Enhanced renal image contrast by ethanol fixation in phase‐contrast X‐ray computed tomography

Phase‐contrast X‐ray imaging using a crystal X‐ray interferometer can depict the fine structures of biological objects without the use of a contrast agent. To obtain higher image contrast, fixation techniques have been examined with 100% ethanol and the commonly used 10% formalin, since ethanol causes increased density differences against background due to its physical properties and greater dehydration of soft tissue. Histological comparison was also performed. A phase‐contrast X‐ray system was used, fitted with a two‐crystal X‐ray interferometer at 35 keV X‐ray energy. Fine structures, including cortex, tubules in the medulla, and the vessels of ethanol‐fixed kidney could be visualized more clearly than that of formalin‐fixed tissues. In the optical microscopic images, shrinkage of soft tissue and decreased luminal space were observed in ethanol‐fixed kidney; and this change was significantly shown in the cortex and outer stripe of the outer medulla. The ethanol fixation technique enhances image contrast by approximately 2.7–3.2 times in the cortex and the outer stripe of the outer medulla; the effect of shrinkage and the physical effect of ethanol cause an increment of approximately 78% and 22%, respectively. Thus, the ethanol‐fixation technique enables the image contrast to be enhanced in phase‐contrast X‐ray imaging.     

Wild ginseng grows in Myanmar

Ginseng, the underground parts of plants of Panax species, has been used in oriental traditional medicine for centuries. Unfortunately, because of extensive exploitation over thousands of years, the natural source of these species has been almost exhausted. Recently, we have found a wild ginseng growing in Myanmar. Here, by a combination of chemical composition study and gene sequence analysis, we unambiguously demonstrate that the wild ginseng is actually P. zingiberensis, commonly known as ginger ginseng. This ginseng was an indigenous to the southwestern China. However, now it is seriously threatened to brink of extinction and is put on the highest level of protection in China. Therefore, an appropriate protection measure is highly recommended to preserve this valuable resource, since this Myanmar ginseng might turn out to be the last P. zingiberensis, which could ever be seen in the planet.     

Prospect of Anterior Gradient 2 homodimer inhibition via repurposing FDA-approved drugs using structure-based virtual screening

Anterior Gradient 2 (AGR2) has recently been reported as a tumor biomarker in various cancers, i.e., breast, prostate and lung cancer. Predominantly, AGR2 exists as a homodimer via a dimerization domain (E60-K64); after it is self-dimerized, it helps FGF2 and VEGF to homo-dimerize and promotes the angiogenesis and the invasion of vascular endothelial cells and fibroblasts. Up till now, no small molecule has been discovered to inhibit the AGR2–AGR2 homodimer. Therefore, the present study was performed to prepare a validated 3D structure of AGR2 by homology modeling and discover a small molecule by screening the FDA-approved drugs library on AGR2 homodimer as a target protein. Thirteen different homology models of AGR2 were generated based on different templates which were narrowed down to 5 quality models sorted by their overall Z-scores. The top homology model based on PDB ID?=?3PH9 was selected having the best Z-score and was further assessed by Verify-3D, ERRAT and RAMPAGE analysis. Structure-based virtual screening narrowed down the large library of FDA-approved drugs to ten potential AGR2–AGR2 homodimer inhibitors having FRED score lower than ? 7.8 kcal/mol in which the top 5 drugs’ binding stability was counter-validated by molecular dynamic simulation. To sum up, the present study prepared a validated 3D structure of AGR2 and, for the first time reported the discovery of 5 FDA-approved drugs to inhibit AGR2–AGR2 homodimer by using structure-based virtual screening. Moreover, the binding of the top 5 hits with AGR2 was also validated by molecular dynamic simulation.

Graphic abstract

A validated 3D structure of Anterior Gradient 2 (AGR2) was prepared by homology modeling, which was used in virtual screening of FDA-approved drugs library for the discovery of prospective inhibitors of AGR2–AGR2 homodimer.

     

Microwave-assisted synthesis of triazole derivatives conjugated with piperidine as new anti-enzymatic agents

The current study was aimed for the study of piperidine-based triazole compounds for their biological potential against various enzymes. A novel library of compounds, 9a-r , having piperidine, 1,2,4-triazole, and propanamides was synthesized through consecutive steps including the formation of sulfonamide, hydrazide, 1,2,4-triazole, and thio-ether. Initially, 4-methoxybenzenesulfonyl chloride ( 1 ) and ethyl isonipecotate ( 2 ) were utilized to develop ethyl 1-(4-methoxyphenylsulfonyl)-4-piperidinecarboxylate ( 3 ). The product 3 was converted into respective hydrazide ( 4 ) which was further cyclized into 1,2,4-triazole ( 5 ) nucleus. A series of propanamides, 8a-r , were synthesized from different amines, 6a-r . These electrophiles, 8a-r , were reacted with compound 5 under conventional and microwave-assisted protocols to acquire the library of hybrids, 9a-r . The structural confirmations were availed by ¹H-NMR, ¹³C-NMR, and IR techniques. The whole series was evaluated for biological potential against acetylcholinesterase (AChE) and α-glucosidase enzymes. The biological evaluation ranges low to high in potential for different compounds based on the structural variations of synthesized compounds. Almost all the compounds remained active against both the enzymes except a few ones. The bovine serum albumin (BSA) binding study demonstrated the flow of drug in the body, and the docking study explained the interactions responsible for active behavior of synthesized compounds.     

