effects-extracorporeal-membrane-oxygenation-on-coagulation

Effects of Extracorporeal Membrane Oxygenation on the Coagulation System

This study aimed to investigate the effects of long-term awake extracorporeal membrane oxygenation (ECMO) on the coagulation system in a sheep model. A ...

Capital Medical University

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by abnormal social behavior and communication. The autism susceptibility candidate 2 (AUTS2) gene has been associated with multiple neurological diseases, including ASD. Glucose metabolism plays an important role in social behaviors associated with ASD, but the potential role of AUTS2 in glucose metabolism has not been studied. Here, we generated Auts2; Emx1 conditional knockout mice with Auts2 deletion specifically in Exm1-positive neurons in the brain (Auts2-cKO mice) to evaluate the effects of Auts2 knockdown on social behaviors and metabolic pathways. Auts2-cKO mice exhibited ASD-like behaviors, including impaired social interactions and repetitive grooming behaviors. At the molecular level, we found that Auts2 knockdown reduced brain glucose uptake and inhibited the pentose phosphate pathway. Auts2 knockdown also resulted in signs of oxidative stress, and we documented increased levels of reactive oxygen species and malondialdehyde as well as decreased levels of antioxidant molecules, including glutathione and superoxide dismutases in Auts2-cKO mouse brains compared to controls. Finally, Auts2 knockdown significantly disrupted mitochondrial homeostasis and inhibited activity of the SIRT1-SIRT3 axis. Taken together, our findings indicate that loss of AUTS2 expression in Emx1-expressing cells induces multiple changes in metabolic pathways that have been linked to the pathology of ASD. Further characterization of the role of AUTS2 in Emx1-expressing cells in regulating the metabolism of brain neurons may identify opportunities to treat ASD and AUTS2-deficiency disorders with metabolism-targeted therapies.

Auts2 regulated autism-like behavior, glucose metabolism and oxidative stress in mice.

Neurologic abnormalities occurring after deep hypothermic circulatory arrest (DHCA) remain a significant concern. However, molecular mechanisms leading to DHCA-related cerebral injury are still ill-defined. Circular RNAs (circRNAs) are a class of covalently closed non-coding RNAs and can play important roles in different types of cerebral injury. This study aimed to investigate circRNAs expression profiles in rat hippocampus after DHCA and explore the potential functions of circRNAs in DHCA-related cerebral injury. Hence, the DHCA procedure in rats was established and a transcriptomic profiling of circRNAs in rat hippocampus was done. As a result, a total of 35192 circRNAs were identified. Among them, 339 circRNAs were dysregulated, including 194 down-regulated and 145 up-regulated between DHCA and sham group. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed based on the host genes of all dysregulated circRNAs. Also, 4 circRNAs were validated by RT-qPCR (rno_circ_0028462, rno_circ_0037165, rno_circ_0045161 and rno_circ_0019047). Then a circRNA-microRNA (miRNA) interaction network involving 4 candidate circRNAs was constructed. Furthermore, functional enrichment analysis of the miRNA-targeting mRNAs of every candidate circRNA was conducted to gain insight into each of the 4 circRNAs. Our study provided a better understanding of circRNAs in the mechanisms of DHCA-related cerebral injury and some potential targets for neuroprotection.

Transcriptomic Profiling of circRNAs in rat Hippocampus after Deep Hypothermic Circulatory Arrest.

Sepsis is an unusual systemic reaction with high mortality and secondary septic liver injury is proposed to be the major cause of mortality. Extracorporeal membrane oxygenation (ECMO) can enhance terminal organ perfusion by elevating circulatory support which is used in severe sepsis patients. However, the interaction of blood components with the biomaterials of the extracorporeal membrane elicits a systemic inflammatory response. Besides, inflammation and apoptosis are the main mediators in the pathophysiology of septic liver injury. Therefore, we investigated the protective effect of Deoxyribonuclease I (DNase I) against septic liver injury supported by ECMO in rats. Sepsis was induced by lipopolysaccharide (LPS) and 24 hours after the administration, the rats were treated with ECMO. Then blood samples and liver tissues were collected. DNase I significantly attenuated the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and significantly decreased hepatic levels of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, myeloperoxidase (MPO), downstream inflammatory factor interleukin-1 β (IL-1 β ) and interleukin-18 (IL-18), and improved neutrophil infiltration. Additionally, DNase I significantly reduced the expression of apoptosis key protein and terminal-deoxynucleotidyl transferase-mediated nick end labeling (TUNEL)-labeled apoptotic hepatocytes. In summary, our findings demonstrated that DNase I alleviates liver injury in ECMO-supported septic rats by reducing the inflammatory and apoptotic responses.

Deoxyribonuclease I Alleviates Septic Liver Injury in a Rat Model Supported by Venoarterial Extracorporeal Membrane Oxygenation.

In on-pump cardiac surgery, the albumin priming strategy could maintain colloid osmotic pressure better than crystalloid solutions and reduce excessive perioperative fluid balance. However, a high-quality meta-analysis is required to compare the safety of these approaches in perioperative red blood cell (RBC) transfusions. Owing to limited direct evidence, we conducted a network meta-analysis (NMA) to increase the pool of studies and provide indirect evidence.

Article	Year
Auts2 regulated autism-like behavior, glucose metabolism and oxidative stress in mice. Experimental neurology\| PubMed ID: 36525998	2023
Transcriptomic Profiling of circRNAs in rat Hippocampus after Deep Hypothermic Circulatory Arrest. International journal of medical sciences\| PubMed ID: 37082735	2023
Deoxyribonuclease I Alleviates Septic Liver Injury in a Rat Model Supported by Venoarterial Extracorporeal Membrane Oxygenation. ASAIO journal (American Society for Artificial Internal Organs : 1992)\| PubMed ID: 37923309	2023
Effects of albumin and crystalloid priming strategies on red blood cell transfusions in on-pump cardiac surgery: a network meta-analysis. BMC anesthesiology\| PubMed ID: 38229019	2024

Mingru Zhang

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