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Topic Review
D2 Dopamine Receptor (D2-R)
The type 2 dopamine receptor D2 (D2-R), member of the G protein-coupled receptor (GPCR) superfamily, exists in two isoforms, short (D2S-R) and long (D2L-R). They differ by an additional 29 amino acids (AA) in the third cytoplasmic loop (ICL3) of the D2L-R. These isoforms differ in their intracellular localization and trafficking functionality, as D2L-R possesses a larger intracellular pool, mostly in the endoplasmic reticulum (ER). 
  • 2.0K
  • 26 Oct 2020
Topic Review
HSP90 inhibitors for IPF/COVID-19
Heat shock protein 90 (HSP90) is an important chaperone that assists the late stage folding of several proteins involved in cell survival in response to environmental stressors. The inhibition of HSP90 is followed by a complex modulation of the proteome and the kinome, that has proved beneficial in cancer and various neurodegenerative diseases. Additionally, accumulating literature suggests that HSP90 may be a key target during the development of pulmonary fibrosis and that its inhibition could serve as a new and exciting therapeutic approach. We have summarized the current evidence about HSP90’s role in Idiopathic Pulmonary Fibrosis (IPF), the results from preclinical studies on its inhibition and the intracellular signaling pathways involved, in a recent review article (Review). In this Article entry, we will introduce the main findings discussed in the review and focus on its translation and possible significance in the era of the SARS-CoV-2 pandemic.
  • 2.0K
  • 07 Aug 2020
Topic Review
IP6K
Inositol and its phosphate metabolites play a pivotal role in several biochemical pathways and gene expression regulation: inositol pyrophosphates (PP-IPs) have been increasingly appreciated as key signaling modulators. Fluctuations in their intracellular levels hugely impact the transfer of phosphates and the phosphorylation status of several target proteins. Pharmacological modulation of the proteins associated with PP-IP activities has proved to be beneficial in various pathological settings. IP7 has been extensively studied and found to play a key role in pathways associated with PP-IP activities. Three inositol hexakisphosphate kinase (IP6K) isoforms regulate IP7 synthesis in mammals. Genomic deletion or enzymic inhibition of IP6K1 has been shown to reduce cell invasiveness and migration capacity, protecting against chemical-induced carcinogenesis. IP6K1 could therefore be a useful target in anticancer treatment.
  • 2.0K
  • 14 Oct 2020
Topic Review
Extreme Microorganisms in the Context of Biogeochemical Nitrogen Cycle
Extreme microorganisms (extremophile) are organisms that inhabit environments characterized by inhospitable parameters for most live beings (extreme temperatures and pH values, high or low ionic strength, pressure, or scarcity of nutrients). To grow optimally under these conditions, extremophiles have evolved molecular adaptations affecting their physiology, metabolism, cell signaling, etc. Due to their peculiarities in terms of physiology and metabolism, they have become good models for (i) understanding the limits of life on Earth, (ii) exploring the possible existence of extraterrestrial life (Astrobiology), or (iii) to look for potential applications in biotechnology. Recent research has revealed that extremophilic microbes play key roles in all biogeochemical cycles on Earth. Nitrogen cycle (N-cycle) is one of the most important biogeochemical cycles in nature; thanks to it, nitrogen is converted into multiple chemical forms, which circulate among atmospheric, terrestrial and aquatic ecosystems. This review summarizes recent knowledge on the role of extreme microorganisms in the N-cycle in extremophilic ecosystems, with special emphasis on members of the Archaea domain. Potential implications of these microbes in global warming and nitrogen balance, as well as their biotechnological applications are also discussed.
  • 2.0K
  • 17 Jun 2020
Topic Review
Nuclear domains 10 (ND10)
Nuclear domains 10 (ND10), a.k.a. promyelocytic leukemia nuclear bodies (PML-NBs), are membraneless subnuclear domains that are highly dynamic in their protein composition in response to cellular cues. They are known to be involved in many key cellular processes including DNA damage response, transcription regulation, apoptosis, oncogenesis, and antiviral defenses.
