Synthesis and characterization of Fe3O4@SiO2@PDA@Ag core-shell nanoparticles and biological application on human lung cancer cell line and antibacterial strains.

Novel magnetic and metallic nanoparticles garner much attention of researchers due to their biological, chemical and catalytic properties in many chemical reactions. In this study, we have successfully prepared a core-shell Fe3O4@SiO2@PDA nanocomposite wrapped with Ag using a simple synthesis method, characterised and tested on small cell lung cancer and antibacterial strains. Incorporating Ag in Fe3O4@SiO2@PDA provides promising advantages in biomedical applications. The magnetic Fe3O4 nanoparticles were coated with SiO2 to obtain negatively charged surface which is then coated with polydopamine (PDA). Then silver nanoparticles were assembled on Fe3O4@SiO2@PDA surface, which results in the formation core-shell nanocomposite. The synthesised nanocomposite were characterized using SEM-EDAX, dynamic light scattering, XRD, FT-IR and TEM. In this work, we report the anticancer activity of silver nanoparticles against H1299 lung cancer cell line using MTT assay. The cytotoxicity data revealed that the IC50 of Fe3O4@SiO2@PDA@Ag against H1299 lung cancer nanocomposites cells was 21.52 µg/mL. Furthermore, the biological data of nanocomposites against Gram-negative 'Pseudomonas aeruginosa' and Gram-positive 'Staphylococcus aureus' were carried out. The range of minimum inhibitory concentration was found to be 115 µg/mL where gentamicin was used as a standard drug. The synthesized AgNPs proves its supremacy as an efficient biomedical agent and AgNPs may act as potential beneficial molecule in lung cancer chemoprevention and antibacterial strains.

In the present study, we have successfully prepared a core-shell Fe₃O₄@SiO₂@PDA@Ag nanocomposite.We have investigated the dose-dependent cellular toxicity of silver nanocomposite in the nonsmall cell lung cancer cell line H1299 using MTT assay.Also, we have evaluated the mode of cell death using apoptosis.We have also evaluated the bioactivity of AgNPs on both Gram-positive and Gram-negative bacterial cells with highly efficient antibacterial potency.

Object recognition in medical images via anatomy-guided deep learning.

PURPOSE: Despite advances in deep learning, robust medical image segmentation in the presence of artifacts, pathology, and other imaging shortcomings has remained a challenge. In this paper, we demonstrate that by synergistically marrying the unmatched strengths of high-level human knowledge (i.e., natural intelligence (NI)) with the capabilities of deep learning (DL) networks (i.e., artificial intelligence (AI)) in garnering intricate details, these challenges can be significantly overcome. Focusing on the object recognition task, we formulate an anatomy-guided deep learning object recognition approach named AAR-DL which combines an advanced anatomy-modeling strategy, model-based non-deep-learning object recognition, and deep learning object detection networks to achieve expert human-like performance. METHODS: The AAR-DL approach consists of 4 key modules wherein prior knowledge (NI) is made use of judiciously at every stage. In the first module AAR-R, objects are recognized based on a previously created fuzzy anatomy model of the body region with all its organs following the automatic anatomy recognition (AAR) approach wherein high-level human anatomic knowledge is precisely codified. This module is purely model-based with no DL involvement. Although the AAR-R operation lacks accuracy, it is robust to artifacts and deviations (much like NI), and provides the much-needed anatomic guidance in the form of rough regions-of-interest (ROIs) for the following DL modules. The 2nd module DL-R makes use of the ROI information to limit the search region to just where each object is most likely to reside and performs DL-based detection of the 2D bounding boxes (BBs) in slices. The 2D BBs hug the shape of the 3D object much better than 3D BBs and their detection is feasible only due to anatomy guidance from AAR-R. In the 3rd module, the AAR model is deformed via the found 2D BBs providing refined model information which now embodies both NI and AI decisions. The refined AAR model more actively guides the 4th refined DL-R module to perform final object detection via DL. Anatomy knowledge is made use of in designing the DL networks wherein spatially sparse objects and non-sparse objects are handled differently to provide the required level of attention for each. RESULTS: Utilizing 150 thoracic and 225 head and neck (H&N) computed tomography (CT) data sets of cancer patients undergoing routine radiation therapy planning, the recognition performance of the AAR-DL approach is evaluated on 10 thoracic and 16 H&N organs in comparison to pure model-based approach (AAR-R) and pure DL approach without anatomy guidance. Recognition accuracy is assessed via location error/ centroid distance error, scale or size error, and wall distance error. The results demonstrate how the errors are gradually and systematically reduced from the 1st module to the 4th module as high-level knowledge is infused via NI at various stages into the processing pipeline. This improvement is especially dramatic for sparse and artifact-prone challenging objects, achieving a location error over all objects of 4.4 mm and 4.3 mm for the two body regions, respectively. The pure DL approach failed on several very challenging sparse objects while AAR-DL achieved accurate recognition, almost matching human performance, showing the importance of anatomy guidance for robust operation. Anatomy guidance also reduces the time required for training DL networks considerably. CONCLUSIONS: (i) High-level anatomy guidance improves recognition performance of DL methods. (ii) This improvement is especially noteworthy for spatially sparse, low-contrast, inconspicuous, and artifact-prone objects. (iii) Once anatomy guidance is provided, 3D objects can be detected much more accurately via 2D BBs than 3D BBs and the 2D BBs represent object containment with much more specificity. (iv) Anatomy guidance brings stability and robustness to DL approaches for object localization. (v) The training time can be greatly reduced by making use of anatomy guidance.

