Human-Organoid Models: Accomplishments to Salvage Test-Animals

Late stage attritions in drug discovery are costly and consuming. Improbable response of test molecules acquired in non-human systems is attributed to be the major cause of clinical failures. While conventional in vitro methods of drug discovery do not truly represent the human system, the animal models used for in vivo validation are also genetically and phenotypically distant from humans. However, recent developments in organoid culture are motivating and elevate hopes for replacing test animals with artificial human tissue models. 

Possibility of creating functional tissue ex vivo has a potential to revolutionize the way human therapeutics is perceived. Not only will it bridge the gap between drug development and its clinical efficacy but also help strategizing regenerative medicine. Successful human-tissue surrogates would liberate test animals or at least minimize their use for research purposes. Potential drug candidates tested on human-tissue equivalents are expected to generate clinically much more relevant data. Here we deliberate upon the options and possibilities of accomplishing human organoid models for in vitro testing and their significance in therapeutics.

Selenoergothionein as a Potential Inhibitor against Amyloid β-Protein (Aβ): Docking and Molecular Dynamics Studies

Alzheimer‘s disease (AD) is a progressive neurodegenerative disorder, encircling the deterioration of cognitive functions and behavioral changes, characterized by the aggregation of amyloid β-protein (Aβ) into fibrillar amyloid plaques in elected areas of the brain with the lipid-carrier protein apolipoprotein E (apoE), the microtubule associated protein tau, and the presynaptic protein α-synuclein. 

High levels of fibrillary Aβ, the main constituent of senile plaques, are deposited in the AD brain that outcome in the thrashing of synapses, neurons and destruction of neuronal role. Aβ is derived from the amyloid precursor protein through sequential protein cleavage by aspartyl protease, β-secretase and presenilin-dependent β-secretase triggering a spill of events such as oxidative damage, neurotoxicity, and inflammation that contributes to the progression of AD. Therefore the Aβ protein may be a target for anti-Alzheimer drugs.

Identification of Double-Step Saccades Elicited by Auditory Double-Step Stimuli

Voluntary Saccadic eye movements can have visual, auditory, and auditory-visual bisensory origins. An experiment may be defined to examine how changing the type of sensory inputs and the number of them in a sequence reveals the type of the saccade generated by the oculomotor system; here in deemed single-step or double-step. This work reports design of experiments of double-step auditory stimuli played for human subjects, recording triggered saccadic eye movements, detecting each saccade, as well as estimating the saccade response characteristics, namely duration and latency. 

Based on the latency, then, it determines the type of the generated saccade by the subject through a clustering technique. We found that when doubling the amplitude of the two separate steps in double-step inputs, while keeping their duration unchanged, the number of triggered double-step saccades rises. The hindsight from this finding is useful because it can guide future stimulus designs to trigger specific saccade types in humans. Such designs, in turn, demystify the nature of dominant saccadic response as we explore the changes of sounds in any controlled environment.

A Review on New Horizons of Bioinformatics in Next Generation Sequencing, Viral and Cancer Genomics

Genomics and molecular biology has always been a constant source of inspiration and motivational research for worldwide researchers in field of biology and biotechnology. These two fields have always generated a huge amount of data and in order to compile and analyze those, bioinformatics came into action during last decade. Implementation of bioinformatics has a clear intention of doing all these analysis of data in efficient and fast manner in order to cut down the expensive laboratory equipment, chemicals and most precious time. 

Mostly genomic data is composed of sequencing results at a higher scale and that is why manual curating and handling of these data is quite difficult. Supreme aim of this review is to make awareness about bioinformatics options in cancer genomics and viral genomics apart from next generation sequencing. Next generation sequencing or high throughput sequencing has helped a lot to replace old conventional method of sequencing and with the help of recent advances in technologies.

A Multiscale Haemorheological Computer-Based Model of Atherosclerosis: An In-Depth Investigation of Erythrocytes-Driven Flow Characteristics in Atheroma Development

The mortality caused by cardiovascular diseases is dramatically increasing. Atherosclerosis is among the main contributors to this extremely high cardiovascular disease mortality. Atherosclerosis is controlled by mechanical forces exerted by the flow of blood on the inner lining of arteries, the endothelium. 

In order to fight this lethal disease a realistic computational model is required that offers an accurate understanding of the effect of blood flow on the arterial wall. In order to realistically describe complex blood flow patterns and their interaction with the arterial wall, we have developed an integrated computational technique that takes into account both the particulate cellular composition of the blood and the interactions between the particulate blood and the vessel wall, in macro-circulation.

DNA/RNA Fragmentation and Cytolysis in Human Cancer Cells Treated with Diphthamide Nano Particles Derivatives

Molecular structure activity studies for some Diphthamide Nano particles derivatives indicate that the conformational characteristics along with the nature and position of the substituents on the Diphthamide Nano particles derivatives ring play an important role in their biological and biochemical activities. 

Therefore, we have calculated the optimized molecular geometries of some Diphthamide Nano particles derivatives. Calculations are carried out on the structures of these medical, medicinal and pharmaceutical Nano drugs using Hartree–Fock calculations and also Density Functional Theory (DFT) by performing HF, PM3, MM2, MM3, AM1, MP2, MP3, MP4, CCSD, CCSD(T), LDA, BVWN, BLYP and B3LYP levels of theory using the standard 31G, 6–31G*, 6–31+G*, 6–31G(3df, 3pd), 6–311G, 6–311G* and 6–311+G* basis sets of the Gaussian 09.

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Preface or the Truth Revealed

The truth revealed was when a young man, Nick Kostovic, made public his findings about the power of the Universe, the achieved knowledge he performs in the healing systems of our days. Doctors, patients, and common people thought of him as a magician who penetrated from the clouds to announce a new truth. And this is what it was-a new truth. 

The community of coastal Los Angeles became stunned when terminally sick people began to feel better, when invalids began to walk, when memories returned to Parkinson’s and Alzheimer’s-diseased patients. For the past thirty years, Kostovic has conducted research on the effects of neurological disorders on human beings and spent the last fifteen years working on several projects in connection with bioenergetic physical therapy. 

A Multi-Layer Non-Newtonian Model of Cardiovascular Inflammation

We found that such locations are correlated to the vulnerable plaque phenotype, which is prone to rupture. Our results demonstrate that at locations of high particle concentration, blood particles change the shear stress distribution and magnitude. 

Therefore, the non-Newtonian blood flow assumption provides new insights in the characterisation of plaque built up. These results are combined to in-vitro experiments that suggest the influence of blood particles in the activity of cytokines. An unbalance in pro and anti-inflammatory cytokines has been associated to an increase in inflammation and, consequently, in the volume of plaques forming.

DNA/RNA Fragmentation and Cytolysis in Human Cancer Cells Treated with Diphthamide Nano Particles Derivatives

Molecular structure activity studies for some Diphthamide Nano particles derivatives indicate that the conformational characteristics along with the nature and position of the substituents on the Diphthamide Nano particles derivatives ring play an important role in their biological and biochemical activities (Figure 1). Therefore, we have calculated the optimized molecular geometries of some Diphthamide Nano particles derivatives. 

Calculations are carried out on the structures of these medical, medicinal and pharmaceutical Nano drugs using Hartree–Fock calculations and also Density Functional Theory (DFT) by performing HF, PM3, MM2, MM3, AM1, MP2, MP3, MP4, CCSD, CCSD(T), LDA, BVWN, BLYP and B3LYP levels of theory using the standard 31G, 6–31G*, 6–31+G*, 6–31G(3df, 3pd), 6–311G, 6–311G* and 6–311+G* basis sets of the Gaussian 09.