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Topic Review
Engineering and Expression Strategies for Optimization of L-Asparaginase
L-asparaginase, an enzyme widely used in the clinic for the treatment of leukemia and in bakeries for the reduction of acrylamide. Newly developed recombinant L-asparaginase (L-ASNase) may have a low affinity for asparagine, reduced catalytic activity, low stability, and increased glutaminase activity or immunogenicity. Some successful commercial preparations of L-ASNase are now available. Therefore, obtaining novel L-ASNases with improved properties suitable for food or clinical applications remains a challenge. 
  • 1.3K
  • 23 Nov 2023
Topic Review
Phytochemicals in Redox Homeostasis
Redox homeostasis, a dynamic process ensuring a balance between cellular oxidizing and reducing reactions, is crucial for maintaining healthy cellular physiology and regulating many biological processes, requiring continuous monitoring and fine-tuning. Reactive species play a critical role in intra/intercellular signaling, and each cell has a specific system guarding cellular redox homeostasis. Reactive oxygen species (ROS) signaling and oxidative stress are involved in cancer initiation and progression.
  • 1.3K
  • 24 Apr 2023
Topic Review
Antioxidant Potential of Psychotropic Drugs
Due to high oxygen consumption, the brain is particularly vulnerable to oxidative stress, which is considered an important element in the etiopathogenesis of several mental disorders, including schizophrenia, depression and dependencies. Despite the fact that it is not established yet whether oxidative stress is a cause or a consequence of clinic manifestations, the intake of antioxidant supplements in combination with the psychotropic therapy constitutes a valuable solution in patients’ treatment. When the psychoactive compounds possess themselves antioxidant capacity, this is an added-value for the therapy.
  • 1.3K
  • 12 Oct 2020
Topic Review
Nutriepigenomics in Environmental-Associated Oxidative Stress
Complex molecular mechanisms define our responses to environmental stimuli. Beyond the DNA sequence itself, epigenetic machinery orchestrates changes in gene expression induced by diet, physical activity, stress and pollution, among others. Importantly, nutrition has a strong impact on epigenetic players and, consequently, sustains a promising role in the regulation of cellular responses such as oxidative stress. As oxidative stress is a natural physiological process where the presence of reactive oxygen-derived species and nitrogen-derived species overcomes the uptake strategy of antioxidant defenses, it plays an essential role in epigenetic changes induced by environmental pollutants and culminates in signaling the disruption of redox control. 
  • 1.3K
  • 18 Apr 2023
Topic Review
Microvesicles
Extracellular vesicles (EV) are secreted by all cell types in a tumor and its microenvironment (TME) and play an essential role in intercellular communication and the establishment of a TME favorable for tumor invasion and metastasis. They encompass a variety of vesicle populations, among them the well-known endosomal-derived small exosomes (Exo), but also larger vesicles (diameter >100 nm) that are shed directly from the plasma membrane, the so-called microvesicles (MV). Increasing evidence suggests that MV, although biologically different, share the tumor-promoting features of Exo in the TME. Due to their larger size, they can be readily harvested from patients’ blood and characterized by routine methods such as conventional flow cytometry exploiting the plethora of molecules expressed on their surface. In this review we summarize the current knowledge about the biology and the composition of MV as well as their role within the TME. We highlight not only the challenges and potential of MV as novel biomarkers for cancer, but also discuss their possible use for therapeutic intervention.
  • 1.3K
  • 05 Nov 2020
Topic Review
Tau protein Interaction Partners
Tau protein belongs to the family of microtubule-associated proteins (MAPs) and can influence axonal transport and growth, neuronal polarization, and thus the normal function of neurons and the brain.
  • 1.3K
  • 15 Dec 2021
Topic Review
TNF Receptor Associated Factor-2 in Immune Signaling Pathways
Tumor necrosis factor (TNF) receptor associated factor-2 (TRAF2) is an intracellular adapter protein with E3 ligase activity, which interacts with a plethora of other signaling proteins, including plasma membrane receptors, kinases, phosphatases, other E3 ligases, and deubiquitinases. TRAF2 is involved in various cancer-relevant cellular processes, such as the activation of transcription factors of the NFκB family, stimulation of mitogen-activated protein (MAP) kinase cascades, endoplasmic reticulum (ER) stress signaling, autophagy, and the control of cell death programs. In a context-dependent manner, TRAF2 promotes tumor development but it can also act as a tumor suppressor.
