Computational Modeling and Simulations in Life Sciences

2013 ◽  
Vol 2 (2) ◽  
pp. 1-7
Author(s):  
Athina Lazakidou ◽  
Maria Petridou ◽  
Dimitra Iliopoulou
Keyword(s):  
Mathematical Modeling ◽  
Protein Expression ◽  
Medical History ◽  
Human Life ◽  
Life Sciences ◽  
Life Time ◽  
Experimental Methods ◽  
Modeling And Simulations ◽  
Molecular Fingerprints ◽  
Tissue Samples

Billions of math operations per second may be performed by computers anymore. Obviously, a human life-time would be needed to do the same number of computations. When used in medication, the groundbreaking potential of the mathematical modeling approach is obvious. In Medicine, mathematical modeling is able to vastly improve both drug creation and clinic technology. Progress in technology and the development of new experimental methods has had a noteworthy effect on the study of disease. This has raised new researching opportunities, such as: gathering in-depth ‘molecular fingerprints’ from patients carrying information, for example, on genotype, gene or protein expression, or metabolism levels; studying intracellular processes in living and diseased tissue through the control of gene activity inside the cells; and creating understandable illness-specific databases that include both patients’ medical history with laboratory and clinical data in addition to storing useful tissue samples. In this article, the authors attempt to provide the readers with a view of current and future use of mathematical modeling in medicine.

scholarly journals TOP2A is overexpressed and is a therapeutic target for adrenocortical carcinoma

2013 ◽  
Vol 20 (3) ◽  
pp. 361-370 ◽  
Author(s):  
Meenu Jain ◽  
Lisa Zhang ◽  
Mei He ◽  
Ya-Qin Zhang ◽  
Min Shen ◽  
...  
Keyword(s):  
Protein Expression ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Antiproliferative Activity ◽  
Adrenocortical Carcinoma ◽  
Cellular Proliferation ◽  
Locally Advanced ◽  
Tissue Samples ◽  
Anchorage Independent Growth ◽  
Mrna And Protein Expression

Adrenocortical carcinoma (ACC) is a rare but aggressive malignancy with no effective therapy for patients with unresectable disease. The aim of the current study was i) to evaluate TOP2A expression and function in human adrenocortical neoplasm and ACC cells and ii) to determine the anticancer activity of agents that target TOP2A. TOP2A mRNA and protein expression levels were evaluated in 112 adrenocortical tissue samples (21 normal adrenal cortex, 80 benign adrenocortical tumors, and 11 ACCs). In vitro siRNA knockdown of TOP2A in ACC cell lines (NCI-H295R and SW13) was used to determine its effect on cellular proliferation, cell cycle, anchorage-independent growth, and cellular invasion. We screened 14 TOP2A inhibitors for their anticancer activity in ACC cells. TOP2A mRNA and protein expression was significantly higher in ACC than in benign and normal adrenocortical tissue samples (P<0.05). Knockdown of TOP2A gene expression in ACC cell lines significantly decreased cell proliferation, anchorage-independent growth, and invasion (P<0.05). A screening assay in NCI-H295R cells showed that 11 of 14 TOP2A inhibitors had antiproliferative activity, 5 of the 14 TOP2A inhibitors had a higher antiproliferative activity than mitotane, and aclarubicin was the agent with the highest activity. Aclarubicin was validated to significantly decrease proliferation and tumor spheroid size in both NCI-H295R and SW13 ACC cell lines (P<0.05). Our results suggest that TOP2A is overexpressed in ACC, regulates cellular proliferation and invasion in ACC cells, and is an attractive target for ACC therapy. Of the TOP2A inhibitors screened, aclarubicin is a good candidate agent to test in future clinical trials for patients with locally advanced and metastatic ACC.

scholarly journals Determination of CYP450 Expression Levels in the Human Small Intestine by Mass Spectrometry-Based Targeted Proteomics

2021 ◽  
Vol 22 (23) ◽  
pp. 12791
Author(s):  
Alexia Grangeon ◽  
Valérie Clermont ◽  
Azemi Barama ◽  
Fleur Gaudette ◽  
Jacques Turgeon ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Small Intestine ◽  
Protein Expression ◽  
Mrna Levels ◽  
Targeted Proteomics ◽  
Tissue Samples ◽  
Human Organ ◽  
Expression Levels ◽  
Protein Levels ◽  
Human Small Intestine

