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Several studies indicated that autophagy activation participates in brain ischemic tolerance (BIT) induced by cerebral ischemic preconditioning (CIP). However, the mechanism of autophagy activation during the process still remains unclear. The present study aimed to evaluate the role of p38 MAPK-peroxisome proliferator-activated receptor γ (PPARγ) signaling cascade in autophagy during the CIP-induced BIT. The results shown that, initially, autophagy activation was observed after CIP in the model of global cerebral ischemia in rats, as was indicated by the upregulation of Beclin 1 expression, an increase in LC3-II/LC3-I ratio, the enhanced LC3 immunofluorescence, and a rise in the number of autophagosomes in the neurons of the hippocampal CA1 area. Besides, the inhibitor of autophagy 3-methyladenine obliterated the neuroprotection induced by CIP. Furthermore, the upregulation of p-p38 MAPK and PPARγ expressions was earlier than autophagy activation after CIP. In addition, pretreatment with SB203580 (the inhibitor of p38 MAPK) reversed CIP-induced PPARγ upregulation, autophagy activation, and neuroprotection. Pretreatment with GW9662 (the inhibitor of PPARγ) reversed autophagy activation and neuroprotection, while it had no effect on p-p38 MAPK upregulation induced by CIP. These data suggested that the p38 MAPK-PPARγ signaling pathway participates in autophagy activation during the induction of BIT by CIP.

Cerebral ischemic preconditioning (CIP)-induced brain ischemic tolerance protects neurons from subsequent lethal ischemic insult. However, the specific mechanisms underlying CIP remain unclear. In the present study, we explored the hypothesis that peroxisome proliferator-activated receptor gamma (PPARγ) participates in the upregulation of Klotho during the induction of brain ischemic tolerance by CIP. First we investigated the expression of Klotho during the brain ischemic tolerance induced by CIP. Lethal ischemia significantly decreased Klotho expression from 6 h to 7 days, while CIP significantly increased Klotho expression from 12 h to 7 days in the hippocampal CA1 region. Inhibition of Klotho expression by its shRNA blocked the neuroprotection induced by CIP. These results indicate that Klotho participates in brain ischemic tolerance by CIP. Furthermore, we tested the role of PPARγ in regulating Klotho expression after CIP. CIP caused PPARγ protein translocation to the nucleus in neurons in the CA1 region of the hippocampus. Pretreatment with GW9962, a PPARγ inhibitor, significantly attenuated the upregulation of Klotho protein and blocked the brain ischemic tolerance induced by CIP. Taken together, it can be concluded that Klotho upregulation via PPARγ contributes to the induction of brain ischemic tolerance by CIP.

Carbon black (CB) has been demonstrated to have adverse effects on the lung tissue. Few studies explored the effects of CB on the cerebellum, widely recognized to contribute to gait and balance coordination and timing in the motor domain. Some studies have reported that inflammatory response and damaged autophagy are important mechanisms of CB toxicity and can be repaired after the recovery. The present study aimed to determine whether long-term CB exposure could induce the inflammation and damaged autophagy of the cerebellum. The rats were randomly divided into four groups. The control group received the filtered air for 90 days; the carbon black (CB) group received CB particles for 90 days; the recovery (R) group received CB for 90 days and recovered for another 14 days; the recovery control (RC) group received filtered air for 104 days. The purpose of the R group was to test whether neuroinflammation and autophagy could be repaired after short-term recovery. The western blot and immunohistochemistry revealed that long-term CB exposure induced augmented level of pro-inflammatory cytokines (Interleukin-1β, IL-1β; Interleukin-6, IL-6; and Tumor Necrosis Factor-α, TNF-α) and anti-inflammatory cytokine (Interleukin-10, IL-10). The autophagic markers (Beclin1 and LC3) were increased in both CB group and R group. These findings clearly demonstrated that long-term CB exposure induced inflammation and autophagy in the cerebellum, which were not obviously improved after short-term recovery.

To evaluate the determinants of failure rate and reproducibility of computed tomography feature tracking (CT-FT) derived left ventricular (LV) strain.Subjects who underwent retrospectively electrocardiogram gated coronary computed tomography angiography (CCTA) were included in this study. CCTA image quality and strain curve were visually evaluated to determine whether the images were optimal for CT-FT strain analysis. Parameters of global strain, regional longitudinal strain (LS), territory LS, segmental LS, and LS mechanical dispersion were obtained. Reproducibility was quantified by intraclass correlation coefficient (ICC), Bland-Altman analysis, and coefficient of variation (CV).A total of 809 subjects were included in the final study cohort, and 625 subjects had complete LV CT-FT strain analysis. The risk factors for failed LV strain analysis were high average heart rate (odds ratios [OR] = 5.52; 95% confidence interval [95 %CI]: 3.59-8.68), high heart rate variation (OR = 2.7; 95% CI = 1.54-3.68), and older age (OR = 1.87; 95% CI = 1.24-2.84). Tube current modulation was inversely related to failure of LV strain analysis (OR = 0.19; 95% CI = 0.11-0.34). The intraobserver reproducibility of global strain was excellent (ICCs: 0.90-0.98, CVs: 3.4-9.7%), and the interobserver reproducibility was excellent (ICCs: 0.84-0.96, CVs: 4.4-11.9%), except for global radial strain. The intra- and interobserver ICCs of territory LS ranged from 0.83 to 0.97 and 0.76 to 0.95, while the CVs ranged from 3.7% to 9.2% and 4.6% to 10.6%.The intra- and inter-observer ICCs of regional LS ranged from 0.82 to 0.95 and 0.79 to 0.94, while the CVs ranged from 5.5% to 10.2% and 5.7% to 11.0%. The reproducibility of segmental LS was variable, and the ICCs were below 0.75 in 60.8% (31/51) segments. The reproducibility of LS mechanical dispersion was poor (the ICCs were below 0.50, and the CVs were greater than 20%).Controlling heart rate during CT scanning is essential to perform a successful analysis of LV CT-FT strain. The reproducibility of CT-FT-derived global strain, regional LS, and territory LS was good to excellent, while the segmental LS should be used with caution in clinical practice, and LS mechanical dispersion is not recommended at present.