Vulnerability of DHCR7+/- mutation carriers to aripiprazole and trazodone exposure

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Behavior of the thermal diffusivity of native and oxidized human low-density lipoprotein solutions studied by the Z-scan technique

Modifications in low-density lipoprotein (LDL) have emerged as a major pathogenic factor of atherosclerosis, which is the main cause of morbidity and mortality in the western world. Measurements of the heat diffusivity of human LDL solutions in their native and in vitro oxidized states are presented by using the Z-Scan (ZS) technique. Other complementary techniques were used to obtain the physical parameters necessary to interpret the optical results, e. g., pycnometry, refractometry, calorimetry, and spectrophotometry, and to understand the oxidation phase of LDL particles. To determine the sample's thermal diffusivity using the thermal lens model, an iterative one-parameter fitting method is proposed which takes into account several characteristic ZS time-dependent and the position-dependent transmittance measurements. Results show that the thermal diffusivity increases as a function of the LDL oxidation degree, which can be explained by the increase of the hydroperoxides production due to the oxidation process. The oxidation products go from one LDL to another, disseminating the oxidation process and caring the heat across the sample. This phenomenon leads to a quick thermal homogenization of the sample, avoiding the formation of the thermal lens in highly oxidized LDL solutions. (C) 2012 Society of Photo-Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.JBO.17.10.105003]National Counsel for Scientific and Technological Development (CNPq)National Counsel for Scientific and Technological Development (CNPq)Sao Paulo Research Foundation (FAPESP)Sao Paulo Research Foundation (FAPESP)National Institute of Science and Technology of Complex Fluid (INCTFCx)National Institute of Science and Technology of Complex Fluid (INCT-FCx)Redoxoma (INCT-Redoxoma)Redoxoma (INCTRedoxoma

Ubiquitous Aberration in Cholesterol Metabolism Across Pancreatic Ductal Adenocarcinoma

Pancreatic cancer (PC) is characterized by metabolic deregulations that often manifest as deviations in metabolite levels and aberrations in their corresponding metabolic genes across the clinical specimens and preclinical PC models. Cholesterol is one of the critical metabolites supporting PC, synthesized or acquired by PC cells. Nevertheless, the significance of the de novo cholesterol synthesis pathway has been controversial in PC, indicating the need to reassess this pathway in PC. We utilized preclinical models and clinical specimens of PC patients and cell lines and utilized mass spectrometry-based sterol analysis. Further, we also performed in silico analysis to corroborate the significance of de novo cholesterol synthesis pathway in PC. Our results demonstrated alteration in free sterol levels, including free cholesterol, across in vitro, in vivo, and clinical specimens of PC. Especially, our sterol analyses established consistent alterations in free cholesterol across the different PC models. Overall, this study demonstrates the significance and consistency in deviation of cholesterol synthesis pathway in PC while showing the aberrations in sterol metabolite intermediates and the related genes using preclinical models, in silico platforms, and the clinical specimens

Ferroptosis: A Promising Therapeutic Target for Neonatal Hypoxic-Ischemic Brain Injury

Ferroptosis is a type of programmed cell death caused by phospholipid peroxidation that has been implicated as a mechanism in several diseases resulting from ischemic-reperfusion injury. Most recently, ferroptosis has been identified as a possible key injury mechanism in neonatal hypoxic-ischemic brain injury (HIBI). This review summarizes the current literature regarding the different ferroptotic pathways, how they may be activated after neonatal HIBI, and which current or investigative interventions may attenuate ferroptotic cell death associated with neonatal HIBI

Neonatal Hypoxic-Ischemic Brain Injury Alters Brain Acylcarnitine Levels in a Mouse Model

Hypoxic-ischemic brain injury (HIBI) leads to depletion of ATP, mitochondrial dysfunction, and enhanced oxidant formation. Measurement of acylcarnitines may provide insight into mitochondrial dysfunction. Plasma acylcarnitine levels are altered in neonates after an HIBI, but individual acylcarnitine levels in the brain have not been evaluated. Additionally, it is unknown if plasma acylcarnitines reflect brain acylcarnitine changes. In this study, postnatal day 9 CD1 mouse pups were randomized to HIBI induced by carotid artery ligation, followed by 30 min at 8% oxygen, or to sham surgery and normoxia, with subgroups for tissue collection at 30 min, 24 h, or 72 h after injury (12 animals/group). Plasma, liver, muscle, and brain (dissected into the cortex, cerebellum, and striatum/thalamus) tissues were collected for acylcarnitine analysis by LC-MS. At 30 min after HIBI, acylcarnitine levels were significantly increased, but the differences resolved by 24 h. Palmitoylcarnitine was increased in the cortex, muscle, and plasma, and stearoylcarnitine in the cortex, striatum/thalamus, and cerebellum. Other acylcarnitines were elevated only in the muscle and plasma. In conclusion, although plasma acylcarnitine results in this study mimic those seen previously in humans, our data suggest that the plasma acylcarnitine profile was more reflective of muscle changes than brain changes. Acylcarnitine metabolism may be a target for therapeutic intervention after neonatal HIBI, though the lack of change after 30 min suggests a limited therapeutic window

Deprotonation of caffeic acid and the respective pKa values.

<p>Deprotonation of caffeic acid and the respective pKa values.</p

Effect of caffeic acid on lipid peroxidation.

<p><b>(A)</b> Effect of CA on the <i>in vitro</i> rat liver peroxidation induced by Fenton reagents. Experimental conditions: 10 mM KPi (pH 7.2); 5% v/v liver homogenate; 100 μM H₂O₂; 50 μM Fe(II) (■); Fe(II) plus 50 μM CA (●); Fe(II) plus 100 μM CA (▲); Fe plus 150 μM CA (▼); Fe plus 100 μM BHT (□). n = 9; <b>(B)</b> Effect of CA on the lag phase of lipid peroxidation. <b>(C)</b> Effect of CA on the log phase of peroxidation—experimental conditions are the same as in panel-A.</p

EPR determinations of DMPO hydroxylation induced by Fenton reagents.

<p><b>(A)</b> Effect of CA on DMPO hydroxylation. Experimental conditions: 10 mM KPi (pH 7.2); 20 mM DMPO; 100 μM H₂O₂; 50 μM Fe(II); 0–300 μM CA. n = 3; <b>(B)</b> Effect of Fe(II) on DMPO hydroxylation in the absence (<i>solid squares</i>) or presence (<i>open squares</i>) of CA. Experimental conditions: 10 mM KPi; 20 mM DMPO; 100 μM H₂O₂; 200 μM CA; 0–100 μM Fe(II). n = 3.</p