Activation of CB1R-Dependent PGC-1α Is Involved in the Improved Mitochondrial Biogenesis Induced by Electroacupuncture Pretreatment.

Electroacupuncture (EA) pretreatment induces cerebral ischemic tolerance; however, the mechanism remains poorly understood. This study aimed to determine the participation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-mediated mitochondrial biogenesis in the neuroprotection of EA and whether cannabinoid receptor 1 (CB1R) is involved in this mechanism. At 2 hours after EA pretreatment, adult male C57BL/6j mice were subjected to 60-minute right middle cerebral artery occlusion (MCAO). Mitochondrial function, the level of mitochondrial biogenesis-related proteins (nuclear transcription factor 1, NRF1; mitochondrial transcription factor A, TFAM), and mitochondrial DNA (mtDNA) were measured. A small interfering RNA (siRNA) targeting PGC-1α and the CB1R antagonists AM251 and SR141716A were given to the animals before EA pretreatment, and mitochondrial function and biogenesis were examined after MCAO. EA ameliorated the mitochondrial function, upregulated the NRF1 and TFAM expression, and increased the mtDNA levels and the volume and number of mitochondria. EA pretreatment increased the expression of PGC-1α, whereas the PGC-1α siRNA and CB1R antagonists reversed the improved neuroprotection and increased mitochondrial biogenesis induced by EA. Our results indicated that EA pretreatment protects the mitochondria and promotes mitochondrial biogenesis by activating CB1R-dependent PGC-1α, which provides a novel mechanism for EA pretreatment-induced ischemic tolerance.

Prophylactic atorvastatin prior to intra-arterial administration of iodinated contrast media for prevention of contrast-induced acute kidney injury: A meta-analysis of randomized trial data
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BACKGROUND: The efficacy of high-dose atorvastatin pretreatment in reducing the incidence of contrast-induced nephropathy in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) has been examined in some randomized studies. However, the results across the trials remain controversial. OBJECTIVE: This study sought to perform a meta-analysis to evaluate the effect of high-dose atorvastatin in the prevention of contrast-induced nephropathy (CIN) while undergoing CAG or PCI. MATERIALS AND METHODS: Comprehensive literature searches for randomized controlled trials (RCTs) comparing high-dose atorvastatin vs. low-dose statin or placebo pretreatment for prevention of contrast-induced acute kidney injury in patients undergoing CAG were performed using PubMed, Embase, and the Cochrane library updated to June 2017. The primary outcome was the incidence of CIN. RESULTS: A total of 11 RCTs were included in this analysis. The high-dose atorvastatin treatment can significantly reduce the incidence of CIN (OR 0.46, 95% CI 0.35 - 0.62, p < 0.00001). The benefit was consistent in comparison with the low-dose group (OR 0.41, 95% CI 0.25 - 0.66, p = 0.0003) and the placebo group (OR 0.50, 95% CI 0.26 - 0.98, p = 0.04). CONCLUSION: Our study demonstrates that high-dose statin pretreatment shows a benefit specifically in reducing the incidence of contrast-induced acute kidney injury in patients undergoing CAG, especially compared with low-dose statin pretreatment.

Electroacupuncture attenuated cerebral ischemic injury and neuroinflammation through α7nAChR-mediated inhibition of NLRP3 inflammasome in stroke rats.

