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Topic Review
Thrombin Cleavage of Osteopontin
Osteopontin (OPN) is a multi-functional protein that is involved in various cellular processes such as cell adhesion, migration, and signaling. There is a single conserved thrombin cleavage site in OPN that, when cleaved, yields two fragments with different properties from full-length OPN. In cancer, OPN has tumor-promoting activity and plays a role in tumor growth and metastasis. High levels of OPN expression in cancer cells and tumor tissue are found in various types of cancer, including breast, lung, prostate, ovarian, colorectal, and pancreatic cancer, and are associated with poor prognosis and decreased survival rates. OPN promotes tumor progression and invasion by stimulating cell proliferation and angiogenesis and also facilitates the metastasis of cancer cells to other parts of the body by promoting cell adhesion and migration. Furthermore, OPN contributes to immune evasion by inhibiting the activity of immune cells. 
  • 912
  • 12 Sep 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.
  • 911
  • 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. 
  • 911
  • 17 Aug 2021
Topic Review
Modified Plant-Derived Nanovesicles for Therapeutics Delivery
Extracellular vesicles (EVs) are a highly heterogeneous population of membranous particles that are secreted by almost all types of cells across different domains of life, including plants. Studies on plant-derived nanovesicles (PDNVs) showed that they could modulate metabolic reactions of the recipient cells, affecting (patho)physiology with health benefits in a trans-kingdom manner. In addition to its bioactivity, PDNV has advantages over conventional nanocarriers, making its application promising for therapeutics delivery. 
  • 911
  • 10 Aug 2022
Topic Review
Astroglial sncRNA Relevance on Early Neurodegeneration Stages
Astrocyte dysfunction with consequential neuronal microenvironment dysregulation (astrocytopathy) has been involved in processes of early neurodegenerative disease. Small non-coding RNA (sncRNA) vary in different detrimental conditions of Central Nervous System (CNS), and sustained changes in sncRNA astrocyte expression profile can be the consequence of these conditions. sncRNA signatures derived from astrocytes, could therefore be a key to reveal early neurodegenerative disease, helping to unravel the astrocyte role in neurodegenerative disease. Current biomarkers for neurodegenerative disease, face strong challenges such as high variability, negative cost-effectiveness, low availability, or invasiveness. For example, cerebrospinal fluid evaluation (CSF tests) is a highly invasive, expensive, risky procedure, often used in the diagnosis of neurodegenerative disease. The alternative to CSF tests, which is neuroimaging requires especial equipment, long operating time and it is highly expensive making their widespread use prohibitive. Still, misdiagnosis could occur after the use of these powerful tools. Therefore, new methods are needed to assess neurodegeneration, and extracellular vesicles from astrocytes (ADEV) represent and interesting target of research. ADEV cross blood brain-barrier (BBB) carrying sncRNA from astrocytes and cell-specific membrane surface proteins, which can be used to allow ADEV separation from vesicles of other sources and other contaminants. This approach could be useful for the analysis of a less invasive, simpler, peripheral sample of blood origin. sncRNA dysregulated in conditions associated with increased risk of neurodegenerative disease and their possible effects on target cells is shown.
  • 910
  • 05 Dec 2022
Topic Review
Metabolic Reprogramming Strategy Targeting Glucose Metabolism
Diabetes is not only a risk factor for breast cancer but also worsens its prognosis. Patients with diabetes usually show hyperglycemia and hyperinsulinemia, which are accompanied by different glucose, protein, and lipid metabolism disorders. Metabolic abnormalities observed in diabetes can induce the occurrence and development of breast cancer. The changes in substrate availability and hormone environment not only create a favorable metabolic environment for tumorigenesis but also induce metabolic reprogramming events required for breast cancer cell transformation. Metabolic reprogramming is the basis for the development, swift proliferation, and survival of cancer cells. Metabolism must also be reprogrammed to support the energy requirements of the biosynthetic processes in cancer cells. In addition, metabolic reprogramming is essential to enable cancer cells to overcome apoptosis signals and promote invasion and metastasis.
  • 910
  • 16 Feb 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. 
  • 909
  • 06 Dec 2022
Topic Review
MERCs in Glioblastoma
Glioblastoma (GB), also known as glioblastoma multiforme, is the most aggressive type of astrocytoma. GB derives both from glial and glioma stem cells and affects glia and astrocytes. Gliomas are heterogeneous neoplasms, classified into grade I to IV according to their malignancy and the presence of specific histological/molecular hallmarks. The higher grade of glioma is known as glioblastoma (GB). Although progress has been made in surgical and radiation treatments, its clinical outcome is still unfavorable. The invasive properties of GB cells and glioma aggressiveness are linked to the reshaping of the cytoskeleton. Recent works suggest that the different susceptibility of GB cells to antitumor immune response is also associated with the extent and function of mitochondria–ER contact sites (MERCs). 
