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Edaravone protects the retina against ischemia/reperfusion-induced oxidative injury through the PI3K/Akt/Nrf2 pathway
摘要： Retinal ischemia/reperfusion (I/R) injury can occur as a result of a number of ocular diseases or ischemic events in the brain, leading to possible vision loss if not treated properly. The overproduction of reactive oxygen species is important in the process of I/R injury. Edaravone, a free radical scavenger, has been demonstrated to have a neuroprotective effect in cerebral ischemia; however, its effect against retinal I/R injury remains to be fully elucidated. Therefore, the present study investigated the effects of edaravone on the oxidative parameters, retinal inflammation and apoptosis induced by I/R injury, and treated photoreceptor-derived 661W cells with hydrogen peroxide (H2O2) and edaravone to examine the underlying mechanism. For the in vivo study, oxidative parameters (malondialdehyde, DNA fragmentation, total antioxidant status, superoxide dismutase and glutathione) in the retina, retinal thickness, and apoptotic index in the ganglionic cell layer and inner nuclear layer were measured. For the in vitro study, the effects of edaravone or nuclear factor erythroid-2-related factor 2 (Nrf2) small interfering RNA or phosphatidylinositol 3-kinase (PI3K)/Akt inhibitors on cell viability, membrane integrity, levels of phosphorylated-Akt, Akt and nuclear Nrf2 of H2O2-treated 661W cells were examined. The results demonstrated that edaravone inhibited the oxidative injury in the retina induced by the retinal I/R procedure and increased retinal inflammation, and apoptosis. The results of the in vitro experiments demonstrated that edaravone effectively protected the viability and the membrane integrity of the H2O2-treated 661W cells via the phosphatidylinositol 3-kinase (PI3K)/Akt/Nrf2 pathway. These results indicated the potential protective effect of edaravone against retinal I/R injury and provided a novel explanation for the protective effects of edaravone.
关键词： edaravone,ischemia/reperfusion injury,retina,oxidative injury,phosphatidylinositol 3-kinase/Akt/nuclear factor erythroid-2-related factor 2 pathway
更新于2025-09-23 15:22:29
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Photobiomodulation Preconditioning Prevents Cognitive Impairment in a Neonatal Rat Model of Hypoxia-ischemia
摘要： Neonatal hypoxia-ischemia (HI) injury caused by oxygen deprivation is the most common cause of mortality and severe neurologic deficits in neonates. The present work evaluated the preventative effect of photobiomodulation (PBM) preconditioning, and its underlying mechanism of action on brain damage in a HI model in neonatal rats. According to the optimal time response of ATP levels in brain samples removed from normal rats, a PBM preconditioning regimen (808 nm CW laser, 1 cm2 spot, 100 mW/cm2, 12 J/cm2) was delivered to the scalp 6 hours before HI. PBM preconditioning significantly attenuated cognitive impairment, volume shrinkage in the brain, neuron loss, dendritic and synaptic injury after HI. Further mechanistic investigation found that PBM preconditioning could restore HI-induced mitochondrial dynamics and inhibit mitochondrial fragmentation, followed by a robust suppression of cytochrome c release, and prevention of neuronal apoptosis by inhibition of caspase activation. Our work suggests that PBM preconditioning can attenuate HI-induced brain injury by maintaining mitochondrial dynamics and inhibiting the mitochondrial apoptotic pathway.
关键词： Hypoxia-ischemia,Mitochondria,Cognitive impairment,Neuroprotection,Photobiomodulation preconditioning
更新于2025-09-23 15:22:29
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How to Utilize Coronary Computed Tomography Angiography in the Treatment of Coronary Artery Disease
摘要： Coronary computed tomography angiography (CCTA) has high negative predictive power for detecting coronary artery disease. However CCTA is limited by moderate positive predictive power in the detection of myocardial ischemia. This is not unexpected because the diameter of a stenosis is a poor indicator of myocardial ischemia and discrepancy between the severity of stenosis and noninvasive tests is not uncommon. The value of stenosis for predicting future development of acute coronary syndrome represented by plaque rupture has been questioned. CCTA identifies the characteristics of high-risk plaque including positive remodeling, low density plaque and spotty or micro-calcification. Also, additional evaluation of myocardial ischemia using computational flow dynamics, and luminal attenuation gradient are expected to increase both diagnostic performance for hemodynamically significant stenosis and the predictive power for future cardiovascular risk. Technical advances in CCTA would enable evaluation of both coronary artery stenosis and myocardial ischemia simultaneously with high predictive performance, and would improve vastly the clinical value of CCTA.
