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Topic Review
Molecular Landscape of Pediatric Thyroid Cancer
Thyroid carcinomas (TC) are rare in the pediatric population; however, they constitute the most common endocrine malignancy. Despite some similarities with adult carcinomas, they have distinct clinical behavior and responses to therapy due to their unique pathology and molecular characteristics. The age cut-off used for defining the pediatric age group has been variable across different studies, and the universally accepted recommendations influence accurate interpretation of the available data. Moreover, factors such as radiation exposure and germline mutations have greater impact in children than in adults. 
  • 924
  • 30 Dec 2022
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. 
  • 924
  • 08 Nov 2023
Topic Review
Castration and Male Peripheral Neurons
This entry deals with the influence of androgens (testosterone) on pelvic autonomic pathways in male mammals. The vast majority of the relevant information has been gained in experiments involving castration (testosterone deprivation) performed in male rats, and recently, in male pigs. In both species, testosterone significantly affects the biology of the pathway components, including the pelvic neurons. However, there are great differences between rats and pigs in this respect. The most significant alteration is that testosterone deprivation accomplished a few days after birth results some months later in the excessive loss (approximately 90%) of pelvic and urinary bladder trigone intramural neurons in the male pig, while no changes in the number of pelvic neurons are observed in male rats (rats do not have the intramural ganglia). In the castrated pigs, much greater numbers of pelvic neurons than in the non-castrated animals express CGRP, GAL, VIP (peptides known to have neuroprotective properties), and caspase 3, suggesting that neurons die due to apoptosis triggered by androgen deprivation. In contrast, only some morpho-electrophysiological changes affecting neurons following castration are found in male rats. Certain clinicopathological consequences of testosterone deprivation for the functioning of urogenital organs are also discussed. 
  • 923
  • 18 Sep 2021
Topic Review
MSC-based Therapy for BBB Preservation
Ischemic stroke is the leading cause of mortality and long-term disability worldwide. Disruption of the blood–brain barrier (BBB) is a prominent pathophysiological mechanism, responsible for a series of subsequent inflammatory cascades that exacerbate the damage to brain tissue. However, the benefit of recanalization is limited in most patients because of the narrow therapeutic time window. Recently, mesenchymal stem cells (MSCs) have been assessed as excellent candidates for cell-based therapy in cerebral ischemia, including neuroinflammatory alleviation, angiogenesis and neurogenesis promotion through their paracrine actions. In addition, accumulating evidence on how MSC therapy preserves BBB integrity after stroke may open up novel therapeutic targets for treating cerebrovascular diseases.
  • 923
  • 22 Oct 2021
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. 
  • 923
  • 04 Nov 2021
Topic Review
Synthesis and Metabolism of H2S in Lung Cancer
Lung cancer is one of the 10 most common cancers in the world, which seriously affects the normal life and health of patients. The mechanisms of action of the occurrence and development of lung cancer have not been fully clarified. As a new type of gas signal molecule, hydrogen sulfide (H2S) has received great attention for its physiological and pathological roles in mammalian cells. It has been found that H2S is widely involved in the regulation of the respiratory system and digestive system, and plays an important role in the occurrence and development of lung cancer.
  • 922
  • 13 Jan 2023
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. 
  • 921
  • 17 Aug 2021
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
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.
  • 921
  • 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. 
  • 921
  • 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.
  • 920
  • 22 Sep 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.
  • 920
  • 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.
  • 919
  • 01 Mar 2022
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
TNFα
About 60 years ago, it was reported that bacterial endotoxin administration to mice resulted in the release of a serological protein with necrotic anti-tumor activity at high concentrations. Due to the latter characteristic, this protein was termed tumor necrosis factor (TNF)  and considered a breakthrough for cancer therapy. Today, the TNF superfamily consists of 19 members and 29 TNF receptors .Within this family, functional TNFα is represented by a trimer of 17.35 kDa monomers, folded into a rigid bell-shaped “jelly roll” composed of antiparallel filaments. It exists in two forms: a transmembrane form (tmTNFα) next to a soluble (sTNFα) form. The latter one is cleaved from tmTNFα by the metalloproteinase TNF-alpha-converting enzyme (TACE).
  • 918
  • 18 Aug 2021
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.
  • 917
  • 28 Jan 2021
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. 
  • 917
  • 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.
  • 916
  • 20 Feb 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. 
  • 915
  • 09 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
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