Pyrrolylquinoxaline-2-One Derivative as a Potent Therapeutic Factor for Brain Trauma Rehabilitation

Traumatic brain injury (TBI) often causes massive brain cell death accompanied by the accumulation of toxic factors in interstitial and cerebrospinal fluids. The persistence of the damaged brain area is not transient and may occur within days and weeks. Chaperone Hsp70 is known for its cytoprotective and antiapoptotic activity, and thus, a therapeutic approach based on chemically induced Hsp70 expression may become a promising approach to lower post-traumatic complications. To simulate the processes of secondary damage, we used an animal model of TBI and a cell model based on the cultivation of target cells in the presence of cerebrospinal fluid (CSF) from injured rats. Here we present a novel low molecular weight substance, PQ-29, which induces the synthesis of Hsp70 and empowers the resistance of rat C6 glioma cells to the cytotoxic effect of rat cerebrospinal fluid taken from rats subjected to TBI. In an animal model of TBI, PQ-29 elevated the Hsp70 level in brain cells and significantly slowed the process of the apoptosis in acceptor cells in response to cerebrospinal fluid action. The compound was also shown to rescue the motor function of traumatized rats, thus proving its potential application in rehabilitation therapy after TBI.

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Analysis of the role of ICAM-3 as a costimulatory molecule through a cell model: CAMY-1 and CAMY-2 (two CD50-negative Jurkat-T cell clones)

Immunology Letters ◽

10.1016/s0165-2478(97)87030-7 ◽

1997 ◽

Vol 56 (1-3) ◽

pp. 52

Author(s):

C Vilardell

Keyword(s):

T Cell ◽

Cell Model ◽

Costimulatory Molecule ◽

T Cell Clones ◽

Cell Clones ◽

Jurkat T Cell ◽

A Cell

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INVERSE UNCERTAINTY QUANTIFICATION OF A CELL MODEL USING A GAUSSIAN PROCESS METAMODEL

International Journal for Uncertainty Quantification ◽

10.1615/int.j.uncertaintyquantification.2020033186 ◽

2020 ◽

Vol 10 (4) ◽

pp. 333-349

Author(s):

Kevin de Vries ◽

Anna Nikishova ◽

Benjamin Czaja ◽

Gábor Závodszky ◽

Alfons G. Hoekstra

Keyword(s):

Gaussian Process ◽

Uncertainty Quantification ◽

Cell Model ◽

A Cell

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Preincubation with Sn-complexes causes intensive intracellular retention of 99mTc in thyroid cells in vitro

Nuklearmedizin ◽

10.3413/nukmed-0450-11-12 ◽

2012 ◽

Vol 51 (05) ◽

pp. 179-185 ◽

Cited By ~ 3

Author(s):

M. Wendisch ◽

D. Aurich ◽

R. Runge ◽

R. Freudenberg ◽

J. Kotzerke ◽

...

Keyword(s):

Cell Model ◽

Low Energy ◽

Thyroid Cells ◽

Low Energy Electrons ◽

A Cell ◽

Vitro Model ◽

Uptake Studies ◽

Radiobiological Effects ◽

Radioactivity Retention

SummaryTechnetium radiopharmaceuticals are well established in nuclear medicine. Besides its well-known gamma radiation, 99mTc emits an average of five Auger and internal conversion electrons per decay. The biological toxicity of these low-energy, high-LET (linear energy transfer) emissions is a controversial subject. One aim of this study was to estimate in a cell model how much 99mTc can be present in exposed cells and which radiobiological effects could be estimated in 99mTc-overloaded cells. Methods: Sodium iodine symporter (NIS)- positive thyroid cells were used. 99mTc-uptake studies were performed after preincubation with a non-radioactive (cold) stannous pyro - phosphate kit solution or as a standard 99mTc pyrophosphate kit preparation or with pure pertechnetate solution. Survival curves were analyzed from colony-forming assays. Results: Preincubation with stannous complexes causes irreversible intracellular radioactivity retention of 99mTc and is followed by further pertechnetate influx to an unexpectedly high 99mTc level. The uptake of 99mTc pertechnetate in NIS-positive cells can be modified using stannous pyrophosphate from 3–5% to >80%. The maximum possible cellular uptake of 99mTc was 90 Bq/cell. Compared with nearly pure extracellular irradiation from routine 99mTc complexes, cell survival was reduced by 3–4 orders of magnitude after preincubation with stannous pyrophosphate. Conclusions: Intra cellular 99mTc retention is related to reduced survival, which is most likely mediated by the emission of low-energy electrons. Our findings show that the described experiments constitute a simple and useful in vitro model for radiobiological investigations in a cell model.

