scholarly journals Computational studies of anti-cancer Aurein peptides

2015 ◽  
Author(s):  
◽  
Neha Manhas
Keyword(s):  
Three Dimensional ◽  
Underlying Mechanism ◽  
Computational Method ◽  
Amphibian Skin ◽  
Comprehensive Information ◽  
Explicit Solvent ◽  
Conformational Preferences ◽  
Anti Cancer ◽  
Implicit And Explicit ◽  
External Stimuli

Peptide folding is a very complicated and dynamic process taking place in all living systems. The understanding of a bioactive conformation of the peptides is very important to understand their biological functions and underlying mechanism of action. However, the high flexible nature of peptides makes this process difficult as they can adopt thousands of conformations within the fraction of a second. The usage of experimental techniques in the characterization process is also limited due to several associated complications including synthesis, isolation and crystallization of peptides. The present computational methodologies, on the other hand, are solid enough to provide detailed complementary information about the intrinsic conformational features of peptides by mimicking their physiological conditions. In the present work, molecular dynamics (MD) computational method was used to explore the configurational space of three Aurein peptides, namely Aurein 2.3, Aurein 2.4 and Aurein 2.5. These peptides are secreted by the amphibian skin when they are exposed to external stimuli. These peptides have been reported to possess anti-cancer and anti-bacterial activity with minimum resistance compared to the available drugs. However, despite their medicinal significance, the precise three dimensional structures of Aurein 2.4 and Aurein 2.5 are not as yet known. First, a validation study was performed on Aurein 2.3 to check the efficiency of the computational protocol. The results obtained revealed the presence of -helicity in all residues of the Aurein 2.3, in accordance with its experimental structure. A similar protocol was further used to explore the conformational profiles of the remaining two peptides (Aurein 2.4 and Aurein 2.5) under implicit and explicit solvent conditions. The results obtained revealed that both these peptides exhibit -helical character in all residues although in varying percentages. The -helical region in the case of Aurein 2.4 was localized predominantly in the central residues extending towards its N-terminal residues, whereas it was flanked by N-terminal and the central residues in Aurein 2.5. However, -helicity was completely absent in the explicit solvents, and the peptides preferred to stay either in -turns or extended forms. Hence, the present work provides comprehensive information about the conformational preferences of Aurein peptides which could lead to a better understanding of their native conformations for future investigations and point the way towards developing their new agonists.

scholarly journals The Revolutionary Roads to Study Cell–Cell Interactions in 3D In Vitro Pancreatic Cancer Models

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 930
Author(s):  
Donatella Delle Cave ◽  
Riccardo Rizzo ◽  
Bruno Sainz ◽  
Giuseppe Gigli ◽  
Loretta L. del Mercato ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Therapeutic Response ◽  
Three Dimensional ◽  
Cellular Models ◽  
Common Cancer ◽  
Cancer Models ◽  
Anti Cancer ◽  
Tumor Environment

Pancreatic cancer, the fourth most common cancer worldwide, shows a highly unsuccessful therapeutic response. In the last 10 years, neither important advancements nor new therapeutic strategies have significantly impacted patient survival, highlighting the need to pursue new avenues for drug development discovery and design. Advanced cellular models, resembling as much as possible the original in vivo tumor environment, may be more successful in predicting the efficacy of future anti-cancer candidates in clinical trials. In this review, we discuss novel bioengineered platforms for anticancer drug discovery in pancreatic cancer, from traditional two-dimensional models to innovative three-dimensional ones.

Three-dimensional Graphene Coated Shape Memory Polyurethane Foam with Fast Responsive Performance

2021 ◽  
Author(s):  
Tianjiao Wang ◽  
Jun Zhao ◽  
Chuanxin Weng ◽  
Tong Wang ◽  
Yayun Liu ◽  
...  
Keyword(s):  
Shape Memory ◽  
Polyurethane Foam ◽  
Three Dimensional ◽  
Shape Memory Polymers ◽  
Practical Applications ◽  
External Stimuli ◽  
Shape Memory Polyurethane

Shape memory polymers (SMPs) that change shapes as designed by external stimuli have become one of the most promising materials as actuators, sensors, and deployable devices. However, their practical applications...

