Background: Liver kinase B1 (LKB1)/5’-adenosine monophosphate-activated protein kinase (AMPK) signaling, a metabolic checkpoint, plays a neuro-protective role in the pathogenesis of Alzheimer’s disease (AD). Amyloid-β (Aβ) acts as a classical biomarker of AD. The aim of the present study was to explore whether berberine (BBR) activates LKB1/AMPK signaling and ameliorates Aβ pathology. Methods: The Aβ levels were detected using enzyme-linked immunosorbent assay and immunohistochemistry. The following biomarkers were measured by Western blotting: phosphorylated (p-) LKB1 (Ser334 and Thr189), p-AMPK (AMPKα and AMPKβ1), synaptophysin, post-synaptic density protein 95 and p-cAMP-response element binding protein (p-CREB). The glial fibrillary acidic protein (GFAP) was determined using Western blotting and immunohistochemistry. Results: BBR inhibited Aβ expression in the brain of APP/PS1 mice. There was a strong up-regulation of both p-LKB1 (Ser334 and Thr189) and p-AMPK (AMPKα and AMPKβ1) in the brains of APP/PS1 transgenic mice after BBR-treatment (P<0.01). BBR promoted the expression of synaptophysin, post-synaptic density protein 95 and p-CREB(Ser133) in the AD brain, compared with the model mice. Conclusion: BBR alleviates Aβ pathogenesis and rescues synapse damage via activating LKB1/AMPK signaling in the brain of APP/PS1 transgenic mice.

Colorectal cancer (CRC) is a global health concern. The role of epigenetics in tumors has garnered increasing interest. ADP ribosylation is an epigenetic modification that is associated with a variety of biological functions and diseases, and its association with tumor development and progression has been hypothesized. However, due to the limitations of available techniques and methods, ADP ribosylation of specific sites is difficult to determine. In previous studies, it was shown that arginine-117 of histone 3 (H3R117) in Lovo cells can be modified by mono-ADP-ribosylation. This site was mutated and Lovo cells overexpressing this mutant construct were established. In the present study, the expression of differentially expressed genes (DEGs) between untransfected Lovo cells and H3R117A Lovo cells was analyzed. A total of 58,174 DEGs were identified, of which 2,324 were significantly differentially expressed (q-value <0.05; fold change >2). Functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment was used to analyze the functions and possible roles of the DEGs. The DEGs were enriched in pathways associated with metabolic process, catalytic activity, organelle and chromatin structure, and dynamics. Through this comprehensive and systematic analysis, the role of mono-ADP-ribosylation in CRC was examined, providing a foundation for future studies.

Background: Colorectal cancer remains a major public health problem with high morbidity and mortality rates. In the search for the mechanisms of colorectal cancer occurrence and development, increasing attention has been focused on epigenetics. The overall level of Mono-ADP-ribosylation, an epigenetic, has not been investigated now. The aim of our study was to analysis of the overall level of mono-ADP-ribosylation in colorectal cancer. Methods: Immunohistochemistry was used to investigate the level of mono-ADPribosylation in colorectal cancer and normal colorectal adjacent tissue from 64 CRC patients. The data of patient demographic, clinical and pathological characteristics were acquired and analyzed. Results: Mono-ADP-ribosylation was present in both colorectal adenocarcinoma and normal colorectal tissue. The overall level of mono-ADP-ribosylation in colorectal cancer was significantly higher than that in normal colorectal adjacent tissue. In the nucleus, the majority of samples in the high-level group were colorectal adenocarcinoma (55/64), but the opposite was true for normal colorectal tissues (7/32). In particular, increases in the level of mono-ADP-ribosylation in the cytoplasm of colorectal cancer cells was associated with a greater invasion depth of the tumor. Conclusion: The increased level of mono-ADP-ribosylation in colorectal cancer enhances tumor invasion, which suggests that mono-ADP-ribosylation is involved in the development of colorectal cancer and may become a new direction to solve the problem of colorectal cancer.

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