scholarly journals Multi-Target Actions of Acridones from Atalantia monophylla towards Alzheimer’s Pathogenesis and Their Pharmacokinetic Properties

2021 ◽  
Vol 14 (9) ◽  
pp. 888
Author(s):  
Pitchayakarn Takomthong ◽  
Pornthip Waiwut ◽  
Chavi Yenjai ◽  
Aonnicha Sombatsri ◽  
Prasert Reubroycharoen ◽  
...  
Keyword(s):  
In Silico ◽  
Cell Damage ◽  
Neuronal Cell ◽  
In Silico Analysis ◽  
Hydrophobic Core ◽  
Ache Inhibition ◽  
Hydrophobic Region ◽  
Aβ Aggregation ◽  
Key Residues

Ten acridones isolated from Atalantia monophylla were evaluated for effects on Alzheimer’s disease pathogenesis including antioxidant effects, acetylcholinesterase (AChE) inhibition, prevention of beta-amyloid (Aβ) aggregation and neuroprotection. To understand the mechanism, the type of AChE inhibition was investigated in vitro and binding interactions between acridones and AChE or Aβ were explored in silico. Drug-likeness and ADMET parameters were predicted in silico using SwissADME and pKCSM programs, respectively. All acridones showed favorable drug-likeness and possessed multifunctional activities targeting AChE function, Aβ aggregation and oxidation. All acridones inhibited AChE in a mixed-type manner and bound AChE at both catalytic anionic and peripheral anionic sites. In silico analysis showed that acridones interfered with Aβ aggregation by interacting at the central hydrophobic core, C-terminal hydrophobic region, and the key residues 41 and 42. Citrusinine II showed potent multifunctional action with the best ADMET profile and could alleviate neuronal cell damage induced by hydrogen peroxide and Aβ1-42 toxicity.

scholarly journals An in vitro and in silico evaluation of the antibacterial activity of the bioactive compounds in Majapahit (Crescentia cujete L.) fruit

2019 ◽  
Vol 12 (12) ◽  
pp. 1959-1965
Author(s):  
Sri Rahmaningsih ◽  
Hernik Pujiastutik
Keyword(s):  
Antibacterial Activity ◽  
In Silico ◽  
Antibacterial Agent ◽  
Cell Damage ◽  
In Silico Analysis ◽  
Bioactive Constituents ◽  
Fruit Extract ◽  
Crescentia Cujete ◽  
Vitro Analysis

Background and Aim: Majapahit (Crescentia cujete L.) fruit extract acts as a natural antibacterial agent due to its bioactive constituents such as tannins, flavonoids, triterpenoids, and saponins. The aim of this study was to determine the antibacterial activity of Majapahit fruit against Vibrio harveyi both in vitro and in silico. Materials and Methods: Column chromatography, minimum inhibitory concentration (MIC) determination, and transmission electron microscopy (TEM) were used for in vitro analysis. In silico analysis was performed using PubChem® database, Pass Online (Way2Drug.com©), Search Tool 17 Interacting Chemicals (STITCH), and UNIPROT database (https://www.uniprot.org/). Results: The MIC was found to be 0.313 mg/mL. Within the concentration range of 0.313 mg/mL-10 mg/mL, Majapahit fruit extract could inhibit the growth of V. harveyi, while lower concentrations of 0.078 mg/mL and 0.165 mg/mL indicated the presence of bacterial growth. The pathogenic mechanism of V. harveyi on vannamei shrimp (Litopenaeus vannamei) involved targeting cytochrome P450, cyclin-dependent kinase 6, and caspases 3 and 8. This was indicated by cell damage observed through TEM. Conclusion: This study provides comprehensive results on the potential of Majapahit fruit as a natural antibacterial agent. Thus, Majapahit fruit can be considered for functional food applications.

