Colonic availability of apple polyphenols--a study in ileostomy subjects

Nutrition is thought to play an essential role in the pathogenesis of inflammatory and malignant gastrointestinal diseases. It is well known that plant ingredients such as polyphenols and flavonoids show anticarcinogenic effects both in vitro and in animal experiments, and may thus reduce the risk of colorectal cancer in man. The aim of the study was to determine the amount of polyphenols reaching the colon after oral intake of apple juice. After consumption of a polyphenol-free diet 11 healthy ileostomy volunteers drank 1 L of a polyphenol-rich cloudy apple juice. Ileostomy effluent was collected immediately before and 1, 2, 4, 6, and 8 h after consumption of apple juice. A broad spectrum of polyphenols was identified using HPLC-diode array detection (HPLC-DAD) as well as HPLC-ESI-MS/MS; quantitation was performed with HPLC-DAD. Most of the orally administered apple polyphenols were absorbed from or metabolized in the small intestine. Between 0 and 33% of the oral dose was recovered in the ileostomy bags with a maximum of excretion after 2 h. Phloretin glucuronide as product of polyphenol metabolism was detected in the ileostomy effluent. The present results show that most of the apple juice polyphenols are absorbed in the small intestine. Minor amounts of unmetabolized polyphenols are recovered in the ileostomy effluent, which would reach the colon under physiologic circumstances. These data have to be considered when polyphenols are used in model systems to show preventive effects in colorectal carcinogenesis.     

Activation of Humoral Immunity during the Pathogenesis of Experimental Chronic Lung Allograft Dysfunction

Alloreactive and autoreactive antibodies have been associated with the development of chronic lung allograft dysfunction (CLAD), but their pathogenic role is disputed. Orthotopic left lung transplantation was performed in the Fischer-344 to Lewis rat strain combination followed by the application of ciclosporine for 10 days. Four weeks after transplantation, lipopolysaccharide (LPS) was instilled into the trachea. Lungs were harvested before (postoperative day 28) and after LPS application (postoperative days 29, 33, 40, and 90) for histopathological, immunohistochemical, and Western blot analyses. Recipient serum was collected to investigate circulating antibodies. Lung allografts were more strongly infiltrated by B cells and deposits of immunoglobulin G and M were more prominent in allografts compared to right native lungs or isografts and increased in response to LPS instillation. LPS induced the secretion of autoreactive antibodies into the circulation of allograft and isograft recipients, while alloreactive antibodies were only rarely detected. Infiltration of B cells and accumulation of immunoglobulin, which is observed in allografts treated with LPS but not isografts or native lungs, might contribute to the pathogenesis of experimental CLAD. However, the LPS-induced appearance of circulating autoreactive antibodies does not seem to be related to CLAD, because it is observed in both, isograft and allograft recipients.     

Prevention of Noise-Induced Hearing Loss In Vivo: Continuous Application of Insulin-like Growth Factor 1 and Its Effect on Inner Ear Synapses,Auditory Function and Perilymph Proteins

As noise-induced hearing loss (NIHL) is a leading cause of occupational diseases, there is an urgent need for the development of preventive and therapeutic interventions. To avoid user-compliance-based problems occurring with conventional protection devices, the pharmacological prevention is currently in the focus of hearing research. Noise exposure leads to an increase in reactive oxygen species (ROS) in the cochlea. This way antioxidant agents are a promising option for pharmacological interventions. Previous animal studies reported preventive as well as therapeutic effects of Insulin-like growth factor 1 (IGF-1) in the context of NIHL. Unfortunately, in patients the time point of the noise trauma cannot always be predicted, and additive effects may occur. Therefore, continuous prevention seems to be beneficial. The present study aimed to investigate the preventive potential of continuous administration of low concentrations of IGF-1 to the inner ear in an animal model of NIHL. Guinea pigs were unilaterally implanted with an osmotic minipump. One week after surgery they received noise trauma, inducing a temporary threshold shift. Continuous IGF-1 delivery lasted for seven more days. It did not lead to significantly improved hearing thresholds compared to control animals. Quite the contrary, there is a hint for a higher noise susceptibility. Nevertheless, changes in the perilymph proteome indicate a reduced damage and better repair mechanisms through the IGF-1 treatment. Thus, future studies should investigate delivery methods enabling continuous prevention but reducing the risk of an overdosage.     

