Search

The study emphasizes the application of gold nanorods (GNRs) with different aspect ratios (ARs) for the development of multiplex assay for oral cancer detection. The tunable optical properties of the GNRs that rely on the geometrical alterations of the nanostructure and the corresponding change in the refractive indices of the local environment form the basis of the label-free biosensing mechanism. In the present work, two GNRs with AR 2.1 and AR 3.9 exhibiting LSPR at 620 and 775 nm were used for sensing oral cancer biomarkers (Cyfra 21-1 and CA-125). Clinically relevant salivary concentrations of CYFRA 21-1 and CA-125 were taken into consideration for designing the assay range. Herein, the antibodies against Cyfra 21-1 and CA-125 have been employed as biospecific probes to functionalize the GNRs with different ARs. Molecular interactions that induce a spectral shift of distinct plasmon band maxima facilitated quantitative assessment of the target analyte. The GNR bioprobe employed for sensing Cyfra 21-1 had a wide linear detection range of 0.496-48.4 ng mL -1 with a detection limit as low as 0.84 ng mL -1 and for CA-125 the detection range was 5-320 U mL -1 with a detection limit of 1.6 U mL -1 . The individual GNR bioprobe also showed high specificity against several interferents. For multiplexed biosensing, the plasmon spectra of the GNR bioprobe mixture showed distinct responses upon binding of single and dual targets in the sample mixture and/or artificial saliva. The quantitative data from the developed method are of high clinical significance that can aid in the understanding of clinicopathological advancements in oral cancer at an early stage. This simple yet novel nanosized optical transducer technology can be further converted into miniaturized biochips and can be deployed in clinics as a nanoparticle-based point-of-care diagnostic adjunct.

The extensive use of semiconducting nanoparticles such as quantum dots in biomedical and industrial products can lead to their inadvertent release into the freshwater system. Natural exudates in the aquatic system comprising extracellular polymeric substance (EPS) and protein-rich metabolites can eventually adsorb onto the quantum dots (QDs) surface and form an eco-corona. The alterations in the physio-chemical and toxicological behavior of CdSe/ZnS QDs under the influence of eco-corona in the freshwater system have not been explored yet. In the present study, lake water medium conditioned with exudate secreted by Scenedesmus obliquus was utilized as an eco-corona forming matrix. The time-based evolution of the eco-corona on the differently charged CdSe/ZnS QDs was analyzed using transmission electron microscopy and dynamic light scattering. Aging of amine-QDs in algal exudate for 72 h showed enhanced aggregation (Mean Hydrodynamic Diameter- 1969 nm) as compared to carboxyl-QDs (1543 nm). Further, eco-coronation tends to impart an overall negative charge to the QDs. The fluorescence intensity of amine-QDs was quenched by 84% due to the accumulation of higher eco-corona. An integrative effect of surface charge and accumulated eco-corona layer influenced the Cd 2+ ion leaching from the QDs. An enhancement in the algal cell viability treated with carboxyl - CdSe/ZnS (90%) and amine- CdSe/ZnS QDs (94%) aged for 72 h suggested that eco-corona can effectively mitigate the inherent toxicity of the QDs. The oxidative stress markers in the algal cells (LPO, SOD, and CAT) were in correlation with the cytotoxicity results. The algal photosynthetic efficiency depended on the deposition of eco-coronated QDs on the cell surface. Cellular uptake results indicated low Cd 2+ concentration of nearly 13.9 and 11.5% for carboxyl- and amine- CdSe/ZnS QDs respectively. This suggests that eco-coronation directly influences the bioavailability of engineered nanoparticles., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Over the past few decades, nanoparticle-based therapeutic and diagnostic systems have gained immense recognition. A relative improvement in the status of the global cancer burden has been successful due to the advent of nanoparticle-based formulations. However, exposure of nanoparticles (NPs) to a real-time biological media alters its native identity due to the formation of the biomolecular corona. Such biological interactions hinder the efficiency of the NPs system. The parameters that govern such intricate interaction are generally overlooked while designing nano drugs and delivery systems (nano-DDS). Fabricating nano-DDS with prolonged circulation time, enhanced drug-loading, and release capacity along with efficient clearance, remain the primary concerns associated with cancer therapeutics. This present review firstly aims to summarize the critical aspects that influence protein coronation on therapeutic nanoparticles designed for anti-cancer therapy. The role of protein corona in modifying the overall pharmacodynamics of the nanoparticle-based DDS has been discussed. Further, the studies and patents that extend the concept of protein corona into diagnostics have been elaborated. An understanding of the pros and cons associated with protein coronation would not only help us gain better insights into the fabrication of effective anti-cancer drug-delivery systems but also improve the shortcomings related to the clinical translation of these nanotherapeutics., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

DNA-dependent protein kinase (DNA-PK), a member of phosphatidylinositol-kinase family, is a key protein in mammalian DNA double-strand break (DSB) repair that helps to maintain genomic integrity. DNA-PK also plays a central role in immune cell development and protects telomerase during cellular aging. Epigenetic deregulation due to endogenous and exogenous factors may affect the normal function of DNA-PK, which in turn could impair DNA repair and contribute to genomic instability. Recent studies implicate a role for epigenetics in the regulation of DNA-PK expression in normal and cancer cells, which may impact cancer progression and metastasis as well as provide opportunities for treatment and use of DNA-PK as a novel cancer biomarker. In addition, several small molecules and biological agents have been recently identified that can inhibit DNA-PK function or expression, and thus hold promise for cancer treatments. This review discusses the impact of epigenetic alterations and the expression of DNA-PK in relation to the DNA repair mechanisms with a focus on its differential levels in normal and cancer cells., (Copyright © 2018. Published by Elsevier B.V.)