scholarly journals Applications of Biomaterials in 3D Cell Culture and Contributions of 3D Cell Culture to Drug Development and Basic Biomedical Research

2021 ◽  
Vol 22 (5) ◽  
pp. 2491
Author(s):  
Yujin Park ◽  
Kang Moo Huh ◽  
Sun-Woong Kang
Keyword(s):  
Cell Culture ◽  
Three Dimensional ◽  
3D Culture ◽  
3D Cell Culture ◽  
Accurate Method ◽  
New Drugs ◽  
Toxicity Screening ◽  
Cellular Functions ◽  
Toxicity Of Drugs ◽  
External Stimuli

The process of evaluating the efficacy and toxicity of drugs is important in the production of new drugs to treat diseases. Testing in humans is the most accurate method, but there are technical and ethical limitations. To overcome these limitations, various models have been developed in which responses to various external stimuli can be observed to help guide future trials. In particular, three-dimensional (3D) cell culture has a great advantage in simulating the physical and biological functions of tissues in the human body. This article reviews the biomaterials currently used to improve cellular functions in 3D culture and the contributions of 3D culture to cancer research, stem cell culture and drug and toxicity screening.

scholarly journals Hereditary Optic Neuropathies: Induced Pluripotent Stem Cell-Based 2D/3D Approaches

Genes ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 112
Author(s):  
Marta García-López ◽  
Joaquín Arenas ◽  
M. Esther Gallardo
Keyword(s):  
Stem Cell ◽  
Retinal Ganglion Cells ◽  
Pluripotent Stem Cell ◽  
Ganglion Cells ◽  
Genetic Disorders ◽  
Three Dimensional ◽  
Induced Pluripotent Stem Cell ◽  
Underlying Mechanism ◽  
Retinal Ganglion ◽  
Induced Pluripotent

Inherited optic neuropathies share visual impairment due to the degeneration of retinal ganglion cells (RGCs) as the hallmark of the disease. This group of genetic disorders are caused by mutations in nuclear genes or in the mitochondrial DNA (mtDNA). An impaired mitochondrial function is the underlying mechanism of these diseases. Currently, optic neuropathies lack an effective treatment, and the implementation of induced pluripotent stem cell (iPSC) technology would entail a huge step forward. The generation of iPSC-derived RGCs would allow faithfully modeling these disorders, and these RGCs would represent an appealing platform for drug screening as well, paving the way for a proper therapy. Here, we review the ongoing two-dimensional (2D) and three-dimensional (3D) approaches based on iPSCs and their applications, taking into account the more innovative technologies, which include tissue engineering or microfluidics.

scholarly journals In Situ Vitrification of Lung Cancer Organoids on a Microwell Array

Micromachines ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 624
Author(s):  
Qiang Liu ◽  
Tian Zhao ◽  
Xianning Wang ◽  
Zhongyao Chen ◽  
Yawei Hu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Sensitivity ◽  
Simple Procedure ◽  
Three Dimensional ◽  
Cancer Drug ◽  
Microwell Array ◽  
Sensitivity Tests ◽  
Anti Cancer

Three-dimensional cultured patient-derived cancer organoids (PDOs) represent a powerful tool for anti-cancer drug development due to their similarity to the in vivo tumor tissues. However, the culture and manipulation of PDOs is more difficult than 2D cultured cell lines due to the presence of the culture matrix and the 3D feature of the organoids. In our other study, we established a method for lung cancer organoid (LCO)-based drug sensitivity tests on the superhydrophobic microwell array chip (SMAR-chip). Here, we describe a novel in situ cryopreservation technology on the SMAR-chip to preserve the viability of the organoids for future drug sensitivity tests. We compared two cryopreservation approaches (slow freezing and vitrification) and demonstrated that vitrification performed better at preserving the viability of LCOs. Next, we developed a simple procedure for in situ cryopreservation and thawing of the LCOs on the SMAR-chip. We proved that the on-chip cryopreserved organoids can be recovered successfully and, more importantly, showing similar responses to anti-cancer drugs as the unfrozen controls. This in situ vitrification technology eliminated the harvesting and centrifugation steps in conventional cryopreservation, making the whole freeze–thaw process easier to perform and the preserved LCOs ready to be used for the subsequent drug sensitivity test.

