scholarly journals In Vitro 1H NMR Metabolic Profiles of Liver, Brain, and Serum in Rats After Chronic Consumption of Alcohol

2021 ◽  
Author(s):  
Mariya S. Pravdivtseva ◽  
Oleg B. Shevelev ◽  
Vadim V. Yanshole ◽  
Mikhail P. Moshkin ◽  
Igor V. Koptyug ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
Ethanol Solution ◽  
The Body ◽  
Control Group ◽  
Water Control ◽  
Serum Samples ◽  
Wide Range ◽  
The Impact ◽  
The Brain

AbstractThe impact of alcohol on the body can be investigated with NMR spectroscopy in vitro, which can detect a wide range of metabolites but preparing samples includes tissue biopsy. Blood sampling is less invasive, but blood metabolic content might not reflect the changes occurring in other tissues. Thus, this study aimed to investigate the liver, brain, and serum metabolism and evaluate the link between tissues and serum metabolic content. Two experimental groups with ten outbred rats each were provided intragastrically with water (control group) and 50% ethanol solution (alcohol group) for 28 days. 1H NMR spectroscopy in vitro was performed on the brain cortex, liver, and serum samples. Student’s t test with Holm–Bonferroni correction was used to investigate significant differences between groups. Partial least-squares discriminant analysis (PLS-DA) and two-way ANOVA were performed to compare liver and serum, brain and serum. In all, 38, 37, and 21 metabolites were identified in the liver, brain, and serum samples, respectively. Significant differences for three metabolites were found in the liver (alanine, proline, and glutathione, p < 0.002) and four in serum (lactate, betaine, acetate, and formic acid, p < 0.002) were detected between the control and alcohol groups. The contents of glucose, betaine, and isoleucine were correlated (r > 0.65) between serum and liver samples. PLS-DA determined separation between all tissues (p < 0.001) and between control and alcohol groups only for liver and serum (p < 0.001). Alcohol had a more substantial effect on liver and serum metabolism than on the brain.

scholarly journals Detection of epistasis between ACTN3 and SNAP-25 with an insight towards gymnastic aptitude identification

2020 ◽  
Author(s):  
Łukasz Płóciennik ◽  
Jan Zaucha ◽  
Jan Maciej Zaucha ◽  
Krzysztof Łukaszuk ◽  
Marek Jóźwicki ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Regression Model ◽  
Characteristic Curve ◽  
Control Group ◽  
Logistic Regression Models ◽  
Berlin Academy ◽  
Chi Squared ◽  
The Impact ◽  
The Brain

AbstractIn this study, we performed an analysis of the impact of performance enhancing polymorphisms (PEPs) on gymnastic aptitude while considering epistatic effects. Seven PEPs (rs1815739, rs8192678, rs4253778, rs6265, rs5443, rs1076560, rs362584) were considered in a case (gymnasts) – control (sedentary individuals) setting. The study sample comprised of two athletes’ sets: 27 elite (aged 24.8 ± 2.1 years) and 46 sub-elite (aged 19.7 ± 2.4 years) sportsmen as well as a control group of 245 sedentary individuals (aged 22.5 ± 2.1 years). The DNA was derived from saliva and PEP alleles were determined by PCR, RT-PCR. Following Multifactor Dimensionality Reduction, logistic regression models were built. The synergistic effect for rs1815739 × rs362584 reached 5.43%. The rs1815739 × rs362584 epistatic regression model exhibited a good fit to the data (Chi-squared = 33.758, p ≈ 0) achieving a significant improvement in sportsmen identification over naïve guessing. The area under the receiver operating characteristic curve was 0.715 (Z-score = 38.917, p ≈ 0). In contrast, the additive ACTN3 – SNAP-25 logistic regression model has been verified as non-significant.We demonstrate that a gene involved in the differentiation of muscle architecture – ACTN3 and a gene, which plays an important role in the nervous system – SNAP-25 interact. From the perspective originally established by the Berlin Academy of Science in 1751, the matter of communication between the brain and muscles via nerves adopts molecular manifestations. Further in-vitro investigations are required to explain the molecular details of the rs1815739 – rs362584 interaction.