Phytochemical profiling,antioxidant, enzyme inhibition and cytotoxic potential of Bougainvillea glabra flowers

Abstract

In this study, phytochemical composition, antioxidant, enzyme inhibition and cytotoxic activities of methanol and dichloromethane (DCM) extracts of Bougainvillea glabra (B. glabra) flowers were investigated. Methanol extract was found to have higher total bioactive contents and UHPLC-MS analysis of methanol extract revealed the presence of well-known phenolic and flavonoid compounds. Antioxidant activities were performed by radical scavenging (DPPH and ABTS), reducing power (FRAP and CUPRAC), phosphomolybdenum (TAC) and metal chelating assays. From our result, we observed that methanol extract had many antioxidant compounds. The DCM extract exhibited higher cholinesterases and α-glucosidase enzyme inhibition, while methanol extract showed significant urease inhibition. Both extracts exhibited strong to moderate cytotoxicity against MCF-7, MDA-MB-231, CaSki, DU-145 and SW-480 cancer cells with IC₅₀ values ranging from 88.49 to 304.7 µg/mL. The findings showed the B. glabra to possess considerable antioxidant, enzyme inhibition and cytotoxic potentials and therefore has potential to discover novel bioactive molecules.     

Is Curcumin the Answer to Future Chemotherapy Cocktail?

The rise in cancer cases in recent years is an alarming situation worldwide. Despite the tremendous research and invention of new cancer therapies, the clinical outcomes are not always reassuring. Cancer cells could develop several evasive mechanisms for their survivability and render therapeutic failure. The continuous use of conventional cancer therapies leads to chemoresistance, and a higher dose of treatment results in even greater toxicities among cancer patients. Therefore, the search for an alternative treatment modality is crucial to break this viscous cycle. This paper explores the suitability of curcumin combination treatment with other cancer therapies to curb cancer growth. We provide a critical insight to the mechanisms of action of curcumin, its role in combination therapy in various cancers, along with the molecular targets involved. Curcumin combination treatments were found to enhance anticancer effects, mediated by the multitargeting of several signalling pathways by curcumin and the co-administered cancer therapies. The preclinical and clinical evidence in curcumin combination therapy is critically analysed, and the future research direction of curcumin combination therapy is discussed.     

An electrochemical impedance study of the effect of pathogenic bacterial toxins on tethered bilayer lipid membrane

Pathogenic bacteria secrete various virulence factors that can directly interact with the outer lipid bilayer membrane of eukaryotic cells, inducing cell death by apoptosis or necrosis. Such virulence factors account for much of the toxic action associated with bacterial infection; therefore the detection of such proteins could provide a methodology for sensing/detection of pathogenic bacteria in, for example, food or human tissue. Detection and identification of pathogenic bacteria by conventional methods such as plating and counting in laboratory is expensive and time consuming. With growing concerns over emergence and re-emergence of pathogenic bacteria with high resistant to current antibiotics, there is a potential need for effective detection of pathogenic toxins in-vitro. This paper presents the application of tethered bilayer lipid membrane (TBLM) as a sensing platform for the detection of the clinically relevant pathogenic bacterial, Staphylococcus aureus MSSA 476 and Pseudomonas aeruginosa PAO1 via their secreted virulence factors, using electrochemical impedance spectroscopy (EIS). A non-pathogenic strain of bacteria, E. coli DH5α was used as a control. A clear difference in the impedance of the TBLM for the pathogenic vs. non-pathogenic species was observed.     

First experimental result with fluorescent X‐ray CT based on sheet‐beam geometry

Fluorescent X‐ray computed tomography (FXCT) enables us to reveal the cross‐sectional distribution of very low concentration of specific elements, e.g. I, Gd, or Au, in biomedical samples at a spatial resolution of several hundred micrometers, and it has been used to evaluate the states of cerebral perfusion and fatty acid metabolic function of small animals in vivo and ex vivo. However, since the current system employs the data‐acquisition scheme of the first‐generation type of CT, it requires a huge amount of time to obtain a whole set of projections. In order to overcome the problem, we propose a novel imaging geometry using a sheet incident beam. We performed a proof‐of‐concept experiment using a preliminary imaging system constructed at beam line BLNE‐5A, KEK. The efficacy of the proposed method is demonstrated by the reconstructed images of a physical phantom containing various concentrations of iodine solution and a mouse brain that is extracted after intravenous injection of ¹²⁷I‐IMP for observing the cerebral perfusion and then fixed with formalin. Copyright © 2009 John Wiley & Sons, Ltd.     

Study of electro-optical properties of liquid crystal/reactive mesogen-coated liquid crystal display fabricated by slit coater

We have recently proposed a slit coater method for printable liquid crystal (LC) devices. In this method, the LC/reactive mesogen (RM) mixture was directly coated uniaxially onto the substrate surface by shear flow between the slit nozzle and the substrate, and the liquid crystalline molecules were anchored by in situ photopolymerisation of RM monomers. In this study, the dependence of electro-optical properties and device parameters of LC sample cells fabricated by the slit coater on ultraviolet (UV) exposure dosage was investigated. Moreover, effects of UV exposure dosage and thermal annealing on the azimuthal anchoring energy of LC sample cells fabricated by the slit coater are presented.