AR-12 Has a Bactericidal Activity and a Synergistic Effect with Gentamicin against Group A Streptococcus

Streptococcus pyogenes (group A Streptococcus (GAS) is an important human pathogen that can cause severe invasive infection, such as necrotizing fasciitis and streptococcal toxic shock syndrome. The mortality rate of streptococcal toxic shock syndrome ranges from 20% to 50% in spite of antibiotics administration. AR-12, a pyrazole derivative, has been reported to inhibit the infection of viruses, intracellular bacteria, and fungi. In this report, we evaluated the bactericidal activities and mechanisms of AR-12 on GAS infection. Our in vitro results showed that AR-12 dose-dependently reduced the GAS growth, and 2.5 μg/mL of AR-12 significantly killed GAS within 2 h. AR-12 caused a remarkable reduction in nucleic acid and protein content of GAS. The expression of heat shock protein DnaK and streptococcal exotoxins was also inhibited by AR-12. Surveys of the GAS architecture by scanning electron microscopy revealed that AR-12-treated GAS displayed incomplete septa and micro-spherical structures protruding out of cell walls. Moreover, the combination of AR-12 and gentamicin had a synergistic antibacterial activity against GAS replication for both in vitro and in vivo infection. Taken together, these novel findings obtained in this study may provide a new therapeutic strategy for invasive GAS infection.

Hybrid Nanoparticles as an Efficient Porphyrin Delivery System for Cancer Cells to Enhance Photodynamic Therapy

Photodynamic therapy (PDT) is a potential non-invasive approach for application in oncological diseases, based on the activation of a photosensitizer (PS) by light at a specific wavelength in the presence of molecular oxygen to produce reactive oxygen species (ROS) that trigger the death tumor cells. In this context, porphyrins are interesting PS because they are robust, have high chemical, photo, thermal, and oxidative stability, and can generate singlet oxygen (1O2). However, porphyrins exhibit low solubility and a strong tendency to aggregate in a biological environment which limits their clinical application. To overcome these challenges, we developed hybrid nanostructures to immobilize 5,10,15,20-tetrakis[(4-carboxyphenyl) thio-2,3,5,6-tetrafluorophenyl] (P), a new third-generation PS. The biological effect of this system was evaluated against bladder cancer (BC) cells with or without light exposition. The nanostructure composed of lipid carriers coated by porphyrin-chitosan (P-HNP), presented a size of ca. 130 nm and low polydispersity (ca. 0.25). The presence of the porphyrin-chitosan (P-chitosan) on lipid nanoparticle surfaces increased the nanoparticle size, changed the zeta potential to positive, decreased the recrystallization index, and increased the thermal stability of nanoparticles. Furthermore, P-chitosan incorporation on nanoparticles increased the stability and enhanced the self-organization of the system and the formation of spherical structures, as observed by small-angle X-ray scattering (SAXS) analysis. Furthermore, the immobilization process maintained the P photoactivity and improved the photophysical properties of PS, minimizing its aggregation in the cell culture medium. In the photoinduction assays, the P-HNP displayed high phototoxicity with IC50 3.2-folds lower than free porphyrin. This higher cytotoxic effect can be correlated to the high cellular uptake of porphyrin immobilized, as observed by confocal images. Moreover, the coated nanoparticles showed mucoadhesive properties interesting to its application in vivo. Therefore, the physical and chemical properties of nanoparticles may be relevant to improve the porphyrin photodynamic activity in BC cells.

Genomic and physiological characterization of Novosphingobium terrae sp. nov., an alphaproteobacterium isolated from Cerrado soil containing a megasized chromid

A novel bacterial strain, designated GeG2T, was isolated from soils of native Cerrado, a highly biodiverse savanna-like Brazilian biome. 16S rRNA gene sequence analysis of strain GeG2T revealed high sequence identity (100%) to the alphaproteobacterium Novosphingobium rosa, however, comparisons with N. rosa DSM7285T showed several distinctive features, prompting a full characterization of the new strain in terms of growth, morphology, biochemistry and, ultimately, its genome. GeG2T cells were Gram-stain negative bacilli, facultatively anaerobic, motile, positive for catalase and oxidase activities and for starch hydrolysis. Strain GeG2T presented planktonic-sessile dimorphism and cell aggregates surrounded by extracellular matrix and nanometric spherical structures were observed in liquid cultures, suggesting the production of exopolysaccharides (EPS) and outer membrane vesicles (OMVs). Whole genome assembly revealed four circular replicons: a 4.1 Mb chromosome, a 2.7 Mb extrachromosomal megareplicon and two plasmids (212.7 and 68.6 kb). The megareplicon contains few core genes and plasmid-type replication/maintenance systems, consistent with its classification as a chromid. Genome annotation shows a vast repertoire of carbohydrate active enzymes and genes involved in the degradation of aromatic compounds, highlighting the biotechnological potential of the new isolate obtained from Cerrado soils, especially regarding EPS production and biodegradation of recalcitrant compounds. Chemotaxonomic features, including polar lipid and fatty acid profiles, as well as physiological, molecular and whole genome comparisons showed significant differences between strain GeG2T and a N. rosa, clearly indicating that it represents a novel species, for which the name Novosphingobium terrae is proposed. The type strain is GeG2T (=CBMAI 2313T =CBAS 753T ).