Substrate Profiling of Anion Methyltransferases for Promiscuous Synthesis of S-Adenosylmethionine Analogs from Haloalkanes

Biocatalytic alkylation reactions can be performed with high chemo-, regio- and stereoselectivity using S-adenosyl-l -methionine (SAM)-dependent methyltransferases (MTs) and SAM analogs. Currently, however, this methodology is limited in application due to the rather laborious protocols to access SAM analogs. It has recently been shown that halide methyltransferases (HMTs) enable synthesis and recycling of SAM analogs with readily available haloalkanes as starting material. Here we expand this work by using substrate profiling of the anion MT enzyme family to explore promiscuous SAM analog synthesis. Our study shows that anion MTs are in general very promiscuous with respect to the alkyl chain as well as the halide leaving group. Substrate profiling further suggests that promiscuous anion MTs cluster in sequence space. Next to iodoalkanes, cheaper, less toxic, and more available bromoalkanes have been converted and several haloalkanes bearing short alkyl groups, alkyl rings, and functional groups such as alkene, alkyne and aromatic moieties are accepted as substrates. Further, we applied the SAM analogs as electrophiles in enzyme-catalyzed regioselective pyrazole allylation with 3-bromopropene as starting material.     

Donor:Acceptor Janus Nanoparticle-Based Films as Photoactive Layers: Control of Assembly and Impact on Performance of Devices

Water-processable organic semiconductor nanoparticles (NPs) are considered promising materials for the next-generation of optoelectronic applications due to their controlled size, internal structure, and environmentally friendly processing. Reasonably, the controllable assembly of donor:acceptor (D:A) NPs on large areas, quality, and packing density of deposited films, as well as layer morphology, will influence the effectiveness of charge transfer at an interface and the final performance of designed optoelectronic devices.This work represents an easy and effective approach for designing self-assembled monolayers of D:A NPs. In this self-assembly procedure, the NP arrays are prepared on a large scale (2 × 2 cm²) at the air/water interface with controlled packing density and morphology. Due to the unique structure of individual D:A Janus particles and their assembled arrays, the Janus nanoparticle (JNP)-based device exhibits an 80% improvement of electron mobility and more balanced charge extraction compared to the conventional core–shell NP-based device. An outstanding performance of polymer solar cells with over 5% efficiency is achieved after post-annealing treatment of assembled arrays, representing one of the best results for NP-based organic photovoltaics. Ultimately, this work provides a new protocol for processing water-processable organic semiconductor colloids and future optoelectronic fabrication.     

Optimization of the Two- and Three-Dimensional Characterization of Rare Earth-Traced Deoxidation Products

Tracing by means of the light rare earths (REs), particularly La and Ce, is a state-of-the-art method used to track deoxidation products during the steelmaking process. Traced heterogeneous multiphase inclusions are analyzed using scanning electron microscopy with energy-dispersive spectroscopy (SEM/EDS) to perform a 2D characterization. The sequential chemical extraction technique is implemented for a 3D investigation to determine traced particles’ actual sizes and shapes. The automated SEM/EDS measurement must be optimized since RE oxides appear brighter in the backscattered electron images due to their high atomic numbers. Therefore, two grayscales are implemented for the detection of RE-containing multiphase inclusions. Within this technique, individual RE-traced heterogeneous nonmetallic inclusions (NMIs) are counted as separate particles. Thus, the measured NMIs must be recombined, which is achieved using a self-developed MATLAB tool. The extracted particles are also analyzed by automated and manual SEM/EDS measurements to determine the 3D morphologies and sizes of traced NMIs.     

Air Cooling Martensites—The Future of Carbon Neutral Steel Forgings?

The air-hardening ductile forging steels belong to the third generation of advanced high-strength steels and achieve their final, martensitic microstructure simply by air cooling from the forging heat. The present conference paper reviews the 15 years of development, different alloying strategies, and metallurgical throwbacks like manganese embrittlement. Furthermore, the most recent results concerning microstructure, mechanical properties, and cyclic material behavior obtained from an industrial trial melt are discussed together with the implications of these results on the carbon footprint (CF) and their impact on the resource efficiency of forged steel components. It is demonstrated that the CF of a steel product needs to be discussed on different levels, as the material-, process-, and product-level contributions need to be considered. Furthermore, a case is made for new high-strength steels in the context of circular economy, as increase fatigue resistance enables lightweighting potentials.