  • 2.0K
  • 25 Mar 2021
Topic Review
Laboratory Diagnosis of Porphyria
Porphyrias are a group of diseases that are clinically and genetically heterogeneous and originate mostly from inherited dysfunctions of specific enzymes involved in heme biosynthesis.
  • 2.0K
  • 28 Sep 2021
Topic Review
PCSK9 Inhibitors
Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors are a novel group of hypolipidemic drugs that are recommended particularly for high-risk hypercholesterolemia patients, including those with primary hypercholesterolemia (PH), where lifelong exposure to high low-density lipoprotein (LDL) cholesterol levels results in an elevated risk of atherosclerosis at an early age. The onset and progression of atherosclerosis is significantly influenced by activated platelets. Oxidized LDL influences platelet activation by interacting with their surface receptors and remodeling the composition of their cell membrane. This results in platelet aggregation, endothelial cell activation, promotion of inflammation and oxidative stress, and acceleration of lipid accumulation in atherosclerotic plaques. PCSK9 inhibitors reduce platelet activation by both significantly lowering LDL levels and reducing the LDL receptor-mediated activation of platelets by PCSK9. They also work synergistically with other hypolipidemic and antithrombotic drugs, including statins, ezetimibe, acetylsalicylic acid, clopidogrel, and ticagrelor, which enhances their antiplatelet and LDL-lowering effects. 
  • 2.0K
  • 28 May 2021
Topic Review
Storage, Preservation and Processing of Toona sinensis
Toona sinensis, a perennial and deciduous tree belonging to the Meliaceae family, has been cultivated for more than 2000 years in China. Storing the buds of T. sinensis is difficult, as it is easy for them to rot during storage, which seriously affects their edible and commodity value. There are three kinds of storage and preservation methods of T. sinensis buds; although they can extend the shelf life of T. sinensis, the nutrients in this vegetable plant experience different degrees of loss. Because bio-preservation methods have the advantages of being natural, safe, and simple, it has become one of the research hotspots of food preservation technology. Furthermore, in order to extend the consumption period of T. sinensis, it is processed into a wide variety of foods.
  • 2.0K
  • 19 Jul 2022
Topic Review
PH-Sensitive Cubosome Liquid Crystalline Nanocarriers
Cubosomes are soft biocontinuous nanoparticles whose 3D geometry can be engineered to render the structures responsive to pH variations, which is of large interest to the production of efficient drug delivery materials. We have reviewed the literature to provide a state of the art in this regard and shed lights on prominent perspectives and strategies for pH-sensitive cubosomes development, taking advantage of the pH changes of the biological media at targeted application sites.
  • 2.0K
  • 27 Oct 2020
Topic Review
WASF3
WASF3 (WAVE3), a Wiskott–Aldrich syndrome protein family member, appears to play a major role not only in the regulation of actin cytoskeleton dynamics but also in cancer cell invasion/metastasis. Blocking the WASF3-dependent metastatic signaling network remains an attractive and promising therapeutic option for the treatment of advanced tumors. 
  • 2.0K
  • 02 Feb 2021
Topic Review
Modular CAR T Platforms
The engineering of T cells through expression of chimeric antigen receptors (CARs) against tumor-associated antigens (TAAs) has shown significant potential for use as an anti-cancer therapeutic. The development of strategies for flexible and modular CAR T systems is accelerating, allowing for multiple antigen targeting, precise programming, and adaptable solutions in the field of cellular immunotherapy. Moving beyond the fixed antigen specificity of traditional CAR T systems, the modular CAR T technology splits the T cell signaling domains and the targeting elements through use of a switch molecule. The activity of CAR T cells depends on the presence of the switch, offering dose-titratable response and precise control over CAR T cells.