The human small intestine can be involved in the first-pass metabolism of drugs. Under this condition, members of the CYP450 superfamily are expected to contribute to drug presystemic biotransformation. The aim of this study was to quantify protein expression levels of 16 major CYP450 isoforms in tissue obtained from nine human organ donors in seven subsections of the small intestine, i.e., duodenum (one section, N = 7 tissue samples), jejunum (three subsections (proximal, mid and distal), N = 9 tissue samples) and ileum (three subsections, (proximal, mid and distal), N = 9 tissue samples), using liquid chromatography tandem mass spectrometry (LC-MS/MS) based targeted proteomics. CYP450 absolute protein expression levels were compared to mRNA levels and enzyme activities by using established probe drugs. Proteins corresponding to seven of sixteen potential CYP450 isoforms were detected and quantified in various sections of the small intestine: CYP2C9, CYP2C19, CYP2D6, CYP2J2, CYP3A4, CYP3A5 and CYP4F2. Wide inter-subject variability was observed, especially for CYP2D6. CYP2C9 (p = 0.004) and CYP2C19 (p = 0.005) expression levels decreased along the small intestine. From the duodenum to the ileum, CYP2J2 (p = 0.001) increased, and a trend was observed for CYP3A5 (p = 0.13). CYP3A4 expression was higher in the jejunum than in the ileum (p = 0.03), while CYP4F2 expression was lower in the duodenum compared to the jejunum and the ileum (p = 0.005). CYP450 protein levels were better correlated with specific isoform activities than with mRNA levels. This study provides new data on absolute CYP450 quantification in human small intestine that could improve physiologically based pharmacokinetic models. These data could better inform drug absorption profiles while considering the regional expression of CYP450 isoforms.

scholarly journals Plasma Level and Expression of Visfatin in the Porcine Hypothalamus During the Estrous Cycle and Early Pregnancy

2020 ◽  
Author(s):  
Tadeusz Kaminski ◽  
Marta Kiezun ◽  
Ewa Zaobidna ◽  
Kamil Dobrzyń ◽  
Barbara Wasilewska ◽  
...  
Keyword(s):  
Protein Expression ◽  
Blood Plasma ◽  
Estrous Cycle ◽  
Early Pregnancy ◽  
Energy Homeostasis ◽  
Plasma Concentrations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tissue Samples ◽  
Hormone Synthesis ◽  
Gene And Protein Expression

Abstract BackgroundVisfatin exists in two forms: the intracellular form which is a rate limiting enzyme engaged in nicotinamide adenine dinucleotide biosynthesis and the extracellular form considered as an adipokine, produced mainly by the adipose tissue. Visfatin could be an energy sensor involved in regulating female fertility, which creates a hormonal link integrating the control of energy homeostasis and reproduction. MethodsThe study compares the expression levels of visfatin gene (quantitative real time PCR) and protein (Western blotting and fluorescent immunohistochemistry) in the selected areas of the porcine hypothalamus responsible for gonadotropin releasing hormone synthesis: the mediobasal hypothalamus (MBH) and preoptic area (POA), and visfatin concentrations in the blood plasma (enzyme-linked immunosorbent assay). The tissue samples were harvested from gilts on days 2-3, 10-12, 14-16 and 17-19 of the estrous cycle, and on days 10-11, 12-13, 15-16, 27-28 of pregnancy. Differences between groups were analyzed by one-way ANOVA followed by Tukey’s post hoc test. ResultsDuring the estrous cycle, visfatin mRNA expression in the MBH was higher on days 2-3 and 17-19, while the visfatin protein concentration on days 17-19. During early pregnancy, the most pronounced gene and protein expression in the MBH was found on days 15-16 and 10-11, respectively. In the POA during the estrous cycle, visfatin gene expression was the highest on days 17-19, and the protein level of visfatin on days 14-16. During early pregnancy, the highest expression of visfatin gene in the POA was observed on days 15-16, whereas the protein concentrations on days 27-28. Blood plasma concentrations of visfatin during the estrous cycle were higher on days 2-3 in relation to other studied phases of the cycle. During early pregnancy, the highest visfatin contents in the blood plasma were observed on days 12-13. Visfatin gene and protein expression in MBH and POA, and visfatin plasma concentrations differed during early pregnancy in relation to days 10-12 of the cycle. ConclusionsThis study demonstrated visfatin expression in the porcine hypothalamus and its dependence on hormonal milieu related to the estrous cycle and early pregnancy.

scholarly journals Extracellular matrix changes in colorectal carcinoma and correlation with lymph node metastasis

2021 ◽  
Author(s):  
Thérèse Rachell Theodoro ◽  
Rodrigo Lorenzetti Serrano ◽  
Karine Corcione Turke ◽  
Sarhan Sydney Saad ◽  
Marcelo Augusto Fontenelle Ribeiro Junior ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Colorectal Carcinoma ◽  
Protein Expression ◽  
Cross Sectional ◽  
Tissue Samples ◽  
Node Metastasis ◽  
Mrna And Protein Expression ◽  
Neoplastic Tissues

