scholarly journals In Silico Studies on Pharmacokinetics and Neuroprotective Potential of 25Mg2+: Releasing Nanocationites - Background and Perspectives

2021 ◽  
Author(s):  
Valentin V. Fursov ◽  
Ilia V. Fursov ◽  
Alexander A. Bukhvostov ◽  
Aleksander G. Majouga ◽  
Dmitry A. Kuznetsov
Keyword(s):  
Targeted Delivery ◽  
In Silico ◽  
Isotope Effects ◽  
Drug Induced ◽  
Promising Tool ◽  
Brain Stroke ◽  
Pharmacological Potential ◽  
Brain Creatine Kinase ◽  
Surrounding Areas ◽  
The Brain

Sharp blood circulation disorders are known for their capability to promote such abundant and hardly treatable pathologies as myocardium infarction and the ischemic brain stroke (“insult”). Noteworthy, the stroke — related brain tissue metabolic damages involve an essential ATP deplete clash along with a suppression of brain specific nucleotide — associated kinases and ATP synthase, both Mg2+ — dependent complex enzyme “machineries”. This itself makes the latter’s a legitimate target for some advanced pharmaceuticals as long as the drug — induced overstimulation of corresponding enzymatic activity is the case. Thus, magnetic isotope effects (MIE) of the nuclear spin possessing paramagnetic 25Mg2+ ions might modulate the brain creatine kinase, alfa-glycerophosphate kinase and pyruvate kinase catalytic activities in a way of a remarkable ATP hyperproduction required to compensate the hypoxia caused acute metabolic breakdown. To realize the Magnesium-25 pharmacological potential, a low-toxic amphiphilic cationite nanoparticles were introduced lately. Particularly, the Magnesium — releasing porphyrin-fullerene nanoadduct (cyclohexyl-C60-porphyrin, PMC16) has been proposed to meet expectations dealing with a targeted delivery of 25Mg2+ towards the brain ischemia surrounding areas. In order to optimize a multi-step [25Mg2+]4PMC16 preclinical trial scenario, the In Silico algorithms are to be developed and analyzed. In this study, these algorithms are in a focus with a special emphasize on a novel combination of slightly modified Gompertzian equation systems and a non-Markov population dynamics concept. This In Silico approach takes into account some literature-available patterns of brain hypoxia pathogenesis, the resulted simulation model could be considered as a promising tool for further research on experimental nanopharmacology of the ischemic stroke.

PEGylated nanocarriers: A promising tool for targeted delivery to the brain

2020 ◽  
Vol 187 ◽  
pp. 110770 ◽  
Author(s):  
K.R. Gajbhiye ◽  
A. Pawar ◽  
K.R. Mahadik ◽  
V. Gajbhiye
Keyword(s):  
Targeted Delivery ◽  
Promising Tool ◽  
The Brain

scholarly journals Pulsed Focal ultrasound as a non-invasive method to deliver exosomes in the brain/stroke

2021 ◽  
Author(s):  
Ahmet Alptekin ◽  
Mohammad B Khan ◽  
Roxan Ara ◽  
Mohammad H Rashid ◽  
Fengchong Kong ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Focused Ultrasound ◽  
Biological Fluids ◽  
Brain Structures ◽  
Non Invasive ◽  
Study Results ◽  
Invasive Method ◽  
Pulsed Focused Ultrasound ◽  
Brain Stroke ◽  
The Brain

