Okadaic acid (OA)-induced neurotoxicity may be considered a novel tool used to study Alzheimer's disease (AD) pathology, and may be helpful in the development of a novel therapeutic approach. It has been reported that galangin inhibits β-site amyloid precursor protein-cleaving enzyme 1 expression, which is a key enzyme for amyloid β (Aβ) generation and is a potential drug candidate for AD therapy. However, further studies are required to confirm its neuroprotective effects in other AD models. The present study aimed to explore the neuroprotective effects of galangin on OA-induced neurotoxicity in PC12 cells. The cells were divided into the following groups: Control group, model group (175 nM OA for 48 h) and galangin groups (0.25, 0.5 and 1 µg/ml). Beclin-1, phosphorylated (p)-protein kinase B (Akt), p-glycogen synthase kinase (GSK)3β and p-mechanistic target of rapamycin (mTOR) expression was also measured in the following PC12 cell groups: Control group, model group, 3-methyladenine group (5 nM), rapamycin group (100 nM) and galangin group (1 µg/ml). The levels of β-secretase, Aβ 42 and p-tau were detected by ELISA, Beclin-1 expression was examined by immunohistochemistry and the protein expression levels of p-Akt, p-mTOR p-GSK3β, and Beclin-1 were detected by western blotting. Galangin treatment enhanced cell viability in cells treated with OA, and decreased β-secretase, Aβ 42 and p-tau levels. In addition, it suppressed Beclin-1 and p-GSK3β expression, but promoted p-Akt and p-mTOR expression by regulating the Akt/GSK3β/mTOR pathway. These results indicated that galangin protected PC12 cells from OA-induced cytotoxicity and inhibited autophagy via the Akt/GSK3β/mTOR pathway, thus suggesting that it may be considered a potential therapeutic agent for AD.
BackgroundApolipoprotein CIII (apoCIII) is an independent risk for coronary heart disease (CHD). In this study, we investigated the associations among plasma apoCIII, hs-CRP and TNF-α levels and their roles in the clinical features of CHD in the Li and Han ethnic groups in China.MethodsA cohort of 474 participants was recruited (238 atherosclerotic patients and 236 healthy controls) from the Li and Han ethnic groups. Blood samples were obtained to evaluate apoCIII, TNF-α, hs-CRP and lipid profiles. Chi-squared, t-tests, and Kruskal–Wallis or Wilcoxon–Mann–Whitney tests, Pearson or Spearman correlation tests and multiple unconditional logistic regression were employed to analyze lipid profiles and variations in plasma apoCIII, TNF-α, hs-CRP in subgroups of CHD and their contributions to CHD using SPSS version 20.0 software.ResultsCompared to healthy participants, unfavorable lipid profiles were identified in CHD patients with enhanced systolic pressure, diastolic pressure, fasting blood sugar (FBS), TG, TC, LDL-C, apoB, Lp(a) (P < 0.05, TC and Lp(a); P < 0.01, FBS, TG, LDL-C, apoB); and lower HDL-C and apoAI (P < 0.05). Plasma apoCIII, TNF-α and hs-CRP levels were higher in CHD individuals (16.77 ± 5.98 mg/dL vs. 10.91 ± 4.97 mg/dL; 17.23 ± 6.34 pg/mL vs. 9.49 ± 3.88 pg/mL; 9.55 ± 7.32 mg/L vs. 2.14 ± 1.56 mg/L; P < 0.01 vs. healthy participants). Identical patterns were obtained in the Li and Han groups (16.46 ± 6.08 mg/dL vs. 11.72 ± 5.16 mg/dL; 15.71 ± 5.52 pg/mL vs. 9.74 ± 4.31 pg/mL; 8.21 ± 7.09 mg/L vs. 2.15 ± 1.51 mg/L in Li people; 17.05 ± 5.90 mg/dL vs. 10.07 ± 4.63 mg/dL; 18.59 ± 6.73 pg/mL vs. 9.23 ± 3.38 pg/mL; 10.75 ± 7.44 mg/L vs. 2.12 ± 1.63 mg/L in Han people; P < 0.01). Paired comparisons of subgroups with stable angina, unstable angina, and acute myocardial infarction (AMI) revealed significant variation in plasma levels of apoCIII, TNF-α and hs-CRP (P < 0.01), but not among subgroups with mild, moderate and severe stenosis (P > 0.05). Plasma apoCIII, TNF-α and hs-CRP contributed to the development of CHD (OR = 2.554, 7.252, 6.035, P < 0.01) with paired correlations in CHD patients (apoCIII vs. TNF-α, r = 0.425; apoCIII vs. hs-CRP, r = 0.319; TNF-α vs. hs-CRP, r = 0.400, P < 0.01).ConclusionsAssociation among plasma apoCIII, hs-CRP and TNF-α interacts with unfavorable lipid profiles to contribute to the clinical features of CHD with stable angina, unstable angina, and AMI in the Li and Han ethnic groups in China.
Heidegger has notoriously named the essence of the technological world the Ge-stell (framework, enframing). Here, we reveal that yet another term, Gestellnis , figures in some of his writings from the 1970s. According to Heidegger, as the essence of the Ge-stell, Gestellnis shows a way toward the fore-garden of Ereignis (appropriating event). In opposing the Ge-stell mode of comportment toward beings, Heidegger glimpses the promise of the other thinking, which seems to be useless from the perspective of traditional metaphysical thinking. In characterizing this mode of thinking, he resorts to Zhuangzi’s parables of uselessness ( wuyong 无用). One way of stepping out of the Ge-stell is to make central the comportment toward beings as embodied in non-metaphysical art. Heidegger designates this as das andere Denken (the other thinking). In charting this course, Heidegger turns toward ancient Asian traditions insofar as they remain uncontaminated by current planetary-interstellar world conditions, which for him epitomize the absence of the dichotomy of appearance and essence. From Heidegger’s standpoint, before the Western tradition gains maturity through its own self-transformation, the allegedly inevitable event of East-West dialogue can only be anticipated. However, at the ontic level East Asian sources have undeniably played a role in his search for ways out of the Ge-stell .
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