Antioxidant Roles of SGLT2 Inhibitors in the Kidney

The reduction-oxidation (redox) system consists of the coupling and coordination of various electron gradients that are generated thanks to serial reduction-oxidation enzymatic reactions. These reactions happen in every cell and produce radical oxidants that can be mainly classified into reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS modulate cell-signaling pathways and cellular processes fundamental to normal cell function. However, overproduction of oxidative species can lead to oxidative stress (OS) that is pathological. Oxidative stress is a main contributor to diabetic kidney disease (DKD) onset. In the kidney, the proximal tubular cells require a high energy supply to reabsorb proteins, metabolites, ions, and water. In a diabetic milieu, glucose-induced toxicity promotes oxidative stress and mitochondrial dysfunction, impairing tubular function. Increased glucose level in urine and ROS enhance the activity of sodium/glucose co-transporter type 2 (SGLT2), which in turn exacerbates OS. SGLT2 inhibitors have demonstrated clear cardiovascular benefits in DKD which may be in part ascribed to the generation of a beneficial equilibrium between oxidant and antioxidant mechanisms.

Fatty Acid Composition and Contents of Fish of Genus Salvelinus from Natural Ecosystems and Aquaculture

Fatty acids (FA) of muscle tissue of Salvelinus species and its forms, S. alpinus, S. boganidae, S. drjagini, and S. fontinalis, from six Russian lakes and two aquacultures, were analyzed. Considerable variations in FA compositions and contents were found, including contents of eicosapentaenoic and docosahexaenoic acids (EPA and DHA), which are important indicators of fish nutritive value for humans. As found, contents of EPA+DHA (mg·g−1 wet weight) in muscle tissue of Salvelinus species and forms varied more than tenfold. These differences were supposed to be primarily determined by phylogenetic factors, rather than ecological factors, including food. Two species, S. boganidae and S. drjagini, had the highest EPA+DHA contents in their biomass and thereby could be recommended as promising species for aquaculture to obtain production with especially high nutritive value. Basing on revealed differences in FA composition of wild and farmed fish, levels of 15-17-BFA (branched fatty acids), 18:2NMI (non-methylene interrupted), 20:2NMI, 20:4n-3, and 22:4n-3 fatty acids were recommended for verifying trade label information of fish products on shelves, as the biomarkers to differentiate wild and farmed charr.

β-Synuclein: An Enigmatic Protein with Diverse Functionality

α-Synuclein (αS) is a small, unstructured, presynaptic protein expressed in the brain. Its aggregated form is a major component of Lewy bodies, the large proteinaceous deposits in Parkinson’s disease. The closely related protein, β-Synuclein (βS), is co-expressed with αS. In vitro, βS acts as a molecular chaperone to inhibit αS aggregation. As a result of this assignation, βS has been largely understudied in comparison to αS. However, recent reports suggest that βS promotes neurotoxicity, implying that βS is involved in other cellular pathways with functions independent of αS. Here, we review the current literature pertaining to human βS in order to understand better the role of βS in homeostasis and pathology. Firstly, the structure of βS is discussed. Secondly, the ability of βS to (i) act as a molecular chaperone; (ii) regulate synaptic function, lipid binding, and the nigrostriatal dopaminergic system; (iii) mediate apoptosis; (iv) participate in protein degradation pathways; (v) modulate intracellular metal levels; and (vi) promote cellular toxicity and protein aggregation is explored. Thirdly, the P123H and V70M mutations of βS, which are associated with dementia with Lewy bodies, are discussed. Finally, the importance of post-translational modifications on the structure and function of βS is reviewed. Overall, it is concluded that βS has both synergistic and antagonistic interactions with αS, but it may also possess important cellular functions independent of αS.