AbstractThe process of proliferation and invasion of tumor cells depends on changes in the extracellular matrix (ECM) through the activation of enzymes and alterations in the profile of ECM components. We aimed to investigate the mRNA and protein expression of ECM components such as heparanase (HPSE), heparanase-2 (HPSE2), matrix metalloproteinase-9 (MMP-9), and syndecan-1 (SYND1) in neoplastic and non-neoplastic tissues of patients with colorectal carcinoma (CRC). It is a cross-sectional study in which twenty-four adult patients that had CRC were submitted to resection surgery. We analyzed the expression of HPSE, HPSE2, MMP-9, and SYND1 by quantitative RT-PCR and immunohistochemistry. Differing from most of the studies that compare the mRNA expression between tumor samples and non-neoplastic tissues, we decided to investigate whether variations exist in the expression of the ECM components between the affected tissue and nontumoral tissue collected from the same patient with CRC. We removed both tissue samples immediately after the surgical resection of CRC. The data showed higher mRNA and protein expression of HPSE2 (P = 0.0058), MMP-9 (P = 0.0268), and SYND1 (P = 0.0002) in tumor samples compared to the non-neoplastic tissues, while there was only an increase in the level of HPSE protein in tumor tissues. A greater expression of HPSE2 was observed in patients with lymph node metastasis (P = 0.048), suggesting that such protein can be a marker of lymph node metastasis in CRC.

scholarly journals The Application of Mathematical Modeling in Building of Social and Environmental Competence of Future Technical Specialists in the Health Care Area

2020 ◽  
Vol 26 ◽  
pp. 00036
Author(s):  
Elena Chekanushkina ◽  
Elena Ryabinova ◽  
Diera Pirova
Keyword(s):  
Mathematical Modeling ◽  
Health Care ◽  
Physical Education ◽  
Human Life ◽  
Interdisciplinary Teams ◽  
Quantitative Composition ◽  
Professional Activities ◽  
Research Activities ◽  
Interdisciplinary Knowledge ◽  
Environmental Events

The paper considers building of social and environmental competence of future technical specialists. It shows that health care competence building is becoming more pressing issue each year. Behavioral patterns are formed in the process of training, upbringing and observing people around. They allow forming the ability or readiness to use the acquired interdisciplinary knowledge in professional activities related to health, safety of human life, as well as in the process of studying such disciplines as the “Elective Courses on Physical Education and Sports” and “Physical Education and Sports”. The patterns offer the possibility to develop a behavioral socio-ecological algorithm efficiently. In pedagogy and didactic processes, mathematical modeling is aimed at clarifying phenomena that are not amenable to experiment or unobservable as well as patterns of education for the development of efficient teaching technologies. The paper considers mathematical descriptions of the models for formation, interaction and efficiency of various target groups exemplified by Nordic walking, indoor soccer and interdisciplinary teams. It shows the dependence of student group population on an activity and quantitative composition of potential participants of sports group. This mathematical model is also applicable for building socioecological competence of future technical specialists in the framework of participation in interdisciplinary projects, research activities, Olympiads, social and environmental events that contribute to the assimilation of socio-ecological patterns of behavior, the condition for the development of which is the unity of cognitive and practical activities in the process of studying at the university. The paper includes the interim experiment results.

Human life sciences research on the Mir space station

1999 ◽  
Author(s):  
Scott Smith ◽  
Boris Morukov
Keyword(s):  
Human Life ◽  
Life Sciences ◽  
Space Station

scholarly journals ACE2 Expression in Lungs of Severe COVID-19 Infection: A Study on Minimally Invasive Post- mortem Tissue Samples

2021 ◽  
Author(s):  
Atish Gheware ◽  
Animesh Ray ◽  
Deeksha Rana ◽  
Prashant Bajpai ◽  
Aruna Nambirajan ◽  
...  
Keyword(s):  
Protein Expression ◽  
Virus Disease ◽  
Diffuse Alveolar Damage ◽  
Severe Infection ◽  
Host Protein ◽  
Post Mortem ◽  
Tissue Samples ◽  
Expression Levels ◽  
Increased Risk ◽  
Lung Biopsies

Abstract Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters and multiplies within cells. The level of ACE2 expression in the lung is hypothesised to correlate with an increased risk of severe infection and complications in COVID-19 (COrona VIrus Disease 2019). To test this hypothesis, we compared the protein expression status of ACE2 by immunohistochemistry (IHC) in post-mortem lung samples of patients who died of severe COVID-19 and lung samples obtained from non-COVID-9 patients for other indications. IHC for CD61 and CD163 were performed for assessment of platelet-rich microthrombi and macrophages, respectively. IHC for SARS-CoV-2 viral antigen was also performed. Quantification of immunostaining, random sampling, and correlation analysis was used to substantiate the morphologic findings. Our results show that among a total of 44 COVID-19 post-mortem lung tissues and 15 lung biopsies in non-COVID-19 patients included, ACE2 protein expression was significantly higher in COVID-19 patients than in controls, regardless of sample size. Histomorphology in COVID-19 lungs showed diffuse alveolar damage (DAD), acute bronchopneumonia, and acute lung injury with SARS-CoV-2 viral protein detected in a subset of cases. ACE2 expression levels positively correlated with increased expression levels of CD61 and CD163. In conclusion, our results show significantly higher ACE2 protein expression in severe COVID-19 disease, correlating with increased macrophage infiltration and microthrombi, suggesting a pathobiological role in disease severity.

