Angiotensin-converting enzyme inhibitor, Enalapril, inhibits tumor growth and potentiates the antitumor efficacy of 5-FU in colorectal cancer

OBJECTIVE: Colorectal cancer (CRC) is among the leading causes of cancer-related death, indicating the need for the identification of novel therapeutic approaches to increase the activity of current therapy or have better efficacy. Angiotensin-converting enzyme (ACE) is being reported to be associated with aggressive behaviors of CRC cells and poor prognosis. Here we explored the therapeutic potency of targeting ACE by Enalapril in CRC in vivo model. MATERIALS AND METHODS: A xenograft model of CRC was used to investigate the effects of Enalapril alone, or in combination with 5-FU, on tumor growth following histological staining (Hematoxylin and Eosin and Masson trichrome staining) and biochemical studies of Malondialdehyde (MDA), total thiols, superoxide dismutase (SOD) and catalase (CAT) activities. RESULTS: Enalapril reduced tumor growth and increased tumor necrosis; this effect was more pronounced in Enalapril plus 5-FU combination. Enalapril/5-FU was able to decrease tumor fibrosis and collagen content. ACE inhibitors also increased MDA level, as an oxidative stress marker, while reducing total thiol group levels, SOD and CAT enzyme activity. CONCLUSIONS: Our findings provide a novel insight on the therapeutic potential targeting of the renin–angiotensin system as a new therapeutic option in combination with current therapeutic agents 5-FU in the treatment of CRC

The Role of NMDA Receptor on Spatial Learning and Memory Consolidation Rat Following Intra-Hippocampal Injection of Aqueous Extract of Leaves of Origanum (Origanum Vulgare L. ssp. viridis)

ABSTRACT Background & Objectives: Intra-hippocampal adminestration of origanum (ORG) improves spatial learning of rats. The aim of the present study was to investigate the possible mechanism for origanum extract on spatial learning and memory in the hippocampus. Methods: In this study 42 adult male Wistar rats were used. Animals were cannulated bilaterally in the posterior laterl of hippocampus. After the recovery period, the spatial learning and memory were assessed using Morris Water Maze (MWM). Saline, ORG (0.03μg/site) glutamate receptor antagonist MK801 (0.08, 0.2 and 0.4 μmol/site) and coinjected of MK + ORG was injected into the posterior lateral of hippocampus 20 minutes before the training and retrival sesions (for 5 consecutive days) (n=7). Results: The results showed that the intra-hippocampal injection of MK 801 significantly blocked the decreased distance and time of reaching (due to ORG injection) to find hidden platform of MWM (p<0.05). On the retrival tests, the average of time spent in the target area is reduced in the co-injected of MK801 + ORG group. Conclusion: The intra-hippocampal injection of aqueous extract of origanum may improve working memory in rats through glutamate-dependent NMDA receptors

Identifying effective characteristics of behavioral weight management interventions for people with serious mental illness: A systematic review with a qualitative comparative analysis

People with serious mental illness (SMI) have identified barriers to engaging in behavioral weight management interventions (BWMIs). We assessed whether BWMIs that addressed these barriers were more effective. First, we systematically reviewed qualitative literature and used a thematic analysis to identify the characteristics of BWMIs that promote engagement for adults with SMI. Second, we systematically reviewed randomized controlled trials (RCTs) of BWMIs in adults with SMI. Data on the characteristics that promoted engagement and weight outcomes were extracted. We then used a crisp-set qualitative comparative analysis (CsQCA) to identify which characteristics were associated with weight loss. For the qualitative review, 20 studies in 515 people with SMI were analyzed and nine characteristics were reported to promote engagement in BWMIs. For the systematic review, 34 RCTs testing 36 interventions in 4305 participants were included. The active interventions resulted in more weight loss (mean = -4.37 to +1 kg at 6 weeks to 18 months follow-up) compared with controls (-1.64 to +3.08 kg). The CsQCA showed BWMIs that offered regular contact, tools to support enactment, and tailored materials were associated with effectiveness. As these are all supplementary strategies, it may be possible to augment BWMIs available for the general population to engage people with SMI