Abnormal productions of amyloid beta (Aβ) plaque and chronic neuroinflammation are commonly observed in the brain of patients with Alzheimer’s disease, and both of which induce neuronal cell death, loss of memory, and cognitive dysfunction. However, many of the drugs targeting the production of Aβ peptides have been unsuccessful in treating Alzheimer’s disease. In this study, we identified synthetic novel peroxisome proliferator-activating receptor (PPAR) agonist, DTMB, which can ameliorate the chronic inflammation and Aβ pathological progression of Alzheimer’s disease. We discovered that DTMB attenuated the proinflammatory cytokine production of microglia by reducing the protein level of NF-κB. DTMB also improved the learning and memory defects and reduced the amount of Aβ plaque in the brain of 5xFAD mice. This reduction in Aβ pathology was attributed to the changes in gliosis and chronic inflammation level. Additionally, bulk RNA-sequencing showed that genes related to inflammation and cognitive function were changed in the hippocampus and cortex of DTMB-treated mice. Our findings demonstrate that DTMB has the potential to be a novel therapeutic agent for Alzheimer’s disease. Graphical abstract

Flavonoids are being increasingly applied for the treatment of various diseases due to their anti-cancer, anti-oxidant, anti-inflammatory, and anti-viral properties. However, it is often challenging to detect their presence in cells and tissues through bioimaging, as most of them are not fluorescent or are too weak to visualize. Here, fluorescence possibilities of nine naturally occurring analogous flavonoids have been investigated through UV/visible spectroscopy, molecular structure examination, fluorescent images in mammalian cells and their statistical analysis employing aluminum chloride and diphenylboric acid 2-aminoethyl ester as fluorescence enhancers. It is found that, in order to form a stable fluorescent complex with an enhancer, flavonoids should have a keto group at C4 position and at least one -OH group at C3 or C5 position. Additionally, the presence of a double bond at C2–C3 can stabilize extended quinonoid structure at the cinnamoyl moiety, which thereby enhances the complex stability. A possible restriction to the free rotation of ring B around C1′–C2 single bond can contribute to the further enhancement of fluorescence. Thus, these findings can act as a guide for distinguishing flavonoids capable of exhibiting fluorescence from thousands of their analogues. Finally, using this technique, flavonoids are detected in neuroblastoma cells and their time course assay is conducted via fluorescence imaging. Their cellular uptake efficiency is found to be high and differential in nature and their distribution throughout the cytoplasm is clearly detected.

Dermal papilla cells (DPCs) are located at the bottom of the hair follicle and play a critical role in hair growth, shape, and cycle. Epidermal growth factor receptor (EGFR) and Wnt/β-catenin signaling pathways are essential in promoting keratinocyte activation as well as hair follicle formation in DPCs. Piperonylic acid is a small molecule that induces EGFR activation in keratinocytes. However, the effects of piperonylic acid on DPCs in regard to the stimulation of hair growth have not been studied. In the present study, piperonylic acid was shown to activate the Wnt/β-catenin signaling pathway in addition to the EGFR signaling pathway in DPCs. Piperonylic acid suppressed DKK1 expression, which presumably promoted the accumulation of β-catenin in the nucleus. In addition, piperonylic acid promoted cyclin D upregulation and cell growth and increased the expression of alkaline phosphatase (ALP), a DPC marker. In a clinical study, the group that applied a formulation containing piperonylic acid had a significantly higher number of hairs per unit area than the placebo group. These results identify piperonylic acid as a promising new candidate for hair loss treatment.

Under the cellular stress, stress granules (SGs) help survival and proliferation of the cell. Unfortunately, the same SGs help unwanted cancer cells under stressful environment, including anti-cancer chemotherapy treatment. While SGs elevate the cancer cell’s resistance to chemotherapy, the mechanism behind the formation of SGs in cancer cell under chemotherapy treatment is still to be revealed. Here, we identified that the level of VRK2 and the phosphorylation of its novel substrate, G3BP1, are reduced when the cellular stress was increased by sodium arsenite (SA) or cisplatin treatment. We also demonstrated that the level of RNF144A is increased in response to the stress and further downregulates VRK2 through proteasomal degradation in various types of cancer cells. Furthermore, inhibition of SG formation by the overexpression of VRK2 sensitized the cells to the stress and chemotherapy. Together, our study establishes an RNF144A-VRK2-G3BP1 axis that regulates SG formation and suggest its potential usage in anti-cancer therapy.