, at least in part, by reducing ROS, inflammation, apoptosis, and suppressing the nuclear factor-κB (NF-κB) and p38 signaling pathways.