NLRP3 and NLRP1 inflammasomes are up-regulated in patients with mesial temporal lobe epilepsy and may contribute to overexpression of caspase-1 and IL-ß in sclerotic hippocampi.

Inflammation plays a role in the pathophysiology of mesial temporal lobe epilepsy (MTLE). Inflammasome pathways, including the NLRP1 and NLRP3-induced ones, promote neuroinflammation and pyroptosis through interleukin (IL)-1ß and caspase-1 action. Evaluation of NLRP1 in sclerotic hippocampi is scarce and there are no data on NLRP3 in human TLE. The aim of this study was to evaluate the expression of these proteins alongside caspase-1 and IL-1ß in the hippocampi of patients with TLE compared to control samples. We also sought to investigate peripheral levels of caspase-1 and IL-1ß in an independent cohort. Sclerotic and control hippocampi were collected for both histological and immunohistochemical analyses of NLRP1, NLRP3, caspase-1 and IL-1ß; plasma was sampled for the measurement of caspase-1 and IL-1ß levels through enzyme-linked immunoassay (ELISA) and cytometric bead array (CBA). Sclerotic hippocampi displayed higher expression of the measured proteins than control. Both glia and neurons showed activation of these pathways. Additionally, increased expression of NLRP1 and NLRP3 was associated with elevated plasma levels of IL-1ß and in TLE, and increased levels of peripheral caspase-1 were associated with bilateral hippocampal sclerosis (HS). In conclusion, NLRP1 and NLRP3 are up-regulated in sclerotic hippocampi, what may be responsible, at least in part, for the increased hippocampal expression of caspase-1 and IL-1ß. Our data suggest a role for inflammasome activation in central and peripheral inflammation in TLE.

Relationship between Sarcopenia and mTOR Pathway in Patients with Colorectal Cancer: Preliminary Report.

Sarcopenia is a syndrome characterized by loss of muscle mass and strength that impacts clinical outcomes and mortality in cancer patients. Although the molecular pathways involved in sarcopenia are not fully elucidated, the decrease in protein synthesis rate appears to be one of the most important events. The objective of this study was to investigate the relationship between sarcopenia and mTOR signaling pathway in patients undergoing colorectal resection surgery. Three groups of patients were assessed: 1) the control group (no cancer, no sarcopenia), 2) the cancer non-sarcopenic group and 3) the cancer sarcopenic group. All individuals were evaluated in relation to presence of sarcopenia and mTOR signaling pathway. Sarcopenia was evaluated by the combination of low muscle mass and low muscle strength, measured using computerized tomography images, and hand grip strength, respectively. Rectus abdominis muscle biopsy was performed at the time of surgery. mTOR pathway was analyzed by MILLIPLEX Map Kit Phospho/total mTOR 2-Plex Magnetic Bead Panel. Results were presented by phosphor/total mTOR ratio. Independent T test, Kruskal-Wallis test, and Dunn-Bonferroni post hoc were performed for statistical analysis and P < 0.05 was considered. Thirty-six patients and five controls were evaluated. A total of 13 cancer patients (36.1%) had sarcopenia. The phospho/total mTOR ratio was different between the control group (0.167 MFI) and the cancer non-sarcopenic group (0.055 MFI) (P = 0.026) as well as between the control group (0.167 MFI) and the cancer sarcopenic group (0.0049 MFI) (P = 0.041). No difference was observed on the median phospho/total mTOR ratio between the cancer groups (P > 0.05). More research is needed to extrapolate these results.