Search

Alzheimer’s disease (AD) is an insidious disease. Its distinctive pathology forms over a considerable length of time without symptoms. There is a need to detect this disease, before even subtle changes occur in cognition. Hallmark AD biomarkers, tau and amyloid-β, have shown promising results in CSF and blood. However, detecting early changes in these biomarkers and others will involve screening a wide group of healthy, asymptomatic individuals. Saliva is a feasible alternative. Sample collection is economical, non-invasive and saliva is an abundant source of proteins including tau and amyloid-β. This work sought to extend an earlier promising untargeted mass spectrometry study in saliva from individuals with mild cognitive impairment (MCI) or AD with age- and gender-matched cognitively normal from the South Australian Neurodegenerative Disease cohort. Five proteins, with key roles in inflammation, were chosen from this study and measured by ELISA from individuals with AD (n = 16), MCI (n = 15) and cognitively normal (n = 29). The concentrations of Cystatin-C, Interleukin-1 receptor antagonist, Stratifin, Matrix metalloproteinase 9 and Haptoglobin proteins had altered abundance in saliva from AD and MCI, consistent with the earlier study. Receiver operating characteristic analysis showed that combinations of these proteins demonstrated excellent diagnostic accuracy for distinguishing both MCI (area under curve = 0.97) and AD (area under curve = 0.97) from cognitively normal. These results provide evidence for saliva being a valuable source of biomarkers for early detection of cognitive impairment in individuals on the AD continuum and potentially other neurodegenerative diseases.

Alzheimer's disease (AD) is an insidious disease. Its distinctive pathology forms over a considerable length of time without symptoms. There is a need to detect this disease, before even subtle changes occur in cognition. Hallmark AD biomarkers, tau and amyloid-b, have shown promising results in CSF and blood. However, detecting early changes in these biomarkers and others will involve screening a wide group of healthy, asymptomatic individuals. Saliva is a feasible alternative. Sample collection is economical, non-invasive and saliva is an abundant source of proteins including tau and amyloid-β. This work sought to extend an earlier promising untargeted mass spectrometry study in saliva from individuals with mild cognitive impairment (MCI) or AD with age- and gender-matched cognitively normal from the South Australian Neurodegenerative Disease cohort. Five proteins, with key roles in inflammation, were chosen from this study and measured by ELISA from individuals with AD (n = 16), MCI (n = 15) and cognitively normal (n = 29). The concentrations of Cystatin-C, Interleukin-1 receptor antagonist, Stratifin, Matrix metalloproteinase 9 and Haptoglobin proteins had altered abundance in saliva from AD and MCI, consistent with the earlier study. Receiver operating characteristic analysis showed that combinations of these proteins demonstrated excellent diagnostic accuracy for distinguishing both MCI (area under curve = 0.97) and AD (area under curve = 0.97) from cognitively normal. These results provide evidence for saliva being a valuable source of biomarkers for early detection of cognitive impairment in individuals on the AD continuum and potentially other neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the anti-inflammatory effects of nobiletin on human osteoarthritic chondrocytes and also to explore possible related molecular events. Methods: Isolated human osteoarthritic chondrocytes were stimulated with IL-1β. The effect of nobiletin (75, 150 or 300 µg) on chondrocyte viability was assessed. Furthermore, the effect on NO production was determined using Griess reagent while the levels of IL-6 and PGE2 were assessed by enzyme linked immunosorbent assay (ELISA). The influence of nobiletin on the expression of COX-2, iNOS and proteins of PI3/Akt, NF-κB and MAPK cascades were also assessed. Results: Nobiletin (75, 150 and 300 μg) significantly (p < 0.05) improved the viability of chondrocytes, and remarkably reduced the levels of NO, IL-6 and PGE2. The expression levels of COX-2 and iNOS both at mRNA and protein levels were strikingly reduced by nobiletin, in a dose-dependent way. In addition, nobiletin caused marked (p < 0.05) down-regulation of the NF-κB signalling pathway. IL-1β- induced activation of PI3/Akt, and JNK, ERK and p38 MAPK cascades were significantly (p < 0.05) inhibited by nobiletin with 300 µg dose exhibiting maximum effects. Conclusion: Inflammatory cytokines are critically involved in the pathogenesis of OA. Significant suppression of cytokines and modulation of PI3/Akt and MAPK signalling cascades by nobiletin suggests its potent anti-inflammatory and anti-osteoarthritic effects. [ABSTRACT FROM AUTHOR]

We analyzed the effects of a traditional Chinese medicine, Qizhi Jiangtang Jiaonang (QJJ), on insulin resistance (IR) in vitro. After an in vitro model of IR was established by treating human liver cancer cells (HepG2 cells) with palmitic acid, the cells were then treated with various concentrations of QJJ. Treatment with 400 µM palmitic acid for 24 h induced IR in HepG2 cells. The survival rate for HepG2 cells in the IR group was significantly lower than that of the untreated control group (P < 0.001); however, QJJ restored HepG2 cell survival (P < 0.001). As compared with HepG2 cells in the IR group, QJJ at all doses analyzed significantly increased glucose consumption (all P < 0.05). Moreover, treatment with all the QJJ doses significantly reduced the mean intracellular reactive oxygen species levels as compared with the IR group (all P < 0.05). Furthermore, high-dose QJJ reduced both TNF-α and IL-6 levels as compared to the IR group (all P < 0.05). QJJ ameliorated the altered PI3K, GLUT4, and RAGE expression observed with IR. In conclusion, QJJ can improve IR in HepG2 cells, which may be mediated through the IRS-1/PI3K/GLUT4 signaling pathway as well as regulation of NF-κB-mediated inflammation and oxidative stress. [ABSTRACT FROM AUTHOR]