scholarly journals Identification and Engineering of Aptamers for Theranostic Application in Human Health and Disorders

2021 ◽  
Vol 22 (18) ◽  
pp. 9661
Author(s):  
Debleena Basu ◽  
Sourabrata Chakraborty ◽  
Riddhi Pal ◽  
Tarun Kumar Sharma ◽  
Siddik Sarkar
Keyword(s):  
Human Health ◽  
In Vitro Selection ◽  
Fungal Infections ◽  
Chemical Properties ◽  
Nuclease Digestion ◽  
History Of ◽  
In Vitro Systems ◽  
Novel Biomarkers ◽  
Physical And Chemical

An aptamer is a short sequence of synthetic oligonucleotides which bind to their cognate target, specifically while maintaining similar or higher sensitivity compared to an antibody. The in-vitro selection of an aptamer, applying a conjoining approach of chemistry and molecular biology, is referred as Systematic Evolution of Ligands by Exponential enrichment (SELEX). These initial products of SELEX are further modified chemically in an attempt to make them stable in biofluid, avoiding nuclease digestion and renal clearance. While the modification is incorporated, enough care should be taken to maintain its sensitivity and specificity. These modifications and several improvisations have widened the window frame of aptamer applications that are currently not only restricted to in-vitro systems, but have also been used in molecular imaging for disease pathology and treatment. In the food industry, it has been used as sensor for detection of different diseases and fungal infections. In this review, we have discussed a brief history of its journey, along with applications where its role as a therapeutic plus diagnostic (theranostic) tool has been demonstrated. We have also highlighted the potential aptamer-mediated strategies for molecular targeting of COVID-19. Finally, the review focused on its future prospective in immunotherapy, as well as in identification of novel biomarkers in stem cells and also in single cell proteomics (scProteomics) to study intra or inter-tumor heterogeneity at the protein level. Small size, chemical synthesis, low batch variation, cost effectiveness, long shelf life and low immunogenicity provide advantages to the aptamer over the antibody. These physical and chemical properties of aptamers render them as a strong biomedical tool for theranostic purposes over the existing ones. The significance of aptamers in human health was the key finding of this review.

scholarly journals Identification and Engineering of Aptamers for Theranostic Application in Human Health and Disorders

2020 ◽  
Author(s):  
SIDDIK SARKAR ◽  
TARUN SHARMA ◽  
DEBLEENA BASU ◽  
SOURABRATA CHAKRABORTY ◽  
RIDDHI PAL
Keyword(s):  
First Generation ◽  
In Vitro Selection ◽  
Fungal Infections ◽  
In Vitro System ◽  
Nuclease Digestion ◽  
History Of ◽  
Novel Biomarkers ◽  
Exponential Enrichment ◽  
Selection Of

Aptamer is short sequence of synthetic oligonucleotides which bind to their cognate target specifically while maintaining similar or higher sensitivity as antibody. Small size, chemical synthesis, low batch variation, cost effectiveness, long shelf life and above all low immunogenicity provide advantages over antibody. The in-vitro selection of aptamer applying a conjoining approach of chemistry and molecular biology is referred as Systematic Evolution of Ligands by Exponential enrichment (SELEX). These initial products of SELEX are considered as first generation aptamers, further modified chemically in an attempt to make it stable in biofluid avoiding nuclease digestion and renal clearance. These types of aptamers are called second generation aptamers. While modification is incorporated, enough care should be taken to maintain its sensitivity and specificity. These modifications and several improvisations have widened the window frame of aptamer application that is currently not only restricted to in-vitro system, but have been used in molecular imaging for disease pathology and treatment. In food industry it is used as sensor for detection of different diseases or fungal infections. In this review we have discussed a brief history of its journey, process of synthesis, different types of modifications to improve its characters. We have also focused on its applications and highlighted its role as therapeutic plus diagnostic; theranostic tools. Finally, the review is concluded with a brief discussion on future prospective in immunotherapy, as well as in identification of novel biomarkers in stem cell, and also in single cell proteomics (scProteomics) to study intra or intertumor heterogeneity at protein level.

scholarly journals Evidence for a New Plasma Thromboplastin Factor I. Case Report, Coagulation Studies and Physicochemical Properties