  • 1.3K
  • 07 Sep 2022
Topic Review
Mechanisms of Neutrophil Activation
Neutrophil extracellular traps (NETs) are major contributors to inflammation and autoimmunity, playing a key role in the development of thrombotic disorders. NETs, composed of DNA, histones, and numerous other proteins serve as scaffolds for thrombus formation and promote platelet activation, coagulation, and endothelial dysfunction.
  • 1.3K
  • 03 Nov 2023
Topic Review
Lysosomal Calcium Channels
Ca2+ is pivotal intracellular messenger that coordinates multiple cell functions such as fertilization, growth, differentiation, and viability. Intracellular Ca2+ signaling is regulated by both extracellular Ca2+ entry and Ca2+ release from intracellular stores. Apart from working as the cellular recycling center, the lysosome has been increasingly recognized as a significant intracellular Ca2+ store that provides Ca2+ to regulate many cellular processes. The lysosome also talks to other organelles by releasing and taking up Ca2+. In lysosomal Ca2+-dependent processes, autophagy is particularly important, because it has been implicated in many human diseases including cancer.
  • 1.3K
  • 27 Apr 2021
Topic Review
Constituents and Identification of Super-Enhancers
Super-enhancers (SEs) are clusters of neighboring enhancers spanning over 10 kb with high-fold enhancer activity that drive cell-type specific gene expression. 3D genome organization enables SEs to interact with specific gene promoters and orchestrates their activity as evidenced by the high frequency of chromatin interactions at the genomic loci containing SEs. SEs contain many TF binding sites, and are heavily loaded with enhancer-associated chromatin features, such as master TFs (e.g., Oct4, Sox2, Nanog, and Klf4 in embryonic stem cells), RNA Pol II, MED1, and chromatin modifiers (p300 and BRD4). The recruited factors alter the chromatin structure, leading to interactions with promoters and RNA Pol II, a process mediated by enhancer–promoter looping. Phase separation may facilitate the assembly and function of SEs.
  • 1.3K
  • 29 Jun 2022
Topic Review
FHL2
Four and a half LIM domains 2 (FHL2) was originally described as ‘Down-regulated in Rhabdomyosarcoma LIM protein’ (DRAL) and is composed of LIM domains that are named after their initial discovery in the proteins Lin11, Isl-1 and Mec-3. FHL2 consists of four and a half LIM domains, each composed of two zinc fingers, except the first ‘half’ LIM-domain which has only one. While the structure of the four and a half LIM domains had been uncovered previously using Nuclear Magnetic Resonance (NMR) spectroscopy, the complete FHL2 protein structure is unknown; however, it has recently been predicted using the protein structure neural network AlphaFold.
  • 1.3K
  • 19 Oct 2021
Topic Review
Hypoxia-Inducible Factors and the Regulation of Lipid Metabolism
Oxygen deprivation or hypoxia characterizes a number of serious pathological conditions and elicits a number of adaptive changes that are mainly mediated at the transcriptional level by the family of hypoxia-inducible factors (HIFs). The HIF target gene repertoire includes genes responsible for the regulation of metabolism, oxygen delivery and cell survival. Although the involvement of HIFs in the regulation of carbohydrate metabolism and the switch to anaerobic glycolysis under hypoxia is well established, their role in the control of lipid anabolism and catabolism remains still relatively obscure. Recent evidence indicates that many aspects of lipid metabolism are modified during hypoxia or in tumor cells in a HIF-dependent manner, contributing significantly to the pathogenesis and/or progression of cancer and metabolic disorders. 
