Evaluation of a deuterated triarylmethyl spin probe for in vivo R2 ∗-based EPR oximetric imaging with enhanced dynamic range.

PURPOSE: In this study, we compared two triarylmethyl (TAM) spin probes, Ox071 and Ox063 for their efficacy in measuring tissue oxygen levels under hypoxic and normoxic conditions by R2 *-based EPR oximetry. METHODS: The R2 * dependencies on the spin probe concentration and oxygen level were calibrated using deoxygenated 1, 2, 5, and 10 mM standard solutions and 2 mM solutions saturated at 0%, 2%, 5%, 10%, and 21% of oxygen. For the hypoxic model, in vivo imaging of a MIA PaCa-2 tumor implanted in the hind leg of a mouse was performed on successive days by R2 *-based EPR oximetry using either Ox071 or Ox063. For the normoxic model, renal imaging of healthy athymic mice was performed using both spin probes. The 3D images were reconstructed by single point imaging and multi-gradient technique was used to determine R2 * maps. RESULTS: The signal intensities of Ox071 were approximately three times greater than that of Ox063 in the entire partial pressure of oxygen (pO2 ) range investigated. The histograms of the tumor pO2 images were skewed for both spin probes, and Ox071 showed more frequency counts at pO2 > 32 mm Hg. In the normoxic kidney model, there was a clear delineation between the high pO2 cortex and the low pO2 medulla regions. The histogram of high-resolution kidney oximetry image using Ox071 was nearly symmetrical and frequency counts were seen up to 55 mm Hg, which were missed in Ox063 imaging. CONCLUSION: As an oximetric probe, Ox071 has clear advantages over Ox063 in terms of sensitivity and the pO2 dynamic range.

Facile synthesis of sericin modified graphene oxide nanocomposites for treating ischemic diseases.

Ischemic heart disease (IHD) is the major reason for death worldwide. Therapeutic angiogenesis serves as an effective approach to treat IHD. Sericin (S), a natural silk protein is widely used in regenerative medicine due to its excellent bioactive properties. Graphene oxide (GO) is extensively used in the field of biomedicine due to its amazing capacity to interact with biomolecules. The main objectives of the present study are to synthesize sericin functionalized graphene oxide (SGO) nanocomposites to treat diseases associated with deficient angiogenesis. Carbodiimide induced cross-linking strategy was employed to functionalize graphene oxide using sericin. The SGO nanocomposites had wrinkled flake like structure with good blood biocompatibility. In vivo chick embryo angiogenesis (CEA) assay was performed to prove the angiogenic potency of SGO nanocomposites. CEA assay results clearly indicated the development of new blood vessels in SGO treated chick embryos when compared with the control.

Neuro-protective effects of nano-formulated hesperetin in a traumatic brain injury model of Danio rerio.

Understanding the mechanism behind neuronal regeneration is critical for treating ischemic stroke and traumatic brain injury. The presence of neural stem cells in and around the sub-ventricular zone of human and also in zebrafish is evidenced. In this current study, the neuro-protective potential of nano-formulated hesperetin on injury-induced neurogenesis in zebrafish was assessed. Nanoformulation of hesperetin was prepared by anti-solvent precipitation technique using sodium dodecyl sulfate (SDS) as the stabilizing agent. The synthesized particles were characterized using SEM, DLS, XRD and FT-IR. Anti-oxidant capacity of nano hesperetin (nHST) in in vitro followed by in vivo studies in a traumatic brain injury (TBI) model of adult zebrafish (Danio rerio), catalase activity, histological analysis and gene expression studies for the genes Sox2, Nestin, Fabp7a and HuC were carried out. The synthesized particles were found to be in nanoscale and SDS had successfully integrated with hesperetin. Moreover, nHST had a significantly higher anti-oxidant capacity in vitro. Catalase levels in nHST treated group were significantly restored compared to other groups. Histological studies supported reduced tissue damage on oral administration of nano-hesperetin as compared to other groups. Gene expression studies showed that nano-hesperetin at a concentration of 10 µM when administered orally induced proliferation of neural stem cells without inducing cell death.

Health hazards of nanoparticles: understanding the toxicity mechanism of nanosized ZnO in cosmetic products.

