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1.
BMC Biotechnol ; 24(1): 26, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38724967

ABSTRACT

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, and it leads to irreversible inflammation in intra-articular joints. Current treatment approaches for RA include non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatic drugs (DMARDs), corticosteroids, and biological agents. To overcome the drug-associated toxicity of conventional therapy and transdermal tissue barrier, an injectable NSAID-loaded hydrogel system was developed and explored its efficacy. RESULTS: The surface morphology and porosity of the hydrogels indicate that they mimic the natural ECM, which is greatly beneficial for tissue healing. Further, NSAIDs, i.e., diclofenac sodium, were loaded into the hydrogel, and the in vitro drug release pattern was found to be burst release for 24 h and subsequently sustainable release of 50% drug up to 10 days. The DPPH assay revealed that the hydrogels have good radical scavenging activity. The biocompatibility study carried out by MTT assay proved good biocompatibility and anti-inflammatory activity of the hydrogels was carried out by gene expression study in RAW 264.7 cells, which indicate the downregulation of several key inflammatory genes such as COX-2, TNF-α & 18s. CONCLUSION: In summary, the proposed ECM-mimetic, thermo-sensitive in situ hydrogels may be utilized for intra-articular inflammation modulation and can be beneficial by reducing the frequency of medication and providing optimum lubrication at intra-articular joints.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Arthritis, Rheumatoid , Hydrogels , Hydrogels/chemistry , Animals , Mice , Arthritis, Rheumatoid/drug therapy , RAW 264.7 Cells , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Extracellular Matrix/metabolism , Extracellular Matrix/drug effects , Diclofenac/pharmacology , Diclofenac/therapeutic use , Drug Liberation
2.
Bioelectrochemistry ; 158: 108681, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38493574

ABSTRACT

Polycystic ovarian syndrome (PCOS) is an endocrinal disorder characterized by multiple tiny cysts, amenorrhea, dysmenorrhea, hirsutism, and infertility. The current diagnostic tools comprise of expensive, time-consuming ultrasonography to serological test, which have low patient compliance. To address these limitations, we have developed a highly sensitive, cost effective and ultrafast immunosensor for the diagnosis of PCOS. Herein, we have fabricated a 2-D electro conductive composites of reduced Graphene oxide (rGO), Molybdenum disulfide (MoS2), and Polyaniline (PANI) as electrode material. Furthermore, for detecting an early and non-cyclic biomarker of PCOS, i.e. anti-Mullerian hormone (AMH). We utilize the specific antigen-antibody mechanism, in which monoclonal Anti-AMH antibodies were covalently immobilized using EDC-NHS chemistry on electrode. The developed biosensor was physicochemical and electrochemically characterized to demonstrate its efficiency. Further we have investigated the biosensor's performance with Cyclic Voltammetry, Differential Pulse Voltammetry, and Electrochemical Impedance Spectroscopy. We have validated that under the optimized condition the immunosensor exhibits higher sensitivity with a LOD of âˆ¼ 2.0 ng/mL with a linear range up to 100 ng/mL. Furthermore, this immunosensor works efficiently with a lower sample volume (>5 µL), which provides a sensitive, reproducible, low-cost, rapid analysis to detect AMH level in PCOS diagnosis.


Subject(s)
Aniline Compounds , Biosensing Techniques , Disulfides , Graphite , Molybdenum , Nanocomposites , Polycystic Ovary Syndrome , Graphite/chemistry , Nanocomposites/chemistry , Humans , Female , Biosensing Techniques/methods , Disulfides/chemistry , Molybdenum/chemistry , Aniline Compounds/chemistry , Polycystic Ovary Syndrome/diagnosis , Polycystic Ovary Syndrome/blood , Immunoassay/methods , Limit of Detection , Electrochemical Techniques/methods , Electric Conductivity , Electrodes
3.
Front Immunol ; 14: 1245343, 2023.
Article in English | MEDLINE | ID: mdl-37849754