Influence of DAFS-25+polizon composition on blood and functional state of liver of steers at fattening

2020 ◽  
pp. 15-18
Author(s):  
Inna R. Kilmetova ◽  
◽  
Igor A. Rodin ◽  
Nazira I. Khayrullina ◽  
Nikolay G. Fenchenko ◽  
...  
Keyword(s):  
Functional State ◽  
White Blood Cells ◽  
Live Weight ◽  
The Body ◽  
Farm Animals ◽  
Control Group ◽  
Standard Diet ◽  
The Impact ◽  
Experimental Group ◽  
Stimulation Of

Summary. The disbalanced feeding and the uneven distribution of micro- and macroelements in the environment leads to a trace element, in particular hypomelanosis. To accelerate the growth and preservation of young farm animals include in the diet of various biological additives and drugs, which include selenium. For stimulation of weight gain in the livestock industry, as well as for the prevention and treatment of pathological processes in addition to micro - and macrouse amino acids, primarily methionine. The aim of this work was to study the influence of composition of DAFS-25+Polizon on morpho-biochemical parameters of blood and functional state of the liver in fattening bulls of black-motley breed in the conditions of the Republic of Bashkortostan. Experiments using were conducted on bull-calves of black-motley breed of the properties in the properties age from 6 to 15 months. The first experimental group during the experiment was additionally given the composition of DAFS-25+Polizon at a dose of 2 mg/kg, the animals of the control group received a standard diet. To assess the impact of the composition DAFS-25+Polizon on metabolism cattle studied morphological and biochemical indicators of blood and conducted histological examination of the liver. It is established that the use of the composition of DAFS-25+Polizon at a dose of 2 mg/kg increases the number of erythrocytes and hemoglobin in the experimental group and reduces the amount of white blood cells. The serum content of total protein, phosphorus and calcium increases in the group of experimental animals. Microscopic examination of the liver revealed no changes in the structure of the organ and hepatocytes in the experimental group, whereas in the control group hemodynamic disorders and dystrophic changes in liver cells were observed. Thus, the use of the composition DAFS-25+Polizon at a dose of 2 mg/kg of live weight in fattening bulls black-and-white breed contributes to the increase of redox processes in the body, stimulation of metabolism, prevent the development of liver disorders of cellular mechanisms of metabolism, optimizes the structure of the liver, which generally provides higher productivity.

scholarly journals 695 Oral delivery of a microbial extracellular vesicle induces potent anti-tumor immunity in mice

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A737-A737
Author(s):  
Loise Francisco-Anderson ◽  
Loise Francisco-Anderson ◽  
Mary Abdou ◽  
Michael Goldberg ◽  
Erin Troy ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Extracellular Vesicles ◽  
Tumor Immunity ◽  
Extracellular Vesicle ◽  
The Body ◽  
Checkpoint Inhibition ◽  
Small Intestinal ◽  
The Impact

BackgroundThe small intestinal axis (SINTAX) is a network of anatomic and functional connections between the small intestine and the rest of the body. It acts as an immunosurveillance system, integrating signals from the environment that affect physiological processes throughout the body. The impact of events in the gut in the control of tumor immunity is beginning to be appreciated. We have previously shown that an orally delivered single strain of commensal bacteria induces anti-tumor immunity preclinically via pattern recognition receptor-mediated activation of innate and adaptive immunity. Some bacteria produce extracellular vesicles (EVs) that share molecular content with the parent bacterium in a particle that is roughly 1/1000th the volume in a non-replicating form. We report here an orally-delivered and gut-restricted bacterial EV which potently attenuates tumor growth to a greater extent than whole bacteria or checkpoint inhibition.MethodsEDP1908 is a preparation of extracellular vesicles produced by a gram-stain negative strain of bacterium of the Oscillospiraceae family isolated from a human donor. EDP1908 was selected for its immunostimulatory profile in a screen of EVs from a range of distinct microbial strains. Its mechanism of action was determined by ex vivo analysis of the tumor microenvironment (TME) and by in vitro functional studies with murine and human cells.ResultsOral treatment of tumor-bearing mice with EDP1908 shows superior control of tumor growth compared to checkpoint inhibition (anti-PD-1) or an intact microbe. EDP1908 significantly increased the percentage of IFNγ and TNF producing CD8+ CTLs, NK cells, NKT cells and CD4+ cells in the tumor microenvironment (TME). EDP1908 also increased tumor-infiltrating dendritic cells (DC1 and DC2). Analysis of cytokines in the TME showed significant increases in IP-10 and IFNg production in mice treated with EDP1908, creating an environment conducive to the recruitment and activation of anti-tumor lymphocytes.ConclusionsThis is the first report of striking anti-tumor effects of an orally delivered microbial extracellular vesicle. These data point to oral EVs as a new class of immunotherapeutic drugs. They are particularly effective at harnessing the biology of the small intestinal axis, acting locally on host cells in the gut to control distal immune responses within the TME. EDP1908 is in preclinical development for the treatment of cancer.Ethics ApprovalPreclinical murine studies were conducted under the approval of the Avastus Preclinical Services’ Ethics Board. Human in vitro samples were attained by approval of the IntegReview Ethics Board; informed consent was obtained from all subjects.