AbstractExosomes, a component of extracellular vesicles are shown to carry important small RNAs, mRNAs, protein, and bioactive lipid from parent cells and are found in most biological fluids. Investigators have demonstrated the importance of mesenchymal stem cells (MSCs) derived exosomes in repairing stroke lesions. However, exosomes from endothelial progenitor cells (EPCs) have not been tested in any stroke model nor has there been an evaluation of whether these exosomes target/home to areas of pathology. Targeted delivery of IV administered exosomes has been a great challenge and a targeted delivery system is lacking to deliver naïve (unmodified) exosomes from EPCs to the site of interest. Pulsed focused ultrasound (pFUS) is being used for therapeutic and experimental purposes. There has not been any report showing the use of pulsed low-intensity pFUS to deliver exosomes to the site of interest in models of stroke. In this proof of principle study, we have shown different parameters of pFUS to deliver exosomes in the intact and stroke brain with or without IV administration of nanobubbles. The study results showed that administration of nanobubbles is detrimental to the brain structures (micro bleeding and white matter destruction) at peak negative pressure (PNP) of >0.25 MPa, despite enhanced delivery of IV administered exosomes. However, without nanobubbles, pFUS PNP = 1 to 2 MPa enhances the delivery of exosomes in the stroke area without altering the brain structures.

Ligand and Structure-based Modeling of Passive Diffusion through the Blood-Brain Barrier

2018 ◽  
Vol 25 (9) ◽  
pp. 1073-1089 ◽  
Author(s):  
Santiago Vilar ◽  
Eduardo Sobarzo-Sanchez ◽  
Lourdes Santana ◽  
Eugenio Uriarte
Keyword(s):  
Blood Brain Barrier ◽  
In Silico ◽  
Passive Diffusion ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
Different Types ◽  
The Brain

Background: Blood-brain barrier transport is an important process to be considered in drug candidates. The blood-brain barrier protects the brain from toxicological agents and, therefore, also establishes a restrictive mechanism for the delivery of drugs into the brain. Although there are different and complex mechanisms implicated in drug transport, in this review we focused on the prediction of passive diffusion through the blood-brain barrier. Methods: We elaborated on ligand-based and structure-based models that have been described to predict the blood-brain barrier permeability. Results: Multiple 2D and 3D QSPR/QSAR models and integrative approaches have been published to establish quantitative and qualitative relationships with the blood-brain barrier permeability. We explained different types of descriptors that correlate with passive diffusion along with data analysis methods. Moreover, we discussed the applicability of other types of molecular structure-based simulations, such as molecular dynamics, and their implications in the prediction of passive diffusion. Challenges and limitations of experimental measurements of permeability and in silico predictive methods were also described. Conclusion: Improvements in the prediction of blood-brain barrier permeability from different types of in silico models are crucial to optimize the process of Central Nervous System drug discovery and development.

Appraisal of the role of In silico Methods in Pyrazole based drug design

2020 ◽  
Vol 20 ◽  
Author(s):  
Smriti Sharma ◽  
Vinayak Bhatia
Keyword(s):  
Drug Design ◽  
In Silico ◽  
Md Simulations ◽  
Quantitative Structure Activity Relationship ◽  
Field Analysis ◽  
Computational Techniques ◽  
Neuroprotective Drugs ◽  
Pharmacological Potential ◽  
Available Information ◽  
Anti Fungal

: Pyrazole and its derivatives are a pharmacologically significant active scaffold that have innumerable physiological and pharmacological activities. They can be very good targets for the discovery of novel anti-bacterial, anticancer, anti-inflammatory, anti-fungal, anti-tubercular, antiviral, antioxidant, antidepressant, anti-convulsant and neuroprotective drugs. This review focuses on the importance of in silico manipulations of pyrazole and its derivatives for medicinal chemistry. The authors have discussed currently available information on the use of computational techniques like molecular docking, structure-based virtual screening (SBVS), molecular dynamics (MD) simulations, quantitative structure activity relationship (QSAR), comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) to drug design using pyrazole moieties. Pyrazole based drug design is mainly dependent on the integration of experimental and computational approaches. The authors feel that more studies need to be done to fully explore the pharmacological potential of the pyrazole moiety and in silico method can be of great help.

