ALBERT

Description: Hypoxia is known to impair mitochondrial and endoplasmic reticulum (ER) homeostasis. Post-hypoxic perturbations of the ER proteostasis result in the accumulation of misfolded/unfolded proteins leading to the activation of the Unfolded Protein Response (UPR). Mitochondrial chaperone TNF receptor-associated protein 1 (TRAP1) is reported to preserve mitochondrial membrane potential and to impede reactive oxygen species (ROS) production thereby protecting cells from ER stress as well as oxidative stress. The first-line antidiabetic drug Metformin has been attributed a neuroprotective role after hypoxia. Interestingly, Metformin has been reported to rescue mitochondrial deficits in fibroblasts derived from a patient carrying a homozygous TRAP1 loss-of-function mutation. We sought to investigate a putative link between Metformin, TRAP1, and the UPR after hypoxia. We assessed post-hypoxic/reperfusion longevity, mortality, negative geotaxis, ROS production, metabolic activity, gene expression of antioxidant proteins, and activation of the UPR in Trap1-deficient flies. Following hypoxia, Trap1 deficiency caused higher mortality and greater impairments in negative geotaxis compared to controls. Similarly, post-hypoxic production of ROS and UPR activation was significantly higher in Trap1-deficient compared to control flies. Metformin counteracted the deleterious effects of hypoxia in Trap1-deficient flies but had no protective effect in wild-type flies. We provide evidence that TRAP1 is crucially involved in the post-hypoxic regulation of mitochondrial/ER stress and the activation of the UPR. Metformin appears to rescue Trap1-deficiency after hypoxia mitigating ROS production and downregulating the pro-apoptotic PERK (protein kinase R-like ER kinase) arm of the UPR.

Description: Herein, a novel form of bicomponent nanofiber membrane containing stereo-complex polylactic acid (SC-PLA) was successfully produced by the side-by-side electrospinning of Poly (L-lactic acid) (PLLA) and Poly (D-lactic acid) (PDLA). We demonstrate that through these environmentally sustainable materials, highly efficient nanofiber assemblies for filtration can be constructed at very low basis weight. The physical and morphological structure, crystalline structure, hydrophobicity, porous structure, and filtration performance of the fibrous membranes were thoroughly characterized. It was shown that the fabricated polylactic acid (PLA) side-by-side fiber membrane had the advantages of excellent hydrophobicity, small average pore size, high porosity, high filtration efficiency, low pressure drop as well as superior air permeability. At the very low basis weight of 1.1 g/m2, the filtration efficiency and pressure drop of the prepared side-by-side membrane reached 96.2% and 30 Pa, respectively. Overall, this biomass-based, biodegradable filtration material has the potential to replace the fossil fuel-based polypropylene commercial meltblown materials for the design and development in filtration, separation, biomedical, personal protection and other fields.

Description: Red ginseng (RG) has been extensively utilized in Asian countries due to its pharmacological effects. For the quality evaluation of RG, small molecules, such as ginsenosides, have been widely considered as candidates of its quality markers (Q-markers), and various analytical techniques have been developed in order to identify these compounds. However, despite the efforts to analyze the hydrophobic constituents, it is worth pointing out that about 60% of the mass of RG is made of carbohydrates, including mono-, oligo- and polysaccharides. Consequently, the quality differentiation and identification of RG from the perspective of sugar-markers should be focused. High performance liquid chromatography and evaporative light scattering detector (HPLC–ELSD) method for the determination of disaccharides in RG was established. Furthermore, high performance size exclusion chromatography–multi-angle laser light scattering–refractive index detector (HPSEC–MALLS–RID) for the determination of molecular weight and high performance liquid chromatography photodiode array (HPLC–PDA) for the determination of compositional monosaccharides in RG polysaccharides were also established. HPLC–ELSD/PDA combined with HPSEC–MALLS–RID could be used to determine the contents of disaccharides, molecular weights, and compositional monosaccharides of RG polysaccharides, which could be used for quality control, and this is a new view on the sugar marker to quality differentiation of various origins of RG.

