Background/Aim: Glioblastoma multiforme (GBM) is a malignant primary brain tumor with high rates of recurrence. This study aimed to investigate the effect of repurposed drug combinations on GBM. Materials and Methods: Viability of U87 MG and 11ST patient-derived GMB cell lines, after valproic acid, tranylcypromine or riluzole alone, in different combinations, as well as combined with standard temozolomide chemotherapy was examined using the MTT assay. Proliferation, mRNA level of tissue factor pathway inhibitor 2 (TFPI2), and cell invasion were evaluated using anti-Ki-67 antibody staining, reverse transcriptase-polymerase chain reaction and xCELLigence system. Results: The strongest effect on cell viability was achieved by the combination of riluzole with valproic acid (U87MG: 27.2%, 11ST: 25.99%). Tranylcypromine significantly enhanced the effect of temozolomide when used in combination, as did valproic acid. The normally high proliferation of GBM significantly declined under treatment with valproic acid with tranylcypromine (p=0.01). Finally, we observed reduction of invasion comparing single tranylcypromine to its combination with valproic acid or riluzole. Conclusion: These results support the idea that combinations of drugs could increase the treatment efficiency of GBM.
Layer IV (LIV) of the rodent somatosensory cortex contains the somatotopic barrel field. Barrels receive much of the sensory input to the cortex through innervation by thalamocortical axons from the ventral posteromedial nucleus. In the reeler mouse, the absence of cortical layers results in the formation of mispositioned barrel-equivalent clusters of LIV fated neurons. Although functional imaging suggests that sensory input activates the cortex, little is known about the cellular and synaptic properties of identified excitatory neurons of the reeler cortex. We examined the properties of thalamic input to spiny stellate (SpS) neurons in the reeler cortex with in vitro electrophysiology, optogenetics, and subcellular channelrhodopsin-2-assisted circuit mapping (sCRACM). Our results indicate that reeler SpS neurons receive direct but weakened input from the thalamus, with a dispersed spatial distribution along the somatodendritic arbor. These results further document subtle alterations in functional connectivity concomitant of absent layering in the reeler mutant. We suggest that intracortical amplification mechanisms compensate for this weakening in order to allow reliable sensory transmission to the mutant neocortex.
In view of disease-related threats, containment measures, and disrupted healthcare, individuals with pre-existing mental illness might be vulnerable to adverse effects of the COVID-19 pandemic. Previous reviews indicated increased mental distress, with limited information on peri-pandemic changes. In this systematic review, we aimed to identify longitudinal research investigating pre- to peri-pandemic and/or peri-pandemic changes of mental health in patients, focusing on the early phase and considering specific diagnoses. PsycINFO, Web of Science, the WHO Global literature on coronavirus disease database, and the Cochrane COVID-19 Study Register weresearched through 31 May 2021. Studies were synthesized using vote counting based on effect direction. We included 40 studies mostly from Western, high-income countries. Findings were heterogeneous, with improving and deteriorating mental health observed compared to pre-pandemic data, partly depending on underlying diagnoses. For peri-pandemic changes, evidence was limited, with some suggestion of recovery of mental distress. Study quality was heterogeneous; only few studies investigated potential moderators (e.g., chronicity of mental illness). Mental health effects on people with pre-existing conditions are heterogeneous within and across diagnoses for pre- to peri-pandemic and peri-pandemic comparisons. To improve mental health services amid future global crises, forthcoming research should understand medium- and long-term effects, controlling for containment measures.
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