Dynamic Peripheral Hemoperfusion Distribution Monitoring Based on Janus Flexible Sensor System.

OBJECTIVE: Peripheral vascular disease is a worldwide leading health concern. Real-time peripheral hemoperfusion monitoring during treatment is essential to plan treatment strategies to improve circulatory enhancement effects. METHODS: The present work establishes a Janus flexible perfusion (JFP) sensor system for dynamic peripheral hemoperfusion monitoring. We develop a Janus structure design with different Young's modulus to improve the mechanical properties for motion artifacts suppression. Besides, we propose a peripheral perfusion index (PPI) to assess the peripheral hemoperfusion based on an optical perfusion model that is experimentally verified using an in-vitro model. The effectiveness of the system is assessed in three experimental scenarios, including motion artifact-robust test, induced vascular occlusion in upper limb, and peripheral hemoperfusion monitoring with the treatment of intermittent pneumatic compression (IPC), with comparison with Laser Doppler flowmetry (LDF). RESULTS: The noise level of the traditional rigid sensor is five times that of the JFP sensor within the effective signal frequency domain when there is movement. The PPI can effectively discriminate between different peripheral hemoperfusion states and has a correlation coefficient of 0.92 with the LDF mean values. The kappa statistic between the JFP sensor and LDF is 0.78, indicating substantial agreement between them to estimate the peripheral hemoperfusion improvements during IPC treatment. CONCLUSION: The sensor system we proposed can monitor peripheral hemoperfusion variation in real-time and is insensitive to motion artifacts. SIGNIFICANCE: The proposed sensing system provides a functional module for real-time estimation of peripheral hemoperfusion during clinical interventions.

Cigarette tar mediates macrophage ferroptosis in atherosclerosis through the hepcidin/FPN/SLC7A11 signaling pathway.

Despite the known promotional effects of cigarette smoking on progression of atherosclerosis (AS), tar as the most dominant toxic component in cigarette smoking has been little studied. Understanding the potential role and mechanisms of tar in AS may be a prerequisite for future reductions in cardiovascular morbidity and mortality. Male ApoE-/- mice were fed with high-fat diet and injected intraperitoneally with cigarette tar (40 mg/kg/day) for 16 weeks. The results showed that cigarette tar significantly promoted the formation of lipid-rich plaques with larger necrotic cores and less fibrous, and caused severe iron overload and lipid peroxidation in AS lesions. Moreover, tar significantly upregulated the expression of hepcidin and downregulated FPN and SLC7A11 of macrophages in AS plaques. Ferroptosis inhibitor (FER-1 and DFO) treatment, hepcidin-knockdown or SLC7A11-overexpression reversed above changes, thereby delaying the progression of atherosclerosis. In vitro, the use of FER-1, DFO, si-hepcidin, and ov-SLC7A11 increased cell viability and inhibited iron accumulation, lipid peroxidation and GSH depletion in tar treated macrophages. These interventions also inhibited the tar induced upregulation of hepcidin, and increased the expression of FPN, SLC7A11, and GPX4. Furthermore, NF-κB inhibitor reversed the regulatory effect of tar on hepcidin/FPN/SLC7A11 axis, and then inhibiting macrophage ferroptosis. These findings indicated that cigarette tar promotes atherosclerosis progression by inducing macrophage ferroptosis via NF-κB-activated hepcidin/FPN/SLC7A11 pathway.

MiR-181c sensitizes ovarian cancer cells to paclitaxel by targeting GRP78 through the PI3K/Akt pathway.

Primary cytoreductive surgery with platinum-taxane-based chemotherapy is the standard treatment for ovarian cancer (OC) patients; however, resistance to chemotherapy is a contributing factor to OC mortality. Paclitaxel (PTX), the most widely used taxane, has become the first-line drug against OC. The molecular mechanism of PTX resistance is different from that of platinum-based agents and is still not completely elucidated. Our previous study showed that glucose-regulated protein 78 (GRP78) is involved in the resistance of OC cells to PTX. However, little is known regarding endogenous inhibitors of this gene. MicroRNAs (miRNAs) play critical roles in the regulation of gene expression; therefore, we sought to identify miRNA(s) with potential to target GRP78 under the hypothesis that miRNA(s) could serve as potential therapeutic targets. Here, we show that miR-181c, predicted to target GRP78, was downregulated in PTX-resistant OC cells and tissues. MiR-181c downregulated GRP78 expression and induced apoptosis by directly targeting its 3'-untranslated region (UTR). Overexpression of miR-181c sensitized resistant OC to PTX by inhibiting the PI3K/Akt pathway in vitro and in vivo. Taken together, our findings indicate that the delivery of miR-181c can efficiently suppress GRP78 expression and GRP78-mediated PTX resistance in OC and suggest that this strategy has therapeutic potential.

Ferroptosis: A Potential Target in Cardiovascular Disease.

Ferroptosis is a new form of regulatory cell death characterized by iron-dependent and intracellular lipid peroxidation. Ferroptosis can be divided into two stages. The first stage is iron overload in the cell, which generates a large amount of reactive oxygen species through the Fenton reaction, and the second stage results from an imbalance of the intracellular antioxidant system. Excessive phospholipid hydroperoxides cannot be removed by reduction reactions, as this could destroy the cell membrane structure and interfere with mitochondrial function, eventually leading to ferroptosis of the cell. Cardiovascular diseases have gradually become the leading cause of death in modern society. The relationship between ferroptosis and the occurrence and progression of cardiovascular disease has become a research hotspot in recent years. In this review, we summarize the mechanism of ferroptosis and its specific role in cardiovascular disease.