Biperiden and mepazine effectively inhibit MALT1 activity and tumor growth in pancreatic cancer

MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms.     

Facial expression recognition in Alzheimer’s disease: A systematic review

Introduction: It is well established that behavioral variant frontotemporal dementia can impair social and emotional function. However, there is no consensus regarding how Alzheimer’s disease can affect facial expression recognition. We aim to systematically review all the literature addressing this issue over the last 10 years.

Method: We conducted a search based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The search for literature was undertaken on 19 September 2017, using Pubmed, SciELO, BIREME, and Thomson Reuters Web of Science electronic databases. The key terms for the search were: Alzheimer’s disease, dementia, and facial expression recognition.

Results: We screened 173 articles, and 22 of them were selected. The most common methodology involved showing participants photographs of people expressing the six basic emotions—fear, anger, sadness, disgust, surprise, and happiness. Results were ambiguous. Among people with mild Alzheimer’s disease, happiness was easier to recognize than the other five basic emotions, with sadness and anger the most difficult to recognize. In addition, the intensity level of the emotions presented seems to be important, and facial expression recognition is related to specific cognitive capacities, including executive function and visuoperceptual abilities. Impairment in facial expression recognition does not appear to be a consistent neuropsychological finding in Alzheimer’s disease.

Conclusions: The lack of standardized assessment instruments and the heterogeneity of the methods and samples used across studies hamper comparisons. Future researches should investigate facial expression recognition through more ecological and standardized methods.     

Astrocyte activation and altered metabolism in normal aging,age-related CNS diseases,and HAND

Journal of NeuroVirology - Astrocytes regulate local cerebral blood flow, maintain ion and neurotransmitter homeostasis, provide metabolic support, regulate synaptic activity, and respond to brain...     

Psychological distress among migrant groups in Australia: results from the 2015 National Health Survey

Social Psychiatry and Psychiatric Epidemiology - To understand the relationship between migration and psychological distress, we (a) calculated the prevalence of psychological distress in specific...