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Fayyaz, S.

Publications and source records attributed to Fayyaz, S..

2 recordsLinked to original sources
bioRxiv2021

Antidepressant Sertraline Hydrochloride Inhibits the Growth of HER2+ AU565 Breast Cancer Cell Line through Induction of Apoptosis, and Arrest of Cell Cycle

Breast cancer is one the most aggressive cancer worldwide, especially Pakistan due to limited therapeutic options. This study was conducted to repurpose the use of selective serotonin reuptake inhibitors (SSRIs), in the treatment of breast cancers, and merit to pursue drug re-positioning in oncology. Anti-proliferative activity of SSRIs, such as fluoxetine, paroxetine, and sertraline hydrochloride on the growth of AU-565, MCF-7, MDA-MB-231, and BT-474 breast cancer cell lines, along with human fibroblast BJ cells was determined in vitro. Changes in nuclear morphology (DAPI staining), and induction of apoptosis (flow cytometry, and caspase-3 activation) were also studied. Sertraline hydrochloride most effectively inhibited the growth of breast cancer cells in vitro. Therefore, pharmacological mechanism involved in sertraline mediated cell death was investigated in HER2+ AU565 cell line. Enhanced nuclear fragmentation, increased Annexin (+) cells, and caspase-3/7 activation indicated that sertraline-mediated cell death could be a result of BCl2-independent apoptosis as evidenced by expression of Bax, and BCl2 genes. Taken together, our results identified sertraline hydrochloride, as a potential candidate for the treatment of HER2-positive breast cancer. Even though these are in vitro results, this study opens great opportunity in the field of drug repurposing for the development of chemotherapeutic agents.

biochemistry↗
bioRxiv2021

Stimulus presentation can enhance spiking irregularity across subcortical and cortical regions

Stimulus presentation is believed to quench neural response variability as measured by fano-factor (FF). However, the relative contribution of within trial spike irregularity (n{Psi}) and trial to trial rate variability (nRV) to FF reduction has remained elusive. Here, we introduce a principled approach for accurate estimation of variability components for a doubly stochastic point process which unlike previous methods allows for a time varying n{Psi} (aka {phi}). Notably, analysis across multiple subcortical and cortical areas showed across the board reduction in rate variability. However, unlike what was previously thought, spiking irregularity was not constant in time and was even enhanced in some regions abating the quench in the post-stimulus FF. Simulations confirmed plausibility of a time varying n{Psi} arising from within and between pool correlations of excitatory and inhibitory neural inputs. By accurate parsing of neural variability, our approach constrains candidate mechanisms that give rise to observed rate variability and spiking irregularity within brain regions.

neuroscience↗