关键词： Functional ischemia,Coronary artery disease,Atherosclerosis,Prognosis,Coronary CT angiography,Myocardial mass
更新于2025-09-23 15:22:29
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Extreme-Learning-Machine-Based Noniterative and Iterative Nonlinearity Mitigation for LED Communication Systems
摘要： Oxidation of substrates to generate ATP in mitochondria is mediated by redox reactions of NADH and FADH2. Cardiac ischemia and reperfusion (IR) injury compromises mitochondrial oxidative phosphorylation. We hypothesize that IR alters the metabolic heterogeneity of mitochondrial redox state of the heart that is only evident in the 3-D optical cryoimaging of the perfused heart before, during, and after IR. The study involved four groups of hearts: time control (TC: heart perfusion without IR), global ischemia (Isch), global ischemia followed by reperfusion (IR) and TC with PCP (a mitochondrial uncoupler) perfusion. Mitochondrial NADH and FAD autofluorescence signals were recorded spectrofluorometrically online in guinea pig ex vivo-perfused hearts in the Langendorff mode. At the end of each specified protocol, hearts were rapidly removed and snap frozen in liquid N2 for later 3-D optical cryoimaging of the mitochondrial NADH, FAD, and NADH/FAD redox ratio (RR). The TC hearts revealed a heterogeneous spatial distribution of NADH, FAD, and RR. Ischemia and IR altered the spatial distribution and caused an overall increase and decrease in the RR by 55% and 64%, respectively. Uncoupling with PCP resulted in the lowest level of the RR (73% oxidation) compared with TC. The 3-D optical cryoimaging of the heart provides novel insights into the heterogeneous distribution of mitochondrial NADH, FAD, RR, and metabolism from the base to the apex during ischemia and IR. This 3-D information of the mitochondrial redox state in the normal and ischemic heart was not apparent in the dynamic spectrofluorometric data.
关键词： Optical cryoimaging,redox state,metabolism,ischemia and reperfusion,mitochondria
更新于2025-09-23 15:21:01
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Multimodal imaging of the receptor for advanced glycation end-products with molecularly targeted nanoparticles
摘要： The receptor for advanced glycation end-products (RAGE) is central to multiple disease states, including diabetes-related conditions such as peripheral arterial disease (PAD). Despite RAGE’s importance in these pathologies, there remains a need for a molecular imaging agent that can accurately assess RAGE levels in vivo. Therefore, we have developed a multimodal nanoparticle-based imaging agent targeted at RAGE with the well-characterized RAGE ligand, carboxymethyllysine (CML)-modified human serum albumin (HSA). Methods: A multimodal tracer (64Cu-Rho-G4-CML) was developed using a generation-4 (G4) polyamidoamine (PAMAM) dendrimer, conjugated with both rhodamine and copper-64 (64Cu) chelator (NOTA) for optical and PET imaging, respectively. First, 64Cu-Rho-G4-CML and its non-targeted analogue (64Cu-Rho-G4-HSA) were evaluated chemically using techniques such as dynamic light scattering (DLS), electron microscopy and nuclear magnetic resonance (NMR). The tracers’ binding capabilities were examined at the cellular level and optimized using live and fixed HUVEC cells grown in 5.5-30 mM glucose, followed by in vivo PET-CT imaging, where the probes’ kinetics, biodistribution, and RAGE targeting properties were examined in a murine model of hindlimb ischemia. Finally, histological assessment of RAGE levels in both ischemic and non-ischemic tissues was performed. Conclusions: Our RAGE-targeted probe demonstrated an average size of 450 nm, a Kd of 340-390 nM, rapid blood clearance, and a 3.4 times greater PET uptake in ischemic RAGE-expressing hindlimbs than their non-ischemic counterpart. We successfully demonstrated increased RAGE expression in a murine model of hindlimb ischemia and the feasibility for non-invasive examination of cellular, tissue, and whole-body RAGE levels with a molecularly targeted tracer.