BACKGROUND: Our previous research confirmed that electroacupuncture (EA) stimulus elicits neuroprotective effects against cerebral ischemic injury through α7 nicotinic acetylcholine receptor (α7nAChR)-mediated inhibition of high-mobility group box 1 release mechanism. This study investigated whether the signal transducer of α7nAChR and inhibition of NLRP3 inflammasome are involved in the neuroprotective effects of EA stimulus. METHODS: In adult male Sprague-Dawley rats, the focal cerebral ischemic injury was induced by middle cerebral artery occlusion (MCAO) models for 1.5 h. The expression of NLRP3 inflammasome in the penumbral tissue following reperfusion was assessed by western blotting and immunoflourescent staining. The infarct size, neurological deficit score, TUNEL staining and the expression of proinflammatory factors or anti-inflammatory cytokines were evaluated at 72 h after reperfusion in the presence or absence of either α7nAChR antagonist (α-BGT) or agonist (PHA-543,613). RESULTS: The contents of inflammasome proteins were gradually increased after cerebral ischemia/reperfusion (I/R). EA stimulus attenuated NLRP3 inflammasome mediated inflammatory reaction and regulated the balance between proinflammatory factors and anti-inflammatory cytokines. The agonist of α7nAChR induced similar neuroprotective effects as EA stimulus. In contrast, α7nAChR antagonist reversed not only the neuroprotective effects, but also the inhibitory effects of NLRP3 inflammasome and the regulatory effects on the balance between proinflammatory factors and anti-inflammatory cytokines. CONCLUSIONS: These results provided compelling evidence that α7nAChR played a pivotal role in regulating the activation and expression of NLRP3 inflammasome in neurons after cerebral I/R. These findings highlighted a novel anti-inflammatory mechanism of EA stimulus by α7nAChR modulating the inhibition of NLRP3 inflammasome, suggesting that α7nAChR-dependent cholinergic anti-inflammatory system and NLRP3 inflammasome in neurons might act as potential therapeutic targets in EA induced neuroprotection against cerebral ischemic injury.

2-Pyridone-functionalized Aza-BODIPY photosensitizer for imaging-guided sustainable phototherapy.

To overcome irradiation-dependence of cancer phototherapy, a near infrared aza-BODIPY-based photothermogenic photosensitizer BDY with 2-Pyridone group has been synthesized for imaging-guided photothermal synergistic sustainable photodynamic therapy. Multifunctional water-soluble BDY nanoparticles (NPs), with high photothermal conversion efficiency of 35.7% and excellent singlet oxygen (1O2) generation ability, are prepared by self-assembling. The reversible transformation between 2-pyridone moiety and its endoperoxide form endows BDY with continuous 1O2 generation ability under illumination and non-illumination conditions. Simultaneously, BDY NPs exhibit excellent tumor targeting properties by enhanced permeability and retention (EPR) effect and photoacoustic imaging (PAI) ability. Furthermore, the photothermal assisted sustainable photodynamic therapy can significantly inhibit tumor growth (93.4% inhibition) with almost no side effects by intermittent laser illumination. The finding highlights that this photothermal synergistic sustainable phototherapy presents great potential for clinical applications.

Efficacy of atorvastatin on the prevention of contrast-induced acute kidney injury: a meta-analysis.

BACKGROUND: Results of studies on the efficacy of atorvastatin pretreatment on reducing the prevalence of contrast-induced acute kidney injury (CIAKI) in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) have been controversial. OBJECTIVE: We undertook a meta-analysis to evaluate the efficacy of atorvastatin on contrast-induced nephropathy (CIN) after CAG or PCI. MATERIALS AND METHODS: We undertook a systematic search of electronic databases (PubMed, Embase, and the Cochrane Library) up to June 2017. A meta-analysis was carried out including randomized controlled trials (RCTs) that compared atorvastatin pretreatment with pretreatment with a low-dose statin or placebo for CIAKI prevention in patients undergoing CAG. The main endpoint was CIN prevalence. RESULTS: Nine RCTs were included in our meta-analysis. Atorvastatin pretreatment reduced the prevalence of CIN significantly (odds ratio [OR] 0.46; 95% confidence interval [95% CI] 0.27-0.79; p=0.004). The benefit of high-dose atorvastatin pretreatment was consistent when compared with the control group (OR 0.45; 95% CI 0.21-0.95; p=0.04). CONCLUSION: At high doses, atorvastatin pretreatment was associated with a significant reduction in the prevalence of CIAKI in patients undergoing CAG. Pretreatment with high-dose atorvastatin could be employed to prevent CIAKI.