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Potentially Pathogenic Calcium Oxalate Dihydrate and Titanium Dioxide Crystals in the Alzheimer's Disease Entorhinal Cortex.

ABSTRACT: Knowing that Alzheimer's disease (AD) nucleates in the entorhinal cortex (EC), samples of 12 EC specimens were probed for crystals by a protocol detecting fewer than 1/5000th of those present. Of the 61 crystals found, 31 were expected and 30 were novel. Twenty-one crystals of iron oxides and 10 atherosclerosis-associated calcium pyrophosphate dihydrate crystals were expected and found. The 30 unexpected crystals were NLRP3-inflammasome activating calcium oxalate dihydrate (12) and titanium dioxide (18). Their unusual distribution raises the possibility that some were of AD origination sites.

SUBMITTER: Heller A

PROVIDER: S-EPMC7592648 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Potentially Pathogenic Calcium Oxalate Dihydrate and Titanium Dioxide Crystals in the Alzheimer's Disease Entorhinal Cortex.

Heller Adam A Coffman Sheryl S SS Jarvis Karalee K

Journal of Alzheimer's disease : JAD 20200101 2

Knowing that Alzheimer's disease (AD) nucleates in the entorhinal cortex (EC), samples of 12 EC specimens were probed for crystals by a protocol detecting fewer than 1/5000th of those present. Of the 61 crystals found, 31 were expected and 30 were novel. Twenty-one crystals of iron oxides and 10 atherosclerosis-associated calcium pyrophosphate dihydrate crystals were expected and found. The 30 unexpected crystals were NLRP3-inflammasome activating calcium oxalate dihydrate (12) and titanium diox ...[more]

PMID: 32804151

Similar Datasets

Shape-dependent cellular toxicity on renal epithelial cells and stone risk of calcium oxalate dihydrate crystals.

Project description:Renal epithelial cell injury causes crystal retention and leads to renal stone formation. However, the effects of crystal shape on cell injury and stone risk remain unclear. This study compared the cytotoxicity degrees of calcium oxalate dihydrate (COD) crystals having different shapes toward human kidney proximal tubular epithelial (HK-2) cells to reveal the effect of crystal shape on cell injury and to elucidate the pathological mechanism of calcium oxalate kidney stones. The effects of exposure to cross-shaped (COD-CS), flower-like (COD-FL), bipyramid (COD-BD), and elongated-bipyramid (COD-EBD) COD crystals on HK-2 cells were investigated by examining the cell viability, cell membrane integrity, cell morphology change, intracellular reactive oxygen species, mitochondrial membrane potential (Δψm), and apoptotic and/or necrotic rate. Crystals with large (100) faces (COD-EBD) and sharp edges (COD-CS) showed higher toxicity than COD-BD and COD-FL, respectively. COD crystal exposure caused cell membrane rupture, upregulated intracellular reactive oxygen, and decreased Δψm. This series of phenomena ultimately led to a high apoptotic rate and a low necrotic rate. Crystals with large active faces have a large contact area with epithelial cell surface, and crystals with sharp edges can easily scratch epithelial cells; these factors could promote crystal adhesion and aggregation, thus increasing stone risk.

| S-EPMC5543119 | biostudies-other

Decomposition of Calcium Oxalate Crystals in Colobanthus quitensis under CO2 Limiting Conditions.

Project description:Calcium oxalate (CaOx) crystals are widespread among plant species. Their functions are not yet completely understood; however, they can provide tolerance against multiple environmental stress factors. Recent evidence suggested that CaOx crystals function as carbon reservoirs since its decomposition provides CO2 that may be used as carbon source for photosynthesis. This might be advantageous in plants with reduced mesophyll conductance, such as the Antarctic plant Colobanthus quitensis, which have shown CO2 diffusion limitations. In this study, we evaluate the effect of two CO2 concentrations in the CaOx crystals decomposition and chlorophyll fluorescence of C. quitensis. Plants were exposed to airflows with 400 ppm and 11.5 ppm CO2 and the number and relative size of crystals, electron transport rate (ETR), and oxalate oxidase (OxO) activity were monitored along time (10 h). Here we showed that leaf crystal area decreases over time in plants with 11.5 ppm CO2, which was accompanied by increased OxO activity and only a slight decrease in the ETR. These results suggested a relation between CO2 limiting conditions and the CaOx crystals decomposition in C. quitensis. Hence, crystal decomposition could be a complementary endogenous mechanism for CO2 supply in plants facing the Antarctic stressful habitat.

| S-EPMC7600318 | biostudies-literature

Roles of Macrophage Exosomes in Immune Response to Calcium Oxalate Monohydrate Crystals.

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Calcium oxalate crystals induce renal inflammation by NLRP3-mediated IL-1β secretion.

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Calcium oxalate crystals and oxalate induce an epithelial-to-mesenchymal transition in the proximal tubular epithelial cells: Contribution to oxalate kidney injury.

