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Topic Review
STAT3 and NRF2 in Tumors
Signal transducer and activator of transcription 3 (STAT3) and nuclear factor erythroid-derived 2-like 2 (NRF2, also known as NFE2L2), are two of the most complicated transcription regulators, which participate in a variety of physiological processes. Numerous studies have shown that they are overactivated in multiple types of tumors. Interestingly, STAT3 and NRF2 can also interact with each other to regulate tumor progression. Hence, these two important transcription factors are considered key targets for developing a new class of antitumor drugs.
  • 797
  • 05 Jan 2023
Topic Review
Polycomb-like Proteins in Gene Regulation and Cancer
Polycomb-like proteins (PCLs) are a crucial group of proteins associated with the Polycomb repressive complex 2 (PRC2) and are responsible for setting up the PRC2.1 subcomplex. In the vertebrate system, three homologous PCLs exist: PHF1 (PCL1), MTF2 (PCL2), and PHF19 (PCL3). Although the PCLs share a similar domain composition, they differ significantly in their primary sequence. PCLs play a critical role in targeting PRC2.1 to its genomic targets and regulating the functionality of PRC2. However, they also have PRC2-independent functions. In addition to their physiological roles, their dysregulation has been associated with various human cancers.
  • 797
  • 15 Jun 2023
Topic Review
RPA Phosphorylation in DNA Double-Strand Break Repair
Human Replication Protein A (RPA) was historically discovered as one of the six components needed to reconstitute simian virus 40 DNA replication from purified components. RPA is now known to be involved in all DNA metabolism pathways that involve single-stranded DNA (ssDNA). Heterotrimeric RPA comprises several domains connected by flexible linkers and is heavily regulated by post-translational modifications (PTMs). The structure of RPA has been challenging to obtain. Various structural methods have been applied, but a complete understanding of RPA’s flexible structure, its function, and how it is regulated by PTMs has yet to be obtained.
  • 797
  • 19 Feb 2024
Topic Review
Sirtuin 1 in Male Germ Cells
Reproduction is the way to immortality for an individual, and it is essential to the continuation of the species. Sirtuins are involved in cellular homeostasis, energy metabolism, apoptosis, age-related problems, and sexual reproduction. Sirtuin 1 (SIRT1) belongs to the sirtuin family of deacetylases, and it is a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase. It removes the acetyl group from a variety of substrates. SIRT1 regulates endocrine/metabolic, reproductive, and placental development by deacetylating histone, different transcription factors, and signal transduction molecules in a variety of cellular processes. It also plays a very important role in the synthesis and secretion of sex hormones via regulating the hypothalamus-pituitary-gonadal (HPG) axis. Moreover, SIRT1 participates in several key stages of spermatogenesis and sperm maturation. 
  • 794
  • 13 Apr 2022
Topic Review
Exosomes in Breast Cancer
In women, breast cancer (BC) is the most commonly diagnosed cancer (24.5%) and the leading cause of cancer death (15.5%). Exosomes are long-range message vesicles that mediate communication between cells in physiological conditions but also in pathology, such as breast cancer. 
  • 794
  • 15 Aug 2022
Topic Review
Deubiquitinating Enzyme in HNSCC
Ubiquitin is a highly-conserved small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Ubiquitin was first identified in 1975. It performs its myriad functions through conjugation to a large range of target proteins. A variety of different modifications can occur. This discovery that ubiquitin can be attached to proteins and label them for destruction won the Nobel Prize for chemistry in 2004. The ubiquitin protein consists of 76 amino acids and has a molecular mass of about 8.5 kDa. Under the conditions where ATP provides energy, ubiquitin molecules bind to the target protein through the cascade catalytic reaction of ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligase (E3). The ubiquitinated target protein is recognized and degraded by 26S proteasome. Ubiquitination and deubiquitination are two popular ways for the post-translational modification of proteins. These two modifications affect intracellular localization, stability, and function of target proteins. The process of deubiquitination is involved in histone modification, cell cycle regulation, cell differentiation, apoptosis, endocytosis, autophagy, and DNA repair after damage. It is involved in the processes of carcinogenesis and cancer development. The deubiquitinating enzyme (DUB) function in head and neck squamous cell carcinoma (HNSCC) is discussed. 
