Beyond BRCA: The Emerging Significance of DNA Damage Response and Personalized Treatment in Pancreatic and Prostate Cancer Patients

The BRCA1/2 germline and/or somatic pathogenic variants (PVs) are key players in the hereditary predisposition and therapeutic response for breast, ovarian and, more recently, pancreatic and prostate cancers. Aberrations in other genes involved in homologous recombination and DNA damage response (DDR) pathways are being investigated as promising targets in ongoing clinical trials. However, DDR genes are not routinely tested worldwide. Due to heterogeneity in cohort selection and dissimilar sequencing approaches across studies, neither the burden of PVs in DDR genes nor the prevalence of PVs in genes in common among pancreatic and prostate cancer can be easily quantified. We aim to contextualize these genes, altered in both pancreatic and prostate cancers, in the DDR process, to summarize their hereditary and somatic burden in different studies and harness their deficiency for cancer treatments in the context of currently ongoing clinical trials. We conclude that the inclusion of DDR genes, other than BRCA1/2, shared by both cancers considerably increases the detection rate of potentially actionable variants, which are triplicated in pancreatic and almost doubled in prostate cancer. Thus, DDR alterations are suitable targets for drug development and to improve the outcome in both pancreatic and prostate cancer patients. Importantly, this will increase the detection of germline pathogenic variants, thereby patient referral to genetic counseling.     

Comparative production of xylanase and the liberation of xylooligosaccharides from lignocellulosic biomass by Aspergillus brasiliensis BLf1 and recombinant Aspergillus nidulans XynC A773

We investigated the simultaneous production of xylanase and the liberation of xylooligosaccharides in rice husk solid‐state cultivations of Aspergillus brasiliensis BLf1 and by the recombinant Aspergillus nidulans XynC A773 strain. The bioprocess was optimised by experimental fractional design and response surface analysis. Results show that both fungi strains produced xylanases and their activities were dependent on the addition of basal medium, moisture content and the interactions between particle size and inoculum size, producing maximum xylanase activities of 230.7 U g^?1 substrate for A. brasiliensis, and 187.9 U g^?1 substrate for A. nidulans XynC. Xylooligosaccharides were liberated in the same cultures, with concentrations up to 17.6 mg g^?1 and 23.9 mg g^?1 of substrate for A. brasiliensis and A. nidulans XynC, respectively, both strains presenting similar profiles, with xylose residues varying from X3 to X6. These results suggest the possibility of lowering production costs of enzymes for food applications and oligosaccharides.     

Production of double‐walled nanoparticles containing meloxicam

Double‐walled nanospheres, containing meloxicam, were fabricated with poly‐(D,L ‐lactide‐co‐glycolide) (PLGA) and poly(L ‐lactide) (PLLA) using the solvent evaporation technique. This article discusses the effect of formulation variables [sonication power, sonication time, concentration of poly(vinyl alcohol), organic/aqueous volume ratio in the first emulsion] on the production of double‐walled nanospheres. The involved phase separation of these two polymers was investigated using differential scanning calorimetry. Double‐walled microspheres containing meloxicam were also produced to determine the composition of the shell and core polymer, based on different solubilities of polymers in ethyl acetate, and to examine the inner morphology and drug distribution using optical and fluorescence microscopy. The produced microparticles have shown a double‐walled structure with meloxicam solubilized in the PLGA‐rich phase. Therefore, adjusting the selected formulation variables and using a mass ratio of 1:1 PLLA/PLGA, double‐walled nanospheres where meloxicam is dispersed within the core can be produced. POLYM. ENG. SCI., 2013. © 2012 Society of Plastics Engineers     

Peripheral Nerve Injury Treatments and Advances: One Health Perspective

Peripheral nerve injuries (PNI) can have several etiologies, such as trauma and iatrogenic interventions, that can lead to the loss of structure and/or function impairment. These changes can cause partial or complete loss of motor and sensory functions, physical disability, and neuropathic pain, which in turn can affect the quality of life. This review aims to revisit the concepts associated with the PNI and the anatomy of the peripheral nerve is detailed to explain the different types of injury. Then, some of the available therapeutic strategies are explained, including surgical methods, pharmacological therapies, and the use of cell-based therapies alone or in combination with biomaterials in the form of tube guides. Nevertheless, even with the various available treatments, it is difficult to achieve a perfect outcome with complete functional recovery. This review aims to enhance the importance of new therapies, especially in severe lesions, to overcome limitations and achieve better outcomes. The urge for new approaches and the understanding of the different methods to evaluate nerve regeneration is fundamental from a One Health perspective. In vitro models followed by in vivo models are very important to be able to translate the achievements to human medicine.     

Polyprenylated benzophenone-enriched extracts obtained using SC–CO2 from the dry ethanolic extract of Brazilian red propolis

Red propolis is a well-known potent antimicrobial source because of its various bioactive compounds. This work aims to submit a sample of Brazilian red propolis to supercritical CO₂ extraction, with subsequent chemical characterisation by HPLC and UHPLC–MS, and to evaluate the antifungal activity against three strains of Candida glabrata. The method proved to be selective for the extraction of benzophenones. The results demonstrated a correlation between the presence of benzophenones and antifungal activity. The supercritical extract that seems to be the richest in benzophenones was the one obtained with a pressure of 300 bar and was the most active against the C. glabrata strains.