In Silico Study of Potential Cross-Kingdom Plant MicroRNA Based Regulation in Chronic Myeloid Leukemia

2020 ◽  
Vol 17 (2) ◽  
pp. 125-132
Author(s):  
Marjanu Hikmah Elias ◽  
Noraziah Nordin ◽  
Nazefah Abdul Hamid
Keyword(s):  
Targeted Therapy ◽  
In Silico ◽  
Structure Prediction ◽  
Tertiary Structure ◽  
Target Prediction ◽  
In Silico Analysis ◽  
Microrna Target ◽  
Good Target

Background: Chronic Myeloid Leukaemia (CML) is associated with the BCRABL1 gene, which plays a central role in the pathogenesis of CML. Thus, it is crucial to suppress the expression of BCR-ABL1 in the treatment of CML. MicroRNA is known to be a gene expression regulator and is thus a good candidate for molecularly targeted therapy for CML. Objective: This study aims to identify the microRNAs from edible plants targeting the 3’ Untranslated Region (3’UTR) of BCR-ABL1. Methods: In this in silico analysis, the sequence of 3’UTR of BCR-ABL1 was obtained from Ensembl Genome Browser. PsRNATarget Analysis Server and MicroRNA Target Prediction (miRTar) Server were used to identify miRNAs that have binding conformity with 3’UTR of BCR-ABL1. The MiRBase database was used to validate the species of plants expressing the miRNAs. The RNAfold web server and RNA COMPOSER were used for secondary and tertiary structure prediction, respectively. Results: In silico analyses revealed that cpa-miR8154, csi-miR3952, gma-miR4414-5p, mdm-miR482c, osa-miR1858a and osa-miR1858b show binding conformity with strong molecular interaction towards 3’UTR region of BCR-ABL1. However, only cpa-miR- 8154, osa-miR-1858a and osa-miR-1858b showed good target site accessibility. Conclusion: It is predicted that these microRNAs post-transcriptionally inhibit the BCRABL1 gene and thus could be a potential molecular targeted therapy for CML. However, further studies involving in vitro, in vivo and functional analyses need to be carried out to determine the ability of these miRNAs to form the basis for targeted therapy for CML.

In-Vitro and In-Silico Characterization of Xylose Reductase from Emericella nidulans

2019 ◽  
Vol 13 (2) ◽  
pp. 159-170 ◽  
Author(s):  
Vishal Ahuja ◽  
Aashima Sharma ◽  
Ranju Kumari Rathour ◽  
Vaishali Sharma ◽  
Nidhi Rana ◽  
...  
Keyword(s):  
Production Process ◽  
In Silico ◽  
Xylose Reductase ◽  
In Silico Analysis ◽  
Emericella Nidulans ◽  
Higher Temperature ◽  
In Silico Characterization ◽  
Silico Analysis

Background: Lignocellulosic residues generated by various anthropogenic activities can be a potential raw material for many commercial products such as biofuels, organic acids and nutraceuticals including xylitol. Xylitol is a low-calorie nutritive sweetener for diabetic patients. Microbial production of xylitol can be helpful in overcoming the drawbacks of traditional chemical production process and lowring cost of production. Objective: Designing efficient production process needs the characterization of required enzyme/s. Hence current work was focused on in-vitro and in-silico characterization of xylose reductase from Emericella nidulans. Methods: Xylose reductase from one of the hyper-producer isolates, Emericella nidulans Xlt-11 was used for in-vitro characterization. For in-silico characterization, XR sequence (Accession No: Q5BGA7) was used. Results: Xylose reductase from various microorganisms has been studied but the quest for better enzymes, their stability at higher temperature and pH still continues. Xylose reductase from Emericella nidulans Xlt-11 was found NADH dependent and utilizes xylose as its sole substrate for xylitol production. In comparison to whole cells, enzyme exhibited higher enzyme activity at lower cofactor concentration and could tolerate higher substrate concentration. Thermal deactivation profile showed that whole cell catalysts were more stable than enzyme at higher temperature. In-silico analysis of XR sequence from Emericella nidulans (Accession No: Q5BGA7) suggested that the structure was dominated by random coiling. Enzyme sequences have conserved active site with net negative charge and PI value in acidic pH range. Conclusion: Current investigation supported the enzyme’s specific application i.e. bioconversion of xylose to xylitol due to its higher selectivity. In-silico analysis may provide significant structural and physiological information for modifications and improved stability.

scholarly journals In Silico Predicted Antifungal Peptides: In Vitro and In Vivo Anti-Candida Activity

