ARTICLE | doi:10.20944/preprints202204.0082.v1
Subject: Biology, Agricultural Sciences & Agronomy Keywords: Caco2/HT-29 cells; lipopolysaccharide(LPS); mucins; focal adhesion pathway; ECM receptor in-teraction pathway
Online: 8 April 2022 (14:04:17 CEST)
Endotoxins are toxic substances that widely exist in the environment and can enter the intestine with food and other substances. Intestinal epithelial cells are protected by a mucus layer that contains MUC2 as its main structural component. However, a detailed understanding of the mechanisms involved in the function of the mucus barrier in endotoxin penetration is lacking. Here, we established the most suitable proportion of Caco-2/HT-29 co-culture cells as a powerful tool to evaluate the intestinal mucus layer. Our findings significantly advance current knowledge as focal adhesion and ECM-receptor interaction were identified as the two most significantly implicated pathways in MUC2 small interfering RNA (siRNA)-transfected Caco-2/HT-29 co-culture cells after 24 h of LPS stimulation. When the mucus layer was not intact, LPS was found to damage the tight junctions of Caco-2/HT29 co-cultured cells. Furthermore, LPS was demonstrated to inhibit the integrin-mediated focal adhesion structure and damage the matrix network structure of the extracellular and actin microfilament skeletons. Ultimately, LPS inhibited the interactive communication between the extracellular matrix and the cytoskeleton for 24 h in the siMUC2 group compared with the LPS(+) and LPS(-) groups. Overall, we recognized the potential of MUC2 as a tool for barrier function in several intestinal bacterial diseases.
ARTICLE | doi:10.20944/preprints202002.0041.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: geranylgeranyl acetone (GGA); heat shock proteins (Hsps); HT-22 (hippocampal neuronal) cells; mitochondrial membrane potentials
Online: 4 February 2020 (10:24:57 CET)
Geranylgeranyl acetone (GGA) protects against various types of cell damages by upregulating heat shock proteins. We investigated whether GGA protect neuronal cells from cell death induced by oxidative stress. Glutamate exposure was lethal to HT-22 cells which comprise a neuronal line derived from mouse hippocampus. This configuration is often used as a model for hippocampus neurodegeneration in vitro. In the present study, GGA protected HT-22 cells from glutamate-induced oxidative stress. GGA pretreatment did not induce Hsps. Moreover, reactive oxygen species increased to the same extent in both GGA-pretreated and untreated cells exposed to glutamate. In contrast, glutamate exposure and GGA pretreatment increased mitochondrial membrane potential. However, increases in intracellular Ca2+ concentration were inhibited by GGA pretreatment. In addition, the increase of phosphorylated ERKs by the glutamate exposure was inhibited by GGA pretreatment. These findings suggest that GGA protects HT-22 cells from glutamate-provoked cell death without Hsp induction and that the mitochondrial calcium buffering capacity plays an important role in this protective effect.
ARTICLE | doi:10.20944/preprints201903.0003.v1
Online: 1 March 2019 (07:35:58 CET)
Electrochemical energy conversion and storage is key for the use of regenerative energies at large scale. A thorough understanding of the individual components, such as the ion conducting membrane and the electrode layers, can be obtained with scattering techniques on atomit to molecular length scales. The largely heterogeneous electrode layers of High-Temperature Polymer Electrolyte Fuel Cells are studied in this work with small- and wide-angle neutron scattering at the same time with the iMATERIA diffractometer at the spallation neutron source at J-PARC, opening a view on structural properties on atomic to mesoscopic length scales.