Abbreviations: SFE, Supercritical Fluid Extraction; MIC, Minimal Inhibitory Concentration; SC, Supercritical; BZP, benzophenones     

Self-healing polymer blend based on PETG and EMAA

In this work, novel immiscible polymer blends with remarkable self-healing properties were developed. The blends are based on poly(ethylene glycol-co-cyclohexane-1,4-dimethanol terephthalate) (PETG), a nonself-healing polymer, and the ionomer sodium-neutralized poly(ethylene-co-methacrylic acid) (EMAA), with self-healing abilities. The ratios of (PETG)/ (EMAA) was varied from 0 to 100% (w/w) and mixtures were prepared using a twin-screw melt extrusion. The blend studied compositions were characterized by scanning electron microscope, differential scanning calorimetry, dynamic mechanical analysis and self-repair tests. The results revealed that blends samples were able to self-repair damages created by Vickers microhardness indentations. The self-repair is presented through video records where the establishment of scars in the damaged area can be observed. For the composition 50/50 (w/w), the whole repair was observed due the synergic effect between polymer chain mobility, new chemical interactions promoted between PETG and EMAA, thus improving its self-healing ability.     

Collagen Fibres Orientation in the Bone Matrix around Dental Implants: Does the Implant’s Thread Design Play a Role?

The aim of this study was to analyse the influence of different thread shapes of titanium dental implant on the bone collagen fibre orientation (BCFO) around loaded implants. Twenty titanium dental implants, divided for thread shapes in six groups (A–F) were analysed in the present study. All implants were immediately loaded and left in function for 6 months before retrieval. The parameters evaluated under scanning electron microscope were the thread width, thread depth, top radius of curvature, flank angle, and the inter-thread straight section. Two undecalcified histological sections were prepared from each implant. Birefringence analysis using circularly polarized light microscopy was used to quantitively measure BCFO. For groups A–F, respectively, transverse BCFO was 32.7%, 24.1%, 22.3%, 18.2%, 32.4%, and 21.2%, longitudinal BCFO was 28.2%, 14.5%, 44.9%, 33.1%, 37.7%, and 40.2%. The percentage differences between transverse and longitudinal orientation were 4.50% (A), 9.60% (B), −22.60% (C), −14.90% (D), −5.30% (E), and −19.00% (F). Following loading, the amount of transverse and longitudinal BCFO were significantly influenced by the thread shape. The greater flank angles and narrower inter-thread sections of the “V” shaped and “concave” shaped implant threads of groups A and B, respectively, promoted the predominance of transverse BCFO, compared to groups C-F (p < 0.05). A narrow inter-thread straight section promotes transverse BCFO, as do “V” shaped and “concave” shaped threads, which can thus be considered desirable design for implant threads.     

Transient three-dimensional simulations of a catalytic combustion monolith using detailed models for heterogeneous and homogeneous reactions and transport phenomena

The application of a newly developed computational tool, DETCHEM^MONOLITH, for the transient two- and three-dimensional simulation of catalytic combustion monoliths is presented. The simulation is based on the coupling of a transient 2D/3D heat balance of the solid monolith structure with steady-state calculations of the reactive flow in a representative number of channels. The two-dimensional single-channel model uses a boundary-layer approximation including detailed models for heterogeneous and homogeneous reactions as well as transport phenomena. As an example, the computational tool is applied to study the hydrogen-assisted catalytic combustion of methane in a platinum-coated honeycomb monolith.     

Novel electrical conductive hybrid nanostructures based on PA 6/MWCNTCOOH electrospun nanofibers and anchored MWCNTCOOH

Electrical conductive nanostructures made of nanofibers of poly (amide 6) (PA6) with carboxyl functionalized multiwall carbon nanotubes (MWCNT_COOH) and anchored MWCNT_COOH were produced. The nanotubes were surface activated with carboxyl groups, dispersed in formic acid and added to a formic acid solution of PA6. The mixture was electrospun by applying a voltage of 30 kV; afterwards, the nanofiber's mats were immersed in an aqueous dispersion of MWCNT_COOH containing a nonionic surfactant. The chemical structure, morphology, thermal stability, and electrical conductivity of the nanostructures were evaluated by UV spectroscopy, scanning (SEM), and transmission electron microscopy (TEM), thermal gravimetric analyses (TGA) and volumetric conductivity measurements. The efficiency of the functionalization was confirmed by the UV peaks in the range between 220 and 250 nm (corresponding to a carbonyl group conjugated with a carbon‐carbon double bond). SEM and TEM micrographs showed the pullout of the MWCNT_COOH from the nanofibers and the formation of a stable, percolated, and anchored MWCNT_COOH network on the nanofibers due to the anchoring of the MWCNT_COOH from the surfactant solution on the MWCNT_COOH of the nanofibers. The coated nanostructures had higher thermal stability and higher electrical conductivity than the noncoated ones, showing the efficiency of this simple procedure. POLYM. ENG. SCI., 55:1263–1272, 2015. © 2015 Society of Plastics Engineers