关键词： multimodal imaging,inflammation,receptor for advanced glycation end-products,hindlimb ischemia,PET-CT
更新于2025-09-23 15:21:01
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Visualising improved peritoneal perfusion at lower intra-abdominal pressure by fluorescent imaging during laparoscopic surgery: A randomised controlled study
摘要： Background: Laparoscopy is the gold standard for many surgical procedures and is embraced as minimally invasive surgery in the enhanced recovery after surgery programme. Lowering intra-abdominal pressure during laparoscopy may decrease the degree of surgical injury and further enhance patient outcomes. This study aims to assess the effect of low pressure pneumoperitoneum on peritoneal perfusion during laparoscopic surgery. Materials and methods: We performed a prospective randomized intervention study in 30 adults undergoing colorectal robot assisted laparoscopic surgery at a secondary care medical center in the Netherlands between June and December 2018. A 3 minute video recording of the parietal peritoneum was made with the Da Vinci? Firefly mode following intravenous injection of 0.2 mg/kg indocyanine green at a pneumoperitoneum pressure of 8, 12 or 16 mmHg. Observers were blinded for the level of intra-abdominal pressure that was used. Fluorescent intensity in [-] over time was extracted from each video in MATLAB. Time to reach maximal fluorescent intensity (TMFI) and maximum fluorescent intensity (MFI) were compared among groups. The study was registered at clinicaltrials.gov (NCTXXXXXXXX). Results: Mean TMFI was shorter at low pressure (8 mmHg) than standard pressure (12 and 16 mmHg): 44 ± 12 versus 58 ± 18 seconds (p=0.032), respectively. Mean MFI was higher at 8 mmHg than 12 and 16 mmHg (222 ± 25 versus 188 ± 54, p=0.033). Regression analysis identified intra-abdominal pressure, mean arterial pressure and female gender as significant predictors of peritoneal perfusion. Conclusion: Low pressure pneumoperitoneum was associated with improved perfusion of the parietal peritoneum. Current available evidence supported feasibility and enhanced postoperative recovery. Future investigations should focus on optimizing factors that facilitate lower intra-abdominal pressure and explore effects on other clinically relevant patient outcomes such as anastomotic leakage and immune homeostasis.
关键词： intra-abdominal pressure,ischemia-reperfusion injury,pneumoperitoneum,perfusion,laparoscopic surgery,immune homeostasis
更新于2025-09-23 15:19:57
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Establishment of optimal exercise therapy using near-infrared spectroscopy monitoring of tissue muscle oxygenation after therapeutic angiogenesis for patients with critical limb ischemia: A multicenter, randomized, controlled trial
摘要： Critical limb ischemia (CLI) is a potentially life-threatening condition that involves severely reduced blood flow to the peripheral arteries due to arteriosclerosis obliterans (ASO) of the limbs or a similar condition. CLI patients must undergo revascularization to avoid amputation of the lower limbs and improve their survival prognosis. However, the outcomes of conventional surgical revascularization or endovascular therapy are inadequate; therefore, establishing further effective treatment methods is an urgent task. We perform therapeutic angiogenesis using autologous bone marrow-derived mononuclear cells in clinical practice and demonstrated its safety and efficacy for CLI patients for whom conventional treatments failed or are not indicated. Exercise therapies must be devised for CLI patients who have undergone therapeutic angiogenesis to save their limbs and improve survival. Because evidence regarding the efficacy and safety of exercise therapy for CLI patients is lacking, we plan to perform a prospective trial of the efficacy and safety of optimal exercise therapy following therapeutic angiogenesis for CLI patients.
关键词： Optimal exercise therapy,Critical limb ischemia,Near-infrared spectroscopy,Arteriosclerosis obliterans,Tissue muscle oxygen saturation,Therapeutic angiogenesis
更新于2025-09-23 15:19:57
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A highly sensitive SERS probe for bisphenol A detection based on functionalized Au@Ag nanoparticles
摘要： Cardiac remodeling is the response of the heart to a range of pathological stimuli. Cardiac remodeling is initially adaptive; however, if sustained, it ultimately causes adverse clinical outcomes. Cardiomyocyte loss or hypertrophy, inflammation and fibrosis are hallmarks of cardiac remodeling. Proteoglycans, which are composed of glycosaminoglycans and a core protein, are a non-structural component of the extracellular matrix. The lack of proteoglycans results in cardiovascular defects during development. Moreover, emerging evidence has indicated that proteoglycans act as significant modifiers in ischemia and pressure overload-related cardiac remodeling. Proteoglycans may also provide novel therapeutic strategies for further improvement in the prognosis of cardiovascular diseases.
