Porcine liver decomposition product-derived lysophospholipids promote microglial activation in vitro

Cognitive impairments such as dementia are common in later life, and have been suggested to occur via a range of mechanisms, including oxidative stress, age-related changes to cellular metabolism, and a loss of phospholipids (PLs) from neuronal membranes. PLs are a class of amphipathic lipids that form plasma membrane lipid bilayers, and that occur at high concentrations in neuronal membranes. Our previous study suggested that a porcine liver decomposition product (PLDP) produced via protease treatment may improve cognitive function at older ages, by acting as a rich source of PLs and lysophospholipids (LPLs); however, its specific composition remains unclear. Thus, the present study used a novel liquid chromatography electrospray ionization tandem mass spectrometric (LC-MS/MS) protocol to identify the major PLs and LPLs in PLDP. Furthermore, it assessed the effect of identified LPLs on microglial activation in vitro, including cell shape, proliferation, and cell morphology. The results of the conducted analyses showed that PLDP and PLDP-derived LPLs concentration-dependently modulate microglial activation in vitro. In particular, lysophosphatidylcholine (LPC) concentration-dependently promotes cell morphology, likely via effects mediated by the enzyme autotaxin (ATX), since inhibiting ATX also promoted cell morphology, while conversely, increasing ATX production (via treatment with high levels of LPC) abolished this effect. These findings suggest that LPC is likely neuroprotective, and thus, support the importance of further research to assess its use as a therapeutic target to treat age-related cognitive impairments, including dementia

Photosynthetic rates of four tree species in the upper canopy of a tropical rain forest at the Pasoh Forest Reserve in Peninsular Malaysia

Measurements of photosynthesis (A) and stomatal conductance (gs) were conducted using the leaves of four tropical tree species (Dipterocarpus sublamellatus, Neobalanocarpus heimii, Ptychopyxis caput-medusae, and Xanthophyllum amoneum) in the canopy of the lowland forest at the Pasoh Forest Reserve in peninsular Malaysia. A canopy walkway was used to reach the canopy of 30- to 40-m-tall trees and diurnal changes in A and gs were determined. The diurnal patterns for A differed between days and between species, though A of the four species were similar but quite low. In general, A increased with increasing photosynthetically active radiation (PAR) before noon, then declined. As well, a linear relationship was detected between gs and A, but no statistically significant correlation could be confirmed between these two factors for D. sublamellatus and P. caput-medusae in November and July. The value of gs decreased with increasing vapor pressure deficit for D. sublamellatus, but the other species did not show this response

Spiral Tissue Microarrays as Next Evolutionary Step in the High-density Tissue Microarray Technology

Tissue microarray (TMA) is a well-established technique that connects basic research with clinical applications that allow the validation of many pathobiologic events from gene expression dysregulation to genomic aberrations. However, conventional TMAs have several limitations such as limited representation of tissue heterogeneity, destruction of donor tissue blocks due to coring and usage of particular specimens that have limited evaluable material (tissue from thin specimens or needle biopsies). We have developed a novel method, which we termed "Spiral TMA" that generates TMAs that allow for improved representation of the donor tissue while keeping the architectural details of the donor block intact. This technology is ideal for specimens with limited tissue without the need to punch holes into the original block and therefore preserving the tissue integrity. In this report, we describe the methodology of constructing Spiral TMA and demonstrate the validation of tumor representation and tissue heterogeneity by comparing Spiral TMA to conventional TMA using immunohistochemical staining to EGFR and CK7

Insulin regulates Presenilin 1 localization via PI3K/Akt signaling.

Recently, insulin signaling has been highlighted in the pathology of Alzheimer's disease (AD). Although the association between insulin signaling and Tau pathology has been investigated in several studies, the interaction between insulin signaling and Presenilin 1 (PS1), a key molecule of amyloid beta (Abeta) pathology, has not been elucidated so far. In this study, we demonstrated that insulin inhibited PS1 phosphorylation at serine residues (serine 353, 357) via phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway and strengthened the trimeric complex of PS1/N-cadherin/beta-catenin, consequently relocalizing PS1 to the cell surface. Since our recent report suggests that PS1/N-cadherin/beta-catenin complex regulates Abeta production, it is likely that insulin signaling affects Abeta pathology by regulating PS1 localization

Cellular Responses of Human Lymphatic Endothelial Cells to Carbon Nanomaterials

One of the greatest challenges to overcome in the pursuit of the medical application of carbon nanomaterials (CNMs) is safety. Particularly, when considering the use of CNMs in drug delivery systems (DDSs), evaluation of safety at the accumulation site is an essential step. In this study, we evaluated the toxicity of carbon nanohorns (CNHs), which are potential DDSs, using human lymph node endothelial cells that have been reported to accumulate CNMs, as a comparison to fibrous, multi-walled carbon nanotubes (MWCNTs) and particulate carbon black (CB). The effect of different surface characteristics was also evaluated using two types of CNHs (untreated and oxidized). In the fibrous MWCNT, cell growth suppression, as well as expression of inflammatory cytokine genes was observed, as in previous reports. In contrast, no significant toxicity was observed for particulate CB and CNHs, which was different from the report of CB cytotoxicity in vascular endothelial cells. These results show that (1) lymph endothelial cells need to be tested separately from other endothelial cells for safety evaluation of nanomaterials, and (2) the potential of CNHs as DDSs.ArticleNANOMATERIALS. 10(7):1374 (2020)journal articl