  • 2.0K
  • 25 Feb 2021
Topic Review
Carbohydrate-Binding Modules of Potential Resources
Carbohydrate-binding modules (CBMs) are a class of multi-module enzyme proteins and their function is to respond to bind to the carbohydrate substrate. Cellulose-binding domains (CBDs) are the earliest-discovered CBMs which were used to be catergozied based on their sequence homology. However, with the in-depth study of carbohydrate hydrolases, more modules in carbohydrate-active enzymes were discovered that could bind, in addition to cellulose, to other types of carbohydrates such as chitin, glucan, xylan, or starch. 
  • 2.0K
  • 07 May 2022
Topic Review
Glucagon-Like Peptide 1 and Taste
Preclinical studies provided some important insights into the action of glucagon-like peptide 1 (GLP-1) in taste perception. This review examines the literature to uncover some molecular mechanisms and connections between GLP-1 and the gustatory coding. Local GLP-1 production in the taste bud cells, the expression of GLP-1 receptor on the adjacent nerves, a functional continuum in the perception of sweet chemicals from the gut to the tongue and an identification of GLP-1 induced signaling pathways in peripheral and central gustatory coding all strongly suggest that GLP-1 is involved in the taste perception, especially sweet. However, the impact of GLP-1 based therapies on gustatory coding in humans remains largely unaddressed. Based on the molecular background we encourage further exploration of the tongue as a new treatment target for GLP-1 receptor agonists in clinical studies. Given that pharmacological manipulation of gustatory coding may represent a new potential strategy against obesity and diabetes, the topic is of utmost clinical relevance.
  • 2.0K
  • 25 Jan 2021
Topic Review
COP9 Signalosome
The COP9 signalosome (CSN) is a regulator of the ubiquitin proteasome system (UPS). In mammalian cells it occurs as an eight-subunit protein complex, six Proteasome-COP9 signalosome-Initiation factor eIF3 (PCI)-domain subunits including CSN1-4, CSN7 and CSN8 and two MOV34-Pad1-N-terminal (MPN)-domain subunits called CSN5 and CSN6. The CSN regulates cullin-RING-ubiquitin ligases (CRLs) by specifically removing NEDD8 from cullins. In cooperation with CAND1 it controls the adaptation of the CRL network to fluctuations in substrate availability. The CSN complex belongs to the JAMM family of deubiquitylating enzymes (DUBs). In addition, it interacts with other deubiquitylating enzymes including USP15 and USP48 coordinating ubiquitylation and deubiquitylation activities.
  • 1.9K
  • 26 Oct 2020
Topic Review
cAMP-Response Element Modulator in Spermatogenesis and Male Fertility
Spermatogenesis is a very complex process with an intricate transcriptional regulation. The transition from the diploid to the haploid state requires the involvement of specialized genes in meiosis, among other specific functions for the formation of the spermatozoon. The transcription factor cAMP-response element modulator (CREM) is a key modulator that triggers the differentiation of the germ cell into the spermatozoon through the modification of gene expression. CREM has multiple repressor and activator isoforms whose expression is tissue-cell-type specific and tightly regulated by various factors at the transcriptional, post-transcriptional and post-translational level. The activator isoform CREMτ controls the expression of several relevant genes in post-meiotic stages of spermatogenesis. In addition, exposure to xenobiotics negatively affects CREMτ expression, which is linked to male infertility. On the other hand, antioxidants could have a positive effect on CREMτ expression and improve sperm parameters in idiopathically infertile men.