Blood ◽  
1965 ◽  
Vol 26 (5) ◽  
pp. 521-532 ◽  
Author(s):  
WILLIAM E. HATHAWAY ◽  
LORETTA P. BELHASEN ◽  
HELEN S. HATHAWAY
Keyword(s):  
Chemical Properties ◽  
Coagulation Factor ◽  
Factor Deficiency ◽  
Coagulation Factor Deficiency ◽  
History Of ◽  
Fresh Plasma ◽  
Physical And Chemical ◽  
Thromboplastin Factor ◽  
Antihemophilic Factor

Abstract Studies of defective plasma thromboplastin formation in four siblings indicated a defect which was different from any of the known coagulation factor deficiency states. Although none of the children had any history of hemorrhagic tendencies, a prolonged whole blood clotting time in an 11-year-old girl led to the findings of a markedly prolonged partial thromboplastin time (PTT), abnormal thromboplastin generation test (TGT), and a normal prothrombin time in the patient and in three of her ten siblings. The abnormal PTT and TGT were corrected by aluminum hydroxide adsorbed fresh plasma and by serum. Using the kaolin-PTT system, equal mixtures of plasma from the patients and normal plasma produced a normal time. In addition, plasmas deficient in plasma thromboplastin antecedent (PTA), Hageman factor (HF), antihemophilic factor (AHF), or plasma thromboplastin component (PTC) corrected the abnormality. Physical and chemical properties of plasma correcting the defect in vitro indicated that the defect is closely related to that found in PTA and HF deficient plasma.

scholarly journals Physicochemical Characteristics of Arginine Enriched NaF Varnish: An In Vitro Study

Polymers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 2998
Author(s):  
Mohammed Nadeem Bijle ◽  
Manikandan Ekambaram ◽  
Edward Lo ◽  
Cynthia Yiu
Keyword(s):  
Molecular Dynamics ◽  
Physical Properties ◽  
Artificial Saliva ◽  
Chemical Properties ◽  
In Vitro Study ◽  
Physicochemical Characteristics ◽  
Vitro Study ◽  
Physical And Chemical ◽  
Stable Matrix

The in vitro study objectives were to investigate the effect of arginine (Arg) incorporation in a 5% sodium fluoride (NaF) varnish on its physical and chemical properties including F/Arg release. Six experimental formulations were prepared with L-arginine (L-Arg) and L-arginine monohydrochloride at 2%, 4%, and 8% w/v in a 5% NaF varnish, which served as a control. The varnishes were subjected to assessments for adhesion, viscosity, and NaF extraction. Molecular dynamics were simulated to identify post-dynamics total energy for NaF=Arg/Arg>NaF/Arg<NaF concentrations. The Arg/F varnish release profiles were determined in polyacrylic lactate buffer (pH-4.5; 7 days) and artificial saliva (pH-7; 1 h, 24 h, and 12 weeks). Incorporation of L-Arg in NaF varnish significantly influences physical properties ameliorating retention (p < 0.001). L-Arg in NaF varnish institutes the Arg-F complex. Molecular dynamics suggests that NaF>Arg concentration denotes the stabilized environment compared to NaF<Arg (p < 0.001). The 2% Arg-NaF exhibits periodic perennial Arg/F release and shows significantly higher integrated mean F release than NaF (p < 0.001). Incorporating 2% L-arginine in 5% NaF varnish improves its physical properties and renders a stable matrix with enduring higher F/Arg release than control.

scholarly journals Co-Crystals of Resveratrol and Polydatin with L-Proline: Crystal Structures, Dissolution Properties, and In Vitro Cytotoxicities

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5722
Author(s):  
Yijie Lou ◽  
Kaxi Yu ◽  
Xiajun Wu ◽  
Zhaojun Wang ◽  
Yusheng Cui ◽  
...  
Keyword(s):  
Cell Line ◽  
Chemical Properties ◽  
Cancer Cell Line ◽  
Lung Cancer Cell Line ◽  
Hek 293 ◽  
Dissolution Properties ◽  
Diphenyltetrazolium Bromide ◽  
Water Ph ◽  
Physical And Chemical