  • 908
  • 29 Apr 2022
Topic Review
Delivery of Nitric Oxide in the Cardiovascular System
Nitric oxide (NO) is a key molecule in cardiovascular homeostasis and its abnormal delivery is highly associated with the occurrence and development of cardiovascular disease (CVD). The assessment and manipulation of NO delivery is crucial to the diagnosis and therapy of CVD, such as endothelial dysfunction, atherosclerotic progression, pulmonary hypertension, and cardiovascular manifestations of coronavirus (COVID-19). 
  • 908
  • 18 Nov 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. 
  • 907
  • 03 Sep 2021
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.
  • 907
  • 17 Oct 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. 
  • 907
  • 16 Jun 2023
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.
  • 906
  • 28 Jan 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.
  • 905
  • 20 Feb 2021
Topic Review
Atopic Dermatitis-Associated Alopecia Areata
Alopecia areata (AA) is regarded as a tissue-specific and cell-mediated autoimmune disorder. Regarding the cytokine balance, AA has been considered a type 1 inflammatory disease. On the other hand, AA often complicates atopic dermatitis (AD) and AD is regarded as type 2 inflammatory disease. However, the immunological aspects of AA in relation to AD are still poorly understood. Therefore, we aim to clarify the immunological properties of AD-associated AA. In this study, we performed comparative analysis of the expression of intracytoplasmic cytokines (IFN-γ, IL-4, and IL-13), chemokine receptors (CXCR3 and CCR4) in peripheral blood which were taken from healthy controls, non-atopic AA patients, AA patients with extrinsic AD, and AA patients with intrinsic AD by flowcytometric analysis. We also compared the scalp skin samples taken from AA patients with extrinsic AD before and after treatment with dupilumab. In non-atopic AA patients, the ratios of CD4+IFN-γ+ cells to CD4+IL-4+ cells and CD4+IFN-γ+ cells to CD4+IL-13+ cells were higher than those in AA patients with extrinsic AD. Meanwhile, the ratio of CD8+IFN-γ+ cells to CD8+IL-13+ cells was significantly higher in the non-atopic AA than in the healthy controls. In AA patients with extrinsic AD, the skin AA lesion showed dense infiltration of not only CXCR3+ cells but also CCR4+ cells around hair bulb before dupilumab treatment. However, after the treatment, the number of CXCR3+ cells had no remarkable change while the number of CCR4+ cells significantly decreased. These results indicate that the immunological condition of AA may be different between atopic and non-atopic patients and between extrinsic and intrinsic AD patients. Our study provides an important notion that type 2 immunity may participate in the development of AA in extrinsic AD patients. It may be considered that the immunological state of non-atopic AA is different from that of atopic AA.
  • 904
  • 10 Mar 2021
Topic Review
Retinoic Acid and Lung Development
Retinoic acid (RA) is a key molecular player in embryogenesis and adult tissue homeostasis. In embryo development, RA plays a crucial role in the formation of different organ systems, namely, the respiratory system. During lung development, there is a spatiotemporal regulation of RA levels that assures the formation of a fully functional organ. RA signaling influences lung specification, branching morphogenesis, and alveolarization by regulating the expression of particular target genes. Moreover, cooperation with other developmental pathways is essential to shape lung organogenesis.
  • 904
  • 23 Jun 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. 
  • 904
  • 04 Nov 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. 
  • 904
  • 09 Mar 2022
Topic Review
Oxidative Stress in Retinal Dystrophies
Retinal cell survival requires an equilibrium between oxygen, reactive oxygen species, and antioxidant molecules that counteract oxidative stress damage. Oxidative stress alters cell homeostasis and elicits a protective cell response, which is most relevant in photoreceptors and retinal ganglion cells, neurons with a high metabolic rate that are continuously subject to light/oxidative stress insults. Any alteration on the retinal cell mechanisms to respond to oxidative stress injuries results in cell damage and apoptosis. Therefore, antioxidants agents, modulators of gene expression and inducers of cytoprotective signaling pathways may be used as potential therapies to ameliorate phenotypic symptoms in multifactorial and rare retinal dystrophies associated to oxidative stress injuries.
  • 903
  • 22 Sep 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.
  • 903
  • 01 Mar 2022
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