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Topic Review
Antioxidant Effects on the Brain and Skeletal Muscle
Erythroid-related nuclear factor 2 (NRF2) and the antioxidant-responsive-elements (ARE) signaling pathway are the master regulators of cell antioxidant defenses, playing a key role in maintaining cellular homeostasis, a scenario in which proper mitochondrial function is essential. Increasing evidence indicates that the regular practice of physical exercise increases cellular antioxidant defenses by activating NRF2 signaling.
  • 921
  • 10 May 2022
Topic Review
Aryl Hydrocarbon Receptor Biology and Signaling
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor involved in regulating a wide range of biological responses. A diverse array of xenobiotics and endogenous small molecules bind to the receptor and drive unique phenotypic responses. Due in part to its role in mediating toxic responses to environmental pollutants, AhR activation has not been traditionally viewed as a viable therapeutic approach. Nonetheless, the expression and activation of AhR can inhibit the proliferation, migration, and survival of cancer cells, and many clinically approved drugs transcriptionally activate AhR. Identification of novel select modulators of AhR-regulated transcription that promote tumor suppression is an active area of investigation. The development of AhR-targeted anticancer agents requires a thorough understanding of the molecular mechanisms driving tumor suppression.
  • 921
  • 19 Apr 2023
Topic Review
Genista tridentata Phytochemical Characterization
Genista tridentata (L.) Willk., known as “prickled broom”, is a Leguminosae (Fabaceae) species native to the Iberian Peninsula, Morocco, Algeria, and Tunisia. It is used in folk medicine as an anti-inflammatory, for gastrointestinal and respiratory disorders, rheumatism, and headaches, to lower blood pressure, against hypercholesterolemia and hyperglycemia. 
  • 921
  • 08 Nov 2023
Topic Review
Plant TPK Ion Channel Evolution
Potassium (K) is a crucial element of plant nutrition, involved in many physiological and molecular processes. K+ membrane transporters are playing a pivotal role in K+ transport and tissue distribution as well as in various plant stress responses and developmental processes. Two-pore K+-channels (TPKs) are essential to maintain plant K+ homeostasis and are mainly involved in potassium transport from the vacuoles to the cytosol. Besides vacuolar specialization, some TPK members display different membrane localization including plasma membrane, protein storage vacuole membrane, and probably the organelles. In this manuscript, we elucidate the evolution of the voltage-independent TPK (two-pore K+-channels) family, which could be represented in some species by one pore, K+-inward rectifier (Kir)-like channels. A comprehensive investigation of existing databases and application of modern bioinformatic tools allowed us to make a detailed phylogenetic inventory of TPK/KCO3 (KCO: potassium channel, outward rectifying) channels through many taxa and gain insight into the evolutionary origin of TPK family proteins. Our results reveal the fundamental evolutional difference between the first and second pores, traced throughout multiple taxa variations in the ion selection filter motif, presence of thansposon, and methylation site in the proximity of some KCO members and suggest virus-mediated horizontal transfer of a KCO3-like ancestor by viruses. Additionally, we suggest several interconnected hypotheses to explain the obtained results and provide a theoretical background for future experimental validation. 
  • 920
  • 04 Nov 2021
Topic Review
Zinc and Health
Zinc is a redox-inert trace element that is second only to iron in abundance in biological systems. In cells, zinc is typically buffered and bound to metalloproteins, but it may also exist in a labile or chelatable (free ion) form. Zinc plays a critical role in prokaryotes and eukaryotes, ranging from structural to catalytic to replication to demise. 
  • 920
  • 17 Mar 2021
Topic Review
9,12-Octadecadiynoic Acid
Human breast milk lipids have major beneficial effects: they promote infant early brain development, growth and health. To identify the relationship between human breast milk lipids and infant neurodevelopment, multivariate analyses that combined lipidomics and psychological Bayley-III scales evaluation were utilized. 
  • 919
  • 03 Sep 2021
Topic Review
Circular RNAs in Pregnancy and the Placenta
The placenta, a product of conception with a transient existence, uniquely supports pregnancy. It plays a critical role in nutrient, waste and gas exchange between the mother and fetus. Correct placentation underpins fetal development, as well as coordinating maternal adaptations to pregnancy to maintain maternal and fetal health. In pregnancy complications characterised by aberrant placentation such as preeclampsia (PE) and intrauterine growth restriction, there is an altered placental transcriptome. Emerging evidence demonstrates the roles of novel RNA species in pregnancy complications, particularly circular RNAs (circRNAs).