scholarly journals Automated Spatially Targeted Optical Micro Proteomics (AutoSTOMP) 2.0 identifies proteins enriched within inflammatory lesions in tissue sections and human clinical biopsies.

2021 ◽  
Author(s):  
BOCHENG YIN ◽  
Laura R Caggiano ◽  
Rung-Chi Li ◽  
Emily McGowan ◽  
Jeffery W. Holmes ◽  
...  
Keyword(s):  
Protein Expression ◽  
Cell Biology ◽  
Cell Types ◽  
Specific Cell ◽  
Fixed Tissue ◽  
Tissue Samples ◽  
Novel Approach ◽  
Esophageal Tissue ◽  
Inflammatory Proteins

Tissue microenvironment properties like blood flow, extracellular matrix or proximity to immune infiltrate are important regulators of cell biology. However, methods to study regional protein expression in context of the native tissue environment are limited. To address this need we have developed a novel approach to visualize, purify and measure proteins in situ using Automated Spatially Targeted Optical Micro Proteomics (AutoSTOMP) 2.0. We previously implemented AutoSTOMP to identify proteins localized to the vacuoles of obligate intracellular microbes at the 1-2 μm scale within infected host cells1. Here we report custom codes in SikuliX to specify regions of heterogeneity in a tissue section and then biotin tag and identify proteins belonging to specific cell types or structures within those regions. To enrich biotinylated targets from fixed tissue samples we developed a biochemical protocol compatible with LC-MS. These tools were applied to a) identify inflammatory proteins expressed by CD68+ macrophages in rat cardiac infarcts and b) characterize inflammatory proteins enriched in IgG4+ lesions in esophageal tissue. These data indicate that AutoSTOMP is a flexible approach to determine regional protein expression in situ on a range of primary tissues and clinical biopsies where current tools are limited.

scholarly journals Early upregulation of AR and steroidogenesis enzyme expression after 3 months of androgen-deprivation therapy.

2020 ◽  
Author(s):  
Agus Rizal A.H. Hamid ◽  
Harun Kusuma Putra ◽  
Ningrum Paramita Sari ◽  
Putri Diana ◽  
Saras Serani Sesari ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Androgen Deprivation Therapy ◽  
Androgen Deprivation ◽  
Relative Gene Expression ◽  
Steroidogenic Enzymes ◽  
Tissue Samples ◽  
Formalin Fixed Paraffin Embedded ◽  
Ffpe Tissues ◽  
Relative Gene

Abstract Background: Androgen deprivation therapy (ADT) is a standard treatment for advanced prostate cancer (PCa). However, PCa recurrence and progression rates during ADT are high. Until now, there has been no evidence regarding when progression begins. This study evaluated the gene expression of intraprostatic androgen receptor (AR) and steroidogenic enzymes in the early stages of ADT. Methods: Prostate tissue samples were taken from PCa patients with urinary retention who received ADT (ADT-PCa; n=10) and were further subgrouped into ADT ≤12 months (n=4) and ADT >12 months (n=6). The ADT-PCa tissues were then compared with BPH (n=12) and primary (no treatment) PCa tissues (n=16). mRNA for gene expression analysis of AR and steroidogenic enzymes was extracted from formalin-fixed paraffin embedded (FFPE) tissues and analyzed by real-time PCR. Protein expression was evaluated by immunohistochemistry with specific antibodies. Results: AR gene expression was higher in the ADT-PCa group than in the BPH or primary PCa group. Both the ADT ≤12 and > 12 months subgroups had significantly higher relative gene expression levels of AR (p<0.01 and 0.03, respectively) than the primary PCa group. In the ADT-PCa group, AR protein expression showed an increasing trend in the ADT ≤12 months subgroup and was significantly elevated in the ADT >12 months subgroup compared with the PCa group (100%; p <0.01). Half (50%) of the patients in the ADT ≤12 months subgroup were found to have upregulation of AR, and one showed upregulation beginning at 3 months of ADT. A trend toward elevated relative gene expression of SRD5A3 was also apparent in the ADT groups. Conclusion: AR and steroidogenic enzymes are upregulated in ADT-PCa patients as early as 3 months, without PSA elevation. Steroidogenic enzymes, particularly SRD5A3, were also upregulated before PSA rose.

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