scholarly journals Miniaturization and Automation of a Human In Vitro Blood–Brain Barrier Model for the High-Throughput Screening of Compounds in the Early Stage of Drug Discovery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 892
Author(s):  
Elisa L. J. Moya ◽  
Elodie Vandenhaute ◽  
Eleonora Rizzi ◽  
Marie-Christine Boucau ◽  
Johan Hachani ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Blood Brain Barrier ◽  
Early Stage ◽  
Molecular Transport ◽  
Brain Barrier ◽  
Blood Brain ◽  
Cns Drugs ◽  
The Impact ◽  
The Brain

Central nervous system (CNS) diseases are one of the top causes of death worldwide. As there is a difficulty of drug penetration into the brain due to the blood–brain barrier (BBB), many CNS drugs treatments fail in clinical trials. Hence, there is a need to develop effective CNS drugs following strategies for delivery to the brain by better selecting them as early as possible during the drug discovery process. The use of in vitro BBB models has proved useful to evaluate the impact of drugs/compounds toxicity, BBB permeation rates and molecular transport mechanisms within the brain cells in academic research and early-stage drug discovery. However, these studies that require biological material (animal brain or human cells) are time-consuming and involve costly amounts of materials and plastic wastes due to the format of the models. Hence, to adapt to the high yields needed in early-stage drug discoveries for compound screenings, a patented well-established human in vitro BBB model was miniaturized and automated into a 96-well format. This replicate met all the BBB model reliability criteria to get predictive results, allowing a significant reduction in biological materials, waste and a higher screening capacity for being extensively used during early-stage drug discovery studies.

scholarly journals Effects of Vitrification on the Blastocyst Gene Expression Profile in a Porcine Model

2021 ◽  
Vol 22 (3) ◽  
pp. 1222
Author(s):  
Cristina Cuello ◽  
Cristina A. Martinez ◽  
Josep M. Cambra ◽  
Inmaculada Parrilla ◽  
Heriberto Rodriguez-Martinez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Analysis ◽  
Survival Rates ◽  
Control Group ◽  
P Value ◽  
Transcriptome Profile ◽  
Embryo Viability ◽  
The Impact

This study was designed to investigate the impact of vitrification on the transcriptome profile of blastocysts using a porcine (Sus scrofa) model and a microarray approach. Blastocysts were collected from weaned sows (n = 13). A total of 60 blastocysts were vitrified (treatment group). After warming, vitrified embryos were cultured in vitro for 24 h. Non-vitrified blastocysts (n = 40) were used as controls. After the in vitro culture period, the embryo viability was morphologically assessed. A total of 30 viable embryos per group (three pools of 10 from 4 different donors each) were subjected to gene expression analysis. A fold change cut-off of ±1.5 and a restrictive threshold at p-value < 0.05 were used to distinguish differentially expressed genes (DEGs). The survival rates of vitrified/warmed blastocysts were similar to those of the control (nearly 100%, n.s.). A total of 205 (112 upregulated and 93 downregulated) were identified in the vitrified blastocysts compared to the control group. The vitrification/warming impact was moderate, and it was mainly related to the pathways of cell cycle, cellular senescence, gap junction, and signaling for TFGβ, p53, Fox, and MAPK. In conclusion, vitrification modified the transcriptome of in vivo-derived porcine blastocysts, resulting in minor gene expression changes.

