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Topic Review
FTO Dioxygenase
The FTO (FaT mass and Obesity-associated) protein is an alpha-ketoglutarate and iron dependent dioxygenase, a member of ALKBH family proteins. FTO removes the methyl groups from modified nucleotides on single stranded DNA or RNA with N6-methyladenozine in the mRNA removed most efficiently. It is engaged in wide range of key physiological processes such as adipogenesis, cell cycle progression, heart remodelling, neural development and osteogenesis. Impairments of FTO activity is lethal or leads to serious developmental disorders. It is also one of the factors responsible for development and maintenance of many type of cancers. FTO acts in cooperation with other proteins e.g. CaMKII, MRS, SFPQ or XPO2. Similarly to other dioxygenases, it shows ability to form homodimer. Recently, it was shown that FTO interacts with the calmodulin (CaM) in Ca2+ dependent manner.
  • 1.3K
  • 26 Oct 2021
Topic Review
Protein Tertiary Structure Prediction
The prediction of three-dimensional (3D) protein structure from amino acid sequences has stood as a significant challenge in computational and structural bioinformatics for decades. The widespread integration of artificial intelligence (AI) algorithms has substantially expedited advancements in protein structure prediction, yielding numerous significant milestones. In particular, the end-to-end deep learning method AlphaFold2 has facilitated the rise of structure prediction performance to new heights, regularly competitive with experimental structures in the 14th Critical Assessment of Protein Structure Prediction (CASP14). 
  • 1.3K
  • 26 Feb 2024
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.
  • 1.2K
  • 05 Nov 2020
Topic Review
Iron Oxide Nanoparticles in Cancer Diagnostics and Therapy
Cancer theranostics remains a vital research niche as a result of the rising mortality rates caused by various cancers globally. This is excarcebated by challenges related to conventional therapies. Iron-oxide-based NPs that possess characteristically large surface areas, small particle sizes, and superparamagnetism have been cited in applications geared towards diagnosis, and targeted drug delivery. When an external magnetic field is applied to superparamagnetic iron oxide NPs (SPIONs), the domains are aligned to the field. Once the field is removed, they return to a non-magnetic state. The NP magnetic moments turn to flip in the direction of the applied field. This flipping of the magnetic moments generates heat, which forms the basis of tumour ablation therapy through hyperthermia. Substituted iron-oxides or ferrites (MFe2O4) have emerged as interesting magnetic NPs due to their unique and attractive properties such as size and magnetic tunability, ease of synthesis, and manipulatable properties. In recent years, they have been explored for use in targeted therapy and drug delivery for anti-cancer treatment.
  • 1.2K
  • 27 May 2022
Topic Review
SRC-3
Steroid receptor coactivator-3 (SRC-3), also known as amplified in breast cancer 1 (AIB1), is a member of the SRC family. SRC-3 regulates not only the transcriptional activity of nuclear receptors but also many other transcription factors. Besides the essential role of SRC-3 in physiological functions, it also acts as an oncogene to promote multiple aspects of cancer.
  • 1.2K
  • 25 May 2021
Topic Review
Gap Junctions in Atrial Fibrillation
Atrial fibrillation (AF) represents the most common type of clinical cardiac arrhythmia worldwide and contributes to substantial morbidity, mortality and socioeconomic burden. Aggregating evidence highlights the strong genetic basis of AF. In addition to chromosomal abnormalities, pathogenic mutations in over 50 genes have been causally linked to AF, of which the majority encode ion channels, cardiac structural proteins, transcription factors and gap junction channels. In the heart, gap junctions comprised of connexins (Cxs) form intercellular pathways responsible for electrical coupling and rapid coordinated action potential propagation between adjacent cardiomyocytes. Among the 21 isoforms of connexins already identified in the mammal genomes, 5 isoforms (Cx37, Cx40, Cx43, Cx45 and Cx46) are expressed in human heart. Abnormal electrical coupling between cardiomyocytes caused by structural remodeling of gap junction channels (alterations in connexin distribution and protein levels) has been associated with enhanced susceptibility to AF and recent studies have revealed multiple causative mutations or polymorphisms in 4 isoforms of connexins predisposing to AF.