  • 1.3K
  • 23 May 2022
Topic Review
PARP Inhibitors
 Poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis) belong to a class of targeted drugs developed for the treatment of homologous recombination repair (HRR)-defective tumors. Preclinical and limited clinical data suggest that PARP inhibition is effective against prostate cancer (PC) in patients with HRR-deficient tumors and that PARPis can improve the mortality rate of PC in patients with BRCA1/2 mutations through a synthetic lethality. 
  • 1.3K
  • 24 May 2021
Topic Review
TKS4 and TKS5 Scaffold Proteins
Scaffold proteins are typically thought of as multi-domain “bridging molecules.” They serve as crucial regulators of key signaling events by simultaneously binding multiple participants involved in specific signaling pathways. In the case of epidermal growth factor (EGF)-epidermal growth factor receptor (EGFR) binding, the activated EGFR contacts cytosolic SRC tyrosine-kinase, which then becomes activated. This process leads to the phosphorylation of SRC-substrates, including the tyrosine kinase substrates (TKS) scaffold proteins. The TKS proteins serve as a platform for the recruitment of key players in EGFR signal transduction, promoting cell spreading and migration. The TKS4 and the TKS5 scaffold proteins are tyrosine kinase substrates with four or five SH3 domains, respectively. Their structural features allow them to recruit and bind a variety of signaling proteins and to anchor them to the cytoplasmic surface of the cell membrane. TKS4 and TKS5 had been recognized for their involvement in cellular motility, reactive oxygen species-dependent processes, and embryonic development. Furthermore, TKS4 has also been implicated in the regulation of homeostasis of mature adipose and bone tissue.
  • 1.3K
  • 19 Jan 2021
Topic Review
m1A RNA Modification in Gene Expression Regulation
N1-methyladenosine (m1A) is a prevalent and reversible post-transcriptional RNA modification that decorates tRNA, rRNA and mRNA. Studies based on technical advances in analytical chemistry and high-throughput sequencing methods have revealed the crucial roles of m1A RNA modification in gene regulation and biological processes.
  • 1.3K
  • 01 Jun 2022
Topic Review
Chronic Inflammation and Radiation-Induced Cystitis
Radiation cystitis is a potential complication following the therapeutic irradiation of pelvic cancers.
  • 1.3K
  • 19 Jan 2021
Topic Review
Glycan-Binding Protein Scaffolds
Glycans—a broad term describing carbohydrates, including oligosaccharides and polysaccharides—are the third class of important biological macromolecules following nucleic acids and proteins. Glycans are found in all domains of life and in viruses. They can exist as free sugars, but are more commonly found as glycoconjugates, including proteoglycans, glycoproteins, and glycolipids. Glycans are involved in a wide variety of physiological functions and have implications in numerous infectious and non-infectious diseases, making them diagnostic and therapeutic targets. Additionally, glycans are targeted in various biotechnological and industrial applications. The broad applications of glycans have spurred interest in the development of glycan binding proteins (GBPs).GBPs include lectins, antibodies, pseudoenzymes, and carbohydrate-binding modules (CBMs). Lectins are non-immunoglobulin proteins containing at least one non-catalytic domain that exhibits reversible carbohydrate binding. CBMs are similar to lectins, but are small binding domains typically found in lectins or carbohydrate-active enzymes (CAZymes). CAZymes can be further classified into glycoside hydrolases, glycosyltransferases, polysaccharide lyases, and carbohydrate esterases—detailed information on these enzymes is available through the Carbohydrate Active Enzymes (CAZy) database.
  • 1.3K
  • 28 Jan 2021
Topic Review
PI3K
The phosphoinositide 3-kinase (PI3K) is a family of kinases that play a key role in the biology of chronic lymphocytic leukemia (CLL).
  • 1.3K
  • 19 Mar 2021
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.
  • 1.3K
  • 04 May 2023
Topic Review
Main Characteristics of CircRNAs
Circular RNAs (circRNAs) represent a category of non-coding RNAs (ncRNAs) and constitute functional RNAs that are predetermined not to be translated, but transcribed. CircRNAs are characterized by single-stranded closed-loop structures without 5′-3′-polarity or a polyadenylated tail. The term “circRNA” was first used by Sanger et al. when identifying the structure of viroids.
  • 1.3K
  • 06 Jan 2022
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