In recent years, nanoparticles are being used extensively in personal healthcare products such as cosmetics, sunscreens, soaps, and shampoos. Particularly, metal oxide nanoparticles are gaining competence as key industrial constituents, progressing toward a remarkable rise in their applications. Zinc oxide and titanium oxide nanoparticles are the most commonly employed metal oxide nanoparticles in sunscreens, ointments, foot care, and over the counter topical products. Dermal exposure to these metal oxides predominantly occurs through explicit use of cosmetic products and airway exposure to nanoparticle dusts is primarily mediated via occupational exposure. There is a compelling need to understand the toxicity effects of nanoparticles which can easily enter the cells and induce oxidative stress. Consequently, these products have become a direct source of pollution in the environment and thereby greatly impact our ecosystem. A complete understanding of the toxicity mechanism of nano-ZnO is intended to resolve whether and to what extent such nanoparticles may pose a threat to the environment and to human beings. In this review article, we have discussed the characteristics of metal oxide nanoparticles and its applications in the cosmetic industry. We have also highlighted about their toxicity effects and their impact on human health.

Haemostatic potency of sodium alginate/aloe vera/sericin composite scaffolds - preparation, characterisation, and evaluation.

Fabrication of haemostatic materials with excellent antimicrobial, biocompatible and biodegradable properties remains as a major challenge in the field of medicine. Haemostatic agents play vital role in protecting patients and military individuals during emergency situations. Natural polymers serve as promising materials for fabricating haemostatic compounds due to their efficacy in promoting hemostasis and wound healing. In the present work, sodium alginate/aloe vera/sericin (SA/AV/S) scaffold has been fabricated using a simple cost-effective casting method. The prepared SA/AV/S scaffolds were characterised for their physicochemical properties such as scanning electron microscope, UV-visible spectroscopy and Fourier transform infra-red spectroscopy. SA/AV/S scaffold showed good mechanical strength, swelling behaviour and antibacterial activity. In vitro experiments using erythrocytes proved the hemocompatible and biocompatible features of SA/AV/S scaffold. In vitro blood clotting assay performed using human blood demonstrated the haemostatic and blood absorption properties of SA/AV/S scaffold. Scratch wound assay was performed to study the wound healing efficacy of prepared scaffolds. Chick embryo chorioallantoic membrane assay carried out using fertilised embryos proved the angiogenic property of SA/AV/S scaffold. Thus, SA/AV/S scaffold could serve as a potential haemostatic healthcare product due to its outstanding haemostatic, antimicrobial, hemocompatible, biocompatible and angiogenic properties.

EPR and Related Magnetic Resonance Imaging Techniques in Cancer Research.

Imaging tumor microenvironments such as hypoxia, oxygenation, redox status, and/or glycolytic metabolism in tissues/cells is useful for diagnostic and prognostic purposes. New imaging modalities are under development for imaging various aspects of tumor microenvironments. Electron Paramagnetic Resonance Imaging (EPRI) though similar to NMR/MRI is unique in its ability to provide quantitative images of pO2 in vivo. The short electron spin relaxation times have been posing formidable challenge to the technology development for clinical application. With the availability of the narrow line width trityl compounds, pulsed EPR imaging techniques were developed for pO2 imaging. EPRI visualizes the exogenously administered spin probes/contrast agents and hence lacks the complementary morphological information. Dynamic nuclear polarization (DNP), a phenomenon that transfers the high electron spin polarization to the surrounding nuclear spins (1H and 13C) opened new capabilities in molecular imaging. DNP of 13C nuclei is utilized in metabolic imaging of 13C-labeled compounds by imaging specific enzyme kinetics. In this article, imaging strategies mapping physiologic and metabolic aspects in vivo are reviewed within the framework of their application in cancer research, highlighting the potential and challenges of each of them.

Structure-reactivity relationship of piperidine nitroxide: electrochemical, ESR and computational studies.

We have synthesized several nitroxides with different substituents which vary the steric and electronic environment around the N-O moiety and have systematically investigated the role of substituents on the stability of the radicals. Our results demonstrated the reactivity toward ascorbate correlates with the redox potential of the derivatives. Furthermore, ab initio calculations also indicated a correlation between the reduction rate and the computed singly occupied molecular orbital-lowest unoccupied molecular orbital energy gap, but not with solvent accessible surface area of the N-O moiety, supporting the experimental results and suggesting that the electronic factors largely determine the radicals' stability. Hence, it is possible to perform virtual screening of nitroxides to optimize their stability, which can help to rationally design novel nitroxides for their potential use in vivo.