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Progesterone Suppresses Cholesterol Esterification in APP/PS1 mice and a cell model of Alzheimer’s Disease

Brain Research Bulletin ◽

10.1016/j.brainresbull.2021.05.020 ◽

2021 ◽

Author(s):

Wenjing Shi ◽

Hang Wu ◽

Sha Liu ◽

Zhigang Wu ◽

Honghai Wu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cell Model ◽

Cholesterol Esterification ◽

Model Of Alzheimer’S Disease ◽

A Cell

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Targeting CAR to the Peptide-MHC Complex Reveals Distinct Signaling Compared to That of TCR in a Jurkat T Cell Model

Cancers ◽

10.3390/cancers13040867 ◽

2021 ◽

Vol 13 (4) ◽

pp. 867

Author(s):

Ling Wu ◽

Joanna Brzostek ◽

Shvetha Sankaran ◽

Qianru Wei ◽

Jiawei Yap ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Cell Model ◽

Cell Receptor ◽

Target Cells ◽

Tcr Signaling ◽

Barr Virus ◽

Car T ◽

Epstein Barr ◽

Lower Magnitude

Chimeric antigen receptor T cells (CAR-T) utilize T cell receptor (TCR) signaling cascades and the recognition functions of antibodies. This allows T cells, normally restricted by the major histocompatibility complex (MHC), to be redirected to target cells by their surface antigens, such as tumor associated antigens (TAAs). CAR-T technology has achieved significant successes in treatment of certain cancers, primarily liquid cancers. Nonetheless, many challenges hinder development of this therapy, such as cytokine release syndrome (CRS) and the efficacy of CAR-T treatments for solid tumors. These challenges show our inadequate understanding of this technology, particularly regarding CAR signaling, which has been less studied. To dissect CAR signaling, we designed a CAR that targets an epitope from latent membrane protein 2 A (LMP2 A) of the Epstein–Barr virus (EBV) presented on HLA*A02:01. Because of this, CAR and TCR signaling can be compared directly, allowing us to study the involvement of other signaling molecules, such as coreceptors. This comparison revealed that CAR was sufficient to bind monomeric antigens due to its high affinity but required oligomeric antigens for its activation. CAR sustained the transduced signal significantly longer, but at a lower magnitude, than did TCR. CD8 coreceptor was recruited to the CAR synapse but played a negligible role in signaling, unlike for TCR signaling. The distinct CAR signaling processes could provide explanations for clinical behavior of CAR-T therapy and suggest ways to improve the technology.

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Gambogic acid protects LPS-induced apoptosis and inflammation in a cell model of neonatal pneumonia through the regulation of TrkA/Akt signaling pathway

BMC Pharmacology and Toxicology ◽

10.1186/s40360-021-00496-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Xu Gao ◽

Jingya Dai ◽

Guifang Li ◽

Xinya Dai

Keyword(s):

Western Blot ◽

Signaling Pathway ◽

Cell Model ◽

Akt Signaling ◽

Gambogic Acid ◽

Akt Signaling Pathway ◽

Western Blot Assay ◽

A Cell ◽

Induced Apoptosis ◽

Apoptosis And Inflammation

Abstract Objective In this work, we investigated the effects of gambogic acid (GA) on lipopolysaccharide (LPS)-induced apoptosis and inflammation in a cell model of neonatal pneumonia. Method Human WI-38 cells were maintained in vitro and incubated with various concentrations of GA to examine WI-38 survival. GA-preincubated WI-38 cells were then treated with LPS to investigate the protective effects of GA on LPS-induced death, apoptosis and inflammation. Western blot assay was utilized to analyze the effect of GA on tropomyosin receptor kinase A (TrkA) signaling pathway in LPS-treated WI-38 cells. In addition, human AKT serine/threonine kinase 1 (Akt) gene was knocked down in WI-38 cells to further investigate the associated genetic mechanisms of GA in protecting LPS-induced inflammation and apoptosis. Results Pre-incubating WI-38 cells with low and medium concentrations GA protected LPS-induced cell death, apoptosis and inflammatory protein productions of IL-6 and MCP-1. Using western blot assay, it was demonstrated that GA promoted TrkA phosphorylation and Akt activation in LPS-treated WI-38 cells. Knocking down Akt gene in WI-38 cells showed that GA-associated protections against LPS-induced apoptosis and inflammation were significantly reduced. Conclusions GA protected LPS-induced apoptosis and inflammation, possibly through the activations of TrkA and Akt signaling pathway. This work may broaden our understanding on the molecular mechanisms of human neonatal pneumonia.

