RESUMO
Ischemic vascular diseases are on the rise globally, including ischemic heart diseases, ischemic cerebrovascular diseases, and ischemic peripheral arterial diseases, posing a significant threat to life. Copper is an essential element in various biological processes, copper deficiency can reduce blood vessel elasticity and increase platelet aggregation, thereby increasing the risk of ischemic vascular disease; however, excess copper ions can lead to cytotoxicity, trigger cell death, and ultimately result in vascular injury through several signaling pathways. Herein, we review the role of cuproptosis and copper deficiency implicated in ischemic injury and repair including myocardial, cerebral, and limb ischemia. We conclude with a perspective on the therapeutic opportunities and future challenges of copper biology in understanding the pathogenesis of ischemic vascular disease states.
Assuntos
Cobre , Isquemia , Cobre/metabolismo , Cobre/deficiência , Humanos , Animais , Isquemia/metabolismo , Isquemia/genética , Isquemia/patologia , Lesões do Sistema Vascular/genética , Lesões do Sistema Vascular/metabolismo , Lesões do Sistema Vascular/patologia , Transdução de SinaisRESUMO
Flow cytometry (FC) is a versatile tool with excellent capabilities to detect and measure multiple characteristics of a population of cells or particles. Notable advancements in in vivo photoacoustic FC, coherent Raman FC, microfluidic FC, and so on, have been achieved in the last two decades, which endows FC with new functions and expands its applications in basic research and clinical practice. Advanced FC broadens the tools available to researchers to conduct research involving cancer detection, microbiology (COVID-19, HIV, bacteria, etc.), and nucleic acid analysis. This review presents an overall picture of advanced flow cytometers and provides not only a clear understanding of their mechanisms but also new insights into their practical applications. We identify the latest trends in this area and aim to raise awareness of advanced techniques of FC. We hope this review expands the applications of FC and accelerates its clinical translation.
Assuntos
COVID-19 , Humanos , Citometria de FluxoRESUMO
The use of traditional finite element method (FEM) in occlusal stress analysis is limited due to the complexity of musculature simulation. The present purpose was to develop a displacement boundary condition (DBC)-FEM, which evaded the muscle factor, to predict the dynamic occlusal stress. The geometry of the DBC-FEM was developed based on the scanned plastic casts obtained from a volunteer. The electrognathographic and video recorded jaw positional messages were adopted to analyze the dynamic occlusal stress. The volunteer exhibited asymmetrical lateral movements, so that the occlusal stress was further analyzed by using the parameters obtained from the right-side eccentric movement, which was 6.9 mm long, in the stress task of the left-side eccentric movement, which was 4.1 mm long. Further, virtual occlusion modification was performed by using the carving tool software aiming to improve the occlusal morphology at the loading sites. T-Scan Occlusal System was used as a control of the in vivo detection for the location and strength of the occlusal contacts. Data obtained from the calculation using the present developed DBC-FEM indicated that the stress distribution on the dental surface changed dynamically with the occlusal contacts. Consistent with the T-Scan recordings, the right-side molars always showed contacts and higher levels of stress. Replacing the left-side eccentric movement trace by the right-side one enhanced the simulated stress on the right-side molars while modification of the right-side molars reduced the simulated stress. The present DBC-FEM offers a creative approach for pragmatic occlusion stress prediction.