Prevascularized, Co-Culture Model for Breast Cancer Drug Development

2012 ◽  
Author(s):  
Lauren Marshall ◽  
Isabel Löwstedt ◽  
Paul Gatenholm ◽  
Joel Berry
Keyword(s):  
Breast Cancer ◽  
Drug Development ◽  
Three Dimensional ◽  
Human Tumor ◽  
3D Models ◽  
Cancer Drug ◽  
Cancer Therapies ◽  
Anti Cancer

The objective of this study was to create 3D engineered tissue models to accelerate identification of safe and efficacious breast cancer drug therapies. It is expected that this platform will dramatically reduce the time and costs associated with development and regulatory approval of anti-cancer therapies, currently a multi-billion dollar endeavor [1]. Existing two-dimensional (2D) in vitro and in vivo animal studies required for identification of effective cancer therapies account for much of the high costs of anti-cancer medications and health insurance premiums borne by patients, many of whom cannot afford it. An emerging paradigm in pharmaceutical drug development is the use of three-dimensional (3D) cell/biomaterial models that will accurately screen novel therapeutic compounds, repurpose existing compounds and terminate ineffective ones. In particular, identification of effective chemotherapies for breast cancer are anticipated to occur more quickly in 3D in vitro models than 2D in vitro environments and in vivo animal models, neither of which accurately mimic natural human tumor environments [2]. Moreover, these 3D models can be multi-cellular and designed with extracellular matrix (ECM) function and mechanical properties similar to that of natural in vivo cancer environments [3].

scholarly journals Three-dimensional quantification of twisting in the Arabidopsis petiole

2021 ◽  
Author(s):  
Yuta Otsuka ◽  
Hirokazu Tsukaya
Keyword(s):  
Cross Sections ◽  
Three Dimensional ◽  
Light Sheet ◽  
Underlying Mechanism ◽  
Two Dimensions ◽  
Observation Angle ◽  
Differential Growth ◽  
Light Sheet Microscopy ◽  
Definition Of ◽  
Twisting Angle

AbstractOrganisms have a variety of three-dimensional (3D) structures that change over time. These changes include twisting, which is 3D deformation that cannot happen in two dimensions. Twisting is linked to important adaptive functions of organs, such as adjusting the orientation of leaves and flowers in plants to align with environmental stimuli (e.g. light, gravity). Despite its importance, the underlying mechanism for twisting remains to be determined, partly because there is no rigorous method for quantifying the twisting of plant organs. Conventional studies have relied on approximate measurements of the twisting angle in 2D, with arbitrary choices of observation angle. Here, we present the first rigorous quantification of the 3D twisting angles of Arabidopsis petioles based on light sheet microscopy. Mathematical separation of bending and twisting with strict definition of petiole cross-sections were implemented; differences in the spatial distribution of bending and twisting were detected via the quantification of angles along the petiole. Based on the measured values, we discuss that minute degrees of differential growth can result in pronounced twisting in petioles.

scholarly journals Right Ventricular Global and Regional Remodeling in American-Style Football Athletes: A Longitudinal 3D Echocardiographic Study

2021 ◽  
Vol 11 (8) ◽  
pp. 3357
Author(s):  
Amir Hodzic ◽  
Gabriel Bernardino ◽  
Damien Legallois ◽  
Patrick Gendron ◽  
Hélène Langet ◽  
...  
Keyword(s):  
Right Ventricular ◽  
Morphological Changes ◽  
Three Dimensional ◽  
Computational Method ◽  
Physiological Adaptation ◽  
Volumetric Assessment ◽  
American Style ◽  
Few Data ◽  
The Right ◽  
Field Position