Liposomes: Structure, Biomedical Applications, and Stability Parameters With Emphasis on Cholesterol

Liposomes are essentially a subtype of nanoparticles comprising a hydrophobic tail and a hydrophilic head constituting a phospholipid membrane. The spherical or multilayered spherical structures of liposomes are highly rich in lipid contents with numerous criteria for their classification, including structural features, structural parameters, and size, synthesis methods, preparation, and drug loading. Despite various liposomal applications, such as drug, vaccine/gene delivery, biosensors fabrication, diagnosis, and food products applications, their use encounters many limitations due to physico-chemical instability as their stability is vigorously affected by the constituting ingredients wherein cholesterol performs a vital role in the stability of the liposomal membrane. It has well established that cholesterol exerts its impact by controlling fluidity, permeability, membrane strength, elasticity and stiffness, transition temperature (Tm), drug retention, phospholipid packing, and plasma stability. Although the undetermined optimum amount of cholesterol for preparing a stable and controlled release vehicle has been the downside, but researchers are still focused on cholesterol as a promising material for the stability of liposomes necessitating explanation for the stability promotion of liposomes. Herein, the prior art pertaining to the liposomal appliances, especially for drug delivery in cancer therapy, and their stability emphasizing the roles of cholesterol.

Tracing ovarian follicles growth in vitro by three-dimensional culture system

In female mammals, the basic reproductive unit in the ovaries is the follicle, which is composed by the oocyte and surrounding somatic granulosa cells (GCs). The development of follicles is a highly programed progress and is regulated by both the paracrine and endocrine factors. To culture the follicle in vitro, various approaches were established in different groups including the 2-dimensional culture and 3-dimensional culture. In this study, we improved a three-dimensional Matrigel system to culture the mouse follicles from secondary stage. In this system, the 3D culture guaranteed spherical structures of the follicles, which was utilized to trace the difference of growth dynamics of follicles in mutant and wild type females.

Molecular dynamics study on structural and atomic evolution between Au and Ni nanoparticles through coalescence

Motivated by the structure evolution experiments of Janus NiAu nanoparticles (NPs), we present a detailed study on the thermodynamic evolution of Ni and Au NPs with different ratios of Au and Ni through the molecular dynamics (MD) simulations. It is found that, for fixed Ni particle size (5.8 nm in diameter), the energy variation with the increasing temperature is related to the Au sizes (1.5–9.6 nm in diameter), due to the diverse atomic segregation modes. For a small Au particle, due to lattice induction, the structure will change from order to disorder and then to order. The interface defects of the merging NPs could be automatically eliminated by coalescence processes. The change in energy as the temperature increases is similar to that of monometallic NPs. For larger Au particles, the irregular variation of energy occurs and the atomic energy experience one or two reductions at least with the increase of the temperature. The segregation of Au atoms to the surface of Ni particle is dominant during the continuous heating process. The coalescence processes of Au atoms strongly determine the final morphology of the particles. Dumbbell-like, Janus and eccentric core–shell spherical structures could be obtained during the heating process. Our results will provide an effective approach to the design of novel materials with specific properties through thermal control.

Recyclable Ir Nanoparticles for the Catalytic Hydrogenation of Biomass-Derived Carbonyl Compounds

The valorisation of biomass-derived platform chemicals via catalytic hydrogenation is an eco-friendly tool which allows us to recover bio-based building blocks and produce fine chemicals with high industrial appeal. In the present study, a novel surfactant-type triazolyl-thioether ligand was prepared, showing excellent catalytic activity in the presence of bis(1,5-cyclooctadiene)diiridium(I) dichloride [Ir(COD)Cl]2 for the hydrogenation of furfural, cinnamaldehyde, levulinic acid, 5-hydroxymethylfurfural, vanillin, and citral. Easy recovery by liquid/liquid extraction allowed us to recover the catalyst, which could then be efficiently recycled up to 11 times for the hydrogenation of furfural. In-depth analysis revealed the formation of spherical structures with metal nanoparticles as big as 2–6 nm surrounded by the anionic ligand, preventing iridium nanoparticle degradation.

A computer-aided diagnosis system for lung nodule detection in pulmonary CT images based on LS-SVM and wavelet transformation

One of the most important areas of biomedical engineering is medical imaging. Fully automated schemes are currently being explored as Computer-Aided Diagnosis (CAD) systems to provide a second opinion to medical professionals; of these systems, abnormal region detector in medical images is one of the most critical CAD systems in development. The primary motivation in using these systems is due to the fact that reading an enormous number of images is a time-consuming task for the radiologist. This task can be sped up by using a CAD system which highlights abnormal regions of interest. Low false positive rates and high sensitivity are essential requirement[s] of such a system. The initial requirement of processing any organ is an accurate segmentation of the target of interest in the images. A segmentation method based on the wavelet transformation is proposed which accurately extracts lung regions in the thoracic CT images. After this step, an Aritifical Intelligence system, known as Least Squares Support Vector Machine (LS-SVM), is employed to classify nodules within the regions of interest. It is a well known fact that the lung nodules, except the pleural nodules, are mostly spherical structures whereas other structures including blood vessels are shaped as other structures such as tubular. Therfore, an enhancment filter is developed in which spherical structures are accentuated. Processing three different real databases revealed that the proposed system has reached the objective of a CAD system to provide reliable opinion for the doctors in the diagnosis fashion.