Marine sponges are a rich source of more than 50% of marine natural compounds that have been isolated from marine organisms. This review article is focused on the importance of biologically active and pharmaceutically important secondary metabolites extracted from one of the important classes of marine sponge Hyrtios sp. This review also deals with reported synthetic routes of some indole alkaloids extracted from the marine sponge Hyrtios sp. A range of bioactivities displayed by indole-based alkaloids is described., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Inflammatory mediators of the arachidonic acid cascade from cyclooxygenase (COX) and lipoxygenase (LOX) pathways are primarily responsible for many diseases in human beings. Chronic inflammation is associated with the pathogenesis and progression of cancer, arthritis, autoimmune, cardiovascular and neurological diseases. Traditional non-steroidal anti-inflammatory agents (tNSAIDs) inhibit cyclooxygenase pathway non-selectively and produce gastric mucosal damage due to COX-1 inhibition and allergic reactions and bronchospasm resulting from increased leukotriene levels. 'Coxibs' which are selective COX-2 inhibitors cause adverse cardiovascular events. Inhibition of any of these biosynthetic pathways could switch the metabolism to the other, which can lead to fatal side effects. Hence, there is undoubtedly an urgent need for new anti-inflammatory agents having dual mechanism that prevent release of both prostaglandins and leukotrienes. Though several molecules have been synthesized with this objective, their unfavourable toxicity profile prevented them from being used in clinics. Here, this integrative review attempts to identify the promising pharmacophore that serves as dual inhibitors of COX-2/5-LOX enzymes with improved safety profile. A better acquaintance of structural features that balance safety and efficacy of dual inhibitors would be a different approach to the process of understanding and interpreting the designing of novel anti-inflammatory agents., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Skin cancer in humans represents about 30% of all new cancers and is by far the most common malignancy in the Caucasian population. Exposure to radiations especially ultraviolet-B (UV-B) radiation is the major cause for development of skin cancers along with other chemical or biological factors. The growing incidence rates of skin cancer around the world, demand the need for new treatment options. Understanding the etiology and pathogenesis of skin cancer is therefore crucial for developing an effective drug against this prevailing disease. Medicinal plants are rich with numerous secondary metabolites such as flavonoids, which are now known to treat various chronic diseases, including inflammations and cancers. Flavonoids are sub-classified in to flavones, flavonols, iosflavones, flavanones, flavanols and anthocyanidins. They act on different targets including scavenging reactive oxygen species (ROS), regulation of the cell cycle, and initiation of DNA repair mechanisms, apoptotic induction and inhibition of metastasis. Innumerable evidence suggested that an increased consumption of flavonoid-rich fruits and vegetables rendered DNA protection to normal skin exposed to carcinogens such as UV-B radiation. Flavonoids also showed the potential to induce cell death mechanisms in melanoma, the most dreadful form of skin cancer. This comprehensive review presents flavonoids and their mechanism of action in relation to inflammation and skin cancer management.

Tubulin has picked up great focus as a major target in drug discovery and consequently, tubulin inhibitors have pulling in a considerable attention as anticancer agents. Numerable naturally occurring agents have focused on tubulin system act as an imperative target of cancer chemotherapy. Substantial number of tubulin inhibitors has been discovered so far and these agents are classified as indicated by their interaction. They are colchicine site binder, vinca- alkaloid related drugs and those interacting with the Taxol binding site and functioning as stabilising agents. We review the recent advances in the advancement of tubulin interfering agents and will render the current trend in the improvement of tubulin inhibitors as anticancer agents.

Methoxy-substituted chalcones, 3 were obtained using simple, efficient method from 2-naphtylethanone, 1 and aromatic aldehydes, 2. The in vitro cytotoxicity activities of the chalcones against a panel of three human cancer cell lines were explored. The tested compounds were found to possess significant cytotoxic activity. The DNA strand break and damage was quantified through alkaline comet assay, flow cytometric analysis, and chromatin condensation studies, which revealed the apoptotic nature of the compounds. Compound 3c, (3-(3,4,5-trimethoxyphenyl)-1-(2-naphthyl) prop-2-en-1-one) showed highest cytotoxicity of 0.019 μm against HeLa, 0.020 μm against HCT15 and 0.022 μm against A549. Compound 3e, (3-(3,5-dimethoxyphenyl)-1-(2-naphthyl) prop-2-en-1-one) showed better IC50 values against all the three cell lines employed for the study., (© 2013 John Wiley & Sons A/S.)

Linear and non-linear QSAR studies have been performed in present investigation with multiple linear regressions (MLR) analysis and Support vector machine (SVM) using different kernels. Three relevant descriptors out of fifteen descriptors calculated are identified as LOGP values, G3e and Rte+. Their relationship with biological activity IC50 have provided structural insights in interpretation and serializing the results into a pragmatic approachable technique. QSAR models obtained show statistical fitness and good predictability. SVM using Gaussian kernel function was found more efficient in prediction of IC50 of training set of thirty small molecules HIV-1 capsid inhibitors. Y-scrambling, PRESS and test set were used as validation parameters. SVM was found superior to training set prediction and internal validations and found inferior to external test set (11 molecules) predictions. Wherein MLR analysis it was vice-versa. Mechanistic interpretation of selected descriptors from both the models actuates further research.