5-Azacytidine incorporated polycaprolactone-gelatin nanoscaffold as a potential material for cardiomyocyte differentiation.

India has an alarming rate of growth of cardiovascular diseases (CVD). Similar to cancer there is a significant role for epigenetic factors in the increasing prevalence of CVD. Targeting the epigenetic mechanism, viz., the DNA methylation processes, histone modifications, and RNA based arrangements is today considered as a potential therapeutic approach to CVD management. 5-Azacytidine is an epigenetic treatment drug that is involved in the demethylation of DNA. 5-Azacytidine is an FDA approved drug for myelodysplastic syndrome. However, the usage of 5-Azacytidine for CVD has not been found acceptable because of its poor stability in neutral solutions and shorter half-live which makes it toxic to the cells. A significant breakthrough in the use of 5-azacytidine for cell therapy and tissue engineering for CVD treatment has been gained based on its ability to differentiate mesenchymal stem cells into cardiomyocytes. This work addresses the further need for a sustained release of this drug, to reduce its toxicity to the stem cells. Electrospun PCL-gelatin fibres that are well aligned to provide a mat-like structure with sufficient porosity for differentiated cells to move forward have been synthesized. The crystalline character, porosity, fibre width, thermal behavior hydrophilicity of these scaffolds are in tune with those reported in the literature as ideal for cell proliferation and adhesion. FTIR measurements confirm the entrapment of 5-azacytidine on to the scaffold. The adsorption of the drug did not alter the characteristic features of the scaffold. Primary results on cell viability and cell morphology, as well as cardiomyocyte differentiation, have shown that PCL-gelatin scaffolds carrying 5-azacytidine developed in this work could serve as an ideal platform for mesenchymal stem cell differentiation into cardiomyocytes.

Biophysical evaluation of two red-shifted hypocrellin B derivatives as novel PDT agents.

Two novel cyclohexane-1,2-diamino and N,N dimethyl amino-propyl substituted hypocrellin B derivatives, abbreviated as CHA2HB and DMAHB, respectively were synthesized. These derivatives exhibited enhanced absorption in phototherapeutic window. Photodynamic action of these derivatives, investigated using optical and electron spin resonance methods, depended on both Type I and Type II mechanisms. Gel electrophoresis indicated 1O2/O2(.-) mediated DNA damage. CHA2HB displayed 20 fold increase in light dependent cytotoxicity on colon cancer cell line (HCT 116) than the well-known hypocrellin B (HB). The light induced, LD(50) values for CHA2HB and DMAHB were found to be 0.1 microM and 1.5 microM, respectively. The singlet oxygen generating efficiency followed the order HB>CHA(2)HB>DMAHB. But, the enhanced red absorption as well as the hydrophilicity renders the CHA2HB a better photodynamic therapeutic agent.

Chlorogenic acid- loaded calcium phosphate chitosan nanogel as biofilm degradative materials.

This work describes an effort to develop an antimicrobial agent (chlorogenic acid - CGA) loaded porous nanogel based on calcium phosphate-chitosan (CaPNP@Chi) nanogel with biofilm degradative properties and has potential applications in restorative dentistry. The nanogel was prepared by ionic gelation of calcium phosphate nanoparticles and chitosan in the ratio of 1.25: 1. Chlorogenic acid was loaded to the nanoparticles as an ethanolic solution and the encapsulation efficiency determined by chromatographic techniques. The particle size and morphology of CaPNP@Chi and CaPNP@Chi@CGA was determined by dynamic light scattering and scanning electron microscopic techniques. The minimum inhibitory concentration against S. aureus and K. pneumoniae was determined through the well diffusion method. The biofilm formation and biofilm decay were studied through staining assays. The toxicity, if any of the nanogel was assessed by MTT assay against HaCaT cells. All data were statistically analyzed. The composite had a CGA encapsulation efficiency of 70% and was thermally stable up to 124 °C. The zone of inhibition was found to be 18.7 mm ± 0.6 against S. aureus. CaPNP@Chi@CGA showed a 68% increase in biofilm degradation when compared with the untreated group. Results obtained in this study suggest that the positively charged nanogel interacted with the bacterial cell membrane and brought about the disruption of the cell membrane. Also, CaPNP@Chi@CGA was observed to be nontoxic up to 40 µg/mL to HaCaT cells. These results support the potential of CaPNP@Chi@CGA nanogel for biofilm degradation and its application as filling material in restorative dentistry.

