ABSTRACT
Recently, functional interactions between neurons and astrocytes have been steadily clarified. In particular, the effects of presynaptic depolarization-induced suppression of excitation (DSE) through endocannabinoid (ECB) and endocannabinoids-mediated synaptic potentiation (eSP) by an astrocyte have been used as an evidence of global heterosynaptic modulation. However, the mechanism of occurrence of spatial modulation in a neural network remains unknown. Although the Ca2+ density in astrocytes is strongly related to eSP through ECB, the mechanism of the rise in the ECB receptor in Ca2+ remains unclear. Since Ca2+ is closely related to inositol-1,4,5-trisphosphate (IP3), it is believed that the released IP3 affects Ca2+ in astrocytes that receive ECB. Therefore, this study approximately showed the spatial distribution of DSE or eSP with astrocyte-neuron computational models, assuming that the IP3 caused by ECB is transmitted in an astrocyte. The results showed doughnut-shaped DSE, eSP, and DSE regions from the central ECB released points to the surroundings. They suggested that IP3 diffusion plays an important role in mediating this synaptic modulation.
ABSTRACT
Every year nearly half a million new cases of cervix cancer are diagnosed worldwide, making this malignancy the fourth commonest cancer in women. In 2018, more than 270,000 women died of cervix cancer globally with 85% of them being from developing countries. The majority of these cancers are caused by the infection with carcinogenic strains of human papillomavirus (HPV), which is also causally implicated in the development of other malignancies, including cancer of the anus, penis cancer and head and neck cancer. HPV is by far the most common sexually transmitted infection worldwide, however, most infected people do not develop cancer and do not even have a persistent infection. The development of highly effective HPV vaccines against most common high-risk HPV strains is a great medical achievement of the 21st century that could prevent up to 90% of cervix cancers. In this article, we review the current understanding of the balanced virus-host interaction that can lead to either virus elimination or the establishment of persistent infection and ultimately malignant transformation. We also highlight the influence of certain factors inherent to the host, including the immune status, genetic variants and the coexistence of other microbe infections and microbiome composition in the dynamic of HPV infection induced carcinogenesis.