ABSTRACT

Being a complex physiological process involving the removal of damaged tissue debris and creating a new microenvironment for host tissue regeneration, wound healing is still a major challenge for healthcare professionals. Disruption of this process can lead to tissue inflammation, pathogenic infections, and scar formation. Current wound healing treatments primarily focus on passive tissue healing, lacking active engagement in the healing process. In recent years, a new class of functional biomaterials based on piezoelectric properties has emerged, which can actively participate in the wound healing process by harnessing mechanical forces generated from body movement. Herein, we have fabricated a bioactive Cellulose Acetate (CA) electrospun nanofibrous mat incorporating zinc oxide (ZnO) and investigated its efficiency for accelerated wound healing. We have characterized the physicochemical properties of the fabricated nanofibrous mats using various assays, including SEM, FTIR, TGA, mechanical testing, degradation analysis, porosity measurement, hemolysis assay, and piezoelectric d33 coefficient measurement. Through our investigation, we discovered the tunned piezoelectric coefficient of fabricated specimens due to incorporating ZnO into the CA fibers. In vitro studies also confirmed enhanced cell adhesion, proliferation, and migration, indicating faster wound healing potential. Overall, our findings support the efficacy of piezoelectric-based ZnO-incorporated bioactive CA nanofibrous mats for efficient wound healing.


Subject(s)
Zinc Oxide , Humans , Zinc Oxide/pharmacology , Zinc Oxide/chemistry , Wound Healing , Cicatrix , Cellulose
4.
Int J Biol Macromol ; 248: 126477, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37640182

ABSTRACT

The quest to design a flawless wound closure system began long ago and is still underway. Introducing surgical staples is one of the most significant breakthroughs in this effort. In this work, we developed a biodegradable surgical staple to meet the optimal wound closure system criteria and other clinical requirements, such as radiography compatibility and secondary infection prevention. To meet these requirements, a naturally derived cellulose acetate (CA) fiber-reinforced poly-(l-lactic acid) (PLLA) composite was synthesized, and its physicochemical properties were determined using several characterizations such as Fourier-transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC) and Universal testing machine (UTM), etc. Taking cues from the Mantis's foreleg, a novel staple design was implemented and verified using Finite Element Analysis (FEA). The CA + PLLA staples were fabricated using melt-casted/3D-printing processes. The staples exhibited excellent biodegradation in both wound and physiological microenvironments with sufficient puncturing strength and later closed the wound's edges mechanically. In addition, the CA + PLLA staples also exhibit metal-like ductility properties to withstand horizontal skin tensions during the healing process. Further, the staples are coated with an antibiotic to combat infections effectively to provide better healing.


Subject(s)
Absorbable Implants , Cellulose , Anti-Bacterial Agents/pharmacology , Biodegradation, Environmental , Calorimetry, Differential Scanning
5.
Methods Mol Biol ; 2660: 357-372, 2023.
Article in English | MEDLINE | ID: mdl-37191809

ABSTRACT

Traditionally, disease causal mutations were thought to disrupt gene function. However, it becomes more clear that many deleterious mutations could exhibit a "gain-of-function" (GOF) behavior. Systematic investigation of such mutations has been lacking and largely overlooked. Advances in next-generation sequencing have identified thousands of genomic variants that perturb the normal functions of proteins, further contributing to diverse phenotypic consequences in disease. Elucidating the functional pathways rewired by GOF mutations will be crucial for prioritizing disease-causing variants and their resultant therapeutic liabilities. In distinct cell types (with varying genotypes), precise signal transduction controls cell decision, including gene regulation and phenotypic output. When signal transduction goes awry due to GOF mutations, it would give rise to various disease types. Quantitative and molecular understanding of network perturbations by GOF mutations may provide explanations for 'missing heritability" in previous genome-wide association studies. We envision that it will be instrumental to push current paradigm toward a thorough functional and quantitative modeling of all GOF mutations and their mechanistic molecular events involved in disease development and progression. Many fundamental questions pertaining to genotype-phenotype relationships remain unresolved. For example, which GOF mutations are key for gene regulation and cellular decisions? What are the GOF mechanisms at various regulation levels? How do interaction networks undergo rewiring upon GOF mutations? Is it possible to leverage GOF mutations to reprogram signal transduction in cells, aiming to cure disease? To begin to address these questions, we will cover a wide range of topics regarding GOF disease mutations and their characterization by multi-omic networks. We highlight the fundamental function of GOF mutations and discuss the potential mechanistic effects in the context of signaling networks. We also discuss advances in bioinformatic and computational resources, which will dramatically help with studies on the functional and phenotypic consequences of GOF mutations.