  • 919
  • 18 May 2022
Topic Review
Glycoprotein Ib-IX-V Receptor Complex
The GPIb-IX-V complex is a profuse membrane receptor complex originating in megakaryocytes and exclusively functional on the surface of platelets. It primarily functions to mediate the first critical step in platelet adhesion, by facilitating binding to von Willebrand factor (VWF) on damaged sub-endothelium under conditions of high fluid shear stress. Although the primary ligand for the GPIb-V-IX receptor is VWF, it can also bind to a number of other ligands in the circulation such as thrombin, P-selectin, factor XI, factor XII, high molecular weight kininogen as well as bacteria. GPIb-IX-V offers a critical role in thrombosis, metastasis, and the life cycle of platelets, and is implicated in a number of thrombotic pathological processes such as stroke or myocardial infarction.
  • 919
  • 17 Oct 2022
Topic Review
NO-Stimulated Guanylyl Cyclase
NO-stimulated guanylyl cyclase (SGC) is a hemoprotein that plays key roles in various physiological functions. SGC is a typical enzyme-linked receptor that combines the functions of a sensor for NO gas and cGMP generator. SGC possesses exclusive selectivity for NO and exhibits a very fast binding of NO, which allows it to function as a sensitive NO receptor. 
  • 919
  • 21 Apr 2023
Topic Review
NADPH Oxidase in Glaucoma
Glaucoma is a heterogeneous group of disorders unified by loss of retinal ganglion cells (RGCs) and their axons, resulting in a characteristic phenotype consisting of an excavated optic nerve head with corresponding visual field defects. The pathogenesis of glaucoma is incompletely understood with multiple pathophysiological factors and pathways postulated to be causative, such as mechanical, vascular, and immunological factors, leading to the final result of apoptotic death of RGCs. Increasingly it is becoming apparent that these factors do not contribute to glaucoma independently, but rather they can be viewed as a continuum in which each factor contributes to the damage of retinal ganglion cell axons.
  • 918
  • 22 Sep 2021
Topic Review
Biomarkers of Melanoma
Tumour biomarkers can be useful in predicting the risk of metastases and thus prognosis. Some of them can also have a diagnostic use. The use of serum biomarkers, such as lactate dehydrogenase (LDH) or S100b, is recommended in some guidelines, while the use of other serum biomarkers, such as melanoma inhibitory activity (MIA) and vascular endothelial growth factor (VEGF) is limited due to low specificity and limited clinical usability. DNA point mutations in melanoma represent another important biomarker that can guide patient selection and predict treatment response. 
  • 918
  • 17 Aug 2021
Topic Review
Targeting Inflammation Driven by HMGB1
HMGB1, originally described as a a protein that binds to DNA, functions as a structural co-factor for somatic cell transcription control. However, it also has numerous functions extracellularly. High mobility group box 1 (HMGB1), when passively released from cells, is capable of activating host innate immunity.
  • 918
  • 27 Oct 2021
Topic Review
Proteomics in Pancreatic Ductal Adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor prognosis, as the clinical symptoms of this disease are only presented at an advanced stage. At a global level, the incidence of PDAC is expected to continue increasing as observed by the trend in the past consecutive years. On the other hand, the available US Food and Drug Administration-approved biomarker for PDAC, CA 19-9, is not reliable for diagnostic purposes but is rather useful for monitoring treatment response among PDAC patients. Nevertheless, there is an urgent need to identify reliable biomarkers for both diagnosis (specifically for the early detection) and ascertain prognosis, as well as to monitor treatment response and tumour recurrence of PDAC. In recent years, proteomic technologies have grown exponentially at an accelerated rate for a wide range of applications in cancer research. Interestingly, myriad of research mainly focused on the identification of potential biomarkers for the use of early detection and/or diagnosis of PDAC. Nonetheless, it is unfortunate that several other studies too have concurrently reported that these ‘identified potential biomarkers’ either as lacking in specificity and/or has prognostic values, instead. Likewise, studies conducted on biomarkers to ascertain the prognosis of PDAC, as well as to monitor treatment response and predict tumour recurrence in PDAC had also evidently shown conflicting results. In view of this, the identification and/or implementation of protein-based biomarkers with improved specificity and sensitivity for clinical utility for PDAC remains much to be desired. On the bright side though, the integration of multi-omics techniques, as well as further research on other novel technologies such as nanoparticle-enabled blood test and artificial intelligence), is hoped to lead to the discovery of superior biomarkers for PDAC that could be implemented into clinical practice in the near future.
  • 916
  • 01 Mar 2022
Topic Review
LncRNAs in the Regulation of Translation
Long non-coding RNAs (lncRNAs), a group of non-protein coding RNAs with lengths of more than 200 nucleotides, exert their effects by binding to DNA, mRNA, microRNA, and proteins and regulate gene expression at the transcriptional, post-transcriptional, translational, and post-translational levels. 
