Cell-type specific circadian transcription factor BMAL1 roles in excitotoxic hippocampal lesions to enhance neurogenesis.

Circadian clocks, generating daily rhythms in biological processes, maintain homeostasis in physiology, so clock alterations are considered detrimental. Studies in brain pathology support this by reporting abnormal circadian phenotypes in patients, but restoring the abnormalities by light therapy shows no dramatic effects. Recent studies on glial clocks report the complex effects of altered clocks by showing their beneficial effects on brain repairs. However, how neuronal clocks respond to brain pathology is elusive. This study shows that neuronal BMAL1, a core of circadian clocks, reduces its expression levels in neurodegenerative excitotoxicity. In the dentate gyrus of excitotoxic hippocampal lesions, reduced BMAL1 in granule cells precedes apoptosis. This subsequently reduces BMAL1 levels in neighbor neural stem cells and progenitors in the subgranular zone, enhancing proliferation. This shows the various BMAL1 roles depending on cell types, and its alterations can benefit brain repair. Thus, cell-type-specific BMAL1 targeting is necessary to treat brain pathology.

ß-catenin correlates with the progression of colon cancers and berberine inhibits the proliferation of colon cancer cells by regulating the ß-catenin signaling pathway.

INTRODUCTION: Berberine was one of the active components in Chinese herb and exerted tumor suppressive role in cancer progression, but the exact antitumor mechanism is still not clearly clarified. In the present study, bioinformatics analysis was performed on COAD patients from TCGA, HPA database, UALCAN and GEPIA 2 platform. We also explored the role of berberine on progression of human colon cancers in vitro and in vivo and clarified weather the antitumor effects of berberine was mediated by Wnt/beta-catenin pathway. METHODS: Cell viability was determined by MTT assay. The protein levels were tested by western blotting and the distribution of ß-catenin was observed by confocal microscope. RESULTS: The results showed the levels of CTNNB1 mRNA was increased in colon cancer patients than normal controls. The diagnostic value of CTNNB1 was AUC = 0.882 (CI:0.854-0.911) with sensitivity of 1.000 and specificity of 0.777. The promoter methylation level of CTNNB1 in COAD patients was significantly decreased. Moreover, univariate analysis and multivariate analysis results showed the expression of CTNNB1 in COAD patients was associated with T stage (p = 0.010), pathological stage (p = 0.025) and perineural invasion (p = 0.025). Furthermore, the in vitro assay results showed ß-catenin signaling was highly activated in human colon cancer cells and berberine inhibited the cell viability of colon cancer cells in vitro and in vivo in a dose-and time-dependent manner. Moreover, berberine induced the translocation of ß-catenin to cytoplasm from nucleus. CONCLUSION: The levels of CTNNB1 mRNA was increased in colon cancer patients than normal controls. Berberine inhibited the proliferation of colon cancer cells by regulating the beta-catenin signaling pathway.

Optimization model for ultrasonic-assisted and scale-up extraction of anthocyanins from Pyrus communis 'Starkrimson' fruit peel.

Ultrasonic effect on extraction of cyanidin-3-galactoside (Cy3-gal) from pear fruit peel was investigated and compared with conventional extraction (CE) method. Different process factors were tested to determine the optimum conditions for ultrasonic-assisted extraction (UAE). Results revealed that under optimized UAE conditions (ultrasonic power = 162 W, temperature = 71 °C, trifluoroacetic acid = 3%, ethanol = 57%, ultrasonication time = 11 min, and sample to solvent ratio = 1:30 g/ml), Cy3-gal yield was significantly higher (0.34 3±â€¯0.005 mg/g) than from CE (0.266 ±â€¯0.004 mg/g), whereas the extract viscosity during UAE showed a negative impact. UPLC-Triple-TOF/MS analysis detected a total number of 13 anthocyanin compounds, out of which 8 were identified and that mainly consisted of cyanidin, delphinidin and petunidin compounds. Higher yield of Cy3-gal under UAE compared to CE was also justified by higher deformations in the cell structure. The possible mechanism of ultrasonication effect during the extraction process is also proposed in the present study. During scale-up UAE process, the extraction yield of Cy3-gal was recorded higher under batch scale-up compared to continuous operation. The present study is an attempt to optimize UAE of valuable anthocyanins from Pyrus communis 'Starkrimson' fruit peel and further scaled-up for higher volume extraction which can be utilized for industrial applications.