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Topic Review
New Vulnerabilities of Melanoma
Melanoma cells are notorious for their high plasticity and ability to switch back and forth between various melanoma cell states, enabling the adaptation to sub-optimal conditions and therapeutics. This phenotypic plasticity, which has gained more attention in cancer research, is proposed as a new paradigm for melanoma progression. Here the researchers present several rational therapeutic approaches, such as exploiting phenotype-specific and metabolic vulnerabilities and targeting components and signals of the tumor microenvironment (TME), to improve the response of melanoma patients to treatments.
  • 413
  • 13 Apr 2022
Topic Review Peer Reviewed
Molecular Aspects of Spike–ACE2 Interaction
A new betacoronavirus (CoV-2) is responsible for the pandemic of severe acute respiratory syndrome (SARS) that began in China at the end of 2019, today known as COronaVIrus Disease 2019 (COVID-19). Subsequent studies confirmed the human angiotensin-converting enzyme 2 (hACE2) as the main cell receptor of spike trimeric glycoprotein, located on the viral envelope, mediating the CoV-2 invasion into the host cells through the receptor-binding domain (RBD) of the spike. Computational analysis of the known experimental 3D structures of spike–ACE2 complexes evidenced distinguishing features in the molecular interactions at the RBD-cell receptor binding interface between CoV-2 and previous CoV-1. The spike represents a key target for drug design as well as an optimal antigen for RNA/viral vector vaccines and monoclonal antibodies in order to maximize prevention and therapy of COVID-19.
  • 1.2K
  • 13 Apr 2022
Topic Review
Targeting CDK4/6 for Anticancer Therapy
Cyclin-dependent kinase 4/6 (CDK4/6) are key regulators of the cell cycle and are deemed as critical therapeutic targets of multiple cancers. Various approaches have been applied to silence CDK4/6 at different levels, i.e., CRISPR to knock out at the DNA level, siRNA to inhibit translation, and drugs that target the protein of interest. Here we summarize the current status in this field, highlighting the mechanisms of small molecular inhibitors treatment and drug resistance.
  • 685
  • 12 Apr 2022
Topic Review
The Role of Polyploidy in the Human Body
Somatic polyploidy was found in the tissues of all multicellular organisms (including algae, mosses, lichens, vascular plants, invertebrates, and vertebrates), which points to its adaptive value. In human and warm-blooded animals, polyploidy can be a part of normal postnatal morphogenetic programs and can be a manifestation of response to pathological stimuli and diseases.
  • 1.1K
  • 11 Apr 2022
Topic Review
Anti-Prostate Cancer Properties of Anthocyanidins/Anthocyanins
As water-soluble flavonoid derivatives, anthocyanidins and anthocyanins are the plants pigments mostly rich in berries, pomegranate, grapes, and dark color fruits. Many bioactivity properties of these advantageous phytochemicals have been reported; among them, their significant abilities in the suppression of tumor cells are of the promising therapeutic features, which have recently attracted great attention. The prostate malignancy, is considered the 2nd fatal and the most distributed cancer type in men worldwide.  In general, the anthocyanins (especifically cyanidin-3-O-glucoside) indicated higher activity against prostatic neoplasms compared to their correlated anthocyanidins (e.g., delphinidin); in which potent anti-inflammatory, apoptosis, and anti-proliferative activities were analyzed. 
  • 925
  • 11 Apr 2022
Topic Review
Evolutionary Medicine
Evolutionary medicine is a rapidly developing field. There are two polyploidy-related aspects of it. Firstly, mutations and changes in expression patterns of many ohnologs are associated with various diseases and developmental disorders. Secondly (and probably more important), cancer is now interpreted as an evolutionary phenomenon, and polyploidy often arises in cancer.
  • 349
  • 11 Apr 2022
Topic Review
Somatic Polyploidy
Somatic polyploidy was found in the tissues of all multicellular organisms (including algae, mosses, lichens, vascular plants, invertebrates, and vertebrates), which points to its adaptive value. In human and warm-blooded animals, polyploidy can be a part of normal postnatal morphogenetic programs and can be a manifestation of response to pathological stimuli and diseases.
  • 580
  • 11 Apr 2022
Topic Review
Microgravity Effects on the Matrisome
Gravity is fundamental factor determining all processes of development and vital activity on Earth. During evolution, a complex mechanism of response to gravity alterations was formed in multicellular organisms. It includes the “gravisensors” in extracellular and intracellular spaces. Inside the cells, the cytoskeleton molecules are the principal gravity-sensitive structures, and outside the cells these are extracellular matrix (ECM) components. The cooperation between the intracellular and extracellular compartments is implemented through specialized protein structures, integrins. The gravity-sensitive complex is a kind of molecular hub that coordinates the functions of various tissues and organs in the gravitational environment. The functioning of this system is of particular importance under extremal conditions, such as spaceflight microgravity.
  • 494
  • 11 Apr 2022
Topic Review
Immunological Synapse and Primary Cilium
The primary cilium is a small microtubule-based organelle that extends from the apical surface of most eukaryotic cells into the extracellular space for sensing and transducing a wide range of cues. Defects in cilia growth and function are associated with a group of human inherited multisystemic diseases, known as ciliopathies. In recent years a rising number of ciliary proteins have been described at extraciliary sites, both in ciliated and non-ciliated cells, and have been implicated in cilium-independent functions and different cellular processes. Hematopoietic cells, including T lymphocytes, do not form primary cilia. However, non-ciliated T cells co-opt the ciliogenesis machinery for the assembly and function of the immunological synapse, a well-organized structure formed by immune cells – multiple types of T cells, mast cells, NK cells, B cells, neutrophils, macrophages, and dendritic cells – allowing for antigen recognition and signaling, information exchange and polarized release of molecules into the synaptic cleft. The identification of many, unexpected similarities between the primary cilium and the T cell immunological synapse at the structural, functional and molecular levels have highlighted the homology between these structures, even though they show disparate morphologies. 
  • 551
  • 11 Apr 2022
Topic Review
Polyploidy in Evolution
Polyploidy or whole-genome duplication (WGD) is widespread in nature, agriculture and aquaculture, normal physiology, regeneration, aging, and pathology. WGD results from the premature termination of the cell cycle or cell fusion. If WGD occurs in germ cells, the progeny organisms become completely polyploid, if in somatic cells, the somatic polyploidy arises in certain tissues of a given organism. Polyploidization leads to long-term consequences both in evolution (organismal) and ontogenesis (somatic). In evolution, WGD is one of the main sources for the growth of organismal complexity and evolutionary plasticity
  • 1.2K
  • 08 Apr 2022
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