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Adamantia Papadopoulou, Vasiliki E. Kalodimou, Eleni Mavrogonatou, Konstantina Karamanou, Andreas M. Yiacoumettis, Petros N. Panagiotou, Harris Pratsinis, Dimitris Kletsas
First published: 14 July 2022
Radiotherapy is widely used for the treatment of breast cancer. However, we have shown that ionizing radiation can provoke premature senescence in breast stromal cells. In particular, breast stromal fibroblasts can become senescent after irradiation both in vitro and in vivo and they express an inflammatory phenotype and an altered profile of extracellular matrix components, thus facilitating tumor progression. Adipose-derived stem cells (ASCs) represent another major component of the breast tissue stroma. They are multipotent cells and due to their ability to differentiate in multiple cell lineages they play an important role in tissue maintenance and repair in normal and pathologic conditions. Here, we investigated the characteristics of human breast ASCs that became senescent prematurely after their exposure to ionizing radiation. We found decreased expression levels of the specific mesenchymal cell surface markers CD105, CD73, CD44, and CD90. In parallel, we demonstrated a significantly reduced expression of transcription factors regulating osteogenic (i.e., RUNX2), adipogenic (i.e., PPARγ), and chondrogenic (i.e., SOX9) differentiation; this was followed by an analogous reduction in their differentiation capacity. Furthermore, they overexpress inflammatory markers, that is, IL-6, IL-8, and ICAM-1, and a catabolic phenotype, marked by the reduction of collagen type I and the increase of MMP-1 and MMP-13 expression. Finally, we detected changes in proteoglycan expression, for example, the upregulation of syndecan 1 and syndecan 4 and the downregulation of decorin. Notably, all these alterations, when observed in the breast stroma, represent poor prognostic factors for tumor development. In conclusion, we showed that ionizing radiation-mediated prematurely senescent human breast ASCs have a decreased differentiation potential and express specific changes adding to the formation of a permissive environment for tumor growth.
Fabio A. Zucca, Andrea Capucciati, Chiara Bellei, Michał Sarna, Tadeusz Sarna, Enrico Monzani, Luigi Casella, Luigi Zecca
First published: 11 June 2022
Neuromelanins are compounds accumulating in neurons of human and animal brain during aging, with neurons of substantia nigra and locus coeruleus having the highest levels of neuromelanins. These compounds have melanic, lipid, peptide, and inorganic components and are contained inside special autolysosomes. Neuromelanins can participate in neuroprotective or toxic processes occurring in Parkinson’s disease according to cellular environment. Their synthesis depends on the concentration of cytosolic catechols and is a protective process since it prevents the toxic accumulation of catechols-derived reactive compounds. Neuromelanins can be neuroprotective also by binding reactive/toxic metals to produce stable and non-toxic complexes. Extraneuronal neuromelanin released by dying dopamine neurons in Parkinson’s disease activates microglia which generate reactive oxygen species, reactive nitrogen species, and proinflammatory molecules, thus producing still neuroinflammation and neuronal death. Synthetic neuromelanins have been prepared with melanic, protein structure, and metal content closely mimicking the natural brain pigment, and these models are also able to activate microglia. Neuromelanins have different structure, synthesis, cellular/subcellular distribution, and role than melanins of hair, skin, and other tissues. The main common aspect between brain neuromelanin and peripheral melanin is the presence of eumelanin and/or pheomelanin moieties in their structure.
SPECIAL ISSUE CALL FOR PAPERS
GUEST EDITOR: Mandeep Kaur, University of the Witwatersrand
Deadline extension for manuscript submission 30 September 2022
Expected issue publication will be summer 2023
NEW VIRTUAL ISSUES
Nao Inoue, Toshihiro Sakurai, Yusuke Yamamoto, Hitoshi Chiba, Shu-Ping Hui
First published: 10 June 2022
Lysophosphatidylethanolamine (LPE) is a major lysophospholipid produced by phospholipids and binds to human serum albumin (HSA). LPEs may play various roles in vivo depending on the differences in their acyl chains. However, only few reports have been published on the biological functions of LPEs. Hence, we determined the exact relative abundance of the major LPEs in the serum of healthy participants (n = 8) using liquid chromatography–tandem mass spectrometry. Consequently, LPE 18:2 (24.1 ± 5.2%) was found to be the most abundant in serum. To understand the distribution of LPEs, the serum separated via gel-filtration high-performance liquid chromatography was subjected to quantitative measurement. LPEs were more observed in the albumin fraction than the lipoprotein fraction. We also performed a fluorescence displacement assay and an in silico molecular docking experiment using AutoDock to confirm the affinity and binding sites of the LPEs on HSA. The binding affinities of the LPEs for drug sites 1 and 2 on HSA were relatively low, with Ki values of approximately 11 and 3.8 μM, respectively. AutoDock analysis revealed the conformation of the LPEs bound to drug sites and the possibility of LPEs binding to other HSA sites. These findings could help to elucidate the biological and pathological functions of LPEs.