scholarly journals EXPERIMENTS ON THE SURVIVAL OF THE FEBRILE HERPETIC AND ALLIED VIRUSES IN VITRO

1924 ◽  
Vol 39 (4) ◽  
pp. 533-542 ◽  
Author(s):  
James E. McCartney
Keyword(s):  
Brain Tissue ◽  
Secondary Infection ◽  
The Body ◽  
Herpes Viruses ◽  
Encephalitis Lethargica ◽  
Aerobic Conditions ◽  
Maximum Period ◽  
Suitable Technique ◽  
The Brain

These studies fail to confirm the statements previously made that microorganisms of the class of the globoid bodies of poliomyelitis may be cultivated in the Smith-Noguchi medium from the so called virus of encephalitis lethargica. They show equally that the herpes virus does not multiply in this medium. The experiments indicate, moreover, that the medium is unfavorable to the survival of the virus, while ordinary broth under aerobic conditions is more favorable for maintaining the activity of both the encephalitic and the herpes viruses. Probably no multiplication of either takes place in the latter medium but merely a survival, and for a maximum period of 6 days in the broth itself, and 12 days in the fragment of brain tissue immersed in the broth. Finally, it has been shown that with a suitable technique the viruses can be passed from the brain of one rabbit to that of another through a long series without contamination with cocci or other common bacterial forms. Hence we regard all reports of the finding of ordinary bacteria in the brain of cases of epidemic or lethargic encephalitis as instances of mixed or secondary infection arising during life, or examples of postmortem invasion of the body, or of faulty technique at the autopsy.

scholarly journals In VivoEfficacy of Anuran Trypsin Inhibitory Peptides against Staphylococcal Skin Infection and the Impact of Peptide Cyclization

2015 ◽  
Vol 59 (4) ◽  
pp. 2113-2121 ◽  
Author(s):  
U. Malik ◽  
O. N. Silva ◽  
I. C. M. Fensterseifer ◽  
L. Y. Chan ◽  
R. J. Clark ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Cyclic Peptide ◽  
Sequence Similarity ◽  
Infection Model ◽  
Content Type ◽  
Wide Range ◽  
Inhibitory Activities ◽  
The Impact

ABSTRACTStaphylococcus aureusis a virulent pathogen that is responsible for a wide range of superficial and invasive infections. Its resistance to existing antimicrobial drugs is a global problem, and the development of novel antimicrobial agents is crucial. Antimicrobial peptides from natural resources offer potential as new treatments against staphylococcal infections. In the current study, we have examined the antimicrobial properties of peptides isolated from anuran skin secretions and cyclized synthetic analogues of these peptides. The structures of the peptides were elucidated by nuclear magnetic resonance (NMR) spectroscopy, revealing high structural and sequence similarity with each other and with sunflower trypsin inhibitor 1 (SFTI-1). SFTI-1 is an ultrastable cyclic peptide isolated from sunflower seeds that has subnanomolar trypsin inhibitory activity, and this scaffold offers pharmaceutically relevant characteristics. The five anuran peptides were nonhemolytic and noncytotoxic and had trypsin inhibitory activities similar to that of SFTI-1. They demonstrated weakin vitroinhibitory activities againstS. aureus, but several had strong antibacterial activities againstS. aureusin anin vivomurine wound infection model. pYR, an immunomodulatory peptide fromRana sevosa, was the most potent, with complete bacterial clearance at 3 mg · kg−1. Cyclization of the peptides improved their stability but was associated with a concomitant decrease in antimicrobial activity. In summary, these anuran peptides are promising as novel therapeutic agents for treating infections from a clinically resistant pathogen.