Resveratrol (RSV) and polydatin (PD) have been widely used to treat several chronic diseases, such as atherosclerosis, pulmonary fibrosis, and diabetes, among several others. However, their low solubility hinders their further applications. In this work, we show that the solubility of PD can be boosted via its co-crystallization with L-proline (L-Pro). Two different phases of co-crystals, namely the RSV-L-Pro (RSV:L-Pro = 1:2) and PD-L-Pro (PD:L-Pro = 1: 3), have been prepared and characterized. As compared to the pristine RSV and PD, the solubility and dissolution rates of PD-L-Pro in water (pH 7.0) exhibited a 15.8% increase, whereas those of RSV-L-Pro exhibited a 13.8% decrease. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of pristine RSV, PD, RSV-L-Pro, and PD-L-Pro against lung cancer cell line A549 and human embryonic kidney cell line HEK-293 indicated that both compounds showed obvious cytotoxicity against A549, but significantly reduced cytotoxicity against HEK-293, with PD/PD-L-Pro further exhibiting better biological safety than that of RSV/RSV-L-Pro. This work demonstrated that the readily available and biocompatible L-Pro can be a promising adjuvant to optimize the physical and chemical properties of RSV and PD to improve their pharmacokinetics.

scholarly journals In Vitro Selection and Characterization of Hepatitis C Virus Serine Protease Variants Resistant to an Active-Site Peptide Inhibitor

2003 ◽  
Vol 77 (6) ◽  
pp. 3669-3679 ◽  
Author(s):  
Caterina Trozzi ◽  
Linda Bartholomew ◽  
Alessandra Ceccacci ◽  
Gabriella Biasiol ◽  
Laura Pacini ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Serine Protease ◽  
In Vitro Selection ◽  
Three Dimensional ◽  
Host Cells ◽  
Dimensional Structure ◽  
In Vitro Systems

ABSTRACT The hepatitis C virus (HCV) serine protease is necessary for viral replication and represents a valid target for developing new therapies for HCV infection. Potent and selective inhibitors of this enzyme have been identified and shown to inhibit HCV replication in tissue culture. The optimization of these inhibitors for clinical development would greatly benefit from in vitro systems for the identification and the study of resistant variants. We report the use HCV subgenomic replicons to isolate and characterize mutants resistant to a protease inhibitor. Taking advantage of the replicons' ability to transduce resistance to neomycin, we selected replicons with decreased sensitivity to the inhibitor by culturing the host cells in the presence of the inhibitor and neomycin. The selected replicons replicated to the same extent as those in parental cells. Sequence analysis followed by transfection of replicons containing isolated mutations revealed that resistance was mediated by amino acid substitutions in the protease. These results were confirmed by in vitro experiments with mutant enzymes and by modeling the inhibitor in the three-dimensional structure of the protease.

Abstract 230: Lipoprotein X Causes Renal Disease in LCAT Deficiency

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Edward B Neufeld ◽  
Alice Ossoli ◽  
Seth G Thacker ◽  
Boris Vaisman ◽  
Milton Pryor ◽  
...  
Keyword(s):  
Renal Disease ◽  
Plasma Clearance ◽  
Mesangial Cells ◽  
Chemical Properties ◽  
Low Hdl ◽  
Lcat Deficiency ◽  
Physical And Chemical ◽  
Dependent Pathway

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is characterized by low HDL, accumulation of an abnormal cholesterol-rich multilamellar particle called lipoprotein-X (LpX) in plasma, and renal disease. The aim of our study was to determine if LpX is nephrotoxic and to gain insight into the pathogenesis of FLD renal disease. We administered a synthetic LpX, nearly identical to endogenous LpX in its physical, and chemical properties, to wild-type and Lcat -/- mice. Our in vitro and in vivo studies demonstrated an apoA-I and LCAT-dependent pathway for LpX conversion to HDL-like particles, which likely mediates normal plasma clearance of LpX. Plasma clearance of exogenous LpX was markedly delayed in Lcat -/- mice, which have low HDL but only minimal amounts of endogenous LpX and do not spontaneously develop renal disease. Chronically administered exogenous LpX deposited in all renal glomerular cellular and matrical compartments of Lcat -/- mice, and induced proteinuria and nephrotoxic gene changes, as well as all of the hallmarks of FLD renal disease as assessed by histological, TEM, and SEM analyses. Extensive in vivo EM studies revealed LpX uptake by macropinocytosis into mouse glomerular endothelial cells, podocytes, and mesangial cells and delivery to lysosomes, where it was degraded. Endocytosed LpX appeared to be degraded by both human podocyte and mesangial cell lysosomal PLA 2 and induced podocyte secretion of pro-inflammatory IL-6 in vitro and renal Cxl10 expression in Lcat -/- mice. In conclusion, LpX is a nephrotoxic particle that in the absence of LCAT induces all of the histological and functional hallmarks of FLD and hence may serve as a biomarker for monitoring recombinant LCAT therapy. In addition, our studies suggest that LpX-induced loss of endothelial barrier function and release of cytokines by renal glomerular cells likely plays a role in the initiation and progression of FLD nephrosis.

