Integrative Analysis of Hub Genes for Postoperative Cognitive Dysfunction Based on Bioinformatics Methods DOI Creative Commons

Shentong Wang,

Jia Zhao,

Chengran Wang

и другие.

Research Square (Research Square), Год журнала: 2023, Номер unknown

Опубликована: Июль 10, 2023

Abstract Background POCD is a frequent condition that originates after surgery and characterized by impaired memory, inattention, diminished learning or language abilities. It seriously threatens the quality of patients’ life, especially in older adults. The identification factors associated to facilites diagnosis prediction clinical outcomes. biomarkers aids Therefore, this study aimed identify hub genes analyze their possible involvement pathogenesis. Methods expression profiles (GSE95070 GSE95426) were obtained from Gene Expression Omnibus (GEO) database, followed differentially expressed miRNAs (DEmiRNAs) mRNAs (DEmRNAs). Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathway analyses used achieve functional enrichment. Subsequently, target DEmiRNAs identified, construction miRNA-mRNA network for POCD. least absolute shrinkage selection operator (LASSO) support vector machine recursive feature elimination (SVM-RFE) algorithms miRNAs. Finally, sorted overlapping DEmRNAs. A mouse model was established tested using open field test (OFT) Morris water maze (MWM). quantitative real-time polymerase chain reaction (qRT-PCR) validation. Results Eleven identified. Among them, mmu-miR-483-5p mmu-miR-362-3p showed highest positive correlation (R = 0.96), whereas mmu-miR-206-3p mmu-miR-190a-3p negative -0.88). GO analysis revealed mainly enriched response stress, anatomical structure development, cellular nitrogen compound metabolic homeostatic processes. KEGG identified pathways regulating actin cytoskeleton, sphingolipid signaling, axon guidance, thyroid hormone signaling. Then, 7062 targeting with DEmiRNAs, 53 DEmRNAs mmu-miR-3065-5p mmu-miR-592-3p as LASSO SVM-RFE analyses, respectively. four ( Prdm14, Slc46a2, Nkx2-1, Lrg1 ) validated model. Conclusions We two model, all which could serve pharmacological targets treatment Targeting gene manipulation methods may help understand mechanism improve outcome

Язык: Английский

Pharmacological inhibition of cGAS ameliorates postoperative cognitive dysfunction by suppressing caspase-3/GSDME-dependent pyroptosis DOI

Xueshan Bu,

Ping Gong, Lei Zhang

и другие.

Neurochemistry International, Год журнала: 2024, Номер 178, С. 105788 - 105788

Опубликована: Июнь 5, 2024

Язык: Английский

Процитировано

8
Inhibition of PINK1-Mediated Mitophagy Contributes to Postoperative Cognitive Dysfunction through Activation of Caspase-3/GSDME-Dependent Pyroptosis DOI
Wei Wang, Bo Zhao, Wenwei Gao

и другие.

ACS Chemical Neuroscience, Год журнала: 2023, Номер 14(7), С. 1249 - 1260

Опубликована: Март 22, 2023

PTEN-induced kinase 1 (PINK1)-mediated mitophagy and caspase-1/gasdermin D canonical pyroptosis pathways have been implicated in the pathogenesis of postoperative cognitive dysfunction (POCD). However, gasdermin E (GSDME), another recently identified executioner that can be specifically cleaved by caspase-3, is highly expressed brain neurons. This study aimed to ascertain whether PINK1-dependent governs capacity through caspase-3/GSDME. Twelve month old male Sprague-Dawley rats underwent exploratory laparotomy under isoflurane anesthesia. Lipopolysaccharide (LPS)-primed SH-SY5Y cells were used mimic postsurgical neuroinflammation. For interventional study, administered with adeno-associated virus serotype 9 (AAV9)-mediated silencing Pink1 and/or caspase-3 inhibitor Ac-DEVD-CHO (Ac-DC). treated siPINK1 Ac-DC. Cognitive performance was assessed using Morris water maze test. The mitophagy- pyroptosis-related parameters determined hippocampus cells. Anesthesia/surgery LPS caused defective PINK1-mediated activation caspase-3/GSDME-dependent pyroptosis. AAV-9 mediated overexpression mitigated impairment Conversely, inhibition PINK1 aggravates POCD overactivates neuronal These abnormalities rescued Ac-DC treatment. Collectively, regulates anesthesia surgery-induced negatively affecting caspase-3/GSDME pathway, which provides a promising therapeutic target for POCD.