Subject(s)
Multiomics , Precision Medicine , Genome-Wide Association Study , Mutation , Gain of Function Mutation
6.
J Chem Phys ; 158(6): 064108, 2023 Feb 14.
Article in English | MEDLINE | ID: mdl-36792489

ABSTRACT

Machine learning (ML) has been used to optimize the matrix product state (MPS) ansatz for the wavefunction of strongly correlated systems. The ML optimization of MPS has been tested for the Heisenberg Hamiltonian on one-dimensional and ladder lattices, which correspond to conjugated molecular systems. The input descriptors and output for the supervised ML are lattice configurations and configuration interaction coefficients, respectively. Efficient learning can be achieved from data over the full Hilbert space via exact diagonalization or full configuration interaction, as well as over a much smaller sub-space via Monte Carlo Configuration Interaction. We show that this circumvents the need to calculate energy and operator expectation values and is therefore a computationally efficient alternative to variational optimization.

7.
Pharmaceutics ; 14(7)2022 Jul 07.
Article in English | MEDLINE | ID: mdl-35890323

ABSTRACT

Dental caries, a preventable disease, is caused by highly-adherent, acid-producing biofilms composed of bacteria and yeasts. Current caries-preventive approaches are ineffective in controlling biofilm development. Recent studies demonstrate definite advantages in using natural compounds such as trans-cinnamaldehyde in thwarting biofilm assembly, and yet, the remarkable difficulty in delivering such hydrophobic bioactive molecules prevents further development. To address this critical challenge, we have developed an innovative platform composed of components with a proven track record of safety. We fabricated and thoroughly characterised porous silicon (pSi) microparticles to carry and deliver the natural phenyl propanoid trans-cinnamaldehyde (TC). We investigated its effects on preventing the development of cross-kingdom biofilms (Streptococcus mutans and Candida albicans), typical of dental caries found in children. The prepared pSi microparticles were roughly cubic in structure with 70-75% porosity, to which the TC (pSi-TC) was loaded with about 45% efficiency. The pSi-TC particles exhibited a controlled release of the cargo over a 14-day period. Notably, pSi-TC significantly inhibited biofilms, specifically downregulating the glucan synthesis pathways, leading to reduced adhesion to the substrate. Acid production, a vital virulent trait for caries development, was also hindered by pSi-TC. This pioneering study highlights the potential to develop the novel pSi-TC as a dental caries-preventive material.

8.
J Funct Biomater ; 14(1)2022 Dec 22.
Article in English | MEDLINE | ID: mdl-36662055

ABSTRACT

Dental caries and traumatic injuries to teeth may cause irreversible inflammation and eventual death of the dental pulp. Nevertheless, predictably, repair and regeneration of the dentin-pulp complex remain a formidable challenge. In recent years, smart multifunctional materials with antimicrobial, anti-inflammatory, and pro-regenerative properties have emerged as promising approaches to meet this critical clinical need. As a unique class of smart materials, piezoelectric materials have an unprecedented advantage over other stimuli-responsive materials due to their inherent capability to generate electric charges, which have been shown to facilitate both antimicrobial action and tissue regeneration. Nonetheless, studies on piezoelectric biomaterials in the repair and regeneration of the dentin-pulp complex remain limited. In this review, we summarize the biomedical applications of piezoelectric biomaterials in dental applications and elucidate the underlying molecular mechanisms contributing to the biological effect of piezoelectricity. Moreover, we highlight how this state-of-the-art can be further exploited in the future for dental tissue engineering.

