scholarly journals An explicitly designed paratope of Amyloid-β prevents neuronal apoptosis in vitro and hippocampal damage in rat brain

2021 ◽  
Author(s):  
Ashim Paul ◽  
Sourav Kumar ◽  
Sujan Kalita ◽  
Sourav Kalita ◽  
Dibakar Sarkar ◽  
...  
Keyword(s):  
Rat Brain ◽  
Biomedical Applications ◽  
Neuronal Apoptosis ◽  
Amyloid Β ◽  
Great Promise ◽  
Hippocampal Damage ◽  
Synthetic Antibody ◽  
Wide Range ◽  
Synthetic Antibodies

Synthetic antibodies hold great promise in combating diseases, diagnosis, and a wide range of biomedical applications. However, designing a therapeutically amenable, synthetic antibody that can arrest the aggregation of Amyloid-β...

scholarly journals Activation of the receptor tyrosine kinase RET improves long-term hematopoietic stem cell outgrowth and potency

Blood ◽  
2020 ◽  
Vol 136 (22) ◽  
pp. 2535-2547 ◽  
Author(s):  
W. Grey ◽  
R. Chauhan ◽  
M. Piganeau ◽  
H. Huerga Encabo ◽  
M. Garcia-Albornoz ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Culture Conditions ◽  
Cellular Growth ◽  
Great Promise ◽  
Bone Marrow Niche ◽  
Hematopoietic Stem ◽  
Intracellular Signaling Pathway ◽  
Wide Range

Abstract Expansion of human hematopoietic stem cells (HSCs) is a rapidly advancing field showing great promise for clinical applications. Recent evidence has implicated the nervous system and glial family ligands (GFLs) as potential drivers of hematopoietic survival and self-renewal in the bone marrow niche; how to apply this process to HSC maintenance and expansion has yet to be explored. We show a role for the GFL receptor, RET, at the cell surface of HSCs in mediating sustained cellular growth, resistance to stress, and improved cell survival throughout in vitro expansion. HSCs treated with the key RET ligand/coreceptor complex, glial-derived neurotrophic factor and its coreceptor, exhibit improved progenitor function at primary transplantation and improved long-term HSC function at secondary transplantation. Finally, we show that RET drives a multifaceted intracellular signaling pathway, including key signaling intermediates protein kinase B, extracellular signal-regulated kinase 1/2, NF-κB, and p53, responsible for a wide range of cellular and genetic responses that improve cell growth and survival under culture conditions.

A Review on Application of Novel Solid Nanostructures in Drug Delivery

2018 ◽  
Vol 53 ◽  
pp. 22-36 ◽  
Author(s):  
Habibollah Faraji ◽  
Reza Nedaeinia ◽  
Esmaeil Nourmohammadi ◽  
Bizan Malaekeh-Nikouei ◽  
Hamid Reza Sadeghnia ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Therapy ◽  
Biomedical Applications ◽  
Imaging Biomarkers ◽  
Cellular Functions ◽  
Scientific Innovation ◽  
Wide Range ◽  
Targeted Drug

Nanotechnology as a multidisciplinary and scientific innovation plays an important role in numerous biomedical applications, such as molecular imaging, biomarkers and biosensors and also drug delivery. A wide range of studies have been conducted on using of nanoparticles for early diagnosis and targeted drug therapy of various diseases. In fact, the small size, customized surface, upgraded solubility, or multi-functionality of nanoparticles enabled them to interact with complex cellular functions in new ways which opened many doors and created new biomedical applications. These studies demonstrated that nanotechnology vehicles can formulate biological products effectively, and this nano-formulated products with a potent ability against different diseases, were represented to have better biocompatibility, bioaccessibility and efficacy, under in vitro and in vivo conditions.

scholarly journals Aβ42 fibril formation from predominantly oligomeric samples suggests a link between oligomer heterogeneity and fibril polymorphism

2019 ◽  
Vol 6 (7) ◽  
pp. 190179 ◽  
Author(s):  
Christine Xue ◽  
Joyce Tran ◽  
Hongsu Wang ◽  
Giovanna Park ◽  
Frederick Hsu ◽  
...  
Keyword(s):  
Growth Rate ◽  
Green Tea ◽  
Epigallocatechin Gallate ◽  
Amyloid Β ◽  
Lag Time ◽  
Aβ Oligomers ◽  
Wide Range ◽  
Aβ Aggregation

Amyloid-β (Aβ) oligomers play a central role in the pathogenesis of Alzheimer's disease. Oligomers of different sizes, morphology and structures have been reported in both in vivo and in vitro studies, but there is a general lack of understanding about where to place these oligomers in the overall process of Aβ aggregation and fibrillization. Here, we show that Aβ42 spontaneously forms oligomers with a wide range of sizes in the same sample. These Aβ42 samples contain predominantly oligomers, and they quickly form fibrils upon incubation at 37°C. When fractionated using ultrafiltration filters, the samples enriched with smaller oligomers form fibrils at a faster rate than the samples enriched with larger oligomers, with both a shorter lag time and faster fibril growth rate. This observation is independent of Aβ42 batches and hexafluoroisopropanol treatment. Furthermore, the fibrils formed by the samples enriched with larger oligomers are more readily solubilized by epigallocatechin gallate, a main catechin component of green tea. These results suggest that the fibrils formed by larger oligomers may adopt a different structure from fibrils formed by smaller oligomers, pointing to a link between oligomer heterogeneity and fibril polymorphism.