Язык: Английский

Процитировано

22
SNAP25 ameliorates postoperative cognitive dysfunction by facilitating PINK1-dependent mitophagy and impeding caspase-3/GSDME-dependent pyroptosis DOI
Wei Wang, Wenwei Gao, Lei Zhang

и другие.

Experimental Neurology, Год журнала: 2023, Номер 367, С. 114463 - 114463

Опубликована: Июнь 8, 2023

Язык: Английский

Процитировано

15
MEF2C Alleviates Postoperative Cognitive Dysfunction by Repressing Ferroptosis DOI Creative Commons
Shanshan Wang,

Zankai Wu,

Xueshan Bu

и другие.

CNS Neuroscience & Therapeutics, Год журнала: 2024, Номер 30(10)

Опубликована: Сен. 30, 2024

Ferroptosis, a form of programmed cell death featured by lipid peroxidation, has been proposed as potential etiology for postoperative cognitive dysfunction (POCD). Myocyte-specific enhancer factor 2C (MEF2C), transcription expressed in various brain types, implicated disorders. This study sought to ascertain whether MEF2C governs capacity affecting ferroptosis.

Язык: Английский

Процитировано

5
Neuronal-specific TNFAIP1 ablation attenuates postoperative cognitive dysfunction via targeting SNAP25 for K48-linked ubiquitination DOI Creative Commons
Wei Wang, Wenwei Gao, Ping Gong

и другие.

Cell Communication and Signaling, Год журнала: 2023, Номер 21(1)

Опубликована: Дек. 15, 2023

Abstract Background Synaptosomal-associated protein 25 (SNAP25) exerts protective effects against postoperative cognitive dysfunction (POCD) by promoting PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy and repressing caspase-3/gasdermin E (GSDME)-mediated pyroptosis. However, the regulatory mechanisms of SNAP25 remain unclear. Methods We employed recombinant adeno-associated virus 9 (AAV9)-hSyn to knockdown tumor necrosis factor α-induced (TNFAIP1) or investigate role TNFAIP1 in POCD. Cognitive performance, hippocampal injury, mitophagy, pyroptosis were assessed. Co-immunoprecipitation (co-IP) ubiquitination assays conducted elucidate which stabilizes SNAP25. Results Our results demonstrated that ubiquitin ligase was upregulated hippocampus mice following isoflurane (Iso) anesthesia laparotomy. The N-terminal region (residues 1–96) formed a conjugate with SNAP25, leading lysine (K) 48-linked polyubiquitination at K69. Silencing enhanced SH-SY5Y cell viability conferred antioxidant, pro-mitophagy, anti-pyroptosis properties response Iso lipopolysaccharide (LPS) challenges. Conversely, overexpression reduced HT22 viability, increased reactive oxygen species (ROS) accumulation, impaired PINK1/Parkin-dependent induced caspase-3/GSDME-dependent suppressing expression. Neuron-specific ameliorated POCD, restored pyroptosis, reversed depletion. Conclusions In summary, our findings inhibiting TNFAIP1-mediated degradation might be promising therapeutic approach for mitigating decline.

Язык: Английский

Процитировано

12
Research progress of postoperative cognitive dysfunction in cardiac surgery under cardiopulmonary bypass DOI Creative Commons
Yiming Zhuang, Jiyang Xu, Kun Zheng

и другие.