Description: Alternative RNA splicing is an important regulatory process used by genes to increase their diversity. This process is mainly executed by specific classes of RNA binding proteins that act in a dosage-dependent manner to include or exclude selected exons in the final transcripts. While these processes are tightly regulated in cells and tissues, little is known on how the dosage of these factors is achieved and maintained. Several recent studies have suggested that alternative RNA splicing may be in part modulated by microRNAs (miRNAs), which are short, non-coding RNAs (~22 nt in length) that inhibit translation of specific mRNA transcripts. As evidenced in tissues and in diseases, such as cancer and neurological disorders, the dysregulation of miRNA pathways disrupts downstream alternative RNA splicing events by altering the dosage of splicing factors involved in RNA splicing. This attractive model suggests that miRNAs can not only influence the dosage of gene expression at the post-transcriptional level but also indirectly interfere in pre-mRNA splicing at the co-transcriptional level. The purpose of this review is to compile and analyze recent studies on miRNAs modulating alternative RNA splicing factors, and how these events contribute to transcript rearrangements in tissue development and disease.

Description: Stainless steels (SS) are the most-used alloys for manufacturing fixed orthodontic appliances due to their attractive set of mechanical properties, biocompatibility, and high corrosion resistance. Nevertheless, during regular orthodontic treatments–taking at least around 2 years–the intraoral environment inevitably degrades these bioalloys, releasing metallic ions into the oral cavity. In the first part of this in vitro study, the corrosion resistance of commercial SS appliances (brackets, tubes, and bands) was evaluated in Fusayama-Meyer artificial saliva at pH values of 2.3 and 6.8 over the course of 30 days. As expected, the results corroborated that salivary pH highly influences corrosion behaviour. Released Ni, Cr, and Fe were within dietary intake values. In the second part, a novel approach for oral corrosion prevention based on the chemical inertness of DLC materials is presented. SS surfaces were functionalized with biocompatible a-C:H-sputtered coatings and submitted to the same experimental conditions. The anticorrosion ability of this system was demonstrated, preventing the pitting corrosion that occurred on the SS substrates. Despite the galvanic coupling effect due to the presence of the Cr-based interlayer, this study enhanced the potential use of the reactive sputter-deposited a-C:H coatings in orthodontics.

Description: The aim of this research was to evaluate the effect of acid whey on changes in the fatty acid profile, oxidative stability, physico-chemical parameters, and microbiological and sensory quality of traditional organic uncured fermented Polish bacon after production and during chilling storage. Three different treatments of fermented bacon were produced: C—control bacon with a nitrite curing mixture; T—bacon with a nitrate curing mixture; and AW—bacon with acid whey and NaCl. The acid whey used in the production of uncured fermented pork bacon positively changed the sensorial characteristics, directly after the ripening process, and had a positive effect in terms of a decrease in the pH of the product. All of the fermented bacon treatments in general were of good microbiological quality. A higher lactic acid bacteria (LAB) level was observed in the AW treatment after the fermentation process, and the bacteria number did not change during storage, whereas in the C and T treatments, the LAB level increased during storage (p 〈 0.05). The application of acid whey did not limit the formation of secondary oxidation products (TBARS) during bacon ripening (1.68 mg MDA kg−1), but had a reduced value during storage time (0.73 mg MDA kg−1). The highest polyunsaturated fatty acid (PUFA) levels, after ripening and after four weeks of refrigerated storage, were found in the C treatment. In the AW treatment, it was found that the PUFA level increased; likewise, the content of n-3 and n-6 fatty acids increased, while saturated fatty acids (SFAs) decreased during storage (p 〈 0.05). The opposite tendency was observed in the C treatment. After four weeks of storage, the PUFA/SFA ratio was the lowest in the nitrate treatment, and higher values of the PUFA/SFA ratio were obtained in the acid whey and nitrite treatment (p 〈 0.05).