  • 794
  • 12 Jan 2023
Topic Review
MiRNA Detection and Biosensing
MicroRNAs (miRNA) are key regulators of gene expression, controlling different biological processes such as cellular development, differentiation, proliferation, metabolism, and apoptosis. The relationships between miRNA expression and the onset and progression of different diseases, such as tumours, cardiovascular and rheumatic diseases, and neurological disorders, are well known. A nanotechnology-based approach could match miRNA delivery and detection to move beyond the proof-of-concept stage. Different kinds of nanotechnologies can have a major impact on the diagnosis and treatment of miRNA-related diseases such as cancer. 
  • 793
  • 01 Jul 2022
Topic Review
Altered Pathways in Fabry Disease
Fabry disease is a rare X-linked disease characterized by deficient expression and activity of alpha-galactosidase A (α-GalA) with consequent lysosomal accumulation of glycosphingolipid in various organs. Enzyme replacement therapy is the cornerstone of the treatment of all Fabry patients, although in the long-term it fails to completely halt the disease’s progression. This suggests on one hand that the adverse outcomes cannot be justified only by the lysosomal accumulation of glycosphingolipids and on the other that additional therapies targeted at specific secondary mechanisms might contribute to halt the progression of cardiac, cerebrovascular, and renal disease that occur in Fabry patients. 
  • 793
  • 15 Mar 2023
Topic Review
Cellular Functions of Liver Kinase B1
The liver kinase B1 (LKB1), also known as serine/threonine kinase 11 (STK11) and Par-4 in C. elegans, has been identified as a master kinase of AMPKs and AMPK-related kinases. LKB1 plays a crucial role in cell growth, metabolism, polarity, and tumor suppression.
  • 791
  • 12 Oct 2022
Topic Review
Multiple Myeloma MRD
Minimal residual disease is important in evaluating response in multiple myeloma. Either NGS or NGF could be done. Laboratory experience and standardization are needed in order to give high quality Analysis.
  • 790
  • 26 Oct 2020
Topic Review
Aryl Hydrocarbon Receptor Signaling
The aryl hydrocarbon receptor (AHR) is a markedly established regulator of a plethora of cellular and molecular processes. Its initial role in the detoxification of xenobiotic compounds has been partially overshadowed by its involvement in homeostatic and organ physiology processes. In fact, the discovery of its ability to bind specific target regulatory sequences has allowed for the understanding of how AHR modulates such processes. Thereby, AHR presents functions in transcriptional regulation, chromatin architecture modifications and participation in different key signaling pathways. Interestingly, such fields of influence end up affecting organ and tissue homeostasis, including regenerative response both to endogenous and exogenous stimuli. Beyond the role of AHR in transcriptional regulation, its implication in multiple signaling pathways has built a field of study regarding its participation in the control and maintenance of different physiological and pathological processes. The variety of responses resulting from AHR activation may be due to the different interactions of the receptor with other proteins or transcriptional cofactors. Therefore, numerous proteins affecting AHR activity and vice versa have been described over the years, constituting a solid trend in cell signaling.
  • 790
  • 14 Dec 2022
Topic Review
Strategies for Over-Expression of Human Membrane Transport Systems
Membrane proteins are crucial for life, because they allow the various body regions to communicate with each other. Ten percent of human genes encode for membrane transport systems, which are key components in maintaining cell homeostasis. They are involved in the transport of nutrients, catabolites, vitamins, and ions, allowing the absorption and distribution of these compounds to the various body regions. In addition, roughly 60% of FDA-approved drugs interact with membrane proteins, among which are transporters, often responsible for pharmacokinetics and side effects. Defects of membrane transport systems can cause diseases; however, knowledge of the structure/function relationships of transporters is still limited. 
  • 789
  • 23 May 2022
Topic Review
Food Peptides, Gut Microbiota and Hypertension
The gut microbiota is a key element in the regulation of various human processes, including metabolisms, immunity, and the overall health. Hypertension, like other metabolic and chronic diseases, has several contributing factors, some of which have not been clarified. Known factors include diet, genetic inheritance, hormonal imbalance, and inflammation.
  • 789
  • 05 Jan 2023
Topic Review
Dysregulation of mir-106a in Non-Cancer Diseases
MicroRNAs (miRNAs) comprise a class of non-coding RNA with extensive regulatory functions within cells. MiR-106a is recognized for its super-regulatory roles in vital processes. MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs that control gene expression at the translation and even transcription levels. miRNAs are critical regulators of biological processes, including cellular proliferation, differentiation, development, apoptosis, and modulation of the host response to viral infection.
