Twelve Antioxidant Peptides From Protein Hydrolysate of Skipjack Tuna (Katsuwonus pelamis) Roe Prepared by Flavourzyme: Purification, Sequence Identification, and Activity Evaluation.

For using aquatic by-products to manufacture high-value products, Skipjack tuna (Katsuwonus pelamis) roes were degreased, pretreated with microwave, and hydrolyzed using five proteases. The protein hydrolysate (TRPH) generated using Flavourzyme displayed the strongest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity. Twelve antioxidative peptides were prepared from TRPH by ultrafiltration and chromatography methods and determined to be SGE, VDTR, AEM, QDHKA, TVM, QEAE, YEA, VEP, AEHNH, QEP, QAEP, and YVM with molecular weights of 291.24, 489.50, 349.41, 597.59, 349.44, 475.42, 381.36, 343.37, 606.58, 372.35, 443.42, and 411.49 Da, respectively. AEM, QDHKA, YEA, AEHNH, and YVM presented the strongest scavenging activity on DPPH radical (EC50 values of 0.250±0.035, 0.279±0.017, 0.233±0.012, 0.334±0.011, and 0.288±0.015 mg/ml, respectively), hydroxyl radical (EC50 values of 0.456±0.015, 0.536±0.021, 0.476 ± 0.051, 0.369 ± 0.052, and 0.413 ± 0.019 mg/ml, respectively), and superoxide anion free radical (EC50 values of 0.348 ± 0.018, 0.281 ± 0.013, 0.305 ± 0.022, 0.198 ± 0.011, and 0.425 ± 0.021 mg/ml, respectively). Moreover, AEM, QDHKA, YEA, AEHNH, and YVM presented high lipid peroxidation inhibition ability, Ferric-reducing power, and significant protective function on H2O2-induced Chang liver cells. Therefore, AEM, QDHKA, YEA, AEHNH, and YVM could be natural antioxidant ingredients used in pharmaceutical and functional products.

Rac1 relieves neuronal injury induced by oxygenglucose deprivation and re-oxygenation via regulation of mitochondrial biogenesis and function.

Certain microRNAs (miRNAs) can function as neuroprotective factors after reperfusion/ischemia brain injury. miRNA-142-3p can participate in the occurrence and development of tumors and myocardial ischemic injury by negatively regulating the activity of Rac1, but it remains unclear whether miRNA-142-3p also participates in cerebral ischemia/reperfusion injury. In this study, a model of oxygen-glucose deprivation/re-oxygenation in primary cortical neurons was established and the neurons were transfected with miR-142-3p agomirs or miR-142-3p antagomirs. miR-142-3p expression was down-regulated in neurons when exposed to oxygen-glucose deprivation/re-oxygenation. Over-expression of miR-142-3p using its agomir remarkably promoted cell death and apoptosis induced by oxygen-glucose deprivation/re-oxygenation and improved mitochondrial biogenesis and function, including the expression of peroxisome proliferator-activated receptor-γ coactivator-1α, mitochondrial transcription factor A, and nuclear respiratory factor 1. However, the opposite effects were produced if miR-142-3p was inhibited. Luciferase reporter assays verified that Rac Family Small GTPase 1 (Rac1) was a target gene of miR-142-3p. Over-expressed miR-142-3p inhibited NOX2 activity and expression of Rac1 and Rac1-GTPase (its activated form). miR-142-3p antagomirs had opposite effects after oxygen-glucose deprivation/re-oxygenation. Our results indicate that miR-142-3p down-regulates the expression and activation of Rac1, regulates mitochondrial biogenesis and function, and inhibits oxygen-glucose deprivation damage, thus exerting a neuroprotective effect. The experiments were approved by the Committee of Experimental Animal Use and Care of Central South University, China (approval No. 201703346) on March 7, 2017.

Mitochondrial D310 instability in Chinese lung cancer patients.

To characterize the somatic mutation spectrum of mitochondrial DNA at D310 in Chinese lung cancer patients and evaluate its potential significance in Chinese lung cancer diagnosis, in this study, 237 samples, including lung tumor, adjacent normal tissue and blood samples of 79 lung cancer patients were analyzed. By comparing sequences of D310 between lung cancer tissues, adjacent normal tissue and blood samples, the somatic mutations at D310 were detected in 17.72% (14/79) of Chinese lung cancer patients; this implied that somatic mutations at D310 could be served as valuable biomarker for diagnostic of Chinese lung cancer. Further analyses indicated that deletion and heterogeneity were the predominant characters for somatic mutations detected at D310 of Chinese lung cancer patients.

Aspirin-triggered lipoxin A4 attenuates LPS-induced pro-inflammatory responses by inhibiting activation of NF-κB and MAPKs in BV-2 microglial cells.

BACKGROUND: Microglial activation plays an important role in neurodegenerative diseases through production of nitric oxide (NO) and several pro-inflammatory cytokines. Lipoxins (LXs) and aspirin-triggered LXs (ATLs) are considered to act as 'braking signals' in inflammation. In the present study, we investigated the effect of aspirin-triggered LXA4 (ATL) on infiammatory responses induced by lipopolysaccharide (LPS) in murine microglial BV-2 cells. METHODS: BV-2 cells were treated with ATL prior to LPS exposure, and the effects of such treatment production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-1ß (IL-1ß) and tumour necrosis factor-α (TNF-α) were analysed by Griess reaction, ELISA, western blotting and quantitative RT-PCR. Moreover, we investigated the effects of ATL on LPS-induced nuclear factor-κB (NF-κB) activation, phosphorylation of mitogen-activated protein kinases (MAPKs) and activator protein-1 (AP-1) activation. RESULTS: ATL inhibited LPS-induced production of NO, IL-1ß and TNF-α in a concentration-dependent manner. mRNA expressions for iNOS, IL-1ß and TNF-α in response to LPS were also decreased by ATL. These effects were inhibited by Boc-2 (a LXA4 receptor antagonist). ATL significantly reduced nuclear translocation of NF-κB p65, degradation of the inhibitor IκB-α, and phosphorylation of extracellular signal-regulated kinase (ERK) and p38 MAPK in BV-2 cells activated with LPS. Furthermore, the DNA binding activity of NF-κB and AP-1 was blocked by ATL. CONCLUSIONS: This study indicates that ATL inhibits NO and pro-inflammatory cytokine production at least in part via NF-κB, ERK, p38 MAPK and AP-1 signaling pathways in LPS-activated microglia. Therefore, ATL may have therapeutic potential for various neurodegenerative diseases.