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INTRODUCTION: We present lipidomic studies that have utilized cadaveric biological samples, including tissues and bodily fluids (excluding blood or serum). Analyses of lipids from cadaveric-derived tissues play vital roles in many different fields, such as in anthropogeny to understand food habits of ancient people, in forensics for postmortem analyses, and in biomedical research to study human diseases. AREAS COVERED: The goal of the review is to demonstrate how cadavers can be utilized for study of lipidome to get biological insight in different fields. Several important considerations need to be made when analyzing lipids from cadaver samples. For example, what important postmortem changes occur due to environmental or other intrinsic factors that introduce deviations in the observed differences versus true differences? Do these factors affect distinct classes of lipids differently? How do we arrive at a reasonable level of certainty that the observed differences are truly biological rather than artifacts of sample collection, changes during transportation, or variations in analytical procedures? These are pressing questions that need to be addressed when performing lipidomics investigations utilizing postmortem tissues, which inherently presents hurdles and unknowns beginning with harvesting methods, transportation logistics, and at analytical techniques. In our review, we have purposefully omitted blood and serum studies since they pose greater challenges in this regard. Several studies have been carried out with cadaveric tissues and fluids that support the successful use of cases of these samples; however, many control studies are still necessary to provide insight into full potential of the cadaveric tissue and fluid resources. Most importantly, additional control studies will allow us to gain important insights into the opportunities lipidomics presents for biomedical studies of complex human disease and disorders. Another goal of the review is to generate awareness about limitations and pitfalls of use of cadaver materials for study of lipidome. EXPERT OPINION: We comment on the current state of lipidomics studies that utilize cadaveric tissues, provide a few pertinent examples, and discuss perspectives on both future technological directions and the applications they will enable.
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Investigación Biomédica , Lipidómica , Cadáver , Humanos , LípidosRESUMEN
Objective- Macrophages participate in the pathogenesis of pulmonary arterial hypertension (PAH). Lgmn (Legumain), a newly discovered cysteine proteinase belonging to the C13 peptidase family, is primarily expressed in macrophages; however, its roles in PAH remain unknown. Approach and Results- Herein, Lgmn was upregulated in lung tissues of PAH mice subjected to hypoxia plus SU5416 and PAH rats challenged with monocrotaline. Global Lgmn ablation and macrophage-specific ablation alleviated PAH compared with wild-type mice, evident from a reduction in right ventricular systolic pressure, the ratio of the right ventricular wall to the left ventricular wall plus the septum, the pulmonary vascular media thickness, and pulmonary vascular muscularization. Increased expression of ECM (extracellular matrix) proteins was correlated with MMP (matrix metalloproteinase)-2 activation and TGF (transforming growth factor)-ß1 signaling in the PAs. Although Lgmn did not affect inflammatory cell infiltration and PA smooth muscle cell proliferation, it drove increased the synthesis of ECM proteins via MMP-2 activation. MMP-2 hydrolyzed the TGF-ß1 precursor to the active form. An Lgmn-specific inhibitor markedly ameliorated PAH. Clinically, serum Lgmn levels were closely associated with the severity of idiopathic PAH. Conclusions- Our results indicate that Lgmn inhibition could be an effective strategy for preventing or delaying PAH.
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Cisteína Endopeptidasas/fisiología , Hipertensión Pulmonar/enzimología , Macrófagos/enzimología , Metaloproteinasa 2 de la Matriz/fisiología , Factor de Crecimiento Transformador beta1/fisiología , Animales , Inhibidores de Caspasas/farmacología , Cisteína Endopeptidasas/deficiencia , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Estudios de Seguimiento , Humanos , Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/patología , Hipertensión Pulmonar/prevención & control , Hipoxia/enzimología , Indoles/toxicidad , Inflamación , Pulmón/metabolismo , Masculino , Ratones , Persona de Mediana Edad , Monocrotalina/toxicidad , Pirroles/toxicidad , Ratas , Índice de Severidad de la Enfermedad , Transducción de Señal , Remodelación Vascular/fisiologíaRESUMEN
This study aimed to investigate the effects of long-term home quarantine on the mental health of people during the COVID-19 epidemic in Shanghai. We conducted an online questionnaire survey on March 26 2020 and collected data on demographics, level of physical activity (PA), and mental health status of the participants. We assessed the mental health status using the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder Scale (GAD-7), whereas PA was assessed using International Physical Activity Questionnaire Short Form (IPAQ-SF). Of all 2,409 valid samples, participants reported performing a total of 2015.20 metabolic equivalent of task (MET)-minutes/week of total PA before the outbreak period and 1720.29 MET-minutes/week of total PA during the outbreak period (p < 0.001). Participants who spent a longer time at home reported to have a better performance on the PHQ-9 (p = 0.087) and GAD-7 (p < 0.001). A high level of PA was considered an protective factor against depression (OR = 0.755, 95% CI 0.603-0.944, p < 0.001). Additionally, a high level of PA had a preventative effect on anxiety (OR = 0.741, 95% CI 0.568-0.967, p < 0.001), and a longer working period during the outbreak was shown to be a risk factor for anxiety (11-29 days, OR 1.455, 95% CI 1.110-1.909; 30-60 days OR 1.619, 95% CI 1.227-2.316). Home confinement during the pandemic might not have a negative effect on mental health provided that people engage in more PA indoors. This study encourages interventions for mental health problems through physical exercise.
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Apoptotic death of cardiac myocytes is associated with ischemic heart disease and chemotherapy-induced cardiomyopathy. Chemoattractant receptor-homologous molecule expressed on T helper type 2 cells (CRTH2) is highly expressed in the heart. However, its specific role in ischemic cardiomyopathy is not fully understood. Here, we demonstrated that CRTH2 disruption markedly improved cardiac recovery in mice postmyocardial infarction and doxorubicin challenge by suppressing cardiomyocyte apoptosis. Mechanistically, CRTH2 activation specifically facilitated endoplasmic reticulum (ER) stress-induced cardiomyocyte apoptosis via caspase-12-dependent pathway. Blockage of m-calpain prevented CRTH2-mediated cardiomyocyte apoptosis under ER stress by suppressing caspase-12 activity. CRTH2 was coupled with Gαq to elicit intracellular Ca2+ flux and activated m-calpain/caspase-12 cascade in cardiomyocytes. Knockdown of caspase-4, an alternative to caspase-12 in humans, markedly alleviated CRHT2 activation-induced apoptosis in human cardiomyocyte response to anoxia. Our findings revealed an unexpected role of CRTH2 in promoting ER stress-induced cardiomyocyte apoptosis, suggesting that CRTH2 inhibition has therapeutic potential for ischemic cardiomyopathy.