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. 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). 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. 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.

MARCH5 is a crucial regulator of mitochondrial fission. However, the expression and function of MARCH5 in ovarian cancer have not been determined. This study investigated the expression and function of MARCH5 in ovarian cancer with respect to its potential role in the tumorigenesis of the disease as well as its usefulness as an early diagnostic marker. We found that the expression of MARCH5 was substantially upregulated in ovarian cancer tissue in comparison with the normal control. Silencing MARCH5 in SKOV3 cells decreased TGFB1-induced cell macroautophagy/autophagy, migration, and invasion in vitro and in vivo, whereas the ectopic expression of MARCH5 in A2780 cells had the opposite effect. Mechanistic investigations revealed that MARCH5 RNA may function as a competing endogenous RNA (ceRNA) to regulate the expression of SMAD2 and ATG5 by competing for MIR30A. Knocking down SMAD2 or ATG5 can block the effect of MARCH5 in A2780 cells. Also, silencing the expression of MARCH5 in SKOV3 cells can inhibit the TGFB1-SMAD2/3 pathway. In contrast, the ectopic expression of MARCH5 in A2780 cells can activate the TGFB1-SMAD2/3 pathway. In turn, the TGFB1-SMAD2/3 pathway can regulate MARCH5 and ATG5 through MIR30A. Overall, the results of this study identified MARCH5 as a candidate oncogene in ovarian cancer and a potential target for ovarian cancer therapy.

Sepsis remains an unacceptably high mortality due to the lack of biomarkers for predicting septic outcomes in the early period. Mitochondrial redox states play a pivotal role in this condition and are disturbed early in the development of sepsis. Here, we hypothesized that visualizing mitochondrial redox states via resonance Raman spectroscopy (RRS) could identify septic outcomes at an early time point. Sepsis was induced by cecal ligation and puncture (CLP). We applied RRS analysis at baseline and 30 min, 1 h, 2 h, 4 h, and 6 h after CLP, and the mitochondrial redox states were identified. The levels of blood lactate as a predictor in sepsis were assessed. Our study is the first to reveal the possibility of in vivo detection of the mitochondrial redox state by using RRS in septic mice. The peak area for the Raman reduced mitochondrial fraction, the indicator of mitochondrial redox states, fluctuated significantly at 2 h after CLP. This fluctuation occurred earlier than the change in lactate level. Moreover, this fluctuation had higher prognostic accuracy for mortality than the lactate level during sepsis and could be a novel diagnostic marker for predicting septic outcomes according to the cutoff value of 1.059, which had a sensitivity of 80% and a specificity of 90%. To explore an effective indicator concerning mitochondrial redox states in the early stage of sepsis and to predict septic outcomes accurately in vivo using non-invasive and label-free Resonance Raman spectroscopy (RRS) analysis. Mitochondria, primary skeletal muscle cells andex-vivo muscles harvested from gastrocnemius were detected mitochondrial redox states respectively by using RRS. Sepsis was induced by cecal ligation and puncture (CLP). We applied RRS analysis at baseline and 30 min, 1 h, 2 h, 4 h, and 6 h after CLP, and the mitochondrial redox states were identified. The levels of blood lactate as a predictor in sepsis were assessed. The predictive correlation of mitochondrial redox states on mortality, inflammation and organ dysfunction was further assessed. Mitochondrial redox states were clearly recognized in ex-vivo gastrocnemius muscles as well as purified mitochondria and primary skeletal muscle cells by using RRS. The peak area for the Raman reduced mitochondrial fraction, the indicator of mitochondrial redox states, fluctuated significantly at 2 h after CLP. This fluctuation occurred earlier than the change in lactate level. Moreover, this fluctuation had higher prognostic accuracy for mortality than the lactate level during sepsis and could be a novel diagnostic marker for predicting septic outcomes according to the cutoff value of 1.059, which had a sensitivity of 80% and a specificity of 90%. This study demonstrated that monitoring mitochondrial redox states using RRS as early as 2 h could indicate outcomes in septic mice. These data may contribute to developing a non-invasive clinical device concerning mitochondrial redox states by using bedside-RRS.

An adjunct and promising tool for cardiac myxoma diagnosis is performed by Raman spectroscopy analysis combined with multivariate algorithms.

Long-term high-fat-diet (HFD)-induced obesity is associated with many comorbidities, such as cognitive impairment and anxiety, which are increasing public health burdens that have gained prevalence in adolescents. Although low-dose alcohol could attenuate the risk of cardiovascular disease, its mechanism on HFD-induced anxiety-related behavior remains not clear. The mice were divided into 4 groups, Control (Con), Alcohol (Alc), HFD and HFD + Alc groups. To verify the effects of low-dose alcohol on HFD-induced anxiety-related behavior, the mice were fed with HFD for 16 weeks. At the beginning of week 13, the HFD-fed mice were administered intragastrically with low-dose alcohol (0.8 g kg⁻¹) for 4 weeks. After 4 weeks of oral administration, low-dose alcohol decreased body weight and Lee's index in HFD-induced obese mice. Moreover, low-dose alcohol alleviated the anxiety-related behaviors of obese mice in the open field test and the elevated plus maze test. The HFD-induced damage to the hippocampus was improved in hematoxylin–eosin staining assay in mice. In addition, low-dose alcohol also suppressed HFD-induced oxidative stress and increased HFD-suppressed adiponectin (APN) expression and nuclear factor erythroid 2-related factor 2 (Nrf2) activation in the hippocampus. Taken together, low-dose alcohol significantly ameliorates HFD-induced obesity, oxidative stress and anxiety-related behavior in mice, which might be related to APN upregulation, Nrf2 activation and related antioxidase expression including SOD1, HO-1, and catalase.