Exploring the anticancer properties of essential oils from family Lamiaceae

Lamiaceae is among the largest families of flowering plants with about 250 genera and over 7,000 species distributed around the world. It is considered as the important source of essential oils, for example, menthol, geraniol, eucalyptol, camphor and thymol. Therefore, it is imperative to study these economically important compounds under in vitro conditions for their sustainable and enhanced production. In addition to proven biological activities, essential oils from this family have recently been evaluated for anticancer activities and considered as a source of anticancer drugs. Mechanisms involved in the essential oils-mediated antiproliferative activity include cell cycle arrest, apoptosis and DNA repair mechanisms. Essential oils also act in the reduction of tumors, inhibiting metastasis and as anti-multidrug resistance molecules. The aim of this review is to assess the anticancer properties of essential oils obtained from different members of family Lamiaceae. The available reports on active components of essential oils and their effect on cancer type and cell line have been discussed. Biotechnological studies to improve the production of essential oils have also been highlighted. Various methods have been adopted to obtain essential oils under in vitro conditions from different plant species of family Lamiaceae, and their production is affected by culture conditions, cultivation mode, utilization of nutrient media and plant growth regulators. The literature survey suggests that essential oils obtained from family Lamiaceae have perspective for the development of new alternatives for disease treatment and prevention.     

Enhancements in sugar immobilization in polymeric macroporous matrices for affinity capture

The use of macroporous monolithic matrices in the purification of biocompounds is constantly growing and developing. In this work, the objective was to optimize the quantity of N-acetyl-D-glucosamine (D-GlcNAc) immobilized on the surface of macroporous polymeric cryogels for capture of lectins from less clarified solutions. Surface response methodology was applied and it was observed that the immobilization temperature of the glutaraldehyde (GLU) and the D-GlcNAc concentration influenced the amount of sugar immobilized. The matrices produced with 1.1% of allyl glycidyl ether were functionalized by GLU. Optimal maximum condition was obtained with mean value of 160.39 ± 26.38 mg of D-GlcNAc immobilized per gram of dry cryogel. Characterization analyses of the matrices showed that the activation process was effective, maintaining the macroporous structure and physical characteristics. The adsorbents produced were tested for capture of lectins from a crude protein solution of barley. At tested conditions, adsorbent capture around 11% of protein in solution but reduce the hemaglutinating capacity in 40%, demonstrating its selectivity. The cryogels functionalized with D-GlcNAc present potential for use in capture compounds by affinity with carbohydrates, such as lectins. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47956.     

The Anti-Inflammatory Effects of the Methanolic Extract and Fractions from Davilla elliptica St. Hil. (Dilleniaceae) on Bothrops jararaca Envenomation

Inflammation and haemorrhage are the main characteristics of tissue injury in botropic envenomation. Although some studies have shown that anti-venom prevents systemic reactions, it is not efficient in preventing tissue injury at the site of the bite. Therefore, this work was undertaken to investigate the anti-inflammatory effects of the methanolic extract and fractions from D. elliptica and to evaluate the role of matrix metalloproteinases (MMPs) in this process. Effects of the extract and fractions from D. elliptica were evaluated using a carrageenan-induced paw oedema model in rats, and leukocyte rolling was visualized by intravital. The quantification of MMPs activities (MMP-2 and MMP-9) extracted from the dermis of mice treated with extract and fractions alone or incubated with venom was determined by zymographic analyses. Our results show that intraperitoneal (i.p.) injection of fractions significantly reduced paw oedema after the carrageenan challenge. Treatment with the tannins fraction also resulted in considerable inhibition of the rolling of leukocytes and this fraction was able to decrease the activation of MMP-9. These results confirmed the anti-inflammatory activity of the methanolic extract and tannins fraction of D. elliptica and showed that the dermonecrosis properties of B. jararaca venom might be mediated through the inhibition of MMP-9 activity.     

Improved Quantum Yield and Excellent Luminescence Stability of Europium‐Incorporated Polymeric Hydrogen‐Bonded Heptazine Frameworks Due to an Efficient Hydrogen‐Bonding Effect

Two of the most persistent challenges for the high‐end application of luminescent lanthanide (Ln) compounds are a low quantum yield and luminescence quenching caused by a liquid medium. In this work, a type of polymeric hydrogen‐bonded heptazine framework is developed incorporating trivalent europium ions (P‐HHF‐Eu) via a low‐cost and facile low‐temperature thermal condensation reaction. Structural characterization clearly reveals that the solid‐phase pyrolyzation reaction results in the formation of P‐HHF‐Eu. Using time‐resolved and steady state photoluminescence (PL) spectroscopies, the photophysics and photochemistry of P‐HHF‐Eu at different hydration degrees are investigated and the role of hydrogen bonding in the significant enhancement of the emission properties is demonstrated. Furthermore, the P‐HHF‐Eu particles suspended in polyvinyl alcohol hydrogel exhibit excellent luminescence stability with a high PL quantum yield of up to ≈46% and wavelength responsive color‐tunable emission, which holds potential for security applications.     

Screening of anionic-modified polymers in terms of stability,disintegration, and swelling behavior

This study aimed to screen the stability, disintegration, and swelling behavior of chemically modified anionic polymers. Investigated polymers were well-known and widely used staples of the pharmaceutical and medical field, namely, alginate (AL), carboxymethyl cellulose (CMC), polycarbophil (PC), and hyaluronic acid (HA). On the basis of amide bond formation between the carboxylic acid moieties of anionic polymers and the primary amino group of the modification ligand cysteine (CYS), the modified polymers were obtained. Unmodified polymers served as controls throughout all studies. With the Ellman’s assay, modification degrees were determined of synthesized polymeric excipients. Stability assay in terms of erosion study at physiological conditions were performed. Moreover, water uptake of compressed polymeric discs were evaluated and further disintegration studies according to the USP were carried out to define the potential ranking. Results ranking figured out PCCYS?>?CMCCYS?>?HACYS?>?ALCYS in terms of water uptake capacity compared to respective controls. Cell viability assays on Caco-2 cell line as well as on RPMI 2650 (ATTC CCL30) proved modification not being harmful to those. Due to the results of this study, an intense screening of prominent anionic polymer derivate was performed in order to help the pharmaceutical research for the best choice of polymeric excipients for developments of controlled drug release systems.     