  • 915
  • 16 Jun 2023
Topic Review
Physiological Importance of Mitochondria
Mitochondria are among the most important organelles in eukaryotic cells and have a distinctive structure composed of lipid-bilayer membranes. A mitochondrion has a unique structure comprising four parts: the outer mitochondrial membrane (OMM), the inter-membranous space (IMS), the inner mitochondrial membrane (IMM), and the matrix, with each part performing a specific role. 
  • 914
  • 06 Dec 2022
Topic Review
SMUG1 in rRNA Quality Control
RNA modifications are essential for proper RNA processing, quality control, and maturation steps. In the last decade, some eukaryotic DNA repair enzymes have been shown to have an ability to recognize and process modified RNA substrates and thereby contribute to RNA surveillance. Single-strand-selective monofunctional uracil-DNA glycosylase 1 (SMUG1) is a base excision repair enzyme that not only recognizes and removes uracil and oxidized pyrimidines from DNA but is also able to process modified RNA substrates. SMUG1 interacts with the pseudouridine synthase dyskerin (DKC1), an enzyme essential for the correct assembly of small nucleolar ribonucleoproteins (snRNPs) and ribosomal RNA (rRNA) processing. Here, we review rRNA modifications and RNA quality control mechanisms in general and discuss the specific function of SMUG1 in rRNA metabolism. Cells lacking SMUG1 have elevated levels of immature rRNA molecules and accumulation of 5-hydroxymethyluridine (5hmU) in mature rRNA. SMUG1 may be required for post-transcriptional regulation and quality control of rRNAs, partly by regulating rRNA and stability.
  • 913
  • 28 Jan 2021
Topic Review
Ventx Family and Its Functional Similarities with Nanog
The Ventx family is one of the subfamilies of the ANTP (antennapedia) superfamily and belongs to the NK-like (NKL) subclass. Ventx is a homeobox transcription factor and has a DNA-interacting domain that is evolutionarily conserved throughout vertebrates. It has been extensively studied in Xenopus, zebrafish, and humans. The Ventx family contains transcriptional repressors widely involved in embryonic development and tumorigenesis in vertebrates. Several studies have documented that the Ventx family inhibited dorsal mesodermal formation, neural induction, and head formation in Xenopus and zebrafish. Moreover, Ventx2.2 showed functional similarities to Nanog and Barx1, leading to pluripotency and neural-crest migration in vertebrates. Among them, Ventx protein is an orthologue of the Ventx family in humans. Studies have demonstrated that human Ventx was strongly associated with myeloid-cell differentiation and acute myeloid leukemia. 
  • 913
  • 09 Mar 2022
Topic Review
Inhibition of Replication Fork Formation and Progression
Over 1.2 million deaths are attributed to multi-drug-resistant (MDR) bacteria each year. Persistence of MDR bacteria is primarily due to the molecular mechanisms that permit fast replication and rapid evolution. As many pathogens continue to build resistance genes, current antibiotic treatments are being rendered useless and the pool of reliable treatments for many MDR-associated diseases is thus shrinking at an alarming rate. In the development of novel antibiotics, DNA replication initiation and the primosome are still largely underexplored targets.
  • 913
  • 05 Jun 2023
Topic Review
CELF Family Proteins in Cancer
CELF (CUGBP Elav-like family) proteins are RBPs (RNA-binding proteins) with pleiotropic capabilities in RNA processing. Their responsibilities extend from alternative splicing and transcript editing in the nucleus to mRNA stability, and translation into the cytoplasm. In this way, CELF family members have been connected to global alterations in cancer proliferation and invasion, leading to their identification as potential tumor suppressors or even oncogenes. Notably, genetic variants, alternative splicing, phosphorylation, acetylation, subcellular distribution, competition with other RBPs, and ultimately lncRNAs, miRNAs, and circRNAs all impact CELF regulation. 
  • 912
  • 25 Oct 2021
Topic Review
Chromatin Architecture and Damage Response
DNA double-strand breaks (DSBs) have been recognized as the most serious lesions in irradiated cells. While several biochemical pathways capable of repairing these lesions have been identified, the mechanisms by which cells select a specific pathway for activation at a given DSB site remain poorly understood. The impact of chromatin and repair foci architecture on these mechanisms can be elucidated by super-resolution microscopy in combination with mathematical approaches of topology. These aspects are discussed in relation to state of the art knowledge of ionizing radiation induced damaging of cell nuclei and DNA repair.
  • 912
  • 20 Feb 2021
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