REVIEW | doi:10.20944/preprints201808.0487.v1
Subject: Medicine & Pharmacology, Allergology Keywords: sex; anxiety disorders; 5-HT; tryptophan; immune system; inflammation
Online: 29 August 2018 (08:58:26 CEST)
Anxiety disorders manifest in women more than in men by almost twofold. This narrative review aims to summarize the sex-related biological factors, which underpin anxiety, focusing on the interactions of sex and tryptophan/serotonin with anxiety.A literature search was conducted using Google Scholar, PubMed/MEDLINE, Scopus, and EMBASE databases from inception until December 31, 2017. This review shows that sex may interact with many serotonin functions thereby modulating anxiety, including 5-HT1A and 5-HT2C receptors, 5-HT transporter and central 5-HT concentrations and metabolism. Sex-steroids modulate the expression of serotonin transporter genes, creating a difference in serotonin availability. Sex and estrous cycle phases lead to varying anxiety responses to tryptophan depletion. Testosterone, progesterone and estrogen are important factors in mediating sex differences in serotonin responses to anxiety-generating behavioral tests. At prenatal levels, there are sex-related differences in the reciprocal relationships between serotonin and the HPA-axis, which modulate anxiety-like behaviors. Activated immune-inflammatory pathways induce indoleamine-2,3-dioxynease (IDO) and the tryptophan catabolite (TRYCAT) pathway thereby increasing tryptophan degradation and increasing the production of TRYCATs including kynurenine and quinolinic acid, which may create an overall anxiogenic effect. The effects of immune activation on IDO are significantly more pronounced in women than men and therefore females may show increased levels of anxiogenic TRYCAT following immune challenge. Aberrations in the IDO-activated TRYCAT pathway are found in pregnant females and parturients and are associated with increased anxiety levels in the postnatal period. The results of this review underscore the necessity of studying the associations between serotonin and anxiety in both sexes taking into account the effects of immune activation on IDO and production of anxiogenic TRYCATs. Future anxiety research should focus on the interactions between serotonin/tryptophan and sex, sex hormones, the menstrual cycle, pregnancy, the HPA axis and the immune system through production of anxiogenic TRYCATs.
Online: 25 July 2020 (11:48:05 CEST)
This paper examines the spatial and temporal distribution of all COVID-19 cases from January to June 2020 against the underlying distribution of population in the United States. It is found that, as time passes, COVID-19 cases become a power law with cut-off, resembling the underlying spatial distribution of populations. The power law implies that many states and counties have a low number of cases, while only a few highly populated states and counties have a high number of cases. To further differentiate patterns between the underlying populations and COVID-19 cases, we derived their inherent hierarchy characterized by the ht-index. We found that the ht-index of COVID-19 cases persistently approaches that of the populations; that is, 5 and 7 at the state and county levels, respectively. Mapping the ht-index of COVID-19 cases against that of populations provides new insights into the development of the pandemic in the United States.
ARTICLE | doi:10.20944/preprints202109.0475.v1
Subject: Life Sciences, Other Keywords: food bioactive compunds; stokes aster ethanolic extarcts; health effects; antiproliferative activity; Caco2 cells; docking; human tankyrase 1
Online: 28 September 2021 (14:23:04 CEST)
In this study, five polyphenol compounds (reference substances, ref.) were added to Stokesia laevis (Slae26) ethanolic extract (5 mg GAE / mL) in order to test their antiproliferative effects on human colon tumor cell line Caco-2 (ATCC-HTB-37). The five phenolics (ref.) are luteolin-7-O-glucoside (orientin), luteolin-8-C-glucoside (cinnaroside), caffeic acid, gentisic acid and para-aminobenzoic acid (PABA), and they were combined in ratio 1:1 between the active compounds in samples (GAE : ref.). Results indicated certain antiproliferative effects of Slae26 (IC50=36 μg GAE/mL sample), of the five reference compounds, but mainly of Slae26 combinations with the five phenolics tested (ref.). Punctually, there were obtained IC50 values around 5 μg/mL sample, signifying real therapeutic usefulness and antitumor potency of Slae26 combinations with the five food bioactive compounds tested. In silico docking studies provided potential therapeutic agents to inhibit the catalytic domain of human tankyrase 1 (TNKS1) in the series of food bioactive compounds tested, and revealed luteolin-7-O-glucoside high effectiveness.