9.
J Chem Phys ; 154(9): 094117, 2021 Mar 07.
Article in English | MEDLINE | ID: mdl-33685176

ABSTRACT

The main bottleneck of a stochastic or deterministic configuration interaction method is determining the relative weights or importance of each determinant or configuration, which requires large scale matrix diagonalization. Therefore, these methods can be improved significantly from a computational standpoint if the relative importance of each configuration in the ground and excited states of molecular/model systems can be learned using machine learning techniques such as artificial neural networks (ANNs). We have used neural networks to train the configuration interaction coefficients obtained from full configuration interaction and Monte Carlo configuration interaction methods and have tested different input descriptors and outputs to find the more efficient training techniques. These ANNs have been used to calculate the ground states of one- and two-dimensional Heisenberg spin chains along with Heisenberg ladder systems, which are good approximations of polyaromatic hydrocarbons. We find excellent efficiency of training and the model this trained was used to calculate the variational ground state energies of the systems.

10.
Measur Sens ; 16: 100052, 2021 Aug.
Article in English | MEDLINE | ID: mdl-36578268

ABSTRACT

World Health Organization (WHO) declares the COVID-19 outbreak as a pandemic. The newly emerging infection has caused around one million deaths worldwide and still counting. There is no specific treatment for the disease, and it can only contain by breaking the spread. So that early and rapid diagnosis of the infection is the only way to control the outbreak. The COVID-19 virus affects the human respiratory system and subsequently infects other vital organs. In consideration of the diagnosis, the present review focuses on the critical diagnostic approaches for COVID-19, including RT-PCR, Chest-CT scan, some biosensor-based systems, etc. Moreover, this review is a specific bird's eye view on recent developments on the point of care devices and related technologies. Additionally, it presented a small glimpse of the pathophysiology and structural aspects of COVID-19. Therefore, the current review can motivate and help the reader to develop cutting-edge diagnostic technologies for the early and rapid detection of the COVID-19.

11.
Int J Biol Macromol ; 165(Pt A): 333-345, 2020 Dec 15.
Article in English | MEDLINE | ID: mdl-32980413

ABSTRACT

The current study aims to check various behavioural, developmental, cytotoxic, and genotoxic effects of Fe3O4-GG nanocomposite (GGNCs) on Drosophila melanogaster. Fe3O4 nanoparticles were prepared by the chemical co-precipitation method and cross-linked with guargum nanoparticles to prepare the nanocomposites. The nanocomposites were characterized by using transmission electron microscopy (TEM), X-ray diffraction (XRD), and FTIR techniques. To investigate the biomolecular interaction, GGNCs was further tagged with Fluorescein isothiocyanate. Various concentrations of nanocomposites were mixed with the food and flies were allowed to complete the life cycle. The life cycle of the flies was studied as a function of various concentrations of GGNCs. The 1st instar larvae after hatching from the egg start eating the food mixed with GGNCs. The 3rd instar larvae were investigated for various behavioural and morphological abnormalities within the gut. The 3rd instar larva has defective crawling speed, crawling path, and more number of micronuclei within the gut. Similarly, in adult flies thermal sensitivity, climbing behaviour was found to be altered. In adult flies, a significant reduction in body weight was found which is further correlated with variation of protein, carbohydrate, triglyceride, and antioxidant enzymes. Altogether, the current study suggests GGNCs as a non-genotoxic nanoparticle for various biological applications.


