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Topic Review
Toxic Effects of Highly Active Antiretroviral Therapy
Highly active antiretroviral therapy (HAART) comprises a combination of two or three antiretroviral (ARV) drugs that are administered together in a single tablet. These drugs target different steps within the human immunodeficiency virus (HIV) life cycle, providing either a synergistic or additive antiviral effect; this enhances the efficiency in which viral replication is suppressed. HIV cannot be completely eliminated, making HAART a lifetime treatment. With long-term HAART usage, an increasing number of patients experience a broadening array of complications, and this significantly affects their quality of life, despite cautious use. 
  • 1.2K
  • 08 Oct 2022
Topic Review
Carotenoids Antioxidant and Anti-Inflammatory Effects in Mood Disorders
Depression has a multifactorial etiology comprising family history and unemployment. Antioxidant supplementation has been found to combat various stress-induced psychiatric disorders, including depression and anxiety. A growing body of evidence indicates that carotenoids have both antioxidant and anti-inflammatory. Studies also suggest that poor dietary intake, particularly low intakes of fruit and vegetables and high intakes of fast food and other convenience foods, may increase the risk of developing depression. Thus, dietary interventions have the potential to help mitigate the risk of mental health decline in both the general population and those with mood disorders. 
  • 1.2K
  • 17 Mar 2023
Topic Review
Cholinesterase Modeling and Simulation
The cholinesterase enzyme family has but two members: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).  Computational efforts to better understand these enzymes, with a focus on their structural and catalytic properties and dynamics, includes docking and other Monte Carlo based calculations, as well as dynamic simulations of varying rigor and resource-demand including molecular dynamics, Langevin dynamics, quantum mechanical/molecular mechanics, and related algorithms. 
  • 1.2K
  • 21 Apr 2021
Topic Review
5-10-Methylenetetrahydrofolate Reductase
The 5-10-methylenetetrahydrofolate reductase (MTHFR) enzyme is vital for cellular homeostasis due to its key functions in the one-carbon cycle, which include methionine and folate metabolism, and protein, DNA, and RNA synthesis. 
  • 1.2K
  • 14 Feb 2022
Topic Review
Reactive Oxygen Species in the Brain
Reactive oxygen and nitrogen species are crucial contributors to the age-dependent decline in all tissues. Neural tissue, one of the main oxygen consumers in the mammalian body, is especially prone to reactive species-mediated damage. Brain cells, including neurons, astrocytes, and microglia, produce reactive oxygen species (ROS) by specific enzymatic systems, including complexes of the mitochondrial respiratory chain, multienzyme flavin-containing complexes, monoamine and xanthine oxidases, microglial and endothelial NADPH oxidases and cyclooxygenases in addition to non-enzymatic and potentially uncontrolled mechanisms of ROS production, such as autooxidation of quinones or other aromatic compounds. Nitric oxide produced by nitric oxide synthases powers the conversion of ROS into reactive nitrogen species (RNS). Both ROS and RNS play important signaling roles and are also capable of modifying other molecules such as proteins, nucleic and fatty acids, lipids and carbohydrates. The antioxidant system, comprising low molecular mass antioxidants (e.g., tocopherol, ascorbic acid and glutathione) and high molecular mass antioxidants such as enzymes (e.g., catalases, peroxidases, superoxide dismutases) and others, protects cells from potential damage caused by ROS or RNS. Powering antioxidant systems by NADPH provides neural tissue with defense against ROS but may also trigger ROS production by NADPH oxidases and cyclooxygenases. In turn, mitochondria start using ketone bodies as an energy source under certain conditions. Increased steady-state levels of ROS and RNS, along with the aforementioned ROS-modified molecules, activate the organisms’ immune system including brain’s microglia.
  • 1.2K
  • 09 Nov 2021
Topic Review
Extracellular Heat Shock Proteins
Heat shock proteins (HSPs) are highly conserved stress proteins known as molecular chaperones, which are considered to be cytoplasmic proteins with functions restricted to the intracellular compartment, such as the cytoplasm or cellular organelles. However, an increasing number of observations have shown that HSPs can also be released into the extracellular matrix and can play important roles in the modulation of inflammation and immune responses.
  • 1.2K
  • 20 Apr 2022
Topic Review
Heme-Copper Oxidases with Nitrite and Nitric Oxide
Nitrite and nitric oxide (NO), two active and critical nitrogen oxides linking nitrate to dinitrogen gas in the broad nitrogen biogeochemical cycle, are capable of interacting with redox-sensitive proteins. The interactions of both with heme-copper oxidases (HCOs) serve as the foundation not only for the enzymatic interconversion of nitrogen oxides but also for the inhibitory activity.
