Use of egg yolk phospholipids to improve the thermal-oxidative stability of fatty acids, capsaicinoids and carotenoids in chili oil.

Phospholipids can act as antioxidants in food. In this study, egg yolk phospholipids (EPL) and sunflower oil were utilized in making chili oil, and proton nuclear magnetic resonance spectroscopy was employed to quantify the concentrations of fatty acyl groups, carotenoids, capsaicinoids in chili oil according to their specific signals in the spectra. The results showed that the changes in the concentrations of fatty acyl groups in the control samples were greater than those in the EPL-treated samples at the same frying temperature, while the contents of carotenoids and capsaicinoids were significantly lower than those of the EPL-treated samples when fried at 150 °C (p < 0.05). Two-way ANOVA indicated that frying temperature and EPL treatment, as well as their interaction had significant impacts on the thermal-oxidative stability of chili oil (p < 0.05). The results suggest that EPL may act as antioxidants during frying, and EPL can improve the thermal-oxidative stability of chili oil.

Investigation on the changes of carotenoids and capsaicinoids in chili oil at different frying temperature by using 1H NMR.

The color and pungency are important indicators for evaluating the quality of chili oil, which are mainly determined by the carotenoids and capsaicinoids, respectively. In this study, the effect of frying temperature on the changes of carotenoids and capsaicinoids in chili oil was qualitatively and quantitatively analyzed by 1H NMR. The increasing frying temperature caused the thermal degradation of carotenoids to be intensified, and the degradation of red carotenoids was greater than that of yellow carotenoids. After 10 min of frying at 130, 150, 170 and 190 °C, the contents of capsanthin in chili oil were 40.3, 15.4, 9.6 and 6.2 mg/kg, respectively. Meanwhile, the contents of total carotenoids were 63.0, 25.5, 17.7 and 13.3 mg/kg, respectively. The observed change of R/Y values correlated well with the degradation of carotenoids. The contents of capsaicinoids were 14.8, 20.9, 19.4 and 7.4 mg/kg, respectively. The best frying temperature for the extraction of carotenoids was 130 °C, and over 90% of the carotenoids were dissolved in the frying oil at this frying condition. However, capsaicinoids were more stable than carotenoids, and the best frying temperature for capsaicinoids was 150-170 °C with over 90% extraction rate. Therefore, the temperature fried at 130-150 °C was suitable for the quality of chili oil, considering the higher extraction rates of both total carotenoids and capsaicinoids. This study is of great significance for the quality control of chili oil.

Carvedilol ameliorates persistent erythema of erythematotelangiectatic rosacea by regulating the status of anxiety/depression.

The treatment of persistent erythema and rosacea flushing is extremely challenging, especially for patients with anxiety. The aim of this study was to verify the efficacy of carvedilol in rosacea patients with persistent erythema and flushing. A total of 156 patients were randomized to use oral carvedilol 5 mg bid (twice per day) (n = 105) or topical brimonidine (n = 51) for a 10-week period with 6 weeks of follow-up. Both the efficacy of carvedilol and the status of anxiety/depression were analyzed by patient self-assessment (PSA), clinician erythema assessment (CEA), generalized anxiety disorder (GAD-7), and patient health questionnaire-9 (PHQ-9). Our study found that carvedilol exerted a dramatic reduction in CEA/PSA scores and sting/burning sensation scores in comparison to topical brimonidine. Additionally, carvedilol treatment dramatically improved telangiectasia, erythema, and pigmentation with no obvious side effects. Patients with carvedilol treatment showed an improvement of depression/anxiety, as reflected by lower GAD-7 and PHQ-9 scores than patients with topical brimonidine. Notably, we found carvedilol treatment had better outcomes among patients under 30 years of age with rosacea younger than 30 years old. Conclusively, our findings reveal that carvedilol could quickly and effectively improve facial erythema, which might stem from the improved the status of anxiety/depression.