Subject(s)
Coated Materials, Biocompatible , DNA Damage , Ferrosoferric Oxide , Galactans , Mannans , Plant Gums , Animals , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Drosophila melanogaster , Ferrosoferric Oxide/chemistry , Ferrosoferric Oxide/pharmacology , Galactans/chemistry , Galactans/pharmacology , Larva/growth & development , Mannans/chemistry , Mannans/pharmacology , Plant Gums/chemistry , Plant Gums/pharmacology
12.
ACS Chem Neurosci ; 11(11): 1610-1619, 2020 06 03.
Article in English | MEDLINE | ID: mdl-32407096

ABSTRACT

The accumulation of an inherently disordered protein α-synuclein (α-syn) aggregates in brain tissue play a pivotal role in the pathology and etiology of Parkinson's disease. Aggregation of α-syn has been found to be complex and heterogeneous, occurring through multitudes of early- and late-stage intermediates. Because of the inherent complexity and large dynamic range (between a few microseconds to several days under in vitro measurement conditions), it is difficult for the conventional biophysical and biochemical techniques to sample the entire time window of α-syn aggregation. Here, for the first time, we introduced the Z-scan technique as a novel tool to investigate different conformations formed in the early and late stage of temperature and mechanical stress-induced α-syn aggregation, in which different species showed its characteristic nonlinear characteristics. A power-dependent study was also performed to observe the changes in the protein nonlinearity. The perceived nonlinearity was accredited to the thermal-lensing effect. A switch in the sign of the refractive nonlinearity was observed for the first time as a signature of the late oligomeric conformation, a prime suspect that triggers cell death associated with neurodegeneration. We validate Z-scan results using a combination of different techniques, like thioflavin-T fluorescence assay, fluorescence correlation spectroscopy, Fourier-transform infrared spectroscopy, and atomic force microscopy. We believe that this simple, inexpensive, and sensitive method can have potential future applications in detecting/monitoring conformations in other essential peptides/proteins related to different neurodegenerative and other human diseases.


Subject(s)
Parkinson Disease , alpha-Synuclein , Brain/metabolism , Humans , alpha-Synuclein/metabolism
13.
Carbohydr Res ; 491: 107983, 2020 May.
Article in English | MEDLINE | ID: mdl-32229325

ABSTRACT

Herein we report the synthesis of newer guar gum cinnamate esters (GGC) following a Hofmeister cation guided homogeneous phase reaction. High degree of substitution (DS) guar gum cinnamate was obtained using, cinnamic acid halide reactant at a 1:3 M ratio. The biopolymer was fully characterized in FT-IR,13C NMR, XRD and thermal analysis. Nanoparticles were further developed in a facile ouzo solvent diffusion technique. SEM studies confirmed quasi spherical shape of the nanoparticles (GGCN) with an average size of 200 nm. Nanoparticles GGCN, expressed antibacterial activity against water borne gram negative and gram positive bacteria. The MIC was recorded at 300 µg mL-1against Escherichia coli and 500 µg mL-1against Staphylococcus aureus. Bacterial contact killing was confirmed from the bacterial morphology studies in SEM. Thus, nanoparticles from GGC may be employed for bacterial killing and water decontamination.


Subject(s)
Anti-Bacterial Agents/pharmacology , Cinnamates/pharmacology , Escherichia coli/drug effects , Esters/pharmacology , Galactans/pharmacology , Mannans/pharmacology , Nanoparticles/chemistry , Plant Gums/pharmacology , Staphylococcus aureus/drug effects , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Cinnamates/chemical synthesis , Cinnamates/chemistry , Dose-Response Relationship, Drug , Esters/chemical synthesis , Esters/chemistry , Galactans/chemical synthesis , Galactans/chemistry , Mannans/chemical synthesis , Mannans/chemistry , Microbial Sensitivity Tests , Molecular Structure , Plant Gums/chemical synthesis , Plant Gums/chemistry , Structure-Activity Relationship , Water Microbiology
14.
Indian Pediatr ; 57(2): 174-175, 2020 02 15.
Article in English | MEDLINE | ID: mdl-32060246

ABSTRACT

This cross-sectional study assessed distribution and pattern of echocardiography confirmed congenital heart disease, among 593 pediatric patients in outpatient departments of a tertiary care hospital in eastern India. Commonest defects were ventricular septal defect (43, 40.7%), atrial septal defect (241, 31.7%), and tetralogy of Fallot (125, 21%).