Monitoring redox-sensitive paramagnetic contrast agent by EPRI, OMRI and MRI.

A comparative study of tissue redox-status imaging using commonly used redox sensitive nitroxides has been carried out using electron paramagnetic resonance imaging (EPRI), Overhauser magnetic resonance imaging (OMRI) and conventional T(1)-weighted magnetic resonance imaging, MRI. Imaging studies using phantoms of different nitroxides at different concentration levels showed that EPRI and OMRI sensitivities were found to be linearly dependent on line width of nitroxides up to 2 mM, and the enhancement in MRI intensity was linear up to 5 mM. The sensitivity and resolution of EPRI and OMRI images depended significantly on the line width of the nitroxides whereas the MRI images were almost independent of EPR line width. Reduction of the paramagnetic 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (3CP) by ascorbic acid (AsA) to the diamagnetic by hydroxylamine was monitored from a sequence of temporal images, acquired using the three imaging modalities. The decay rates determined by all the three modalities were found to be similar. However the results suggest that T(1)-weighted MRI can monitor the redox status, in addition to providing detailed anatomical structure in a short time. Therefore, a combination of MRI with nitroxides as metabolically responsive contrast agents can be a useful technique for the in vivo imaging probing tissue redox status.

Influence of Divalent Cation on Morphology and Drug Delivery Efficiency of Mixed Polymer Nanoparticles.

BACKGROUND: Biopolymeric nanoparticles comprising chitosan-alginate have attracted interest in drug delivery due to their protective nature, biocompatibility, biodegradability and hydrophilicity. OBJECTIVE: The present study was designed to encapsulate levofloxacin in chitosan-alginate hybrid gel for controlled release and to evaluate the effect of divalent alkaline earth metal ions (Mg2+, Ca2+, Sr2+, Ba2+) on encapsulation efficiency and drug release kinetics considering their role in polyelectrolyte gelation method. METHOD: Divalent metal ions control the rigidity and elasticity of the hydrogels and have the ability to change the shape and size of nanostructure formed by chitosan-alginate. The particle size increases and encapsulation efficiency decreases with the size of the divalent ions. Spherical shaped particles were formed by Mg2+ and Ca2+, whereas Sr2+ and Ba2+ produced non-spherical particles. RESULTS: SEM image clearly shows transformation of sphere to truncated tetrahedron by Sr2+ and clear rod shape by Ba2+. CONCLUSION: Therefore, it is concluded that metal ions have significant influence on the morphology and drug encapsulation and release profile of the chitosan-alginate hybrid polymer nanoparticles.

Concise Review on Clinical Applications of Conditioned Medium Derived from Human Umbilical Cord-Mesenchymal Stem Cells (UC-MSCs).

In recent years, mesenchymal stem cells have provoked much attentiveness in the field of regenerative medicine because of their differentiation potential and the capability to facilitate tissue repair via the emancipation of biologically active molecules. They have gained interest because of their distinctive curative properties. Mesenchymal stem cells are isolated from the Wharton's jelly part of umbilical cord possessing higher proliferation capacity, immunomodulatory activity, plasticity, as well as self-renewal capacity than the mesenchymal stem cells from various origins, and it is considered to be the best resource for allogeneic transplantation. The isolated umbilical cord-derived mesenchymal stem cells are cultured in the Dulbecco's Modified Eagle's Medium, and thereby it begins to release soluble factors into the medium during the period of culture which is termed as conditioned medium. This conditioned media has both differentiation capacity and therapeutic functions. Thus, it can be able to differentiate the cells into different lineages and the paracrine effect of these cells helps in replacement of the damaged cells. This medium may accord to optimization of diagnostic and prognostic systems as well as the generation of novel and targeted therapeutic perspectives.

Role of Hippo Pathway Effector Tafazzin Protein in Maintaining Stemness of Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSC).