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Positively Charged Lipid as Potential Tool to Influence the Fate of Ethosomes

Applied Sciences ◽

10.3390/app11157060 ◽

2021 ◽

Vol 11 (15) ◽

pp. 7060

Author(s):

Antonia Mancuso ◽

Maria Chiara Cristiano ◽

Massimo Fresta ◽

Daniele Torella ◽

Donatella Paolino

Keyword(s):

Cell Model ◽

Human Keratinocytes ◽

Skin Delivery ◽

Physico Chemical ◽

Cell Mortality ◽

Mean Size ◽

A Cell ◽

Negative Surface ◽

Cytotoxic Studies

Ethosomes® are one of the main deformable vesicles proposed to overcome the stratum corneum. They are composed of lecithin, ethanol and water, resulting in round vesicles characterized by a narrow size distribution and a negative surface charge. Taking into account their efficiency to deliver drugs into deeper skin layers, the current study was designed to evaluate the influence of different lipids on the physico-chemical features of traditional ethosomes in the attempt to influence their fate. Three lipids (DOPE, DSPE and DOTAP) were used for the study, but only DOTAP conferred a net positive charge to ethosomes, maintaining a narrow mean size lower than 300 nm and a good polydispersity index. Stability and in vitro cytotoxic studies have been performed using Turbiscan Lab analysis and MTT dye exclusion assay, respectively. Data recorded demonstrated the good stability of modified ethosomes and a reasonable absence of cell mortality when applied to human keratinocytes, NCTC 2544, which are used as a cell model. Finally, the best formulations were selected to evaluate their ability to encapsulate drugs, through the use of model compounds. Cationic ethosomes encapsulated oil red o and rhodamine b in amounts comparable to those recorded from conventional ethosomes (over 50%). Results recorded from this study are encouraging as cationic ethosomes may open new opportunities for skin delivery.

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Steam temperature regulation characteristics in a flexible ultra-supercritical boiler with a double reheat cycle based on a cell model

Energy ◽

10.1016/j.energy.2021.120701 ◽

2021 ◽

Vol 229 ◽

pp. 120701

Author(s):

Haojie Fan ◽

Wei Xu ◽

Jian Zhang ◽

Zhongxiao Zhang

Keyword(s):

Temperature Regulation ◽

Cell Model ◽

Steam Temperature ◽

A Cell

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PapRIV, a BV-2 microglial cell activating quorum sensing peptide

Scientific Reports ◽

10.1038/s41598-021-90030-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yorick Janssens ◽

Nathan Debunne ◽

Anton De Spiegeleer ◽

Evelien Wynendaele ◽

Marta Planas ◽

...

Keyword(s):

Quorum Sensing ◽

Cell Model ◽

Dependent Manner ◽

Communication Signals ◽

Gram Positive Bacteria ◽

A Cell ◽

Gastro Intestinal Tract

AbstractQuorum sensing peptides (QSPs) are bacterial peptides produced by Gram-positive bacteria to communicate with their peers in a cell-density dependent manner. These peptides do not only act as interbacterial communication signals, but can also have effects on the host. Compelling evidence demonstrates the presence of a gut-brain axis and more specifically, the role of the gut microbiota in microglial functioning. The aim of this study is to investigate microglial activating properties of a selected QSP (PapRIV) which is produced by Bacillus cereus species. PapRIV showed in vitro activating properties of BV-2 microglia cells and was able to cross the in vitro Caco-2 cell model and reach the brain. In vivo peptide presence was also demonstrated in mouse plasma. The peptide caused induction of IL-6, TNFα and ROS expression and increased the fraction of ameboid BV-2 microglia cells in an NF-κB dependent manner. Different metabolites were identified in serum, of which the main metabolite still remained active. PapRIV is thus able to cross the gastro-intestinal tract and the blood–brain barrier and shows in vitro activating properties in BV-2 microglia cells, hereby indicating a potential role of this quorum sensing peptide in gut-brain interaction.

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