Design Considerations and Assays for Hemocompatibility of FDA-Approved Nanoparticles

2019 ◽  
Vol 46 (05) ◽  
pp. 637-652
Author(s):  
Amit K. Saha ◽  
Min-Yi S. Zhen ◽  
Folarin Erogbogbo ◽  
Anand K. Ramasubramanian
Keyword(s):  
Biomedical Applications ◽  
Inflammatory Responses ◽  
Mode Of Delivery ◽  
Systemic Circulation ◽  
In Vitro Assays ◽  
Cardiovascular Tissues ◽  
Wide Range ◽  
The Us ◽  
Imaging Sensors

AbstractNanoparticles have numerous biomedical applications including, but not limited to, targeted drug delivery, diagnostic imaging, sensors, and implants for a wide range of diseases including cancer, diabetes, heart disease, and tuberculosis. Although the mode of delivery of the nanoparticles depends on the application and the disease, the nanoparticles are often in immediate contact with the systemic circulation either because of intravenous administration or their ability to enter the bloodstream with relative ease or their longer survival time in circulation. Once in circulation, the nanoparticles may elicit unintended hemostatic and inflammatory responses, and hence the design of nanoparticles for therapeutic applications should take broad hemocompatibility concerns into consideration. In this review, we present the principles underlying the structural and functional design of various classes of nanoparticles that are currently approved by the US Food and Drug Administration, categorize these particles based on their interactions with cardiovascular tissues and ensuing adverse events, and also describe various in vitro assays that may be used evaluate their hemocompatibility.

In Vitro Examination of Poly(glycerol sebacate) Degradation Kinetics: Effects of Porosity and Cure Temperature

2014 ◽  
Vol 1621 ◽  
pp. 87-92 ◽  
Author(s):  
Nadia M. Krook ◽  
Courtney LeBlon ◽  
Sabrina S. Jedlicka
Keyword(s):  
Biomedical Applications ◽  
Degradation Kinetics ◽  
Morphological Changes ◽  
Scanning Calorimetry ◽  
Tissue Engineering Scaffolds ◽  
Degradation Study ◽  
Wide Range ◽  
Thermal Changes ◽  
Cure Temperature

ABSTRACTPoly(glycerol sebacate) (PGS) is a biodegradable and biocompatible elastomer that has been used in a wide range of biomedical applications. While a porous format is common for tissue engineering scaffolds, to allow cell ingrowth, PGS degradation has been primarily studied in a nonporous format. The purpose of this research was to investigate the degradation of porous PGS at three frequently used cure temperatures: 120°C, 140°C, and 165°C. The thermal, chemical, mechanical, and morphological changes were examined using thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, compression testing, and scanning electron microscopy. Over the course of the 16-week degradation study, the samples’ pores collapsed. The specimens cured at 120°C demonstrated the most degradation and became gel-like after 16 weeks. Thermal changes were most evident in the 120°C and 140°C cure PGS specimens, as shifts in the melting and recrystallization temperatures occurred. Porous samples cured at all three temperatures displayed a decrease in compressive modulus after 16 weeks. This in vitro study helped to elucidate the effects of porosity and cure temperature on the biodegradation of PGS and will be valuable for the design of future PGS scaffolds.

scholarly journals Squalamine and Its Derivatives Modulate the Aggregation of Amyloid-β and α-Synuclein and Suppress the Toxicity of Their Oligomers

2021 ◽  
Vol 15 ◽  
Author(s):  
Ryan Limbocker ◽  
Roxine Staats ◽  
Sean Chia ◽  
Francesco S. Ruggeri ◽  
Benedetta Mannini ◽  
...  
Keyword(s):  
Small Molecules ◽  
Neuroblastoma Cells ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Human Neuroblastoma Cells ◽  
Human Neuroblastoma ◽  
Parkinson’S Diseases ◽  
Wide Range ◽  
Opposing Effects