Targeting mitochondria-associated membranes as a potential therapy against endothelial injury induced by hypoxia.

Mitochondrial dysfunction plays a principal role in hypoxia-induced endothelial injury, which is involved in hypoxic pulmonary hypertension and ischemic cardiovascular diseases. Recent studies have identified mitochondria-associated membranes (MAMs) that modulate mitochondrial function under a variety of pathophysiological conditions such as high-fat diet-mediated insulin resistance, hypoxia reoxygenation-induced myocardial death, and hypoxia-evoked vascular smooth muscle cell proliferation. However, the role of MAMs in hypoxia-induced endothelial injury remains unclear. To explore this further, human umbilical vein endothelial cells and human pulmonary artery endothelial cells were exposed to hypoxia (1% O2 ) for 24 hours. An increase in MAM formation was uncovered by immunoblotting and immunofluorescence. Then, we performed small interfering RNA transfection targeted to MAM constitutive proteins and explored the biological effects. Knockdown of MAM constitutive proteins attenuated hypoxia-induced elevation of mitochondrial Ca2+ and repressed mitochondrial impairment, leading to an increase in mitochondrial membrane potential and ATP production and a decline in reactive oxygen species. Then, we found that MAM disruption mitigated cell apoptosis and promoted cell survival. Next, other protective effects, such as those pertaining to the repression of inflammatory response and the promotion of NO synthesis, were investigated. With the disruption of MAMs under hypoxia, inflammatory molecule expression was repressed, and the eNOS-NO pathway was enhanced. This study demonstrates that the disruption of MAMs might be of therapeutic value for treating endothelial injury under hypoxia, suggesting a novel strategy for preventing hypoxic pulmonary hypertension and ischemic injuries.

Nogo-B Receptor Directs Mitochondria-Associated Membranes to Regulate Vascular Smooth Muscle Cell Proliferation.

Mitochondria-associated membranes (MAM) are a well-recognized contact link between the mitochondria and endoplasmic reticulum that affects mitochondrial biology and vascular smooth muscle cells (VSMCs) proliferation via the regulation of mitochondrial Ca2+(Ca2+m) influx. Nogo-B receptor (NgBR) plays a vital role in proliferation, epithelial-mesenchymal transition, and chemoresistance of some tumors. Recent studies have revealed that downregulation of NgBR, which stimulates the proliferation of VSMCs, but the underlying mechanism remains unclear. Here, we investigated the role of NgBR in MAM and VSMC proliferation. We analyzed the expression of NgBR in pulmonary arteries using a rat model of hypoxic pulmonary hypertension (HPH), in which rats were subjected to normoxic recovery after hypoxia. VSMCs exposed to hypoxia and renormoxia were used to assess the alterations in NgBR expression in vitro. The effect of NgBR downregulation and overexpression on VSMC proliferation was explored. The results revealed that NgBR expression was negatively related with VSMCs proliferation. Then, MAM formation and the phosphorylation of inositol 1,4,5-trisphosphate receptor type 3 (IP3R3) was detected. We found that knockdown of NgBR resulted in MAM disruption and augmented the phosphorylation of IP3R3 through pAkt, accompanied by mitochondrial dysfunction including decreased Ca2+m, respiration and mitochondrial superoxide, increased mitochondrial membrane potential and HIF-1α nuclear localization, which were determined by confocal microscopy and Seahorse XF-96 analyzer. By contrast, NgBR overexpression attenuated IP3R3 phosphorylation and HIF-1α nuclear localization under hypoxia. These results reveal that dysregulation of NgBR promotes VSMC proliferation via MAM disruption and increased IP3R3 phosphorylation, which contribute to the decrease of Ca2+m and mitochondrial impairment.

Hypoxia Exacerbates Inflammatory Acute Lung Injury via the Toll-Like Receptor 4 Signaling Pathway.

