BackgroundPsychological stress increases the circulating levels of the stress hormones cortisol and norepinephrine (NE). Chronic exposure to elevated stress hormones has been linked to a reduced response to chemotherapy through induction of DNA damage. We hypothesize that stress hormone signalling may induce DNA damage through the production of reactive oxygen species (ROS)/reactive nitrogen species (RNS) and interference in DNA repair processes, promoting tumourigenesis.MethodsBreast cancer cell lines were incubated with physiological levels of cortisol and NE in the presence and absence of receptor antagonists and inducible nitric oxide synthase (iNOS) inhibitors and DNA damage measured using phosphorylated γ-H2AX. The rate of DNA repair was measured using comet assays and electrochemical sensors were used to detect ROS/RNS in the cell lysates from cells exposed to stress hormones. A syngeneic mouse model was used to assess the presence of iNOS in mammary tumours in stressed versus control animals and expression of iNOS was examined using western blotting and qRT-PCR.ResultsAcute exposure to cortisol and NE significantly increased levels of ROS/RNS and DNA damage and this effect was diminished in the presence of receptor antagonists. Cortisol induced DNA damage and the production of RNS was further attenuated in the presence of an iNOS inhibitor. An increase in the expression of iNOS in response to psychological stress was observed in vivo and in cortisol-treated cells. Inhibition of glucocorticoid receptor-associated Src kinase also produced a decrease in cortisol-induced RNS.ConclusionThese results demonstrate that glucocorticoids may interact with iNOS in a non-genomic manner to produce damaging levels of RNS, thus allowing an insight into the potential mechanisms by which psychological stress may impact breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-017-0823-8) contains supplementary material, which is available to authorized users.

Inhalable poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulating all-trans-Retinoic acid (ATRA) as a host-directed, adjunctive treatment for Mycobacterium tuberculosis (Mtb) infection.

Serotonin (5-HT) is a key neurotransmitter that is found in the brain, blood and gastrointestinal tract. Due to the interest in measuring this important biogenic amine in these various environments, measurements have been conducted using carbonbased sensors without understanding the influence of the matrix on the stability of recordings. Electrochemical recordings were carried out in PBS buffer, 0.5 % w/v mucin and 5 % w/v albumin on the glassy carbon (GC) and boron-doped diamond (BDD) electrodes. During recordings of 5-HT on the GC electrode, the 5 % w/v albumin matrix was protective against electrode fouling compared to 0.5 % w/v mucin, which enhanced the rate of electrode fouling. On the BDD electrode, 0.5 % w/v mucin once again enhanced the rate of electrode fouling, however 5 % w/v albumin did not alter the rate of fouling compared to PBS buffer. This data suggests that all proteins cannot be considered to behave in a similar fashion for electroanalytical measurements and thus careful consideration on the matrix effect needs to be considered before biological monitoring.

The activity of the colon is regulated by chemical signaling, of which serotonin (5-HT) is a key transmitter. Monitoring of mucosal 5-HT overflow has been achieved to date using microelectrodes on a small segment of colonic tissue; however, little is known if such measurements are reflective with regards to 5-HT signaling from the entire colon. This study focused on developing an electrochemical array device that could be utilized to conduct multisite measurements of 5-HT overflow from the entire colon. A 3D printed mold was fabricated that could house 6 multiwall carbon nanotube composite electrodes and provide a fixed distance between the electrodes and the tissue along the entire length of the colon. The electrodes were assessed for sensitivity, stability, and crosstalk before conducting in vitro measurements using colons obtained from 6- and 24-month old mice. As composite electrodes can have a high degree of variability, normalization factors were required between electrodes for a given array. The device had the sensitivity and stability required for 5-HT measurements from intestinal tissue. Regio-specific changes in 5-HT overflow were observed with age, where increases in 5-HT overflow were observed in the distal colon due to an impairment/loss in the serotonin transporter (SERT). Our strategy can be utilized to develop arrays of varying sizes and geometries, which can offer practical solutions for large-scale tissue measurements.

11 Serotonin (5-HT) is an important neurochemical that is present in high

Various investigations have focused on understanding the relationship between mucosal serotonin (5-HT) and colonic motility, however contradictory studies have questioned the importance of this intestinal transmitter. Here we described the fabrication and use of a fecal pellet electrochemical sensor that can be used to simultaneously detect the release of luminal 5-HT and colonic motility. Fecal pellet sensor devices were fabricated using carbon nanotube composite electrodes that were housed in 3D printed components in order to generate a device that had shape and size that mimicked a natural fecal pellet. Devices were fabricated where varying regions of the pellet contained the electrode. Devices showed that they were stable and sensitive for ex vivo detection of 5-HT, and no differences in the fecal pellet velocity was observed when compared to natural fecal pellets. The onset of mucosal 5-HT was observed prior to the movement of the fecal pellet. The release of mucosal 5-HT occurred oral to the fecal pellet and was linked to the contraction of the bowel wall that drove pellet propulsion. Taken, together these findings provide new insights into the role of mucosal 5-HT and suggest that the transmitter acts as a key initiator of fecal pellet propulsion.

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