The aberrant aggregation of proteins is a key molecular event in the development and progression of a wide range of neurodegenerative disorders. We have shown previously that squalamine and trodusquemine, two natural products in the aminosterol class, can modulate the aggregation of the amyloid-β peptide (Aβ) and of α-synuclein (αS), which are associated with Alzheimer’s and Parkinson’s diseases. In this work, we expand our previous analyses to two squalamine derivatives, des-squalamine and α-squalamine, obtaining further insights into the mechanism by which aminosterols modulate Aβ and αS aggregation. We then characterize the ability of these small molecules to alter the physicochemical properties of stabilized oligomeric species in vitro and to suppress the toxicity of these aggregates to varying degrees toward human neuroblastoma cells. We found that, despite the fact that these aminosterols exert opposing effects on Aβ and αS aggregation under the conditions that we tested, the modifications that they induced to the toxicity of oligomers were similar. Our results indicate that the suppression of toxicity is mediated by the displacement of toxic oligomeric species from cellular membranes by the aminosterols. This study, thus, provides evidence that aminosterols could be rationally optimized in drug discovery programs to target oligomer toxicity in Alzheimer’s and Parkinson’s diseases.

scholarly journals Thymodepressin—Unforeseen Immunosuppressor

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6550
Author(s):  
Vladislav I. Deigin ◽  
Julia E. Vinogradova ◽  
Dmitry L Vinogradov ◽  
Marina S. Krasilshchikova ◽  
Vadim T. Ivanov
Keyword(s):  
Experimental Evidence ◽  
Synthetic Peptide ◽  
Biomedical Applications ◽  
Biological Properties ◽  
Peptide Drug ◽  
Wide Range ◽  
History Of ◽  
Available Information

The paper summarizes the available information concerning the biological properties and biomedical applications of Thymodepressin. This synthetic peptide drug displays pronounced immunoinhibitory activity across a wide range of conditions in vitro and in vivo. The history of its unforeseen discovery is briefly reviewed, and the current as well as potential expansion areas of medicinal practice are outlined. Additional experimental evidence is obtained, demonstrating several potential advantages of Thymodepressin over another actively used immunosuppressor drug, cyclosporin A.

A Peptide Based Pro-Drug Ameliorates Amyloid-β Induced Neuronal Apoptosis in In Vitro SH-SY5Y Cells

2017 ◽  
Vol 14 (12) ◽  
Author(s):  
Sourav Kumar ◽  
Ashim Paul ◽  
Sourav Kalita ◽  
Awanish Kumar ◽  
Saurabh Srivastav ◽  
...  
Keyword(s):  
Neuronal Apoptosis ◽  
Amyloid Β

scholarly journals Compartmental Analysis of Diprenorphine Binding to Opiate Receptors in the Rat in vivo and its Comparison with Equilibrium Data in vitro

1991 ◽  
Vol 11 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Vincent J. Cunningham ◽  
Susan P. Hume ◽  
Gary R. Price ◽  
Randall G. Ahier ◽  
Jill E. Cremer ◽  
...  
Keyword(s):  
Rat Brain ◽  
Rate Constant ◽  
Compartmental Model ◽  
Forward Rate ◽  
Receptor Ligand ◽  
Wide Range ◽  
Regional Estimates ◽  
Specific Activities

The regional binding of the opiate receptor ligand diprenorphine has been examined in rat brain both in vivo and in vitro. The time course of total label in specific brain regions was followed up to 2 h after intravenous bolus injection of [3H]diprenorphine, with or without a pulse chase of unlabelled diprenorphine at 30 min. In addition, total label was measured 30 min after injection of labelled diprenorphine at nontracer concentrations over a range of specific activities. Total data sets for each region were fitted simultaneously to a compartmental model to give estimates of maximal binding capacity (Bmax), the second-order apparent association rate constant, and the first-order dissociation rate constant of the receptor-ligand complex. The model incorporated the use of a reference region with low specific binding (cerebellum). The binding of diprenorphine to rat brain homogenates was measured in vitro under equilibrium conditions at 37°C, pH 7.4, in the presence and absence of naloxone, to give corresponding regional estimates of Bmax and the half-saturation constant Kd The results showed a close correlation between in vitro and in vivo regional estimates of Bmax over a wide range. There were no significant interregional differences either in Kd in vitro or in the Kd derived from the in vivo analysis, although in vitro and in vivo estimates differed by an order of magnitude. This work was carried out as part of a validation study with a view to the application of the compartmental model to data obtained in vivo in humans using positron emission tomography, when successive studies over a range of specific activities are not feasible. Restriction of the rat data to tracer alone and pulse chase protocols showed that the compartmental model gave regional estimates of the combined forward rate constant consistent with estimates obtained using the complete data set.

Protective effects of β-sheet breaker α/β-hybrid peptide against amyloid β-induced neuronal apoptosis in vitro

2016 ◽  
Vol 89 (6) ◽  
pp. 888-900 ◽  
Author(s):  
Sourav Kumar ◽  
Ashim Paul ◽  
Sourav Kalita ◽  
Anup Kumar Ghosh ◽  
Bhubaneswar Mandal ◽  
...  
Keyword(s):  
Neuronal Apoptosis ◽  
Amyloid Β ◽  
Protective Effects ◽  
Hybrid Peptide ◽  
Β Sheet
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