Chemistry and Biochemistry Aspects of the 4-Hydroxy-2,3-trans-nonenal

4-hydroxy-2,3-trans-nonenal (C9H16O2), also known as 4-hydroxy-2E-nonenal (C9H16O2; HNE) is an α,β-unsaturated hydroxyalkenal. HNE is a major aldehyde, formed in the peroxidation process of ω-6 polyunsaturated fatty acids (ω-6 PUFAs), such as linoleic and arachidonic acid. HNE is not only harmful but also beneficial. In the 1980s, the HNE was regarded as a “toxic product of lipid peroxidation” and the “second toxic messenger of free radicals”. However, already at the beginning of the 21st century, HNE was perceived as a reliable marker of oxidative stress, growth modulating factor and signaling molecule. Many literature data also indicate that an elevated level of HNE in blood plasma and cells of the animal and human body is observed in the course of many diseases, including cancer. On the other hand, it is currently proven that cancer cells divert to apoptosis if they are exposed to supraphysiological levels of HNE in the cancer microenvironment. In this review, we briefly summarize the current knowledge about the biological properties of HNE.

O-methylated N-glycans Distinguish Mosses from Vascular Plants

In the animal kingdom, a stunning variety of N-glycan structures have emerged with phylogenetic specificities of various kinds. In the plant kingdom, however, N-glycosylation appears to be strictly conservative and uniform. From mosses to all kinds of gymno- and angiosperms, land plants mainly express structures with the common pentasaccharide core substituted with xylose, core α1,3-fucose, maybe terminal GlcNAc residues and Lewis A determinants. In contrast, green algae biosynthesise unique and unusual N-glycan structures with uncommon monosaccharides, a plethora of different structures and various kinds of O-methylation. Mosses, a group of plants that are separated by at least 400 million years of evolution from vascular plants, have hitherto been seen as harbouring an N-glycosylation machinery identical to that of vascular plants. To challenge this view, we analysed the N-glycomes of several moss species using MALDI-TOF/TOF, PGC-MS/MS and GC-MS. While all species contained the plant-typical heptasaccharide with no, one or two terminal GlcNAc residues (MMXF, MGnXF and GnGnXF, respectively), many species exhibited MS signals with 14.02 Da increments as characteristic for O-methylation. Throughout all analysed moss N-glycans, the level of methylation differed strongly even within the same family. In some species, methylated glycans dominated, while others had no methylation at all. GC-MS revealed the main glycan from Funaria hygrometrica to contain 2,6-O-methylated terminal mannose. Some mosses additionally presented very large, likewise methylated complex-type N-glycans. This first finding of the methylation of N-glycans in land plants mirrors the presumable phylogenetic relation of mosses to green algae, where the O-methylation of mannose and many other monosaccharides is a common trait.

Mass Spectrometry-Based Structural Proteomics for Metal Ion/Protein Binding Studies

Metal ions are critical for the biological and physiological functions of many proteins. Mass spectrometry (MS)-based structural proteomics is an ever-growing field that has been adopted to study protein and metal ion interactions. Native MS offers information on metal binding and its stoichiometry. Footprinting approaches coupled with MS, including hydrogen/deuterium exchange (HDX), “fast photochemical oxidation of proteins” (FPOP) and targeted amino-acid labeling, identify binding sites and regions undergoing conformational changes. MS-based titration methods, including “protein–ligand interactions by mass spectrometry, titration and HD exchange” (PLIMSTEX) and “ligand titration, fast photochemical oxidation of proteins and mass spectrometry” (LITPOMS), afford binding stoichiometry, binding affinity, and binding order. These MS-based structural proteomics approaches, their applications to answer questions regarding metal ion protein interactions, their limitations, and recent and potential improvements are discussed here. This review serves as a demonstration of the capabilities of these tools and as an introduction to wider applications to solve other questions.

Smart Bioinks for the Printing of Human Tissue Models

3D bioprinting has tremendous potential to revolutionize the field of regenerative medicine by automating the process of tissue engineering. A significant number of new and advanced bioprinting technologies have been developed in recent years, enabling the generation of increasingly accurate models of human tissues both in the healthy and diseased state. Accordingly, this technology has generated a demand for smart bioinks that can enable the rapid and efficient generation of human bioprinted tissues that accurately recapitulate the properties of the same tissue found in vivo. Here, we define smart bioinks as those that provide controlled release of factors in response to stimuli or combine multiple materials to yield novel properties for the bioprinting of human tissues. This perspective piece reviews the existing literature and examines the potential for the incorporation of micro and nanotechnologies into bioinks to enhance their properties. It also discusses avenues for future work in this cutting-edge field.

