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Alzheimer's disease (AD) pathogenesis has been attributed to extracellular aggregates of amyloid β (Aβ) plaques and neurofibrillary tangles in the human brain. It has been reported that butyrylcholinesterase (BChE) also accumulates in the brain Aβ plaques in AD. We have previously found that the BChE substitution in 5'UTR caused an in-frame N-terminal extension of 41 amino acids of the BChE signal peptide. The resultant variant with a 69 amino acid signal peptide, designated N-BChE, could play a role in AD development. Here, we report that the signal sequence of the BChE, if produced in an extended 69 aa version, can self-aggregate and could form seeds that enhance amyloid fibril formation in vitro in a dose-dependent manner and create larger co-aggregates. Similar phenomena could have been observed in the human brain if such an extended form of the signal sequence had been, in some circumstances, translated., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The role of microRNAs in controlling angiogenesis is recognized as a promising therapeutic target in both cancer and cardiovascular disorders. However, understanding a miRNA's pleiotropic effects on angiogenesis is a limiting factor for these types of therapeutic approaches. Using genome-wide next-generation sequencing, we examined the role of an antiangiogenic miRNA, miR-200b, in primary human endothelial cells. The results indicate that miR-200b has complex effects on hypoxia-induced angiogenesis in human endothelia and importantly, that many of the reported miR-200b effects using miRNA overexpression may not be representative of the physiological role of this miRNA. We also identified the antiangiogenic KLF2 gene as a novel target of miR-200b. Our studies indicate that the physiological changes in miR-200b levels during acute hypoxia may actually have a proangiogenic effect through Klf2 downregulation and subsequent stabilization of HIF-1 signaling. Moreover, we provide a viable approach for differentiating direct from indirect miRNA effects in order to untangle the complexity of individual miRNA networks., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Butyrylcholinesterase (BChE) activity assay and inhibitor phenotyping can help to identify individuals at risk of prolonged paralysis following the administration of neuromuscular blocking agents, like succinylcholine, pesticides and nerve agents. In this study, the activity of BChE and its sensitivity to inhibition by dibucaine and fluoride was evaluated in 1200 Polish healthy individuals. In addition, molecular analysis of all exons, exon-intron boundaries and the 3'UTR sequence of the BCHE gene was performed in a group of 72 subjects with abnormal BChE activity (<2000 U/L and >5745 U/L) or with DN (Dibucaine Number) or FN (Fluoride-Number) values outside the reference range (DN < 78 and FN < lower than wild type). In a studied group, BChE activity range was similar to those observed in other populations. BChE activity screening allowed to detect UA and UF phenotypes in 26 (2.2%) and 15 (1.2%) individuals, respectively. Observed UA or UF phenotypes were confirmed by direct sequencing and heterozygous c.293A > G or c.1253G > T substitutions were identified in all cases. Nine out of 18 (50%) individuals with BChE activity below 2000 U/L had a mutation in 5'UTR (32G/A), intron 2 (c.1518-121T/C) or exon 4 (c.1699G/A; the K variant mutation). Majority of the individuals with BChE activity ≥6000 U/L were wild type. To summarize, the range of BChE activity in a Polish population is similar to those observed in other countries. We conclude that the BChE phenotyping assay is a reliable method for identification of individuals with the UA and UF genotypes., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The ecto-nucleotide pyrophosphatase/phosphodiesterase family (E-NPPs) contains two membrane-bound members: E-NPP1 and E-NPP3. These enzymes mediate hydrolysis of extracellular nucleotides and their abnormal expression may affect intracellular signal transduction pathways, leading to cellular dysfunction, e.g., insulin resistance. Podocytes are insulin-dependent glomerular epithelial cells that regulate the glomerular filtration rate. Pathology of podocytes is a hallmark of diabetic nephropathy. Here, we investigated the expressions of E-NPP1 and E-NPP3 and activity of E-NPP enzymes in rat podocytes cultured with 5mM (NG) or 30 mM glucose (HG). Insulin resistance was determined by measuring changes in [1,2-(3)H]-deoxy-D-glucose uptake in response to insulin. mRNAs of E-NPP1 and E-NPP3 were detected within podocytes. The E-NPP expressions were confirmed at the protein level using western blot and immunofluorescence techniques. At NG, insulin (300 nM, 3 min) increased glucose uptake 1.5-fold; however, this effect was abolished at HG. The protein expressions of E-NPP1 and E-NPP3 were not affected at HG. The E-NPP activities were 24.68±0.72 and 26.51±1.55 nmol/min/mg protein at NG and HG, respectively. In conclusion, ecto-nucleotide pyrophosphatase/phosphodiesterase 1 and 3 are expressed on podocytes, but changes in expression of these enzymes are most likely not involved in etiology of insulin resistance in podocytes., (Copyright © 2011 Elsevier Inc. All rights reserved.)