Quinone‐Fused Pyrazoles through 1,3‐Dipolar Cycloadditions: Synthesis of Tricyclic Scaffolds and in vitro Cytotoxic Activity Evaluation on Glioblastoma Cancer Cells

A novel and straightforward synthesis of highly substituted isoquinoline‐5,8‐dione fused tricyclic pyrazoles is reported. The key step of the synthetic sequence is a regioselective, Ag₂CO₃ promoted, 1,3‐dipolar cycloaddition of C‐heteroaryl‐N‐aryl nitrilimines and substituted isoquinoline‐5,8‐diones. The broad functional group tolerability and mild reaction conditions were found to be suitable for the preparation of a small library of compounds. These scaffolds were designed to interact with multiple biological residues, and two of them, after brief synthetic elaborations, were analyzed by molecular docking studies as potential anticancer drugs. In vitro studies confirmed the potent anticancer effects, showing promising IC₅₀ values as low as 2.5 μm against three different glioblastoma cell lines. Their cytotoxic activity was finally positively correlated to their ability to inhibit PI3K/mTOR kinases, which are responsible for the regulation of diverse cellular processes in human cancer cells.     

MicroRNA-16 Restores Sensitivity to Tyrosine Kinase Inhibitors and Outperforms MEK Inhibitors in KRAS-Mutated Non-Small Cell Lung Cancer

Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer death worldwide. Chemotherapy, the treatment of choice in non-operable cases, achieves a dismal success rate, raising the need for new therapeutic options. In about 25% of NSCLC, the activating mutations of the KRAS oncogene define a subclass that cannot benefit from tyrosine kinase inhibitors (TKIs). The tumor suppressor miR-16 is downregulated in many human cancers, including NSCLC. The main objectives of this study were to evaluate miR-16 treatment to restore the TKI sensitivity and compare its efficacy to MEK inhibitors in KRAS-mutated NSCLC. Methods: We performed in vitro and in vivo studies to investigate whether miR-16 could be exploited to overcome TKI resistance in KRAS-mutated NSCLC. We had three goals: first, to identify the KRAS downstream effectors targeted by mir-16, second, to study the effects of miR-16 restoration on TKI resistance in KRAS-mutated NSCLC both in vitro and in vivo, and finally, to compare miR-16 and the MEK inhibitor selumetinib in reducing KRAS-mutated NSCLC growth in vitro and in vivo. Results: We demonstrated that miR-16 directly targets the three KRAS downstream effectors MAPK3, MAP2K1, and CRAF in NSCLC, restoring the sensitivity to erlotinib in KRAS-mutated NSCLC both in vitro and in vivo. We also provided evidence that the miR-16–erlotinib regimen is more effective than the selumetinib–erlotinib combination in KRAS-mutated NSCLC. Conclusions: Our findings support the biological preclinical rationale for using miR-16 in combination with erlotinib in the treatment of NSCLC with KRAS-activating mutations.     

Morphology and molecular orientation in sexithiophene and N,N′-bis (n-octyl)-dicyanoperylenediimide heterostructures

We report on the growth mode of N,N′-bis (n-octyl)-dicyanoperylenediimide (PDI-8CN₂) on sexithiophene (T6) thin films, studied with different structural, morphological and optical techniques. We aim to individuate the most favorable conditions for the realization of heterostructure devices. The crystalline quality was established by X-ray patterns and Atomic Force Microscopy (AFM) images, and found to be generally high. The anisotropic optical constants extracted from ellipsometry measurements shed light on the mean molecular orientation in the PDI-8CN₂ film. AFM images evidence two different growth modes: at T6 thickness less than 2 monolayers (ML), the growth of PDI-8CN₂ on T6 is favored with respect to SiO₂, while, at higher thickness (2-6 ML), the situation is reversed. An optimum T6 underlayer thickness of approximately 1 ML provides the best quality of PDI-8CN₂ layer corresponding to the highest island dimension, the highest molecular order parameter, and the lowest roughness. Spectrum broadening was observed for extinction coefficient of PDI-8CN₂ in the heterostructures, as compared with a sole material film, and explained by two effects: increase in molecular disorder and formation of charge transfer complexes.     

Trends in nanotechnology patents applied to the health sector

The aim of the article is to present a method for identifying trends in patent applications for nanotechnology applied to the health sector around the world, based on the International Patent Classification. This classification divides the sector into: dental care, drugs, diagnostic kits, and medical apparatus & medical care. The Derwent database was mined for patent documents using nanotechnology terms associated with the IPC subclasses from the health subsectors. The number of patents was found to be rising, led by the United States, particularly universities and R centers. In the dental care subsector, nanotechnology was found to be used in composite material for manufacturing dental appliances. In drugs, the focus is on the use of nanoparticulate compositions comprising agents that are useful for a variety of diseases. In diagnostic kits, nanostructures have been patented that are capable of detecting target analytes. Meanwhile, in medical apparatus & medical care, patent applications have been made for nanocapsules and/or nanocomposite materials inserted in devices and guide catheters. A study was also made of patents in Brazil, where the same assignees and the same country (United States) as in the survey of global patents were found to be the leading patent applicants / holders.