Glioma is the most malignant primary tumor of the central nervous system and is characterized by an extremely low overall survival. Recent breakthroughs in cancer therapy using immune checkpoint blockade have attracted significant attention. However, despite representing the most promising (immunotherapy) treatment for cancer, the clinical application of immune checkpoint blockade in glioma patients remains challenging due to the “cold phenotype” of glioma and multiple factors inducing resistance, both intrinsic and acquired. Therefore, comprehensive understanding of the tumor microenvironment and the unique immunological status of the brain will be critical for the application of glioma immunotherapy. More sensitive biomarkers to monitor the immune response, as well as combining multiple immunotherapy strategies, may accelerate clinical progress and enable development of effective and safe treatments for glioma patients.

Metastatic melanoma is a leading cause of death from skin diseases, and is often associated with activation of Wnt/β-catenin signaling pathway. We have examined the inhibitory effect of silymarin, a plant flavanoid from Silybum marianum, on cell migration of metastasis-specific human melanoma cell lines (A375 and Hs294t) and assessed whether Wnt/β-catenin signaling is the target of silymarin. Using an in vitro invasion assay, we found that treatment of human melanoma cell lines with silymarin resulted in concentration-dependent inhibition of cell migration, which was associated with accumulation of cytosolic β-catenin, while reducing the nuclear accumulation of β-catenin (i.e., β-catenin inactivation) and reducing the levels of matrix metalloproteinase (MMP) -2 and MMP-9 which are the down-stream targets of β-catenin. Silymarin enhanced: (i) the levels of casein kinase 1α, glycogen synthase kinase-3β and phosphorylated-β-catenin on critical residues Ser45, Ser33/37 and Thr41, and (ii) the binding of β-transducin repeat-containing proteins (β-TrCP) with phospho forms of β-catenin in melanoma cells. These events play important roles in degradation or inactivation of β-catenin. To verify whether β-catenin is a potent molecular target of silymarin, the effect of silymarin was determined on β-catenin-activated (Mel 1241) and β-catenin-inactivated (Mel 1011) melanoma cells. Treatment of Mel 1241 cells with silymarin or FH535, an inhibitor of Wnt/β-catenin pathway, significantly inhibited cell migration of Mel 1241 cells, which was associated with the elevated levels of casein kinase 1α and glycogen synthase kinase-3β, and decreased accumulation of nuclear β-catenin and inhibition of MMP-2 and MMP-9 levels. However, this effect of silymarin and FH535 was not found in Mel 1011 melanoma cells. These results indicate for the first time that silymarin inhibits melanoma cell migration by targeting β-catenin signaling pathway.

The incidence and mortality of strokes have increased over the past three decades in China. Ischemic strokes can cause a sequence of detrimental events in patients, including increased permeability and dysfunction of the blood-brain barrier, brain edema, metabolic disturbance, endoplasmic reticulum stress, autophagy, oxidative stress, inflammation, neuron death and apoptosis, and cognitive impairment. Thrombolysis using recombinant tissue plasminogen activator (rtPA) and mechanical embolectomy with a retrievable stent are two recognized strategies to achieve reperfusion after a stroke. Nevertheless, rtPA has a narrow therapeutic timeframe, and mechanical embolectomy has limited rates of good neurological outcomes. EGb761 is a standardized and extensively studied extract of Ginkgo biloba leaves. The ginkgolides and bilobalide that constitute a critical part of EGb761 have demonstrated protective properties towards cerebral injury. Ginkgolides include Ginkgolide A (GA), Ginkgolide B (GB), Ginkgolide C (GC), Ginkgolide J (GJ), Ginkgolide K (GK), Ginkgolide L (GL), and Ginkgolide M (GM). This review seeks to elucidate the neuroprotective effects and mechanisms of ginkgolides, especially GA and GB, and bilobalide in cerebral injury following ischemic strokes.

The importance of epigenetic alterations in the development of various diseases including the cancers has been realized. As epigenetic changes are reversible heritable changes, these can be utilized as an effective strategy for the prevention of cancers. DNA methylation is the most characterized epigenetic mechanism that can be inherited without changing the DNA sequence. Although limited, but available data suggest that silencing of tumor suppressor genes in ultraviolet (UV) radiation-exposed epidermis leads to photocarcinogenesis and is associated with a network of epigenetic modifications including alterations in DNA methylation, DNA methyltransferases and histone acetylations. Various bioactive dietary components have been shown to protect skin from UV radiation-induced skin tumors in animal models. The role of bioactive dietary components, such as, (−)-epicatechins from green tea and proanthocyanidins from grape seeds, has been assessed in chemoprevention of UV-induced skin carcinogenesis and underlying epigenetic mechanism in vitro and in vivo animal models. These bioactive components have the ability to block UV-induced DNA hypermethylation and histone modifications in the skin required for the silencing of tumor suppressor genes (e.g., Cip1/p21, p16INK4a). These information are of importance for understanding the role of epigenetic modulation in UV-induced skin tumor and the chemopreventive mechanism of bioactive dietary components.