In vitro Degradation Analysis of 3D-architectured Gelatin-based Hydrogels

MRS Advances ◽  
2019 ◽  
Vol 5 (12-13) ◽  
pp. 633-642
Author(s):  
Jun Hon Pang ◽  
Christian Wischke ◽  
Andreas Lendlein
Keyword(s):  
Rational Design ◽  
Loss Modulus ◽  
Hydrolytic Stability ◽  
Hydrolytic Degradation ◽  
Chemical Properties ◽  
In Vitro Models ◽  
Polypeptide Backbone ◽  
Tan Δ ◽  
Physical And Chemical

ABSTRACT:Multifunctional biopolymer-based materials are promising candidates for next generation regenerative biomaterials. Understanding the degradation behavior of biomaterials is vital for ensuring biological safety, as well as for better control of degradation properties based on rational design of a material’s physical and chemical characteristics. In this study, we decipher the degradation of a hydrogel prepared from gelatin and lysine diisocyanate ethyl ester (LDI) using in vitro models, which simulate hydrolytic, oxidative and enzymatic degradation (collagenase). Gravimetrical, morphological, mechanical and chemical properties were evaluated. Notably, the hydrogels were relatively resistant to hydrolytic degradation, but degraded rapidly within 21 days (>95% mass loss) under oxidative and collagenase degradation. Oxidative and collagenase degradation rapidly decreased the storage and loss modulus of the hydrogels, and slightly increased their viscous component (tan δ). For each degradation condition, the results suggest different possible degradation pathways associated to the gelatin polypeptide backbone, urea linkages and ester groups. The primary degradation mechanisms for the investigated gelatin based hydrogels are oxidative and enzymatic in nature. The relative hydrolytic stability of the hydrogels should ensure minimal degradation during storage and handling prior to application in surgical theatres.

scholarly journals In Vitro Selection of an ATP-Binding TNA Aptamer

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4194
Author(s):  
Li Zhang ◽  
John C. Chaput
Keyword(s):  
In Vitro Selection ◽  
Hydrolytic Enzymes ◽  
Atp Binding ◽  
Biological Stability ◽  
Protein Targets ◽  
Dna And Rna ◽  
Nuclease Digestion ◽  
Polymerase Engineering ◽  
Threose Nucleic Acid

Recent advances in polymerase engineering have made it possible to isolate aptamers from libraries of synthetic genetic polymers (XNAs) with backbone structures that are distinct from those found in nature. However, nearly all of the XNA aptamers produced thus far have been generated against protein targets, raising significant questions about the ability of XNA aptamers to recognize small molecule targets. Here, we report the evolution of an ATP-binding aptamer composed entirely of α-L-threose nucleic acid (TNA). A chemically synthesized version of the best aptamer sequence shows high affinity to ATP and strong specificity against other naturally occurring ribonucleotide triphosphates. Unlike its DNA and RNA counterparts that are susceptible to nuclease digestion, the ATP-binding TNA aptamer exhibits high biological stability against hydrolytic enzymes that rapidly degrade DNA and RNA. Based on these findings, we suggest that TNA aptamers could find widespread use as molecular recognition elements in diagnostic and therapeutic applications that require high biological stability.

Reduction Roasting of Titaniferous Ores

2019 ◽  
Vol 391 ◽  
pp. 215-220 ◽  
Author(s):  
Andrey N. Dmitriev ◽  
R.V. Petukhov ◽  
G.Yu. Vitkina ◽  
E.A. Vyaznikova
Keyword(s):  
Blast Furnace ◽  
Iron Ore ◽  
Chemical Properties ◽  
Furnace Process ◽  
Transfer Processes ◽  
Mass Transfer Processes ◽  
Titanium Dioxide Content ◽  
Physical And Chemical ◽  
And Chemical Properties

Questions regarding the oxidizing roasting of raw iron ore materials (agglomerate and pellets) are studied. Features of the phase structure of raw iron ore materials containing titanium and vanadium are discussed. Reducibility, durability, and temperatures of the softening and melting of metallurgical raw iron ore materials are studied in vitro. Object of research – titaniferous ores with various titanium dioxide content. The behavior of agglomerate and pellets in a blast furnace are studied, as well as the influence of their physical and chemical properties on heat and mass transfer processes using a mathematical model of the blast furnace process [1].

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