Description: Sugar content and bacterial contamination levels are important indicators for the health and safety of food, respectively. Therefore, it is important to construct a method that can detect both glucose and bacterial activity. Herein, natural compounds (gallic acid and glucose oxidase) were assembled into nanozyme (GOx@GA-Fe (ii)) for mild cascade detection. The nanozyme catalyzes glucose to produce hydrogen peroxide, which is then converted to ·OH and oxidized colorless TMB from blue oxidized TMB. Under the optimal conditions, the method has a good linear relationship in the glucose concentration range of 1–500 μM (R2 = 0.993) with minimum detection concentration of 0.43 μM. Based on the glucose consumption of bacteria metabolism, the cascade reaction was then applied to detect the viability of 5 common bacteria. As such, a cascade method based on a natural self-assembled nanozyme was fabricated to monitor the quality of food.

Description: TAAR1 is a neuroregulator with emerging evidence suggesting a role in immunomodulation. Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Here, we investigate TAAR1 expression in human primary monocytes, peripherally-derived macrophages, and MS brain tissue. RT-qPCR was used to assess TAAR1 levels in MS monocytes. Using a previously validated anti-human TAAR1 antibody and fluorescence microscopy, TAAR1 protein was visualized in lipopolysaccharide-stimulated or basal human macrophages, as well as macrophage/microglia populations surrounding, bordering, and within a mixed active/inactive MS lesion. In vivo, TAAR1 mRNA expression was significantly lower in MS monocytes compared to age- and sex-matched healthy controls. In vitro, TAAR1 protein showed a predominant nuclear localization in quiescent/control macrophages with a shift to a diffuse intracellular distribution following lipopolysaccharide-induced activation. In brain tissue, TAAR1 protein was predominantly expressed in macrophages/microglia within the border region of mixed active/inactive MS lesions. Considering that TAAR1-mediated anti-inflammatory effects have been previously reported, decreased mRNA in MS patients suggests possible pathophysiologic relevance. A shift in TAAR1 localization following pro-inflammatory activation suggests its function is altered in pro-inflammatory states, while TAAR1-expressing macrophages/microglia bordering an MS lesion supports TAAR1 as a novel pharmacological target in cells directly implicated in MS neuroinflammation.

Description: Arginyl dipeptides like Arg-Ser, Arg-Ala, and Arg-Gly are salt-taste enhancers and can potentially be used to reduce the salt content of food. The l-amino acid ligase RizA from B. subtilis selectively synthesizes arginyl dipeptides. However, industrial application is prevented by the high cost of the cofactor adenosine triphosphate (ATP). Thus, a coupled reaction system was created consisting of RizA and acetate kinase (AckA) from E. coli providing ATP regeneration from acetyl phosphate. Both enzymes were recombinantly produced in E. coli and purified by affinity chromatography. Biocatalytic reactions were varied and analyzed by RP-HPLC with fluorescence detection. Under optimal conditions the system produced up to 5.9 g/L Arg-Ser corresponding to an ATP efficiency of 23 g Arg-Ser per gram ATP. Using similar conditions with alanine or glycine as second amino acid, 2.6 g/L Arg-Ala or 2.4 g/L Arg Gly were produced. The RizA/AckA system selectively produced substantial amounts of arginyl dipeptides while minimizing the usage of the expensive ATP.

Description: Epilepsy is a chronic disease of the brain that affects over 65 million people worldwide. Acquired epilepsy is initiated by neurological insults, such as status epilepticus, which can result in the generation of ROS and induction of oxidative stress. Suppressing oxidative stress by upregulation of the transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown to be an effective strategy to increase endogenous antioxidant defences, including in brain diseases, and can ameliorate neuronal damage and seizure occurrence in epilepsy. Here, we aim to test the neuroprotective potential of a naturally occurring Nrf2 activator sulforaphane, in in vitro epileptiform activity model and a temporal lobe epilepsy rat model. Sulforaphane significantly decreased ROS generation during epileptiform activity, restored glutathione levels, and prevented seizure-like activity-induced neuronal cell death. When given to rats after 2 h of kainic acid-induced status epilepticus, sulforaphane significantly increased the expression of Nrf2 and related antioxidant genes, improved oxidative stress markers, and increased the total antioxidant capacity in both the plasma and hippocampus. In addition, sulforaphane significantly decreased status epilepticus-induced neuronal cell death. Our results demonstrate that Nrf2 activation following an insult to the brain exerts a neuroprotective effect by reducing neuronal death, increasing the antioxidant capacity, and thus may also modify epilepsy development.