Role of Lipopolysaccharide, Derived from Various Bacterial Species, in Pulpitis—A Systematic Review

Lipopolysaccharide (LPS) is widely used for induction of inflammation in various human tissues, including dental pulp. The purpose of this study was to summarize current medical literature focusing on (1) cell types used by researchers to simulate dental pulp inflammation, (2) LPS variants utilized in experimental settings and how these choices affect the findings. Our study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched for studies reporting outcomes of lipopolysaccharide application on dental pulp cells in vitro using electronic databases: MEDLINE, Web of Science and Scopus. Having gathered data from 115 papers, we aimed to present all known effects LPS has on different cell types present in dental pulp. We focused on specific receptors and particles that are involved in molecular pathways. Our review provides an essential foundation for further research using in vitro models of pulpitis.

Association of Angio-LncRNAs MIAT rs1061540/MALAT1 rs3200401 Molecular Variants with Gensini Score in Coronary Artery Disease Patients Undergoing Angiography

Long non-coding RNAs (lncRNAs) have emerged as essential biomolecules with variable diagnostic and/or prognostic utility in several diseases, including coronary artery disease (CAD). We aimed for the first time to investigate the potential association of five angiogenesis-related lncRNAs (PUNISHER, SENCR, MIAT, MALAT1, and GATA6-AS) variants with CAD susceptibility and/or severity. TaqMan Real-Time genotyping for PUNISHER rs12318065A/C, SENCR rs12420823C/T, MIAT rs1061540C/T, MALAT1 rs3200401T/C, and GATA6-AS1 rs73390820A/G were run on the extracted genomic DNA from 100 unrelated patients with stable CAD undergoing diagnostic coronary angiography and from 100 controls. After adjusting covariates, the studied variants showed no association with disease susceptibility; however, MIAT*T/T genotype was associated with a more severe Gensini score. In contrast, MALAT1*T/C heterozygosity was associated with a lower score. The lipid profile, and to a lesser extent smoking status, male sex, weight, hypertension, and MALAT1 (T > C) (negative correlation), explained the variance between patients/control groups via a principal component analysis. Incorporating the principal components into a logistic regression model to predict CAD yielded a 0.92 AUC. In conclusion: MIAT rs1061540 and MALAT1 rs3200401 variants were associated with CAD severity and Gensini score in the present sample of the Egyptian population. Further large multi-center and functional analyses are needed to confirm the results and identify the underlying molecular mechanisms.

How Far Are We from the Completion of the Human Protein Interactome Reconstruction?

After more than fifteen years from the first high-throughput experiments for human protein–protein interaction (PPI) detection, we are still wondering how close the completion of the genome-scale human PPI network reconstruction is, what needs to be further explored and whether the biological insights gained from the holistic investigation of the current network are valid and useful. The unique structure of PICKLE, a meta-database of the human experimentally determined direct PPI network developed by our group, presently covering ~80% of the UniProtKB/Swiss-Prot reviewed human complete proteome, enables the evaluation of the interactome expansion by comparing the successive PICKLE releases since 2013. We observe a gradual overall increase of 39%, 182%, and 67% in protein nodes, PPIs, and supporting references, respectively. Our results indicate that, in recent years, (a) the PPI addition rate has decreased, (b) the new PPIs are largely determined by high-throughput experiments and mainly concern existing protein nodes and (c), as we had predicted earlier, most of the newly added protein nodes have a low degree. These observations, combined with a largely overlapping k-core between PICKLE releases and a network density increase, imply that an almost complete picture of a structurally defined network has been reached. The comparative unsupervised application of two clustering algorithms indicated that exploring the full interactome topology can reveal the protein neighborhoods involved in closely related biological processes as transcriptional regulation, cell signaling and multiprotein complexes such as the connexon complex associated with cancers. A well-reconstructed human protein interactome is a powerful tool in network biology and medicine research forming the basis for multi-omic and dynamic analyses.