2021 ◽  
Vol 7 (6) ◽  
pp. 439
Author(s):  
Tecla Ciociola ◽  
Walter Magliani ◽  
Tiziano De Simone ◽  
Thelma A. Pertinhez ◽  
Stefania Conti ◽  
...  
Keyword(s):  
In Silico ◽  
Mammalian Cells ◽  
Galleria Mellonella ◽  
Ex Vivo ◽  
Consensus Sequence ◽  
In Silico Analysis ◽  
Significant Activity ◽  
Synthetic Antibody

It has been previously demonstrated that synthetic antibody-derived peptides could exert a significant activity in vitro, ex vivo, and/or in vivo against microorganisms and viruses, as well as immunomodulatory effects through the activation of immune cells. Based on the sequence of previously described antibody-derived peptides with recognized antifungal activity, an in silico analysis was conducted to identify novel antifungal candidates. The present study analyzed the candidacidal and structural properties of in silico designed peptides (ISDPs) derived by amino acid substitutions of the parent peptide KKVTMTCSAS. ISDPs proved to be more active in vitro than the parent peptide and all proved to be therapeutic in Galleria mellonella candidal infection, without showing toxic effects on mammalian cells. ISDPs were studied by circular dichroism spectroscopy, demonstrating different structural organization. These results allowed to validate a consensus sequence for the parent peptide KKVTMTCSAS that may be useful in the development of novel antimicrobial molecules.

Investigation of indole functionalized pyrazoles and oxadiazoles as anti-inflammatory agents: synthesis, in-vivo, in-vitro and in-silico analysis

2021 ◽  
pp. 105068
Author(s):  
Devendra Kumar ◽  
Ravi Ranjan Kumar ◽  
Shelly Pathania ◽  
Pankaj Kumar Singh ◽  
Sourav Kalra ◽  
...  
Keyword(s):  
In Silico ◽  
In Silico Analysis ◽  
Anti Inflammatory ◽  
Silico Analysis

Abstract 121: Pro-inflammatory Cytokine Ifng Modulates Hepatic Sortilin Expression and Lipid Metabolism.

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
John Pirault ◽  
Konstantinos Polyzos ◽  
Daniel F Ketelhuth ◽  
Göran K Hansson
Keyword(s):  
Lipid Metabolism ◽  
Binding Sites ◽  
In Silico ◽  
In Silico Analysis ◽  
Lipid Uptake ◽  
Regulatory T Lymphocytes ◽  
Inflammatory Conditions ◽  
Ldl Particles ◽  
Inflammatory Milieu

Rationale: Hypercholesterolemia and immunity are two major risk factors for cardiovascular diseases (CVDs). Yet, we reported increased atherosclerosis upon depletion of regulatory T lymphocytes (Tregs). The effect was associated with increased hepatic inflammation and reduction of Sortilin expression and lipid uptake in the liver. Objective: To define how inflammatory milieu in the liver can modulate Sortilin and lipid metabolism. Methods: To reproduce the inflammatory milieu, hepatocytes (AML-12) were treated in vitro with IFNg. Expression of genes and proteins of interest were followed by qPCR and western blot. In silico method was used to find binding sites of signal transducer and activator of transcription (STAT1) on Sortilin, confirmed later by chromatin immune precipitation assays (Chip). Lipid uptake by hepatocytes was assessed via incubation of cells with radioactive lipoproteins. Results: Culture of AML-12 cells with IFNg induced the phosphorylation of STAT1 showing an active signaling pathway. In the same inflammatory conditions, Sort1 mRNA is decreased meanwhile its inhibitor (Atf3) expression is increased. Kinetic experiments revealed the reduction of Sortilin after 12 hours of culture, suggesting a post-transcriptional regulation of Sort1 by STAT1. In silico analysis revealed putative binding sites for STAT1 on Sortilin gene which was confirmed by chromatin immunoprecipitation assay (Chip). IFNg treated hepatocytes that were incubated with radioactive lipoproteins demonstrated a reduced uptake capacity of VLDL and LDL particles compared to control cultures. Conclusion: All together, these results suggest that inflammation through production of IFNg is able to directly modulate the lipid metabolism in hepatocytes by acting on Sortilin expression.