Subject(s)
Heart Defects, Congenital/diagnosis , Heart Defects, Congenital/epidemiology , Child , Child, Preschool , Cross-Sectional Studies , Delayed Diagnosis , Female , Humans , India/epidemiology , Infant , Male
15.
Proc Natl Acad Sci U S A ; 116(17): 8107-8118, 2019 04 23.
Article in English | MEDLINE | ID: mdl-30975745

ABSTRACT

We show that for the blackbox polynomial identity testing (PIT) problem it suffices to study circuits that depend only on the first extremely few variables. One needs only to consider size-s degree-s circuits that depend on the first [Formula: see text] variables (where c is a constant and composes a logarithm with itself c times). Thus, the hitting-set generator (hsg) manifests a bootstrapping behavior-a partial hsg against very few variables can be efficiently grown to a complete hsg. A Boolean analog, or a pseudorandom generator property of this type, is unheard of. Our idea is to use the partial hsg and its annihilator polynomial to efficiently bootstrap the hsg exponentially w.r.t. variables. This is repeated c times in an efficient way. Pushing the envelope further we show that (i) a quadratic-time blackbox PIT for 6,913-variate degree-s size-s polynomials will lead to a "near"-complete derandomization of PIT and (ii) a blackbox PIT for n-variate degree-s size-s circuits in [Formula: see text] time, for [Formula: see text], will lead to a near-complete derandomization of PIT (in contrast, [Formula: see text] time is trivial). Our second idea is to study depth-4 circuits that depend on constantly many variables. We show that a polynomial-time computable, [Formula: see text]-degree hsg for trivariate depth-4 circuits bootstraps to a quasipolynomial time hsg for general polydegree circuits and implies a lower bound that is a bit stronger than that of Kabanets and Impagliazzo [Kabanets V, Impagliazzo R (2003) Proceedings of the Thirty-Fifth Annual ACM Symposium on Theory of Computing STOC '03].

16.
Biochemistry ; 58(8): 1109-1119, 2019 02 26.
Article in English | MEDLINE | ID: mdl-30694039

ABSTRACT

In this study, we have designed and synthesized a new hybrid ligand (SCG) that can selectively detect cysteine in the free and protein-bound states within minutes at the subnanomolar level. Photoinduced electron transfer was responsible for the visible color change as well as a large increase in steady state fluorescence. This detection was validated by using multiple model protein systems with differing cysteine environments and spatial arrangements. SCG was able to monitor the early events of the folding/aggregation kinetics of α-synuclein, a protein involved in the pathology of Parkinson's disease. The early events consisted of conformational fluctuations between different forms of the protein and oligomer formation. SCG was found to be effective in detecting early isomers of α-syn in vitro and in live cell environments.


Subject(s)
Cell Proliferation , Cysteine/chemistry , Fluorescent Dyes/chemistry , Neuroblastoma/pathology , Protein Multimerization , Small Molecule Libraries/chemistry , alpha-Synuclein/chemistry , Humans , Neuroblastoma/metabolism , Tumor Cells, Cultured , alpha-Synuclein/metabolism
17.
ACS Chem Neurosci ; 10(3): 1300-1310, 2019 03 20.
Article in English | MEDLINE | ID: mdl-30620180

ABSTRACT

The aggregation of α-synuclein (α-Syn) has been implicated strongly in Parkinson's disease (PD). The intrinsically disordered nature of α-Syn makes this protein prone to self-association or heteroassociation with another protein or lipid. While conformational fluctuation and free radical chemistry have been shown to play important roles in its ability toward self- and heteroassociation, any systematic understanding of their contributions is missing. Here, we report an in vitro investigation of the interaction between α-Syn and cytochrome c in the oxidized (cyt c III) and reduced forms (cyt c II), in which cyt c III was found to induce a large compaction of α-Syn and inhibit the aggregation by favoring a hetero-dityrosine bond formation. In contrast, the presence of cyt c II did not result in any compaction and its presence was found to facilitate α-Syn aggregation. The variation in the charge distribution of the surface residues of cyt c III and cyt c II is expected to play a decisive role in their interaction with α-Syn.