  • 1.2K
  • 11 Apr 2022
Topic Review
RNA Interference in Fungi
RNA interference (RNAi) was discovered at the end of last millennium, changing the way scientists understood regulation of gene expression. Within the following two decades, a variety of different RNAi mechanisms were found in eukaryotes, reflecting the evolutive diversity that RNAi entails. The essential silencing mechanism consists of an RNase III enzyme called Dicer that cleaves double-stranded RNA (dsRNA) generating small interfering RNAs (siRNAs), a hallmark of RNAi. These siRNAs are loaded into the RNA-induced silencing complex (RISC) triggering the cleavage of complementary messenger RNAs by the Argonaute protein, the main component of the complex. Consequently, the expression of target genes is silenced. This mechanism has been thoroughly studied in fungi due to their proximity to the animal phylum and the conservation of the RNAi mechanism from lower to higher eukaryotes. However, the role and even the presence of RNAi differ across the fungal kingdom, as it has evolved adapting to the particularities and needs of each species. Fungi have exploited RNAi to regulate a variety of cell activities as different as defense against exogenous and potentially harmful DNA, genome integrity, development, drug tolerance, or virulence. This pathway has offered versatility to fungi through evolution, favoring the enormous diversity this kingdom comprises. 
  • 1.2K
  • 11 Oct 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).
  • 1.2K
  • 19 Mar 2021
Topic Review
Secondary Metabolism's Main Biosynthetic Pathways in Solid-State Fermentation
Microbial secondary metabolites are low-molecular-weight compounds synthesized by microorganisms after the growth phase. Secondary metabolites are not directly involved in microbial growth. Solid-state fermentation (SSF) is a process whereby microorganisms grow in the absence of free water or with low water content. It has been used since ancient times to obtain fermented foods such as koji, bread, and cheeses.
  • 1.2K
  • 13 Oct 2023
Topic Review
Calcium Dyshomeostasis in Alzheimer’s Disease
Alzheimer’s disease (AD) is the most common age-related neurodegenerative disorder that is characterized by amyloid β-protein deposition in senile plaques, neurofibrillary tangles consisting of abnormally phosphorylated tau protein, and neuronal loss leading to cognitive decline and dementia. Despite extensive research, the exact mechanisms underlying AD remain unknown and effective treatment is not available. Many hypotheses have been proposed to explain AD pathophysiology; however, there is general consensus that the abnormal aggregation of the amyloid β peptide (Aβ) is the initial event triggering a pathogenic cascade of degenerating events in cholinergic neurons. The dysregulation of calcium homeostasis has been studied considerably to clarify the mechanisms of neurodegeneration induced by Aβ. Intracellular calcium acts as a second messenger and plays a key role in the regulation of neuronal functions, such as neural growth and differentiation, action potential, and synaptic plasticity. The calcium hypothesis of AD posits that activation of the amyloidogenic pathway affects neuronal Ca2+ homeostasis and the mechanisms responsible for learning and memory. Aβ can disrupt Ca2+ signaling through several mechanisms, by increasing the influx of Ca2+ from the extracellular space and by activating its release from intracellular stores. Here, we review the different molecular mechanisms and receptors involved in calcium dysregulation in AD and possible therapeutic strategies for improving the treatment.
  • 1.2K
  • 11 Oct 2021
Topic Review
Hydroxy Fatty Acid
Fatty acid esters of hydroxy fatty acids (FAHFAs) are a new class of endogenous lipids with interesting physiological functions in mammals. Despite their structural diversity and links with nuclear factor erythroid 2-related factor 2 (NRF2) biosynthesis, FAHFAs are less explored as NRF2 activators. 
  • 1.2K
  • 06 Aug 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.