Tafazzin (TAZ) protein has been upregulated in various types of human cancers, although the basis for elevation is uncertain, it has been made definite that the effect of mutation in the hippo pathway, particularly when it is switched off, considerably activates tafazzin transcriptionally and thus this results in tissue or tumor overgrowth. Recent perceptions into the activity of tafazzin, have ascribed to it, a role as stem cell factor in mouse mesenchymal and as well as in neural stem cells. Being a downstream molecule in Hippo signalling, phosphorylation or dephosphorylation of tafazzin gene regulates its transcriptional activity and the stemness of mesenchymal stem cells. Commonly, extracellular matrix controls the stem cell fate commitment and perhaps tafazzin controls stemness through altering the extra cellular matrix. Extracellular matrix is generally made up of prime proteoglycans and the fate stabilization of the resulting lineages is surveilled by engineering these glycans. Tafazzin degradation and addition of proteoglycans affect physical attributes of the extracellular matrix that drives cell differentiation into various lineages. Thus, tafazzin along with major glycans present in the extracellular matrix is involved in imparting stemness. However, there are incoherent molecular events, wherein both tafazzin and the extracellular matrix components, together either activate or inhibit differentiation of stem cells. This review discusses about the role of tafazzin oncoprotein as a stemness factor.

Review on comparative efficacy of bevacizumab, panitumumab and cetuximab antibody therapy with combination of FOLFOX-4 in KRAS-mutated colorectal cancer patients.

Colorectal cancer, fourth leading form of cancer worldwide and is increasing in alarming rate in the developing countries. Treating colorectal cancer has become a big challenge worldwide and several antibody therapies such as bevacizumab, panitumumab and cetuximab are being used with limited success. Moreover, mutation in KRAS gene which is linked with the colorectal cancer initiation and progression further interferes with the antibody therapies. Considering median progression free survival and overall survival in account, this review focuses to identify the most efficient antibody therapy in combination with chemotherapy (FOLFOX-4) in KRAS mutated colorectal cancer patients. The bevacizumab plus FOLFOX-4 therapy shows about 9.3 months and 8.7 months of progression free survival for KRAS wild and mutant type, respectively. The overall survival is about 34.8 months for wild type whereas for the mutant it is inconclusive for the same therapy. In comparison, panitumumab results in better progression-free survival which is about (9.6 months) and overall survival is about (23.9 months) for the wild type KRAS and the overall survival is about 15.5 months for the mutant KRAS. Cetuximab plus FOLFOX-4 therapy shows about 7.7 months and 5.5 months of progression-free survival for wild type KRAS and mutant type, respectively. Thus, panitumumab shows significant improvement in overall survival rate for wild type KRAS, validating as a cost effective therapeutic for colorectal cancer therapy. This review depicts that panitumumab along with FOLFOX-4 has a higher response in colorectal cancer patients than the either of the two monoclonal antibodies plus FOLFOX-4.

Evaluation of potential anti-cancer activity of cationic liposomal nanoformulated Lycopodium clavatum in colon cancer cells.

Research dealing with early diagnosis and efficient treatment in colon cancer to improve patient's survival is still under investigation. Chemotherapeutic agent result in high systemic toxicity due to their non-specific actions on DNA repair and/or cell replication. Traditional medicine such as Lycopodium clavatum (LC) has been claimed to have therapeutic potentials against cancer. The present study focuses on targeted drug delivery of cationic liposomal nanoformulated LC (CL-LC) in colon cancer cells (HCT15) and comparing the efficacy with an anti-colon cancer drug, 7-ethyl-10-hydroxy-camptothecin (SN38) along with its nanoformulated form (CL-SN38). The colloidal suspension of LC was made using thin film hydration method. The drugs were characterised using ultraviolet, dynamic light scattering, scanning electron microscopy, energy, dispersive X-ray spectroscopy. Invitro drug release showed kinetics of 49 and 89% of SN38 and LC, whereas CL-SN38 and CL-LC showed 73 and 74% of sustained drug release, respectively. Studies on morphological changes, cell viability, cytotoxicity, apoptosis, cancer-associated gene expression analysis of Bcl-2, Bax, p53 by real-time polymerase chain reaction and western blot analysis of Bad and p53 protein were performed. Nanoformulated LC significantly inhibited growth and increased the apoptosis of colon cancer cells indicating its potential anti-cancer activity against colon cancer cells.

Spatially resolved biologic information from in vivo EPRI, OMRI, and MRI.