  • 1.2K
  • 26 Jan 2022
Topic Review
Pulmonary Stem Cell Senescence and Differentiation Disorders
Pulmonary senescence is accelerated by unresolved DNA damage response, underpinning susceptibility to pulmonary fibrosis. Recently it was reported that the SARS-Cov-2 viral infection induces acute pulmonary epithelial senescence followed by fibrosis. Notably, the TGF-β signalling pathway mediates alveolar epithelial stem cell senescence by mechanisms involving suppression of the telomerase reverse transcriptase gene in pulmonary fibrosis. Alternatively, telomere uncapping caused by stress-induced telomeric shelterin protein TPP1 degradation mediates DNA damage response, pulmonary senescence and fibrosis. However, targeted intervention of cellular senescence disrupts pulmonary remodelling and fibrosis by clearing senescent cells using senolytics or preventing senescence using telomere dysfunction inhibitor (TELODIN). Studies indicate that the development of senescence-associated differentiation disorders is reprogrammable and reversible by inhibiting stem cell replicative senescence in pulmonary fibrosis, providing a framework for targeted intervention of the molecular mechanisms of alveolar stem cell senescence and pulmonary fibrosis.
  • 1.2K
  • 18 Mar 2022
Topic Review
Selenium and Ageing
Selenium (Se) is an essential dietary trace element that plays an important role in the prevention of inflammation, cardiovascular diseases, infections, and cancer. Selenoproteins contain selenocysteine in the active center and include, i.a., the enzymes thioredoxin reductases (TXNRD1–3), glutathione peroxidases (GPX1–4 and GPX6) and methionine sulfoxide reductase, involved in immune functions, metabolic homeostasis, and antioxidant defense. Ageing is an inevitable process, which, i.a., involves an imbalance between antioxidative defense and reactive oxygen species (ROS), changes in protein and mitochondrial renewal, telomere attrition, cellular senescence, epigenetic alterations, and stem cell exhaustion. These conditions are associated with mild to moderate inflammation, which always accompanies the process of ageing and age-related diseases. In older individuals, Se, by being a component in protective enzymes, operates by decreasing ROS-mediated inflammation, removing misfolded proteins, decreasing DNA damage, and promoting telomere length. Se-dependent GPX1–4 and TXNRD1–3 directly suppress oxidative stress. Selenoprotein H in the cell nucleus protects DNA, and selenoproteins residing in the endoplasmic reticulum (ER) assist in the removal of misfolded proteins and protection against ER stress.
  • 1.2K
  • 11 Nov 2021
Topic Review
Core Collections of Plant Genetic Resources
The core collection is a small subset that minimizes genetic redundancy while preserving the maximum genetic diversity of the entire population. Research on the core collection is crucial for the efficient management and utilization of germplasm resources.
  • 1.2K
  • 11 May 2023
Topic Review
Glycosaminoglycans in Cancer Therapy
The tumor microenvironment (TME) is composed of cancerous, non-cancerous, stromal, and immune cells that are surrounded by the components of the extracellular matrix (ECM). Glycosaminoglycans (GAGs), natural biomacromolecules, essential ECM, and cell membrane components are extensively altered in cancer tissues. During disease progression, the GAG fine structure changes in a manner associated with disease evolution. Thus, changes in the GAG sulfation pattern are immediately correlated to malignant transformation. Their molecular weight, distribution, composition, and fine modifications, including sulfation, exhibit distinct alterations during cancer development. GAGs and GAG-based molecules, due to their unique properties, are suggested as promising effectors for anticancer therapy. Considering their participation in tumorigenesis, their utilization in drug development has been the focus of both industry and academic research efforts. These efforts have been developing in two main directions; (i) utilizing GAGs as targets of therapeutic strategies and (ii) employing GAGs specificity and excellent physicochemical properties for targeted delivery of cancer therapeutics.
  • 1.2K
  • 24 Mar 2021
Topic Review
Cannabis and Cannabinoids for Treatment of Cancer
Cancer is a disease which affects approximately 40% of people in their lifetime. Chemotherapy, the primary choice for treatment of cancer, is often ineffective or/and presents itself with many debilitating side effects, including loss of appetite, nausea, insomnia, and anxiety. Components of cannabis extracts, including cannabinoids and terpenes, may present an alternative for controlling side effects and may be used for tumor shrinkage together with chemodrugs. Cannabinoids act on so called endocannabinoid system (ECS) that operates in human body to maintain homeostasis. ECS promotes healthy development of tissues and regulates many processes in our organism and when disbalanced may lead to disease, including cancer. 
  • 1.2K
  • 25 Oct 2022
Topic Review
Causes and Mechanisms of PARP Inhibitor Resistance
Poly (ADP-ribose) polymerase (PARP) inhibitors are one of the most successful examples of clinical translation of targeted therapies in medical oncology, and this has been demonstrated by their effective management of BRCA1/BRCA2 mutant cancers, most notably in breast and ovarian cancers. PARP inhibitors target DNA repair pathways that BRCA1/2-mutant tumours are dependent upon. Inhibition of the key components of these pathways leads to DNA damage triggering subsequent critical levels of genomic instability, mitotic catastrophe and cell death. This ultimately results in a synthetic lethal relationship between BRCA1/2 and PARP, which underpins the effectiveness of PARP inhibitors.