scholarly journals The Bioactivity Prediction of Peptides from Tuna Skin Collagen Using Integrated Method Combining In Vitro and In Silico

Foods ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2739
Author(s):  
Liza Devita ◽  
Hanifah Nuryani Lioe ◽  
Mala Nurilmala ◽  
Maggy T. Suhartono
Keyword(s):  
Antioxidant Activity ◽  
In Silico ◽  
Antioxidant Activities ◽  
In Silico Analysis ◽  
Weight Fraction ◽  
Amino Acid Sequences ◽  
Skin Collagen ◽  
Dpph Method ◽  
Peptide Fractions

The hydrolysates and peptide fractions of bigeye tuna (Thunnus obesus) skin collagen have been successfully studied. The hydrolysates (HPA, HPN, HPS, HBA, HBN, HBS) were the result of the hydrolysis of collagen using alcalase, neutrase, and savinase. The peptide fractions (PPA, PPN, PPS, PBA, PBN, PBS) were the fractions obtained following ultrafiltration of the hydrolysates. The antioxidant activities of the hydrolysates and peptide fractions were studied using the DPPH method. The effects of collagen types, enzymes, and molecular sizes on the antioxidant activities were analyzed using profile plots analysis. The amino acid sequences of the peptides in the fraction with the highest antioxidant activity were analyzed using LC-MS/MS. Finally, their bioactivity and characteristics were studied using in silico analysis. The hydrolysates and peptide fractions provided antioxidant activity (6.17–135.40 µmol AAE/g protein). The lower molecular weight fraction had higher antioxidant activity. Collagen from pepsin treatment produced higher activity than that of bromelain treatment. The fraction from collagen hydrolysates by savinase treatment had the highest activity compared to neutrase and alcalase treatments. The peptides in the PBN and PPS fractions of <3 kDa had antidiabetic, antihypertensive and antioxidant activities. In conclusion, they have the potential to be used in food and health applications.

scholarly journals Stress and strain distributions on short implants with two different prosthetic connections – an in vitro and in silico analysis

2017 ◽  
Vol 20 (3) ◽  
Author(s):  
João Paulo Mendes Tribst ◽  
Amanda Maria de Oliveira Dal Piva ◽  
Vinicius Anéas Rodrigues ◽  
Alexandre Luiz Souto Borges ◽  
Renato Sussumo Nishioka
Keyword(s):  
Strain Gauge ◽  
In Silico ◽  
Axial Load ◽  
In Silico Analysis ◽  
Surrounding Tissue ◽  
Stress And Strain ◽  
Element Analysis ◽  
Osseointegrated Implants ◽  
Short Implants

<p><strong>Objective:</strong> An ideal biomechanics minimizes the stress between implant and bone that can provide success for osseointegrated implants. This study evaluated the strain concentration in surrounding tissue and stress in the components of two implants with different prosthetic connections through an <em>in vitro</em> and <em>in silico</em> methods. <strong>Methods:</strong> Twenty  polyurethane blocks were divided into two groups (n=10) followed by the installation of internal hexagon (IH) (AS Technology – Titanium Fix, São José dos Campos, Brazil) or locking taper implants (LT) (Bicon Dental Implants). For strain gauge (SG) method, four sensors were placed around the implants. For finite element analysis (FEA), the same block was modeled and analyzed. An axial load (30 kgf) was applied for both methodologies.  The values of stress and strain were analyzed for correlation to SG. <strong>Results:</strong> For SG, LT presented a mean of strain most aggressive (-932) than IH (-632). For FEA, LT showed less stress (-547) then IH (-1169).  <strong>Conclusion:</strong>  For two implant’s system, microstrain values capable to induce unwanted bone remodeling were not measured.  However, for IH implant, the presence of a retention screw has the disadvantage to concentrate stress while a solid abutment dissipates the axial load through the implant that suggests a better performance for LT group.</p><p><strong> </strong></p><p><strong><strong>Keywords: </strong></strong>Finite elements analyses; Dental implant; Strain gauge. </p><p> </p>

Sign in / Sign up

Export Citation Format

Share Document