Ibrain, Год журнала: 2023, Номер unknown

Опубликована: Авг. 14, 2023

Abstract Cardiopulmonary bypass (CPB) is often used in cardiothoracic surgery because its nonphysiological state causes pathophysiological changes the body, causing multiorgan and multitissue damage to varying degrees. Postoperative cognitive dysfunction (POCD) a common central nervous system complication after cardiac surgery. The etiology mechanism of POCD are not clear. Neuroinflammation, brain mitochondrial dysfunction, cerebral embolism, ischemia, hypoxia, other factors related pathogenesis POCD. There close relationship between CPB POCD, as can cause inflammation, hypoxia reperfusion injury, microemboli formation, all which trigger increases medical costs, seriously affects patients' quality life, mortality. Currently, there lack effective treatment methods for Commonly include preoperative health management, reducing inflammation response during surgery, preventing implementing individualized rehabilitation programs Strengthening preventive measures minimize occurrence adverse effects.

Язык: Английский

Процитировано

6
Neuroprotection of celastrol against postoperative cognitive dysfunction through dampening cGAS-STING signaling DOI

Xueshan Bu,

Hui Guo, Wenwei Gao

и другие.

Experimental Neurology, Год журнала: 2024, Номер 382, С. 114987 - 114987

Опубликована: Окт. 5, 2024

Язык: Английский

Процитировано

2
Construction and analysis of circular RNA-associated competing endogenous RNA network in the hippocampus of aged mice for the occurrence of postoperative cognitive dysfunction DOI Creative Commons
Mingzhu Zhang, Zizheng Suo, Yinyin Qu

и другие.

Frontiers in Aging Neuroscience, Год журнала: 2023, Номер 15

Опубликована: Март 27, 2023

Circular RNAs are highly stable single-stranded circular and enriched in the brain. Previous studies showed that circRNAs, as part of competing endogenous (ceRNAs) network, play an important role neurodegenerative psychiatric diseases. However, mechanism circRNA-related ceRNA networks postoperative cognitive dysfunction (POCD) has not been elucidated yet. POCD usually occurs elderly patients is characterized by hippocampal dysfunction. Here, aged C57BL/6 mice were subjected to exploratory laparotomy under sevoflurane anesthesia, this model was verified Morris water maze test. Whole-transcriptome sequencing performed on hippocampus control group (Con) surgery group. One hundred seventy-seven DEcircRNAs, 221 DEmiRNAs 2,052 DEmRNAs identified between two groups. A network established with 92 DEcircRNAs having binding sites 76 549 target DEmRNAs. In functional enrichment analysis, a pathological pattern highlighted network: Abnormal metabolic process neural cells, including oxygen metabolism, could promote apoptosis then affect synaptic function, which may undermine plasticity eventually lead changes function other behavioral patterns. conclusion, specific circRNAs-miRNAs-mRNAs provided novel insights into regulatory mechanisms revealed potential therapeutic gene targets.

Язык: Английский

Процитировано

5
Integrative analysis of circRNA networks in postoperative cognitive dysfunction DOI
Jian Tang,

Yanhong Tang,

Peimin Lin

и другие.

International Journal of Neuroscience, Год журнала: 2024, Номер unknown, С. 1 - 33

Опубликована: Янв. 23, 2024

Objective In the quest to decipher molecular intricacies of Postoperative Cognitive Dysfunction (POCD), this study focused on circular RNA (circRNA) and their regulatory networks.

Язык: Английский

Процитировано

0
Progression in the study of protective effect of microRNAs against sevoflurane-induced postoperative cognitive dysfunction and potential mechanisms DOI Creative Commons
Jun Chen,

Lin-Yan Li,

Bo-Ya Zhang

и другие.

Turkish Journal of Biochemistry, Год журнала: 2024, Номер unknown

Опубликована: Дек. 5, 2024

Abstract As one of the volatile anaesthetic drugs commonly used in clinical anaesthesia, sevoflurane is extensively general anaesthesia surgery because its rapid induction, hemodynamic stability, and metabolism. However, postoperative cognitive dysfunction (POCD) most prevalent complications application. Neuroinflammation neuronal apoptosis are currently believed to be primary mechanisms responsible for development dysfunction. MicroRNAs (miRNAs) can negatively regulate expression target genes, thereby influencing neurological processes. Therefore, effects potential miRNAs on function may provide new ideas prevention treatment sevoflurane-induced POCD, a topic intense research interest at moment. The involved regulation by sevoflurane, genes downstream signalling pathways were reviewed order obtain comprehensive understanding function.

Язык: Английский

Процитировано

0