  • 1.2K
  • 04 May 2023
Topic Review
Extracellular Vesicles Based Drug Delivery
Extracellular vesicles (EVs) play major roles in intracellular communication and participate in several biological functions in both normal and pathological conditions. Surface modification of EVs via various ligands, such as proteins, peptides, or aptamers, offers great potential as a means to achieve targeted delivery of therapeutic cargo, i.e., in drug delivery systems (DDS). This study summarizes recent studies pertaining to the development of EV-based DDS and its advantages compared to conventional nano drug delivery systems (NDDS). 
  • 1.2K
  • 30 Mar 2021
Topic Review
PVT1: novel colorectal cancer biomarker
Colorectal cancer is a very deadly disease with a current lack of a reliable biomarker for early detection, non-invasive diagnosis, treatment, prognostication, and monitoring of treatment. This entry provides information that indicates that PVT1 is a novel biomarker in colorectal cancer. Further research is required to establish how this knowledge can be used for clinical applications.
  • 1.2K
  • 04 Aug 2020
Topic Review
Tumour Immune Microenvironment
Targeting altered tumour metabolism is an emerging therapeutic strategy for cancer treatment. The metabolic reprogramming that accompanies the development of malignancy creates targetable differences between cancer cells and normal cells, which may be exploited for therapy. In this entry, we focus on the metabolic dysregulation exerted by tumour cells on the immune microenvironment, leading to tumour immunosuppression. This metabolic rewiring and crosstalk with the tumour microenvironment also play a key role in cell proliferation, metastasis, and the development of treatment resistance. Nonetheless, greater understanding of the metabolic crosstalk presents strategies that aid in the precision targeting of altered tumour metabolism, including therapeutic strategies combining metabolic inhibition with immunotherapy.
  • 1.2K
  • 09 Dec 2020
Topic Review
Thrombospondin-1 CD47 Signalling
Recent advances provide evidence that the cellular signalling pathway comprising the ligand-receptor duo of thrombospondin-1 (TSP1) and CD47 is involved in mediating a range of diseases affecting renal, vascular, and metabolic function, as well as cancer. In several instances, research has barely progressed past pre-clinical animal models of disease and early phase 1 clinical trials, while for cancers, anti-CD47 therapy has emerged from phase 2 clinical trials in humans as a crucial adjuvant therapeutic agent. This has important implications for interventions that seek to capitalize on targeting this pathway in diseases where TSP1 and/or CD47 play a role. Despite substantial progress made in our understanding of this pathway in malignant and cardiovascular disease, knowledge and translational gaps remain regarding the role of this pathway in kidney and metabolic diseases, limiting identification of putative drug targets and development of effective treatments. This review considers recent advances reported in the field of TSP1-CD47 signalling, focusing on several aspects including enzymatic production, receptor function, interacting partners, localization of signalling, matrix-cellular and cell-to-cell cross talk. The potential impact that these newly described mechanisms have on health, with a particular focus on renal and metabolic disease, is also discussed.
  • 1.2K
  • 02 Jul 2021
Topic Review
Radiolabeled Gold Nanoseeds and Glioblastoma Multiforme
Glioblastoma multiforme (GBM), classified as a grade IV brain tumor, represents the most frequent brain tumor, accounting for approximately 12–15% of all intracranial neoplasms. Current therapeutic strategies for GBM rely on open surgery, chemotherapy and radiotherapy. Despite some progress in the past 30 years, the overall survival of patients with glioblastoma remains extremely poor. The average lifespan is approximately 15 months after diagnosis, with most patients experiencing tumor relapse and outgrowth within 7–10 months of initial radiation therapy.
  • 1.2K
  • 14 Jan 2022
Topic Review
S-adenosyl-l-homocysteine Hydrolase
S-adenosyl-l-homocysteine hydrolase (SAHase) is a major regulator of cellular methylation reactions that occur in eukaryotic and prokaryotic organisms. SAHase activity is also a significant source of l-homocysteine and adenosine, two compounds involved in numerous vital, as well as pathological processes. Therefore, apart from cellular methylation, the enzyme may also influence other processes important for the physiology of particular organisms.
  • 1.2K
  • 17 Feb 2021
Topic Review
Curved Lipid Membranes
Eukaryotic cells contain membranes with various curvatures, from the near-plane plasma membrane to the highly curved membranes of organelles, vesicles, and membrane protrusions. These curvatures are generated and sustained by curvature-inducing proteins, peptides, and lipids, and describing these mechanisms is an important scientific challenge. In addition to that, some molecules can sense membrane curvature and thereby be trafficked to specific locations. 
  • 1.2K
  • 08 Aug 2022
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