The Brain In Silico

2021 ◽  
pp. 1-36
Author(s):  
Joaquin Marro ◽  
Joaquin J. Torres
Keyword(s):  
In Silico ◽  
The Brain

scholarly journals Optical Imaging of Beta-Amyloid Plaques in Alzheimer’s Disease

Biosensors ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 255
Author(s):  
Ziyi Luo ◽  
Hao Xu ◽  
Liwei Liu ◽  
Tymish Y. Ohulchanskyy ◽  
Junle Qu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Optical Imaging ◽  
Imaging Techniques ◽  
High Sensitivity ◽  
Pathological Feature ◽  
Promising Tool ◽  
Abnormal Accumulation ◽  
Accumulation Mechanism ◽  
The Brain

Alzheimer’s disease (AD) is a multifactorial, irreversible, and incurable neurodegenerative disease. The main pathological feature of AD is the deposition of misfolded β-amyloid protein (Aβ) plaques in the brain. The abnormal accumulation of Aβ plaques leads to the loss of some neuron functions, further causing the neuron entanglement and the corresponding functional damage, which has a great impact on memory and cognitive functions. Hence, studying the accumulation mechanism of Aβ in the brain and its effect on other tissues is of great significance for the early diagnosis of AD. The current clinical studies of Aβ accumulation mainly rely on medical imaging techniques, which have some deficiencies in sensitivity and specificity. Optical imaging has recently become a research hotspot in the medical field and clinical applications, manifesting noninvasiveness, high sensitivity, absence of ionizing radiation, high contrast, and spatial resolution. Moreover, it is now emerging as a promising tool for the diagnosis and study of Aβ buildup. This review focuses on the application of the optical imaging technique for the determination of Aβ plaques in AD research. In addition, recent advances and key operational applications are discussed.

Estimation of uncertainty in multi-level in silico models predicting biomarkers of drug-induced proarrhythmic risk

2021 ◽  
Vol 350 ◽  
pp. S64-S65
Author(s):  
K. Kopanska ◽  
J.C. Gómez-Tamayo ◽  
J. Llopis-Lorente ◽  
B.A. Trenor-Gomis ◽  
J. Sáiz ◽  
...  
Keyword(s):  
In Silico ◽  
Drug Induced ◽  
Proarrhythmic Risk ◽  
Multi Level ◽  
In Silico Models ◽  
Estimation Of Uncertainty

scholarly journals Cannabinoids in health and disease: pharmacological potential in metabolic syndrome and neuroinflammation

2018 ◽  
Vol 36 (2) ◽  
Author(s):  
Andrea Mastinu ◽  
Marika Premoli ◽  
Giulia Ferrari-Toninelli ◽  
Simone Tambaro ◽  
Giuseppina Maccarinelli ◽  
...  
Keyword(s):  
Cannabis Sativa ◽  
Cannabinoid Receptor ◽  
Receptor Type ◽  
History Of ◽  
Health And Disease ◽  
Pharmacological Potential ◽  
The Brain ◽  
Synthesis And Degradation

Abstract The use of different natural and/or synthetic preparations of Cannabis sativa is associated with therapeutic strategies for many diseases. Indeed, thanks to the widespread diffusion of the cannabinoidergic system in the brain and in the peripheral districts, its stimulation, or inhibition, regulates many pathophysiological phenomena. In particular, central activation of the cannabinoidergic system modulates the limbic and mesolimbic response which leads to food craving. Moreover, cannabinoid agonists are able to reduce inflammatory response. In this review a brief history of cannabinoids and the protagonists of the endocannabinoidergic system, i.e. synthesis and degradation enzymes and main receptors, will be described. Furthermore, the pharmacological effects of cannabinoids will be outlined. An overview of the involvement of the endocannabinoidergic system in neuroinflammatory and metabolic pathologies will be made. Finally, particular attention will also be given to the new pharmacological entities acting on the two main receptors, cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2), with particular focus on the neuroinflammatory and metabolic mechanisms involved.

In silico assessment of drug-induced liver injury in humans

2016 ◽  
Vol 258 ◽  
pp. S118
Author(s):  
C. Yang ◽  
S. Thakkar ◽  
A. Mostrag ◽  
V. Gombar ◽  
B. Bienfait ◽  
...  
Keyword(s):  
Liver Injury ◽  
In Silico ◽  
Drug Induced ◽  
Drug Induced Liver Injury
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