Vascular Endothelial Growth Factor-A (VEGFA) signaling is crucial to the cellular processes involved in angiogenesis. Previously, we assembled a network of molecular reactions induced by VEGFA in human umbilical vein endothelial cell populations. Considering transcriptome as a read-out of the transcriptional and epigenomic regulatory network, we now present an analysis of VEGFA-induced temporal transcriptome datasets from 6 non-synchronized studies. From these datasets, applying a confidence criterion, a set of early VEGFA-responsive signature genes were derived and evaluated for their co-expression potential with respect to multiple cancer gene expression datasets. Further, inclusive of a set of ligand-receptor pairs, a list of ligand and receptor signaling systems that potentially fine-tune the endothelial cell functions subsequent to VEGFA signaling were also derived. We believe that a number of these signaling systems would concurrently and/or hierarchically fine-tune the signaling network of endothelial cell populations towards the processes associated with angiogenesis through autocrine, paracrine, juxtacrine, and matricrine modes. By further analysis of published literature on VEGFA signaling, we also present an improved update-version of our previous VEGFA signaling network model in endothelial cells as a platform for analysis of crosstalk with these signaling systems.

Lymphatic lariasis is one of the major diseases that belong to the category of neglected tropical illness.Filarial nematodes are the cause of the disease and are transmitted to humans via blood-feeding arthropod vectors. Drugs such as Albendazole, Ivermectin and diethylcarbamazine are administered either individually or in combination to overcome the progress of the lymphatic lariasis. However, these drugs have some disadvantages like temporary hair loss, dizziness, nausea etc. The larial parasites have multifunctional proteins including the Glutathione-s-transferase (GST) enzyme which plays a major role in detoxi cation of endogenous electrophilic compounds. This study aims at the identi cation of a natural molecule that has the potential to bind with the GST enzyme and thus interrupt the detoxi cation process within the larial parasite, Brugia malayi. A medicinal plant Calotropis procera, owing to its anthelmintic properties was searched for the presence of potential phytocompounds. The phytocompounds were docked against the homology modeled GST enzyme using the MOE software. The results were screened and analyzed based on the Lipinski rule of 5. N-octanoate was the phytocompound obtained based on molecular docking, subjected to molecular dynamics. These results require further in vitro and in vivo validation to consider n-octanoate as a potential drug candidate for lymphatic lariasis treatment.

No abstract

Notch signaling and its downstream target, HES1, play a critical role in regulating and maintaining cancer stem cells (CSCs), similar to embryonic development. Here, we report a unique subclass of Notch Independent Hes-1(NIHes-1) expressing Cancer Stem Cells (CSCs) in neuroblastoma. These CSCs maintain sustained HES1 expression by activation of HES1 promoter region upstream of classical CBF-1 binding sites thereby, completely bypassing Notch receptor mediated activation. These stem cells have self-renewal ability and potential to generate tumor. Interestingly, we observed that NIHes-1 CSCs could transit to Notch dependent Hes-1 expressing (NDHes-1) CSCs where HES1 is expressed by Notch receptor mediated promoter activation. We observed that NDHes-1 expressing CSCs also had the potential to transit to NIHes-1 CSCs and during this coordinated bidirectional transition, both CSCs gave rise to the majority of the bulk cancer cells, which had HES1 promoter inactive (PIHes-1). A few of these PIHes-1 cells were capable of reverting to a CSC state. These findings explain the existence of heterogenic mode of Hes-1 promoter activation within IMR-32 and the potential to switch between them.

Lymphatic filariasis is one of the major diseases that belong to the category of neglected tropical illness. Filarial nematodes are the cause of the disease and are transmitted to humans via blood-feeding arthropod vectors. Drugs such as Albendazole, Ivermectin and diethylcarbamazine are administered either individually or in combination to overcome the progress of the lymphatic filariasis. However, these drugs have some disadvantages like temporary hair loss, dizziness, nausea etc. The filarial parasites have multifunctional proteins including the Glutathione-s-transferase (GST) enzyme which plays a major role in detoxification of endogenous electrophilic compounds. This study aims at the identification of a natural molecule that has the potential to bind with the GST enzyme and thus interrupt the detoxification process within the filarial parasite, Brugia malayi. A medicinal plant Calotropis procera, owing to its anthelmintic properties was searched for the presence of potential phytocompounds. The phytocompounds were docked against the homology modeled GST enzyme using the MOE software. The results were screened and analyzed based on the Lipinski rule of 5. N-octanoate was the phytocompound obtained based on molecular docking, subjected to molecular dynamics. These results require further in vitro and in vivo validation to consider n-octanoate as a potential drug candidate for lymphatic filariasis treatment.