Subject: Medicine & Pharmacology, Allergology Keywords: predator scent; aldosterone; corticosterone; adrenal gland; dorsal raphe nucleus (DRN); serotonin (5-HT); electrophysiology
Online: 15 July 2021 (10:40:31 CEST)
Exposure to predator scent (PS) has been used as a model of stress associated with danger to life and body integrity. We tested the hypothesis that repeated PS exposure alters the excitability of serotonin (5-HT) neurons of the dorsal raphe nucleus. To study the mechanisms involved, we approached serum and adrenal corticosterone and aldosterone concentrations, as well as cortical brain-derived neurotrophic factor (BDNF) expression. Adult male Sprague-Dawley rats were exposed to PS for ten minutes daily for ten consecutive days. Two weeks after the last exposure, electrophysiological and biochemical assessments were performed. Measurements by in vivo electrophysiology showed increased spontaneous firing activity of 5-HT neurons in rats exposed to PS. PS exposure resulted in reduced serum corticosterone and aldosterone concentrations. Concentrations of both corticosteroids in the adrenal glands, as well as the relative weight of the adrenals, were unaffected. The gene expression of hippocampal BDNF of rats exposed to PS remained unaltered. In conclusion, repeated exposure of rats to PS leads to enhanced firing activity of 5-HT neurons accompanied by reduced serum, but not adrenal aldosterone and corticosterone concentrations. Reduced corticosteroid concentrations in the blood appear to be the result of increased metabolism and/or tissue uptake rather than altered steroidogenesis. The decrease in circulating corticosterone in rats experienced repeated PS may represent part of the mechanisms leading to increased excitability of 5-HT neurons. The increase in 5-HT neuronal firing activity might be an important compensatory mechanism designated to diminish the harmful effects of the repeated PS exposure on the brain.
ARTICLE | doi:10.20944/preprints201907.0033.v1
Subject: Physical Sciences, Atomic & Molecular Physics Keywords: laser-induced plasma; atomic spectroscopy; laser-induced breakdown spectroscopy; 29 atomic spectroscopy; principal component analysis; partial least-square regression; gypsum; Mars
Online: 2 July 2019 (08:03:52 CEST)
The first detection of gypsum (CaSO4.2H2O) by the Mars Science Laboratory (MSL) rover Curiosity in the Gale Crater, Mars created a profound impact on planetary science and exploration. The unique capability of plasma spectroscopy involving in situ elemental analysis in extraterrestrial environments, suggesting the presence of water in the red planet based on phase characterization and providing a clue to Martian paleoclimate. The key to gypsum as an ideal paleoclimate proxy lies in its textural variants, and in this study terrestrial gypsum samples from varied locations and textural types have been analyzed by Laser Induced Breakdown Spectroscopy (LIBS) technique. Petrographic, sub-microscopic and powder X-ray diffraction characterizations confirm the presence of gypsum (hydrated calcium sulphate; CaSO4.2H2O), bassanite (semi-hydrated calcium sulphate; CaSO4.1/2H2O) and anhydrite (anhydrous calcium sulphate; CaSO4) along with accessory phases (quartz and jarosite). The principal component analysis of LIBS spectra from texturally varied gypsums can be differentiated from one another because of the chemical variability in their elemental concentrations. The concentration of gypsum is determined from the partial least-square regressions model. Rapid characterization of gypsum samples with LIBS is expected to work well in extraterrestrial environments.