Guar gum based nanocomposites: Role in water purification through efficient removal of dyes and metal ions.

Researchers nowadays are relentlessly on a race exploring sustainable materials and techniques for the sequestration of toxic dyes and metal ions from water bodies. Biopolymers such as guar gum, owing to its high abundance, low cost and non-toxicity, are potential candidates in this field. Plenty of hydroxyl groups in the polymer backbone enable guar gum to be functionalised or grafted in a versatile manner proving itself as an excellent starting substance for fabricating upgraded materials meant for diverse applications. This review offers a comprehensive coverage of the role of guar gum-based nanocomposites in removal of dyes and heavy metal ions from waste water through adsorption and photo-catalytic degradation. Isotherm and kinetics models, fabrication routes, characterisation techniques, swelling properties and reusability as well as adsorption and degradation mechanisms are outlined. A detailed analysis with convincing results suggests a good future perspective of implementation of these materials in real-time wastewater treatment technology.

Fabrication of a Gold-Supported NiAlTi-Layered Double Hydroxide Nanocatalyst for Organic Transformations.

This work is mainly focused on the synthesis of an efficient and reusable heterogeneous Au/NiAlTi layered double hydroxide (LDH) nanocatalyst and its applications in the preparation of biologically important xanthene, 1,4-dihydropyridine, polyhydroquinoline, and 4H-pyran derivatives. NiAlTi LDH was designed hydrothermally and then gold was supported over the surface of LDH by using ion-exchange and NaBH4 reduction methods. The synthesized nanocatalyst was physicochemically characterized by X-ray diffractrometry, Fourier-transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, and transmission electron microscopy (TEM). The TEM images confirmed the support of gold nanoparticles over the surface of LDH with a size distribution of 7-9 nm. The well-characterized nanocatalyst was tested for the synthesis of biologically important xanthene, 1,4-dihydropyridine, polyhydroquinoline, and 4H-pyran derivatives. The advantages obtained were excellent yields in a lesser reaction time. Stability and reusability were also accessed; the catalyst was stable even after five cycles. High catalytic efficiency, easy fabrication, and recycling ability of Au/NiAlTi LDH make it a potential catalyst for the synthesis of xanthene, 1,4-dihydropyridine, polyhydroquinoline, and 4H-pyran derivatives.

Privileged Scaffold Chalcone: Synthesis, Characterization and Its Mechanistic Interaction Studies with BSA Employing Spectroscopic and Chemoinformatics Approaches.