Subject(s)
Cytochromes c/metabolism , Protein Aggregation, Pathological/metabolism , alpha-Synuclein/metabolism , Cytochromes c/chemistry , Enzyme Inhibitors/chemistry , Escherichia coli , Free Radicals/chemistry , Free Radicals/metabolism , Humans , Imidazoles/chemistry , Oxidation-Reduction , Protein Binding , Recombinant Proteins/chemistry , Recombinant Proteins/metabolism , alpha-Synuclein/chemistry
18.
Chem Sci ; 10(40): 9270-9276, 2019 Oct 28.
Article in English | MEDLINE | ID: mdl-32055312

ABSTRACT

Combining the roles of spin frustration and geometry of odd and even numbered rings in polyaromatic hydrocarbons (PAHs), we design small molecules that show exceedingly small singlet-triplet gaps and stable triplet ground states. Furthermore, a computationally efficient protocol with a model spin Hamiltonian is shown to be capable of qualitative agreement with respect to high level multireference calculations and therefore, can be used for fast molecular discovery and screening.

19.
Int J Biol Macromol ; 120(Pt B): 1823-1833, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30287366

ABSTRACT

The present work reports the synthesis of new generation semi-interpenetrating (s-IPN) hydrogels from carboxymethyl guar gum (CMGG) and gelatin with enhanced gel properties for suitable drug delivery applications. Hydrogels are three dimensional polymer networks which respond to water and ion interactions. Irreversible s-IPN hydrogels were prepared by CMGG interactions in gelatin and characterized in FT-IR, SEM and thermal studies. CMGG was synthesized by Hofmeister ion guided homogeneous phase reactions. The swelling kinetics of the newer s-IPN hydrogels followed Schott's pseudo second order model. Furthermore, the hydrogels were hemocompatible, non-cytotoxic and appropriate for applications in physiological environment. Model drug ciprofloxacin was loaded within the hydrogels and the drug release was found to be a combination of both diffusion and hydrogel degradation. New generation s-IPN biopolymer hydrogels of carboxymethyl guar gum and gelatin holds promise for its application as sustained drug delivery device or alternatively as hydrogel sorbents for bio-toxins and molecules of biomedical importance.


Subject(s)
Ciprofloxacin/chemistry , Drug Carriers/chemistry , Galactans/chemistry , Gelatin/chemistry , Hydrogels/chemistry , Mannans/chemistry , Plant Gums/chemistry , Animals , Delayed-Action Preparations , Drug Carriers/toxicity , Hydrogels/toxicity , Kinetics , Materials Testing , Mechanical Phenomena , Mice , NIH 3T3 Cells , Temperature
20.
Sci Rep ; 8(1): 5481, 2018 04 03.
Article in English | MEDLINE | ID: mdl-29615762

ABSTRACT

Aggregation of alpha synuclein has strong implications in Parkinson's disease. The heterogeneity of folding/aggregation landscape and transient nature of the early intermediates result in difficulty in developing a successful therapeutic intervention. Here we used fluorescence measurements at ensemble and single molecule resolution to study how the late and early events of alpha synuclein aggregation modulate each other. In-vitro aggregation data was complemented using measurements inside live neuroblastoma cells by employing a small molecule labeling technique. An inhibitor molecule (arginine), which delayed the late event of amyloidosis, was found to bind to the protein, shifting the early conformational fluctuations towards a compact state. In contrast, a facilitator of late aggregation (glutamate), was found to be excluded from the protein surface. The presence of glutamate was found to speed up the oligomer formation at the early stage. We found that the effects of the inhibitor and facilitator were additive and as a result they maintained a ratio at which they cancelled each other's influence on different stages of alpha synuclein aggregation.


Subject(s)
Amyloid/chemistry , Protein Multimerization/drug effects , Small Molecule Libraries/pharmacology , alpha-Synuclein/chemistry , Arginine/pharmacology , Glutamic Acid/pharmacology , HeLa Cells , Humans , Kinetics , Protein Structure, Secondary
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