Project description:TGF-β1 is the main mediator of epithelial-to-mesenchymal transition (EMT). Hyperoxaluria induces crystalluria, interstitial fibrosis, and progressive renal failure. This study analyzed whether hyperoxaluria is associated with TGF-β1 production and kidney fibrosis in mice and if oxalate or calcium oxalate (CaOx) could induce EMT in proximal tubule cells (HK2) and therefore contribute to the fibrotic process. Hyperoxaluria was induced by adding hydroxyproline and ethylene glycol to the mice's drinking water for up to 60 days. Renal function and oxalate and urinary crystals were evaluated. Kidney collagen production and TGF-β1 expression were assessed. EMT was analyzed in vitro according to TGF-β1 production, phenotypic characterization, invasion, cell migration, gene and protein expression of epithelial and mesenchymal markers. Hyperoxaluric mice showed a decrease in renal function and an increase in CaOx crystals and Ox urinary excretion. The deposition of collagen in the renal interstitium was observed. HK2 cells stimulated with Ox and CaOx exhibited a decreased expression of epithelial as well as increased expression mesenchymal markers; these cells presented mesenchymal phenotypic changes, migration, invasiveness capability and TGF-β1 production, characterizing EMT. Treatment with BMP-7 or its overexpression in HK2 cells was effective at preventing it. This mechanism may contribute to the fibrosis observed in hyperoxaluria.

| S-EPMC5384284 | biostudies-literature

Titanium dioxide nanoparticles exposure

Project description:This project utilized oligonucleotide microarrays to examine gene expression patterns in adult male fathead minnows (Pimephales promelas) exposed to a common nanomaterial, titanium dioxide (TiO2, stearate-coated particles, MT-100TV®). We exposed adult male fathead minnows for 96 hr to three doses (0, 1, and 10 mg/L nominal) of TiO2 under static renewal conditions. TiO2 is stearate coated, 15 nm particle size.

2010-12-22 | GSE17902 | GEO

Effects of secretome derived from macrophages exposed to calcium oxalate crystals on renal fibroblast activation

Project description:The association between kidney stone disease and renal fibrosis has been widely explored in recent years but its underlying mechanisms remain far from complete understanding. Using label-free quantitative proteomics (nanoLC-ESI-LTQ-Orbitrap MS/MS), this study identified 23 significantly altered secreted proteins from calcium oxalate monohydrate (COM)-exposed macrophages (COM-MP) compared with control macrophages (Ctrl-MP) secretome. Functional annotation and protein-protein interactions network analysis revealed that these altered secreted proteins were involved mainly in inflammatory response and fibroblast activation. BHK-21 renal fibroblasts treated with COM-MP secretome had more spindle-shaped morphology with greater spindle index. Immunofluorescence study and gelatin zymography revealed increased levels of fibroblast activation markers (α-smooth muscle actin and F-actin) and fibrotic factors (fibronectin and matrix metalloproteinase-9 and -2) in the COM-MP secretome-treated fibroblasts. Our findings indicate that proteins secreted from macrophages exposed to COM crystals induce renal fibroblast activation and may play important roles in renal fibrogenesis in kidney stone disease.

2021-11-03 | PXD027039 | Pride

Calcium Oxalate Crystals in Leaves of the Extremophile Plant Colobanthus quitensis (Kunth) Bartl. (Caryophyllaceae).

Project description:The presence of calcium oxalate (CaOx) crystals has been widely reported in the plant kingdom. These structures play a central role in various physiological functions, including calcium regulation, metal detoxification, and photosynthesis. However, precise knowledge about their possible roles and functions in plants is still limited. Therefore, the present work aims to study the ecotypic variability of Colobanthus quitensis, an extremophile species, concerning CaOx crystal accumulation. The CaOx crystals were studied in leaves of C. quitensis collected from different provenances within a latitudinal gradient (From Andes mountains in central Chile to Antarctica) and grown under common garden conditions. Polarized light microscopy, digital image analysis, and electron microscopy were used to characterize CaOx crystals. The presence of CaOx crystals was confirmed in the four provenances of C. quitensis, with significant differences in the accumulation among them. The Andean populations presented the highest accumulation of crystals and the Antarctic population the lowest. Electron microscopy showed that CaOx crystals in C. quitensis are classified as druses based on their morphology. The differences found could be linked to processes of ecotypic differentiation and plant adaptation to harsh environments.

| S-EPMC8470922 | biostudies-literature

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Project description:Calcium phosphate has attracted enormous attention as a bone regenerative material in biomedical fields. In this study, we investigated the effect of microwave treatment on calcium phosphate deposited TiO2 nanoflower to improve protein adsorption. Hierarchical rutile TiO2 nanoflowers (TiNF) fabricated by a hydrothermal method were soaked in modified simulated body fluid for 3 days to induce calcium phosphate (CAP) formation, followed by exposure to microwave radiation (MW). Coating the dental implants with CAP/TiNF provides a means of improving the biological properties, as the structure, morphology, and thickness of the composites can be controlled. The composites were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), field emission transmission electron microscopy (TEM), and Fourier-transform infrared spectroscopy (FTIR), respectively. The composites were identified to be composed of aggregated nano-sized particles with sphere-like shapes, and the calcium phosphate demonstrated low crystallinity. The ability of bovine serum albumin (BSA) to adsorb on MW-treated CAP/TiNF composites was studied as a function of BSA concentration. The Sips isotherm was used to analyze the BSA adsorption on MW-treated CAP/TiNF composites. The MW-treated samples showed high protein adsorption capacity, thereby indicating their potential in various biomedical applications.

| S-EPMC9316246 | biostudies-literature

Defective titanium dioxide single crystals exposed by high-energy {001} facets for efficient oxygen reduction.

Project description:The cathodic material plays an essential role in oxygen reduction reaction for energy conversion and storage systems. Titanium dioxide, as a semiconductor material, is usually not recognized as an efficient oxygen reduction electrocatalyst owning to its low conductivity and poor reactivity. Here we demonstrate that nano-structured titanium dioxide, self-doped by oxygen vacancies and selectively exposed with the high-energy {001} facets, exhibits a surprisingly competitive oxygen reduction activity, excellent durability and superior tolerance to methanol. Combining the electrochemical tests with density-functional calculations, we elucidate the defect-centred oxygen reduction reaction mechanism for the superiority of the reductive {001}-TiO2-x nanocrystals. Our findings may provide an opportunity to develop a simple, efficient, cost-effective and promising catalyst for oxygen reduction reaction in energy conversion and storage technologies.

| S-EPMC4846326 | biostudies-literature

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