  • 1.2K
  • 19 Jan 2021
Topic Review
ATRA and EMT-Related Proteins in Breast Cancer
The knowledge of the structure, function, and abundance of specific proteins related to the EMT process is essential for developing effective diagnostic approaches to cancer with the perspective of diagnosis and therapy of malignancies. The success of all-trans retinoic acid (ATRA) differentiation therapy in acute promyelocytic leukemia has stimulated studies in the treatment of other tumors with ATRA. 
  • 1.2K
  • 23 Dec 2021
Topic Review
Human Pluripotent Stem Cell-derived Cardiomyocytes
Atrial fibrillation (AF) is a type of sustained arrhythmia in humans often characterized by devastating alterations to the cardiac conduction system as well as the structure of the atria. AF can lead to decreased cardiac function, heart failure, and other complications. Long non-coding RNAs (lncRNAs) have been shown to play important roles in the cardiovascular system, including AF; however, a large group of lncRNAs is not conserved between mouse and human. Furthermore, AF has complex networks showing variations in mechanisms in different species, making it challenging to utilize conventional animal models to investigate the functional roles and potential therapeutic benefits of lncRNAs for AF. Fortunately, pluripotent stem cell (PSC)-derived cardiomyocytes (CMs) offer a reliable platform to study lncRNA functions in AF because of certain electrophysiological and molecular similarities with native human CMs.
  • 1.2K
  • 27 Oct 2020
Topic Review
Topical Insulin Delivery
Insulin is one of the cheapest growth factors in the market able to accelerate the re-epithelialization and stimulate angiogenesis and cell migration. However, the effectiveness of topical insulin in wound healing is hampered by the proteases in the wound bed. The encapsulation into nanoparticles improves its stability in the wound, providing adhesion to the mucosal surface and allowing its sustained release. 
  • 1.2K
  • 13 Sep 2021
Topic Review
Wnt Signalling in Alzheimer’s Brain
The Wnt signalling system is essential for both the developing and adult central nervous system. It regulates numerous cellular functions ranging from neurogenesis to blood brain barrier biology. Dysregulated Wnt signalling can thus have significant consequences for normal brain function, which is becoming increasingly clear in Alzheimer's disease (AD), an age-related neurodegenerative disorder that is the most prevalent form of dementia. AD exhibits a range of pathophysiological manifestations including aberrant amyloid precursor protein processing, tau pathology, synapse loss, neuroinflammation and blood brain barrier breakdown, which have been associated to a greater or lesser degree with abnormal Wnt signalling. 
  • 1.2K
  • 23 Jan 2021
Topic Review
Acetylcholine Receptors
Acetylcholine is a widely distributed excitatory neurotransmitter. Within the human body, it is present in both branches of the autonomic nervous system: within the parasympathetic system in pre- and postganglionic cells, and within the sympathetic system in preganglionic cells. It is also a neurotransmitter at the periphery within the neuromuscular junction.
  • 1.2K
  • 22 Jun 2021
Topic Review
CRISPR-Cas9 Genome Editing in GBM
Glioblastoma multiforme (GBM) is an aggressive malignancy of the brain and spinal cord with a poor life expectancy. The low survivability of GBM patients can be attributed, in part, to its heterogeneity and the presence of multiple genetic alterations causing rapid tumor growth and resistance to conventional therapy. The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR associated (Cas) nuclease 9 (CRISPR-Cas9) system is a cost-effective and reliable gene editing technology, which is widely used in cancer research. It leads to novel discoveries of various oncogenes that regulate autophagy, angiogenesis, and invasion and play important role in pathogenesis of various malignancies, including GBM.
  • 1.2K
  • 23 Sep 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.
  • 1.2K
  • 07 Sep 2022
Topic Review
Photodynamic Therapy (PDT)
Photodynamic therapy (PDT) using oxygen, light, and photosensitizers, which has potential for making up for the weakness of the existing therapies such as surgery, radiation therapy, and chemotherapy. It has been mainly used to treat cancer, and clinical tests for second-generation photosensitizers with improved physicochemical properties, pharmacokinetic profiles, or singlet oxygen quantum yield have been conducted.
  • 1.2K
  • 13 Apr 2021
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