RESUMO
BACKGROUND: Previous studies have indicated that the JAK/STAT signaling pathway is involved in modulating arterial adventitia inflammation response. In this study, we designed experiments to further investigate the effect of JAK2/STAT3/SOCS3 signaling in rabbit atherosclerosis process. METHODS: Atherosclerosis was induced in the abdominal arteries of rabbits by balloon injury of the aorta supplemented by the atherogenic diet. Simultaneously, in the process of atherosclerosis, animals underwent either ruxolitinib treatment or not for 12 weeks. At the end of the experimental period, all rabbits were sacrificed. The plaque areas in abdominal artery, the lipid burden of plaque and the calcium burden of plaque were detected by H&E staining, Oil Red O staining and Alizarin Red staining, respectively. In addition, rabbit plasma lipids and inflammatory cytokines were measured by biochemical test kits or ELISA kits. Finally, the expression and phosphorylation levels of JAK2/STAT3/SOCS3 pathway-related proteins were detected by RT-qPCR, western blot and immunohistochemistry assays. RESULTS: H&E staining and CT scan analysis showed that rabbit atherosclerosis model was constructed successfully. Ruxolitinib, an inhibitor of the Janus kinase 2 (JAK2), substantially reduced the area of atherosclerotic plaques in rabbits treated with high fat diet and balloon injury of the aorta. Moreover, ruxolitinib significantly decreased IL-6, IL-1ß, IFN-γ and TNF-α, but increased IL-10 and IL-17 levels in plasma of atherosclerotic rabbits. Additionally, ruxolitinib reduced plasma TC, TG and LDL-C contents and AIP value, while enhanced HDL-C level in atherosclerotic rabbits. Furthermore, we found that JAK2 and STAT3 phosphorylation were up-regulated in rabbits with atherosclerosis when compared with those of the control group, followed by the expression of SOCS3 was also increased due to the activation of JAK2 and STAT3. Interestingly, ruxolitinib could inactivate JAK2 and STAT3 pathway and decrease SOCS3 expression. CONCLUSION: Taken together, the inhibition of JAK2/STAT3/SOCS3 signaling pathway may be a novel method for the clinical treatment of artery atherosclerosis.
Assuntos
Aorta Abdominal/efeitos dos fármacos , Doenças da Aorta/prevenção & controle , Aterosclerose/prevenção & controle , Janus Quinase 2/antagonistas & inibidores , Inibidores de Janus Quinases/farmacologia , Placa Aterosclerótica , Pirazóis/farmacologia , Fator de Transcrição STAT3/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Animais , Aorta Abdominal/enzimologia , Aorta Abdominal/patologia , Doenças da Aorta/sangue , Doenças da Aorta/enzimologia , Doenças da Aorta/patologia , Aterosclerose/sangue , Aterosclerose/enzimologia , Aterosclerose/patologia , Citocinas/sangue , Modelos Animais de Doenças , Mediadores da Inflamação/sangue , Janus Quinase 2/metabolismo , Lipídeos/sangue , Masculino , Nitrilas , Fosforilação , Pirimidinas , Coelhos , Transdução de SinaisRESUMO
One-dimensional (1D) hemodynamic models of arteries have increasingly been applied to coronary circulation. In this study, we have adopted flow and pressure profiles in Olufsen's 1D structured tree as coronary boundary conditions, with terminals coupled to the dynamic pressure feedback resulting from the intra-myocardial stress because of ventricular contraction. We model a trifurcation structure of the example coronary tree as two adjacent bifurcations. The estimated results of blood pressure and flow rate from our simulation agree well with the clinical measurements and published data. Furthermore, the 1D model enables us to use wave intensity analysis to simulate blood flow in the developed coronary model. Six characteristic waves are observed in both left and right coronary flows, though the waves' magnitudes differ from each other. We study the effects of arterial wall stiffness on coronary blood flow in the left circumflex artery (LCX). Different diseased cases indicate that distinct pathological reactions of the cardiovascular system can be better distinguished through Wave Intensity analysis, which shows agreement with clinical observations. Finally, the feedback pressure in terminal vessels and measurement deviation are also investigated by changing parameters in the LCX. We find that larger feedback pressure increases the backward wave and decreases the forward one. Although simplified, this 1D model provides new insight into coronary hemodynamics in healthy and diseased conditions. We believe that this approach offers reference resources for studies on coronary circulation disease diagnosis, treatment and simulation.
RESUMO
A new lumped-parameter model for coronary hemodynamics is developed. This model is developed for the whole coronary network based on CT scans of a patient-specific geometry including the right coronary tree, which is absent in many previous mathematical models. The model adopts the structured tree model boundary conditions similar to the work of Olufsen et al., thus avoiding the necessity of invasive perfusion measurements. In addition, we also incorporated the effects of the head loss at the two inlets of the large coronary arteries for the first time. The head loss could explain the phenomenon of a sudden increase of the resistance at the inlet of coronary vessel. The estimated blood pressure and flow rate results from the model agree well with the clinical measurements. The computed impedances also match the experimental perfusion measurement. The effects of coronary arterial stenosis are considered and the fractional flow reserve and relative flow in the coronary vessels for a stenotic vessel computed in this model show good agreement with published experimental data. It is believed that the approach could be readily translated to clinical practice to facilitate real time clinical diagnosis.