THE UPTAKE OF TRITIATED LYSINE VASOPRESSIN BY RAT AND PIG PITUITARY NEURAL LOBES IN VITRO

1971 ◽  
Vol 50 (4) ◽  
pp. 669-677 ◽  
Author(s):  
B. A. EDWARDS
Keyword(s):  
Tap Water ◽  
Exchange Chromatography ◽  
Control Group ◽  
Breakdown Product ◽  
Nacl Solution ◽  
Water Control ◽  
Neural Lobe ◽  
Lysine Vasopressin ◽  
And Control

SUMMARY Uptake of tritiated lysine vasopressin ([3H]LVP) was studied in halved neural lobes of rats (which had been given either tap water (control group) or 2% (w/v) NaCl solution as drinking water for 4 days) as well as in slices of pig neural lobe. Uptake of radioactivity into the neural lobes was shown but analysis of the extracts of incubated lobes of both species by ion exchange chromatography showed that very little of it remained in the tissue as hormone. In addition, some radioactivity was associated with trichloroacetic acid-insoluble proteins. After 90 min of incubation, and after correction for the breakdown, the uptake of unchanged [3H]LVP, expressed as a tissue: medium ratio, was 0·14 ± 0·04 and 0·09 ± 0·03 (mean ± s.e.m.) for the saline-treated and control rats respectively, while the tissue: medium ratios for the breakdown product(s) were 6·47 ± 0·45 and 5·50 ± 0·36. The results suggest uptake of [3H]LVP into the cell with almost complete intracellular breakdown of the hormone.

scholarly journals Hyaluronan and the Fascial Frontier

2021 ◽  
Vol 22 (13) ◽  
pp. 6845
Author(s):  
Rebecca L. Pratt
Keyword(s):  
Nerve Fibers ◽  
The Body ◽  
Water Volume ◽  
Cell Behavior ◽  
Connective Tissues ◽  
Wide Range ◽  
The World ◽  
Extracellular Microenvironment ◽  
The Impact ◽  
The Relationship

The buzz about hyaluronan (HA) is real. Whether found in face cream to increase water volume loss and viscoelasticity or injected into the knee to restore the properties of synovial fluid, the impact of HA can be recognized in many disciplines from dermatology to orthopedics. HA is the most abundant polysaccharide of the extracellular matrix of connective tissues. HA can impact cell behavior in specific ways by binding cellular HA receptors, which can influence signals that facilitate cell survival, proliferation, adhesion, as well as migration. Characteristics of HA, such as its abundance in a variety of tissues and its responsiveness to chemical, mechanical and hormonal modifications, has made HA an attractive molecule for a wide range of applications. Despite being discovered over 80 years ago, its properties within the world of fascia have only recently received attention. Our fascial system penetrates and envelopes all organs, muscles, bones and nerve fibers, providing the body with a functional structure and an environment that enables all bodily systems to operate in an integrated manner. Recognized interactions between cells and their HA-rich extracellular microenvironment support the importance of studying the relationship between HA and the body’s fascial system. From fasciacytes to chronic pain, this review aims to highlight the connections between HA and fascial health.

The impact of SARS-Cov-2 on the Nervous system and Mental Health

2021 ◽  
Vol 19 ◽  
Author(s):  
Mohamed Said Boulkrane ◽  
Victoria Ilina ◽  
Roman Melchakov ◽  
Mikhail Arisov ◽  
Julia Fedotova ◽  
...  
Keyword(s):  
Mental Health ◽  
Respiratory Illness ◽  
World Health ◽  
Current Review ◽  
Wide Range ◽  
Serious Disease ◽  
Health Organization ◽  
The Impact ◽  
The Brain ◽  
Severe Acute Respiratory Illness

: The World Health Organization declared the pandemic situation caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) in March 2020, but the detailed pathophysiological mechanisms of Coronavirus disease 2019 (COVID-19) are not yet completely understood. Therefore, to date, few therapeutic options are available for patients with mild-moderate or serious disease. In addition to systemic and respiratory symptoms, several reports have documented various neurological symptoms and impairments of mental health. The current review aims to provide the available evidence about the effects of SARS-CoV-2 infection on mental health. The present data suggest that SARS-CoV-2 produces a wide range of impairments and disorders of the brain. However, a limited number of studies investigated the neuroinvasive potential of SARS-CoV-2. Although the main features and outcomes of COVID-19 are linked to severe acute respiratory illness. The possible damages on the brain should be considered, too.

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