EPR spectroscopy can give biologically important information, such as tissue redox status, pO2, pH, and microviscosity, based on variation of EPR spectral characteristics (i.e., intensity, linewidth, hyperfine splitting, and spectral shape of free radical probes. EPR imaging (EPRI) can obtain 1D-3D spatial distribution of such spectral components using several combinations of magnetic field gradients. Overhauser enhanced MRI (OMRI) is a double-resonance technique of electron and nuclear spins. Because the Overhauser enhancement depends on transverse relaxation rate of the electron spin, OMRI can provide pO2 information indirectly, along with a high-resolution MR image. MRI can also indirectly detect paramagnetic behaviors of free radical contrast agents. Imaging techniques and applications relating to paramagnetic species (i.e., EPRI, OMRI, and MRI) have the potential to obtain maximally 5D information (i.e., 3D spatial + 1D spectral + 1D temporal dimensions, theoretically). To obtain suitable dimensionality, several factors, such as the EPR spectral information, spatial resolution, temporal resolution, will have to be taken into account. For this review, the EPRI, OMRI, and MRI applications for the study biological systems were evaluated for researchers to apply the method of choice and the mode of measurements to specific experimental systems.

Continuous wave EPR oximetric imaging at 300 MHz using radiofrequency power saturation effects.

A novel continuous wave (CW), radiofrequency (RF), electron paramagnetic resonance (EPR) oximetric imaging technique is proposed, based on the influence of oxygen concentration on the RF power saturation of the EPR resonance. A linear relationship is demonstrated between the partial oxygen pressure (pO(2)) and the normalized signal intensity (I(N)), defined as, I(N) = (I(HP) - I(LP))/I(LP), where I(LP) and I(HP) refer to signal intensities at low (P(L)) and high (P(H)) RF power levels, respectively. A formula for the determination of pO(2), derived on the basis of the experimental results, reliably estimated various oxygen concentrations in a five-tube phantom. This new technique was time-efficient and also avoided the missing angle problem associated with conventional spectral-spatial CW EPR oximetric imaging. In vivo power saturation oximetric imaging in a tumor bearing mouse clearly depicted the hypoxic foci within the tumor.

A neural network approach for image reconstruction in electron magnetic resonance tomography.

An object-oriented, artificial neural network (ANN) based, application system for reconstruction of two-dimensional spatial images in electron magnetic resonance (EMR) tomography is presented. The standard back propagation algorithm is utilized to train a three-layer sigmoidal feed-forward, supervised, ANN to perform the image reconstruction. The network learns the relationship between the 'ideal' images that are reconstructed using filtered back projection (FBP) technique and the corresponding projection data (sinograms). The input layer of the network is provided with a training set that contains projection data from various phantoms as well as in vivo objects, acquired from an EMR imager. Twenty five different network configurations are investigated to test the ability of the generalization of the network. The trained ANN then reconstructs two-dimensional temporal spatial images that present the distribution of free radicals in biological systems. Image reconstruction by the trained neural network shows better time complexity than the conventional iterative reconstruction algorithms such as multiplicative algebraic reconstruction technique (MART). The network is further explored for image reconstruction from 'noisy' EMR data and the results show better performance than the FBP method. The network is also tested for its ability to reconstruct from limited-angle EMR data set.

In vitro and in vivo insulin amyloid degradation mediated by Serratiopeptidase.

A transition of amyloidogenic protein by alternative folding pathway under certain conditions leads to the formation of protease resistant amyloid fibrils, having predominantly cross ß structure. These amyloids are related to various neurodegenerative diseases and clearance of such amyloids may be a therapeutic approach for amyloid-related diseases. Insulin, that can form amyloids, is widely used as a model amyloidogenic protein for the study of various amyloid related diseases. In this study, insulin amyloids were formed in vitro and the potential of Serratiopeptidase (SP), a fibrinolytic-like serine protease, towards the dissociation of insulin amyloids was explored. The dissociation of the amyloids was demonstrated using in vitro and in vivo using zebrafish model. The amyloid dissociation property was compared with a standard amyloid dissociating enzyme nattokinase (NK). SP shows better amyloid dissociation ability than NK and therefore, SP can be considered as amyloid dissociating agent with potential as a drug candidate for different amyloid related disorders.