  • 1.9K
  • 01 Nov 2023
Topic Review
Calcium Indicator NCaMP7
Green fluorescent genetically encoded calcium indicators (GECIs) are the most popular tool for visualization of calcium dynamics in vivo. However, most of them are based on the EGFP protein and have similar molecular brightnesses. The NTnC indicator, which is composed of the mNeonGreen fluorescent protein with the insertion of troponin C, has higher brightness as compared to EGFP-based GECIs, but shows a limited inverted response with an ΔF/F of 1. By insertion of a calmodulin/M13-peptide pair into the mNeonGreen protein, we developed a green GECI called NCaMP7. In vitro, NCaMP7 showed positive response with an ΔF/F of 27 and high affinity (Kd of 125 nM) to calcium ions. NCaMP7 demonstrated a 1.7-fold higher brightness and similar calcium-association/dissociation dynamics compared to the standard GCaMP6s GECI in vitro. According to fluorescence recovery after photobleaching (FRAP) experiments, the NCaMP7 design partially prevented interactions of NCaMP7 with the intracellular environment. The NCaMP7 crystal structure was obtained at 1.75Å resolution to uncover the molecular basis of its calcium ions sensitivity.The NCaMP7 indicator retained a high and fast response when expressed in cultured HeLa and neuronal cells. Finally, we successfully utilized the NCaMP7 indicator for in vivo visualization of grating-evoked and place-dependent neuronal activity in the visual cortex and the hippocampus of mice using a two-photon microscope and an NVista miniscope, respectively.
  • 1.9K
  • 26 Oct 2020
Topic Review Video
Cyclodextrin-Based Polymers
Cyclodextrins (CDs) are cyclic oligosaccharide structures that could be used for theranostic applications in personalized medicine. These compounds have been widely utilized not only for enhancing drug solubility, stability, and bioavailability but also for controlled and targeted delivery of small molecules. These compounds can be complexed with various biomolecules, such as peptides or proteins, via host-guest interactions. CDs are amphiphilic compounds with water-hating holes and water-absorbing surfaces. Architectures of CDs allow the drawing and preparation of CD-based polymers (CDbPs) with optimal pharmacokinetic and pharmacodynamic properties. These polymers can be cloaked with protein corona consisting of adsorbed plasma or extracellular proteins to improve nanoparticle biodistribution and half-life. Besides, CDs have become famous in applications ranging from biomedicine to environmental sciences.
  • 1.9K
  • 16 Nov 2022
Topic Review
Seaweeds
Seaweeds have a long history of use as food, as flavouring agents, and also used in traditional folk medicine. Seaweed products range from food, feed, and dietary supplements to pharmaceuticals, and from bioenergy intermediates to materials. At present, 98% of the seaweed required by the seaweed industry is provided by five genera and only ten species. The two brown kelp seaweeds Laminaria digitata, a native Irish species, and Macrocystis pyrifera, a native New Zealand species, are not included in these eleven species, although they have been used as dietary supplements and as animal and fish feed. The properties associated with the polysaccharides and proteins from these two species have resulted in increased interest in them, enabling their use as functional foods. Improvements and optimisations in aquaculture methods and bioproduct extractions are essential to realise the commercial potential of these seaweeds.
  • 1.9K
  • 16 Jan 2022
Topic Review
Brain Microvascular Pericytes in Breast Cancer Brain Metastasis
Brain tissue contains the highest number of perivascular pericytes compared to other organs. Pericytes are known to regulate brain perfusion and to play an important role within the neurovascular unit (NVU). The high phenotypic and functional plasticity of pericytes make this cell type a prime candidate to aid physiological adaptations but also propose pericytes as important modulators in diverse pathologies in the brain. This research highlights known phenotypes of pericytes in the brain, discusses the diverse markers for brain pericytes, and reviews current in-vitro and in-vivo experimental models to study pericyte function.
  • 1.9K
  • 05 May 2022
Topic Review
The HSP40/DnaJ Proteins Existing in Leishmania
Abrupt environmental changes are faced by Leishmania parasites during transmission from a poikilothermic insect vector to a warm-blooded host. Adaptation to harsh environmental conditions, such as nutrient deprivation, hypoxia, oxidative stress and heat shock needs to be accomplished by rapid reconfiguration of gene expression and remodeling of protein interaction networks. Chaperones play a central role in the maintenance of cellular homeostasis, and they are responsible for crucial tasks such as correct folding of nascent proteins, protein translocation across different subcellular compartments, avoiding protein aggregates and elimination of damaged proteins. Nearly one percent of the gene content in the Leishmania genome corresponds to members of the HSP40 family, a group of proteins that assist HSP70s in a variety of cellular functions. 
  • 1.9K
  • 12 May 2022
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