Few data exist concerning the right ventricular (RV) physiological adaptation in American-style football (ASF) athletes. We aimed to analyze the RV global and regional responses among ASF-trained athletes. Fifty-nine (20 linemen and 39 non-linemen) ASF athletes were studied before and after inter-seasonal training. During this period, which lasted 7 months, all athletes were exposed to combined dynamic and static exercises. Cardiac longitudinal changes were examined using three-dimensional transthoracic echocardiography. A computational method based on geodesic distances was applied to volumetrically parcellate the RV into apical, outlet, and inlet regions. RV global and regional end-diastolic volumes increased significantly and similarly in linemen and non-linemen after training, with predominant changes in the apex and outlet regions. RV global and regional ejection fractions were preserved. Morphological changes were uniformly distributed among the four cardiac chambers, and it was independent of the field position. Assessment of RV end-diastolic global, inlet and apical volumes showed low intra-observer (3.3%, 4.1%, and 5.3%, respectively) and inter-observer (7%, 12.2%, and 9%, respectively) variability, whereas the outlet regional volumetric assessment was less reproducible. To conclude, ASF inter-seasonal training was associated with a proportionate biventricular enlargement, regardless of the field position. Regional RV analysis allowed us to quantify the amount of exercise-induced remodeling that was larger in the apical and outlet regions.

Effective Shear Area in One Dimensional Ship Hull Finite Element Models to Predict Natural Frequencies of Vibration

2013 ◽  
Author(s):  
Osvaldo Pinheiro de Souza e Silva ◽  
Severino Fonseca da Silva Neto ◽  
Ilson Paranhos Pasqualino ◽  
Antonio Carlos Ramos Troyman
Keyword(s):  
Finite Element ◽  
Natural Frequencies ◽  
Three Dimensional ◽  
Experimental Tests ◽  
Numerical Results ◽  
Computational Method ◽  
Scale Model ◽  
Dimensional Model ◽  
One Dimensional ◽  
Shear Area

This work discusses procedures used to determine effective shear area of ship sections. Five types of ships have been studied. Initially, the vertical natural frequencies of an acrylic scale model 3m in length in a laboratory at university are obtained from experimental tests and from a three dimensional numerical model, and are compared to those calculated from a one dimensional model which the effective shear area was calculated by a practical computational method based on thin-walled section Shear Flow Theory. The second studied ship was a ship employed in midshipmen training. Two models were made to complement some studies and vibration measurements made for those ships in the end of 1980 decade when some vibration problems in them were solved as a result of that effort. Comparisons were made between natural frequencies obtained experimentally, numerically from a three dimensional finite element model and from a one dimensional model in which effective shear area is considered. The third and fourth were, respectively, a tanker ship and an AHTS (Anchor Handling Tug Supply) boat, both with comparison between three and one dimensional models results out of water. Experimental tests had been performed in these two ships and their results were used in other comparison made after the inclusion of another important effect that acts simultaneously: the added mass. Finally, natural frequencies experimental and numerical results of a barge are presented. The natural frequencies numerical results of vertical hull vibration obtained from these approximations of effective shear areas for the five ships are finally discussed.

Crystal structure of the hinge domain of Smchd1 reveals its dimerization mode and nucleic acid–binding residues

2020 ◽  
Vol 13 (636) ◽  
pp. eaaz5599 ◽  
Author(s):  
Kelan Chen ◽  
Richard W. Birkinshaw ◽  
Alexandra D. Gurzau ◽  
Iromi Wanigasuriya ◽  
Ruoyun Wang ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Muscular Dystrophy ◽  
Three Dimensional ◽  
Underlying Mechanism ◽  
Structural Features ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Dimensional Structure ◽  
Nucleic Acid Binding ◽  
X Ray Crystallography ◽  
Hinge Domain

Structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1) is an epigenetic regulator in which polymorphisms cause the human developmental disorder, Bosma arhinia micropthalmia syndrome, and the degenerative disease, facioscapulohumeral muscular dystrophy. SMCHD1 is considered a noncanonical SMC family member because its hinge domain is C-terminal, because it homodimerizes rather than heterodimerizes, and because SMCHD1 contains a GHKL-type, rather than an ABC-type ATPase domain at its N terminus. The hinge domain has been previously implicated in chromatin association; however, the underlying mechanism involved and the basis for SMCHD1 homodimerization are unclear. Here, we used x-ray crystallography to solve the three-dimensional structure of the Smchd1 hinge domain. Together with structure-guided mutagenesis, we defined structural features of the hinge domain that participated in homodimerization and nucleic acid binding, and we identified a functional hotspot required for chromatin localization in cells. This structure provides a template for interpreting the mechanism by which patient polymorphisms within the SMCHD1 hinge domain could compromise function and lead to facioscapulohumeral muscular dystrophy.

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