ARTICLE | doi:10.20944/preprints201901.0173.v1
Subject: Earth Sciences, Geoinformatics Keywords: third definition of fractal; fractal or living geometry; wholeness; head/tail breaks (ht-index); scaling law
Online: 17 January 2019 (03:30:08 CET)
As noted in the introductory quotation, an ideal map was long ago seen as the map of the map, the map of the map, of the map, and so on endlessly. This recursive perspective on maps, however, has received little attention in cartography. Cartography, as a scientific discipline, is essentially founded on Euclidean geometry and Gaussian statistics, which deal with respectively regular shapes, and more or less similar things. It is commonly accepted that geographic features – such as rivers, cities, streets and building – are not regular and that the Earth’s surface is full of fractal or scaling or living phenomena with far more small things than large ones at different levels of scale. This paper argues for a new paradigm in mapping, based on fractal or living geometry and Paretian statistics, and – more critically – on the new conception of space, conceived and developed by Christopher Alexander, that space is neither lifeless nor neutral, but a living structure capable of being more living or less living. The fractal geometry is not limited to Benoit Mandelbrot’s framework, but is extended towards Christopher Alexander’s living geometry and based upon the third definition of fractal: A set or pattern is fractal if the scaling of far more small things than large ones recurs multiple times. Paretian statistics deals with far more small things than large ones, so it differs fundamentally from Gaussian statistics, which deals with more or less similar things. Under the new paradigm, I make several claims about maps and mapping: (1) Topology of geometrically coherent things – in addition to that of geometric primitives – enables us to see a scaling or fractal or living structure; (2) Under the third definition, all geographic features are fractal or living, given the right perspective and scope; (3) Exactitude is not truth – to paraphrase Henri Matisse – but the living structure is; and (4) Töpfer’s law is not universal, but scaling law is. All these assertions are supported by evidence, drawn from a series of previous studies. This paper demands a monumental shift in perspective and thinking from what we are used to on the legacy of cartography and GIS.
ARTICLE | doi:10.20944/preprints201804.0245.v1
Subject: Materials Science, Polymers & Plastics Keywords: Chitosan-g-PMMA amphiphilic nanoparticles; thiolated polymers; mucoadhesion; mucosal drug delivery; Caco2 and HT29-MTX cell lines; apparent permeability in vitro.
Online: 18 April 2018 (16:28:21 CEST)
Engineering of drug nanocarriers combining fine-tuned mucoadhesive/mucopenetrating properties is currently being investigated to ensure more efficient mucosal drug delivery. Aiming to improve the transmucosal delivery of hydrophobic drugs, we designed a novel kind nanogel produced by the self-assembly of amphiphilic chitosan graft copolymers ionotropically crosslinked with sodium tripolyphosphate. In this work, we synthesized for the first time chitosan-g-poly(methyl methacrylate) nanoparticles thiolated by the conjugation of N-acetyl cysteine. First, we confirmed that both non-crosslinked and crosslinked nanoparticles in the 0.05-0.1% w/v concentration range display very good cell compatibility in two cell lines that are relevant to oral delivery, Caco2 cells that mimic the intestinal epithelium and HT29-MTX cells that produce mucin. Then, we evaluated the effect of crosslinking, nanoparticle concentration and thiolation on the permeability in vitro utilizing monolayers of (i) Caco2 and (ii) Caco2:HT29-MTX cells (9:1 cell number ratio). Results confirmed that the ability of the nanoparticles to cross Caco2 monolayer was affected by the crosslinking. In addition, thiolated nanoparticles interact more strongly with mucin, resulting in a decrease of the apparent permeability coefficient (Papp) compared to the pristine nanoparticles. Moreover, for all the nanoparticles, higher concentration resulted in lower Papp suggesting indicating that the transport pathways could undergo saturation.
REVIEW | doi:10.20944/preprints201912.0096.v1
Subject: Life Sciences, Other Keywords: brain connectivity; brain development; gut-brain axis; neurodevelopmental diseases; neuronal cytoarchitecture; neuroplasticity; regulatory T cells; serotonin (5-HT)
Online: 7 December 2019 (16:55:39 CET)
Our knowledge on the plastic functions of the serotonin (5-HT) receptor subtype 7 (5-HT7R) in the brain physiology and pathology considerably advanced in the last few years. A wealth of data show that the 5-HT7R is a key player in the establishment and remodeling of neuronal cytoarchitecture during development and in the mature brain, and its dysfunction is linked to neuropsychiatric and neurodevelopmental diseases. The involvement of this receptor in synaptic plasticity is further demonstrated by data showing that its activation allows to rescue long term potentiation (LTP) and long term depression (LTD) deficits in various animal models of neurodevelopmental diseases. In addition, it is becoming clear that the 5-HT7R is involved in inflammatory intestinal diseases, possibly playing a role in the gut-brain axis, and modulates the function of immune cells. In this review, we will mainly focus on recent findings on this receptor’s role in the structural and synaptic plasticity of the mammalian brain, although we will also illustrate novel aspects highlighted in gut and immune system.