RESUMO
Acute lung injury (ALI) is defined as the acute onset of diffuse bilateral pulmonary infiltration, leading to PaO2/FiO2 ≤ 300 mmHg without clinical evidence of left atrial hypertension. Acute respiratory distress syndrome (ARDS) involves more severe hypoxemia (PaO2/FiO2 ≤ 200 mmHg). Treatment of ALI and ARDS has received renewed attention as the incidence of ALI caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has increased. Itaconate and its derivatives have shown therapeutic potential against ALI. This review provides an in-depth summary of the mechanistic research of itaconate in the field of acute lung injury, including inducing autophagy, preventing ferroptosis and pyroptosis, shifting macrophage polarization to an anti-inflammatory M2 phenotype, inhibiting neutrophil activation, regulating epigenetic modifications, and repressing aerobic glycolysis. These compounds merit further consideration in clinical trials. We anticipate that the clinical translation of itaconate-based drugs can be accelerated.
RESUMO
OBJECTIVE: To explore the relationship between the scores of episodic memory (EM) encoding and retrieving and the resting-state changes of brain functional connectivity (FC) network of Alzheimer's disease (AD) and mild cognition impairment (MCI) patients. METHODS: All subjects were recruited from special care clinic and ward and health physical examination center, Qingdao Huanxiu Community and Affiliated Hospital, Medical College of Qingdao university from January 2009 to July 2012.They were divided into AD group (n = 16), MCI group (n = 24) and normal control (NC) group (n = 24). The resting-state fMRI scans were performed with GE3.0T to acquire the blood oxygenation level dependent signals for EM encoding and retrieving. The two-sample t test was conducted between the groups and linear correlation analysis performed between EM and FC. RESULTS: Compared to the NC group, the AD and MCI groups exhibited decreased FC to posterior cingulated cortex (PCC) mainly in bilateral lateral temporal lobe, medial prefrontal cortex and right insula.Increased regions existed in posterior cerebellar lobe. Compared with the MCI group, the AD group showed decreased FC to PCC in medial prefrontal cortex, bilateral insulas, right inferior temporal gyrus and right fusiform gyrus.And increased regions lied in posterior cerebellar lobe, right occipital lobe and left superior parietal lobule. Compared with the NC group, the MCI group exhibited decreased FC to PCC in left lingualis gyrus, left frontal lobe, right middle temporal gyrus and corpus callosum.And increased regions lied in posterior cerebellar lobe.EM encoding scores (%) (AD group 34 ± 20, MCI group 47 ± 17, NC group 69 ± 15) were significantly different among three groups (P < 0.05).And retrieving scores (%) (AD group 31 ± 18, MCI group 57 ± 22, NC group 81 ± 16) were significantly different among three groups (P < 0.05). Altered functional connectivity regions of left triangle orbital-inferior frontal gyrus (r = 0.642 98), left cuneus (r = 0.642 98) and left caudate nucleus (r = 0.642 68) showed positive correlations with the EM encoding scores in AD group (all P < 0.005). Other groups were not statistically significant. CONCLUSION: The resting-state FC networks of AD and MCI groups show significant differences. The MCI and AD patients have progressively decreased scores of episodic memory encoding and retrieving.And the declines of episodic memory encoding and partial regions of resting-state FC network are positively correlated in the AD group.