关键词： Cardiac remodeling,Pressure overload,Proteoglycan,Myocardial ischemia,Heart failure
更新于2025-09-19 17:15:36
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Gastroscopy assisted laser Doppler flowmetry and visible light spectroscopy in patients with chronic mesenteric ischemia
摘要： Mucosal pathology due to chronic mesenteric ischemia (CMI) is rarely seen during upper endoscopy. Combining Laser Doppler Flowmetry (LDF) and Visible Light Spectroscopy (VLS) may aid in detection of CMI at an early stage. We aimed to investigate the utility of LDF and VLS in detecting microcirculatory changes in patients with CMI during upper endoscopy. In a single center, prospective study, 104 patients were evaluated for mesenteric ischemia during a 24 months period. Patients with a consensus diagnosis of CMI (n ? 40) were examined with LDF and VLS. Thirty-two were successfully treated and had a definitive diagnosis of CMI. Results were compared with controls (n ? 38) with normal intestinal circulation evaluated with duplex ultrasonography (DUS). Treatment response was evaluated clinically and with DUS at 1 month and with VLS and LDF at 3 months. A significant reduction in mucosal capillary hemoglobin oxygen saturation (SO2) was found in CMI patients compared to controls before treatment: mean ± SD: 67 ± 9%, 81 ± 4%, respectively (p < .001). A significant reduction was also seen for the relative hemoglobin (rHb) amount, flow and velocity (p < .001). The sensitivity of SO2 measured by VLS for diagnosing CMI was 94% and the specificity 72% (cut-off 78%), calculated with ROC curve analysis. A combination of SO2 and rHb increased the test sensitivity and specificity to 97% and 79%, respectively. Conclusion: CMI patients have significantly reduced microcirculation in the stomach and duodenum compared to controls. The results suggest that VLS should be included when performing an upper endoscopy in patients with suspected CMI.
关键词： laser doppler flowmetry,acute mesenteric ischemia,Chronic mesenteric ischemia,upper endoscopy,visible light spectroscopy
更新于2025-09-12 10:27:22
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Chronic Hindlimb Ischemia Assessment; Quantitative Evaluation Using Laser Doppler in a Rodent Model of Surgically Induced Peripheral Arterial Occlusion
摘要： Therapeutic neoangiogenesis (TNA) holds promise as a treatment for peripheral arterial disease. Nevertheless, proper tools for in vivo pre-clinical investigation of different TNA approaches and their effects are still lacking. Here we describe a chronic ischemic hindlimb model in rats using laser Doppler quantitative evaluation of tissue perfusion. Male Wistar rats (n = 20), aged between 6–8 months, with an average weight of 287 ± 26.74 g, were used. Animals were divided into two experimental groups: group A (n = 17; hindlimb chronic ischemia model) and group B (n = 3; control). Hindlimb ischemia was induced by concomitant ligation of the right femoral and popliteal artery. Evaluation of tissue perfusion was quantified in perfusion units (PU) on a scale from 0 to 500 (500 PU = maximal detectable perfusion) by laser Doppler analysis at day 0, day 15 and day 30 after induction of ischemia. Induction of chronic ischemia in the rat hindlimb by concomitant ligation of the femoral and popliteal artery can be readily obtained but requires basic microsurgical skills. Laser Doppler analysis has shown unaltered ischemia levels throughout the study (129,17 PU ± 3.13 day 0 vs. 130,33 PU day 30 ± 3,27, p = not significant (n.s.)). We demonstrate a simple and reproducible model of chronic hindlimb ischemia in rats, with stable tissue perfusion levels that are accurately quantified using laser Doppler technology. Hence, this model can represent a valid tool for further studies involving therapeutic neoangiogenesis.
关键词： laser Doppler,chronic ischemia,experimental model,hindlimb
更新于2025-09-12 10:27:22