Acute lung injury (ALI) is characterized by non-cardiogenic diffuse alveolar damage and often leads to a lethal consequence, particularly when hypoxia coexists. The treatment of ALI remains a challenge: pulmonary inflammation and hypoxia both contribute to its onset and progression and no effective prevention approach is available. Here, we aimed to investigate the underlying mechanism of hypoxia interaction with inflammation in ALI and to evaluate hypoxia-inducible factor 1 alpha (HIF-1α)-the crucial modulator in hypoxia-as a potential therapeutic target against ALI. First, we developed a novel ALI rat model induced by a combined low-dose of lipopolysaccharides (LPS) with acute hypoxia. Second, we used gene microarray analysis to evaluate the inflammatory profiles of bronchi alveolar lavage fluid cells of ALI rats. Third, we employed an alveolar macrophage cell line, NR8383 as an in vitro system together with a toll-like receptor 4 (TLR4) antagonist TAK-242, to verify our in vivo findings from ALI animals. Finally, we tested the therapeutic effects of HIF-1α augmentation against inflammation and hypoxia in ALI. We demonstrated that (i) LPS upregulated inflammatory genes, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), and interleukin-6 (IL-6), in the alveolar macrophages of ALI rats, which were further enhanced when ALI combined with hypoxia; (ii) hypoxia exposure could further enhance the upregulation of alveolar macrophageal TLR4 that was noticed in LPS-induced inflammatory ALI, conversely, TLR4 antagonist TAK-242 could suppress the macrophageal expression of TLR4 and inflammatory cytokines, including TNF-α, IL-1ß, and IL-6, suggesting that the TLR4 signaling pathway as a central link between inflammation and hypoxia in ALI; (iii) manipulation of HIF-1α in vitro could suppress TLR4 expression induced by combined LPS and hypoxia, via suppressing promoter activity of the TLR4 gene; (iv) preconditioning augmentation of HIF-1α in vivo by HIF hydroxylase inhibitor, DMOG excreted protection against inflammatory, and hypoxic processes in ALI. Together, we see that hypoxia can exacerbate inflammation in ALI via the activation of the TLR4 signaling pathway in alveolar macrophages and predispose impairment of the alveolar-capillary barrier in the development of ALI. Targeting HIF-1α can suppress TLR4 expression and macrophageal inflammation, suggesting the potential therapeutic and preventative value of HIF-1α/TLR4 crosstalk pathway in ALI.

Adenosine A2A receptor involves in neuroinflammation-mediated cognitive decline through activating microglia under acute hypobaric hypoxia.

Hypobaric hypoxia (HH) at high altitudes leads to a wide range of cognitive impairments which can handicap human normal activities and performances. However, the underlying mechanism is still unclear. Adenosine A2A receptors (A2ARs) of the brain are pivotal to synaptic plasticity and cognition. Besides, insult-induced up-regulation of A2AR regulates neuroinflammation and therefore induces brain damages in various neuropathological processes. The present study was designed to determine whether A2AR-mediate neuroinflammation involves in cognitive impairments under acute HH. A2AR knock-out and wild-type male mice were exposed to a simulated altitude of 8000 m for 7 consecutive days in a hypobaric chamber and simultaneously received behavioral tests including Morris water maze test and open filed test. A2AR expression, the activation of microglia and the production of TNF-α were evaluated in the hippocampus by immunohistochemistry and ELISA, respectively. Behavioral tests showed that acute HH exposure caused the dysfunction of spatial memory and mood, while genetic inactivation of A2AR attenuated the impairment of spatial memory but not that of mood. Double-labeled immunofluorescence showed that A2ARs were mainly expressed on microglia and up-regulated in the hippocampus of acute HH model mice. Acute HH also induced the accumulation of microglia and increased production of TNF-α in the hippocampus, which could be markedly inhibited by A2AR inactivation. These findings indicate that microglia-mediated neuroinflammation triggered by A2AR activation involves in acute HH-induced spatial memory impairment and that A2AR could be a new target for the pharmacotherapy of cognitive dysfunction at high altitudes.