  • 789
  • 03 Aug 2023
Topic Review
Inhibitors for Novel Coronavirus Protease
The rapid outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China followed by its spread around the world poses a serious global concern for public health. To this date, no specific drugs or vaccines are available to treat SARS-CoV-2. Thus, there remains an urgent need for the development of specific antiviral therapeutics against SARS-CoV-2. To conquer viral infections, the inhibition of proteases essential for proteolytic processing of viral polyproteins is a conventional therapeutic strategy. In order to find novel inhibitors, we computationally screened a compound library of over 606 million compounds for binding at the recently solved crystal structure of the main protease (Mpro) of SARS-CoV-2. A screening of such a vast chemical space for SARS-CoV-2 Mpro inhibitors has not been reported before. After shape screening, two docking protocols were applied followed by the determination of molecular descriptors relevant for pharmacokinetics to narrow down the number of initial hits. Next, molecular dynamics simulations were conducted to validate the stability of docked binding modes and comprehensively quantify ligand binding energies. After evaluation of potential off-target binding, we report a list of 12 purchasable compounds, with binding affinity to the target protease that is predicted to be more favorable than that of the cocrystallized peptidomimetic compound. In order to quickly advise ongoing therapeutic intervention for patients, we evaluated approved antiviral drugs and other protease inhibitors to provide a list of nine compounds for drug repurposing. Furthermore, we identified the natural compounds (−)-taxifolin and rhamnetin as potential inhibitors of Mpro.
  • 788
  • 02 Nov 2020
Topic Review
Normal and Aberrant MiRNA and Alternative Splicing Events
MiRNAs are short non-coding RNAs that play a central role in regulating RNA silencing and gene expression. Alternative splicing increases the diversity of the proteome by producing several different spliced mRNAs from a single gene for translation. MiRNA expression and alternative splicing events are rigorously regulated processes. Dysregulation of miRNA and splicing events promote carcinogenesis and drug resistance in cancers including breast, cervical, prostate, colorectal, ovarian and leukemia. Alternative splicing may change the target mRNA 3′UTR binding site.
  • 788
  • 10 Dec 2021
Topic Review
Various Microglial Receptors Interact with α-Synuclein
Synucleinopathies are a set of devastating neurodegenerative diseases that share a pathologic accumulation of the protein α-synuclein (α-syn). This accumulation causes neuronal death resulting in irreversible dementia, deteriorating motor symptoms, and devastating cognitive decline. α-Syn is an intrinsically disordered 140-amino acid protein consisting of an amphipathic N-terminus (residues 1–60), hydrophobic central region (residues 61–95), and acidic C-terminus (residues 86–140). Synucleinopathies are characterized by the accumulation of α-syn in the CNS. The structural form of the accumulation varies across different patients and different conditions. While the etiology of these conditions remains largely unknown, microglia, the resident immune cells of the central nervous system (CNS), have been consistently implicated in the pathogenesis of synucleinopathies. Microglia are generally believed to be neuroprotective in the early stages of α-syn accumulation and contribute to further neurodegeneration in chronic disease states.
  • 788
  • 23 May 2023
Topic Review
Nucleotide Sugar Transporters
Nucleotide sugars (NSs) serve as substrates for glycosylation reactions. The majority of these compounds are synthesized in the cytoplasm, whereas glycosylation occurs in the endoplasmic reticulum (ER) and Golgi lumens, where catalytic domains of glycosyltransferases (GTs) are located. Therefore, translocation of NS across the organelle membranes is a prerequisite. This process is thought to be mediated by a group of multi-transmembrane proteins from the SLC35 family, i.e., nucleotide sugar transporters (NSTs).
  • 786
  • 15 Aug 2022
Topic Review
Nanoparticle Interaction with Biofilms
A biofilm is an aggregation of surface-associated microbial cells that is confined in an extracellular polymeric substance (EPS) matrix. Infections caused by microbes that form biofilms are linked to a variety of animals, including insects and humans. Antibiotics and other antimicrobials can be used to remove or eradicate biofilms in order to treat infections.
  • 785
  • 19 Jan 2023
Topic Review
Battling Chemoresistance in Cancer
Chemoresistance remains a lethal challenge in the realm of cancer biology and clinics. Various determinants with their modes of action have been reported with clinical implications. However, many patients regrettably die due to chemoresistance-induced failure in treatment.
  • 784
  • 22 Sep 2021
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