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Polycationic biomaterials are currently widely applied in neuronal cell cultures to promote cell adhesion and viability. However, polycations generally have cytotoxic properties that limit their application in the field of biomaterials. In this study, we examined the use of a novel polycation poly(allylguanidine) (PAG), which contains a guanidine group in the side chain and a structure similar to poly(allylamine hydrochloride) (PAH), an example of another commonly used polycation. Our findings showed that exposure to PAG induced apoptosis in glioblastoma (GBM) cells, while exposure to PAH induced necrosis. Compared to control groups, the PAG coating significantly limited the proliferation of GBM8901 in vitro and in vivo . Furthermore, GBM8901 cells exposed to the PAG coating exhibited increased levels of phospho-p65 and phosphor-IκB, implying that GBM8901 cells underwent apoptotic cell death via the NF-κB pathway by the regulation of TGF-β. This result was further confirmed to be consistent with the experimental results from western blot protein analysis and apoptosis/necrosis assays. These findings indicate that the polycation PAG has the potential to not only suppress the proliferation of GBM8901 cancer cells but also improve the neural viability and promote the differentiation of neural stem/precursor cells into mature neurons. In conclusion, biomaterials such as PAG act as extremely potent options for applications in the treatment of pathological conditions such as brain cancer.

Alzheimer's disease (AD) is characterized by extracellular deposition of amyloid plaques, which are predominantly composed of amyloid-β (Aβ) peptide derived from amyloid precursor protein (APP) cleavage. APP interacts with tropomyosin receptor kinase A, a neurotrophic receptor associated with gangliosides and mediating neuronal survival and differentiation through the extracellular signal-regulated protein kinase (ERK) pathway. The ganglioside Hp-s1's analogue Hp-s1A exerts neuritogenic activity; however, its effect on AD pathology remains unknown. To test the hypothesis that Hp-s1A is a potential candidate to treat AD, we established the AD-modeled cell line by expressing human Swedish and Indiana APP gene (APP-Swe/Ind) in N2a mouse neuroblastoma cells. The cells were treated with Hp-s1A or monosialoganglioside GM1 for comparison. The AD model cells expressing APP-Swe/Ind exhibited a significant reduction in viability, as well as neurite outgrowth rate, in comparison to the control cells expressing APP-695. APP C-terminal fragment-β (CTFβ) and Aβ42 were increased in the AD cell lysates and the culture media, respectively. With the treatment of either Hp-s1A or GM1 at 1 μM, the AD model cells showed a significant increase in viability; however, only Hp-s1A reduced CTFβ levels in these cells. Further analysis of the culture media revealed that Hp-s1A also reduced Aβ42 production from AD model cells. The phosphorylation of ERK was elevated and the neurite outgrowth rate was restored with Hp-s1A treatment. In conclusion, the ganglioside analogue Hp-s1A inhibited amyloidogenic processing of APP and promoted neurotrophic activity and survival of AD model cells. Hp-s1A has great potential in AD therapeutic development.

Resveratrol functions as an agonist for estrogen receptor (ER)-mediated transcription. However, other researchers have reported that resveratrol decreases proliferation of breast cancer cells that are either ER-positive or ER-negative, which suggests that the interaction of resveratrol with the ER may not fully explain its inhibitory effect on proliferation. Similar to those effects associated with caloric restriction (CR), resveratrol has multiple beneficial activities, such as increased life span and delay in the onset of diseases associated with aging. One key enzyme thought to be activated during CR is the AMP-activated kinase (AMPK), a sensor of cellular energy levels. The suppression of nonessential energy expenditure by activated AMPK along with the CR mimetic and antiproliferative properties of resveratrol has led us to hypothesize that resveratrol activity might have an important role in the activation of AMPK. Here, we show that resveratrol activated AMPK in both ER-positive and ER-negative breast cancer cells. Once activated, AMPK inhibited 4E-BP1 signaling and mRNA translation via mammalian target of rapamycin (mTOR). Moreover, we also found that AMPK activity mediated by resveratrol in cancer cells was due to inducing the expression of Sirtuin type 1 (SIRT1) via elevation in the cellular NAD(+)/NADH in ER-positive cells. To our knowledge, we demonstrate here for the first time that resveratrol induces the expression of SIRT1 protein in human cancer cells. These observations raise the possibility that SIRT1 functions as a novel upstream regulator for AMPK signaling and may additionally modulate tumor cell proliferation. Targeting SIRT1/AMPK signaling by resveratrol may have potential therapeutic implications for cancer and age-related diseases.

In the present study, we successively extracted the pu-erh raw tea with methanol (PR-1), chloroform (PR-2), ethyl acetate (PR-3), n-butanol (PR-4), and water (PR-5). Among these extracts, PR-3 extract contained ingredients with the most effective hypolipidemic potential and was further purified by column chromatography. Moreover, chronic administration of PR-3 provoked a significant reduction in levels of serum triglyceride and low-density lipoprotein (LDL) in rats. Our study demonstrated that fraction 5 from the PR-3 extract (PR-3-5s) showed a hypolipidemic effect in human hepatoma HepG2 cells. PR-3-5s decreased the expression of fatty acid synthase (FASN) and inhibited the activity of acetyl-coenzyme A carboxylase (ACC) by stimulating AMP-activated protein kinase (AMPK) through the LKB1 pathway. Moreover, PR-3-5s blocked the progression of the cell cycle at the G1 phase by inducing p53 expression and in turn upregulating p21 expression.