Biotechnology and Applied Biochemistry
Zizhuo Li, Xin Wan, Mingming Li, Qiuxia He, Haichao Yang, Wei Zhang, Xiuhua Yang
First published: 13 June 2022
Glioma is a tumor in the brain and spinal cord originating in the glial cells that surround the nerve cells. Among several microRNAs reported, miRNA-363 is associated with human glioma. Based on miRNA-363 levels, the development and progression of glioma can be monitored. The current study used an interdigitated electrode sensor to monitor microRNA-363 levels, which indeed reflects the severity of glioma. The interdigitated electrode was generated using a photolithography technique followed by surface chemical modification carried out to insert miRNA-363 complementary oligo as the probe complexed with gold nanoparticles. The proposed sensor works based on the dipole moment between two electrodes, and when molecular immobilization or interaction occurs, the response by the signal output changes. The changes in the target microRNA-363 sequence were standardized to identify glioma. The limit of detection of miRNA-363 was 10 fM with an R2 value of 0.996 on the linear coefficient regression ranges between 1 fM and 100 pM. Furthermore, unrelated sequences failed to increase the response of the current with the complementary probe, indicating specific miRNA-363 detection on the interdigitated electrode. This study demonstrates the platform to be used for determining the presence of microRNA-363 in glioma and as the basis for other biomarker analyses.
Wenyu Wang, Mengli Li, Ming Miao, Tao Zhang
First published: 27 June 2022
In recent years, arginine deiminase (ADI, EC 126.96.36.199) has attracted much attention as a biocatalyst that produces the functional amino acid l-citrulline from l-arginine and also as an anticancer enzyme. Here, we identified and characterized a putative ADI from the thermophilic bacterium Halothermothrix orenii. The H. orenii ADI (H-ADI) protein was expressed in Escherichia coli BL21(DE3) with a specific activity of 91.8 U/mg protein at 55°C and pH 6.5. The enzyme remained at 74% relative activity after incubation at 45°C for 180 min, only 25% at 50°C. The melting temperature was 56°C. H-ADI is not a metal-requiring enzyme; Ni2+ slightly improved the catalytic activity. The Km and Vmax for l-arginine were 55.5 mM and 156.8 μmol/min/mg protein, respectively. Moreover, three residues (Arg183, Arg237, and His273) were key to the formation of l-citrulline, as analyzed by alanine-scanning mutagenesis. Finally, the enzymatic synthesis of l-citrulline was carried out at 50°C with a conversion ratio reaching 99.03%. Together, these findings show that H-ADI is a promising biocatalyst for the production of l-citrulline.
Biochemistry and Molecular Biology Education
Evan N. Bennett, Shallee T. Page
First published: 09 July 2022
The ability to analyze large data sets (“Big Data”) is an increasingly important skill in modern science. In Biochemistry, the increased volume and velocity of data is particularly evident in the rapid expansion of biological databases. We present a modular bioinformatics course to survey the analysis of genomic data for advanced undergraduates. Research activities include genome scanning for endogenous retroviruses, annotating genomic sequences and a brief exploration of programming in R. A summative poster session was used to disseminate their work. This course is amenable to remote or online instruction. Supplemental materials provided include a schedule and outline. This article reports a session from the virtual international 2021 IUBMB/ASBMB workshop, “Teaching Science on Big Data.”
Angela K. Hilliker, Kristine L. Grayson
First published: 15 July 2022
As biologists accumulate or encounter increasingly large and complex data sets, our field creates the need for students to develop skills in data exploration and visualization. Many biology courses lack the time for students to develop the skills needed to parse complex datasets and visualize them appropriately. We developed a new upper-level undergraduate biology course to focused on data exploration and communication without requiring previous coding experience. We emphasized data visualization principles and best practices and taught students how to manage and visualize data via Tableau and R. We also explored scientific ethics, how to refute misinformation, and inequities that can occur in data collection and usage
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Molecular Aspects of Medicine
Volume 85 (June 2022) 100995
by Zsolt I. Koml´osi, Willem van de Veen, N´ora Kov´acs, Gerg˝o Sz˝ucs, Milena Sokolowska, Liam O’Mahony, Mübeccel Akdis, Cezmi A. Akdis,