Chalcone, a privileged structure, is considered as an effective template in the field of medicinal chemistry for potent drug discovery. In the present study, a privileged template chalcone was designed, synthesized, and characterized by various spectroscopic techniques (NMR, high-resolution mass spectrometry, Fourier transform infrared (FT-IR) spectroscopy, UV spectroscopy, and single-crystal X-ray diffraction). The mechanism of binding of chalcone with bovine serum albumin (BSA) was determined by multispectroscopic techniques and computational methods. Steady-state fluorescence spectroscopy suggests that the intrinsic fluorescence of BSA was quenched upon the addition of chalcone by the combined dynamic and static quenching mechanism. Time-resolved spectroscopy confirms complex formation. FT-IR and circular dichroism spectroscopy suggested the presence of chalcone in the BSA molecule microenvironment and also the possibility of rearrangement of the native structure of BSA. Moreover, molecular docking studies confirm the moderate binding of chalcone with BSA and the molecular dynamics simulation analysis shows the stability of the BSA-drug complex system with minimal deformability fluctuations and potential interaction by the covariance matrix. Moreover, pharmacodynamics and pharmacological analysis show good results through Lipinski rules, with no toxicity profile and high gastrointestinal absorptions by boiled egg permeation assays. This study elucidates the mechanistic profile of the privileged chalcone scaffold to be used in therapeutic applications.

Biology of Heme: Drug Interactions and Adverse Drug Reactions with CYP450.

Heme is central to functions of many biologically important enzymes (hemoproteins). It is an assembly of four porphyrin rings joined through methylene bridges with a central Fe (II). Heme is present in all cells, and its synthesis and degradation balance its amount in the cell. The deregulations of heme networks and incorporation in hemoproteins lead to pathogenic state. This article addresses the detailed structure, biosynthesis, degradation, and transportation associated afflictions to heme. The article is followed by its roles in various diseased conditions where it is produced mainly as the cause of increased hemolysis. It manifests the symptoms in diseases as it is a pro-oxidant, pro-inflammatory and pro-hemolytic agent. We have also discussed the genetic defects that tampered with the biosynthesis, degradation, and transportation of heme. In addition, a brief about the largest hemoprotein group of enzymes- Cytochrome P450 (CYP450) has been discussed with its roles in drug metabolism.

Designing of a Novel Indoline Scaffold Based Antibacterial Compound and Pharmacological Evaluation Using Chemoinformatics Approach.

Antibiotic resistance is not only a global public health threat but also a huge economic burden to our society that urgently needs to be addressed by improved antibiotics and continuing development of novel molecules to treat resistant bacterial infections. Nowadays combination therapies offer a competent approach to counteract antibiotic resistance in bacteria. Better knowledge of mechanisms of antibiotic resistance has lead to the finding of new alternatives to antibiotic therapy. Hence, in this article, we report a novel series of indoline derivatives and their computational study as potent antimicrobials. The present study investigates the indoline based derived library interaction with DNA gyrase B enzyme to be used as a potential antimicrobial drug. Computational approaches were employed to carry out the molecular interactions and pharmacological studies. In this study, we have compared indoline with its derivatives and have found that compound 13 (1m) resulted in the strong binding with the highest score (-9.02 kcal/mol) in the designed library where indoline showed (-6.43 kcal/mol). Furthermore, molecular dynamics simulation run also confirmed the strongest interaction of a compound and target protein with less RMSD and RMSF deviation of the complex. Notably, the compound was also found to possess the good pharmacological properties and pharmacokinetic properties.

Antibacterial and Pharmacological Evaluation of Fluoroquinolones: A Chemoinformatics Approach.

Fluoroquinolone (FQ) antibiotics are an important class of synthetic antibacterial agents. These are the most extensively used drugs for treating bacterial infections in the field of both human and veterinary medicine. Herein, the antibacterial and pharmacological properties of four fluoroquinolones: lomefloxacin, norfloxacin, ciprofloxacin, and ofloxacin have been studied. The objective of this study was to analyze the antibacterial characteristics of the different fluoroquinolones. Also, the pharmacological properties of the compounds including the Lipinski rule of five, absorption, distribution, metabolism, and excretion, LD50, drug likeliness, and toxicity were evaluated. We found that among all four FQ molecules, ofloxacin showed the highest antibacterial activity through in silico assays with a strong interaction (‒38.52 kJ/mol) with the antibacterial target protein (topoisomerase-II DNA gyrase enzyme). The pharmacological and pharmacokinetic analysis also showed that the compounds ciprofloxacin, ofloxacin, lomefloxacin and norfloxacin have good pharmacological properties. Notably, ofloxacin was found to possess an IGC50 (concentration needed to inhibit 50% growth) value of 0.286 µg/L against the Tetrahymena pyriformis protozoa. It also tested negative for the Ames toxicity test, showing its non-carcinogenic character.