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Topic Review
Cell-Penetrating Peptides
Cell-penetrating peptides (CPPs) comprise a class of short polypeptides that possess the ability to selectively interact with the cytoplasmic membrane of certain cell types, translocate across plasma membranes and accumulate in the cell cytoplasm, organelles (e.g., the nucleus and mitochondria), and other subcellular compartments. CPPs are either of natural origin or de novo designed and synthesized from segments and patches of larger proteins or designed by algorithms. With such intrinsic characteristics, along with membrane permeation, translocation, and cellular uptake properties, CPPs can intracellularly convey diverse substances and nanomaterials, such as hydrophilic organic compounds and drugs, macromolecules (nucleic acids and proteins), nanoparticles (nanocrystals and polyplexes), metals and radionuclides, which can be covalently attached via CPP N- and C-terminals or through the preparation of CPP complexes. A cumulative number of studies on animal toxins, primarily isolated from the venom of arthropods and snakes, have revealed the cell-penetrating activities of venom peptides and toxins, which can be harnessed for application in biomedicine and pharmaceutical biotechnology.
  • 1.4K
  • 12 Mar 2021
Topic Review
Heterogeneous Nuclear Ribonucleoproteins
Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a superfamily of RNA-binding proteins consisting of more than 20 members. These proteins play a crucial role in various biological processes by regulating RNA splicing, transcription, and translation through their binding to RNA.
  • 1.4K
  • 09 Oct 2023
Topic Review
Regulated Cell Death Modes
Most animal cell types have the ability to undergo turnover at different rates throughout the organism's life span, dying either accidentally or in a deliberate manner. If a cell suffers from irreparable structural or organelle damage, it most likely passively disintegrates and dies. In this case, the plasma membrane ruptures and the noxious intracellular components are released into the extracellular matrix, where they trigger an inflammatory response. However, if a cell sustains non-fatal damage, or if it is too old, contains dysfunctional organelles, has suffered oxidative damage, etc, it is deliberately eliminated through an active, physiologically-regulated process of cell death termed regulated cell death (RCD), which is not accompanied by an inflammatory response. RCD plays beneficial physiological roles in development and in systems maintenance, but can become malignant and lead to pathological conditions when it is impaired, insufficient or in excess.  In the context of liver injury and disease, RCD is pivotal in directing the severity and outcome of the disease. Hepatocyte death is a critical event in the progression of disease due to resultant inflammation, which may lead to fibrosis, cirrhosis, and other morbidities if not treated in a timely manner.
  • 1.4K
  • 18 Feb 2021
Topic Review
Click Reaction in Chemical Proteomics
Proteomics is a kind of omics which studies the protein composition, distribution and changing rules in cells, tissues or organisms. Essentially, it refers to the macroscale study of protein characteristics, including protein expression level, post-translational modification, small molecule–protein interaction and so on. Research on the proteome cannot only provide the material foundation for the law of the activities of life, but also provides a theoretical foundation and solutions to elucidate and conquer numerous types of mechanisms of illness. Click chemistry was first put forward by K B Sharpless in 2001 which provides a quick and reliable synthesis method for different molecules to offer a range of reactivities, orthogonality and utility in various applications. Click chemistry is characterized by good chemical selectivity, favorable solvent compatibility, diverse modularization, minimum synthesis requirements and high yield, upon which it considerably reduces the effect of sensor incorporation on protein activity and reveals the structure and functionality of proteins.
  • 1.4K
  • 24 Sep 2021
Topic Review
Acyclic Nucleic Acids with Phosphodiester Linkages
The pseudo-rotational flexibility of the ribonucleotide is considerably limited due to the anomeric effect, and RNA/RNA and RNA/DNA duplexes are generally more thermally stable than DNA/DNA duplexes. The rigidity of the cyclic scaffold has been considered important for the formation of thermally stable duplexes, and the unexpectedly high thermal stability of duplexes formed with the participation of LNA oligomers could serve as an excellent justification for this point of view. However, this generalization is not consistent with the behavior of Peptide Nucleic Acids (PNA), in which the heterocyclic bases are attached to a linear peptide-like backbone, since duplexes composed of RNA or DNA and PNA strands are far more stable than RNA/RNA and DNA/DNA ones. This phenomenon may be attributed to the absence of a negative charge in the backbone, such that the absence of repulsive interactions balances the entropic cost of proper spatial organization of the flexible PNA scaffolds. Nonetheless, the widely accepted importance of the cyclic sugar components for the stability of the duplexes could be questioned. There is another perspective that can be applied to the acyclic analogs of nucleic acids that is related to the origin of life. The synthetic efforts on acyclic analogs of nucleic acids and provides information on the most interesting features of selected classes of such compounds, are here described. The selection includes the following types of analogs: Flexible (FNA), Unlocked (UNA), Glycol (GNA), Butyl (BuNA), Threoninol (TNA) and Serinol Nucleic Acids (SNA). These classes of analogs are discussed in terms of their synthetic methods, the thermal stability of their homo- and hetero-duplexes and their applicability in biological and biochemical research and nanotechnology.
  • 1.4K
  • 10 Feb 2022
Topic Review
A Long-Lasting PARP1-Activation Mediates Signal-Induced Gene Expression
PolyADP-ribosylation is an evolutionary conserved, reversible post-translational modification of proteins. Numerous nuclear proteins act as substrates of the abundant nuclear polyADP-ribose polymerase 1 (PARP1). In this modification, negatively charged ADP-ribose chains constructed on chromatin-bound proteins, cause their repulsion from the negatively charged DNA. In accordance, polyADP-ribosylation is a post-translational modification of proteins that causes relaxation of the highly condensed structure of the chromatin. Histone H1, which is bound to the linker DNA, located between the nucleosomes, is a prominent substrate of PARP1.
  • 1.4K
  • 19 May 2022
Topic Review
The Origin of Geranylgeraniol and Farnesol
Isoprenoids are the output of the polymerization of five-carbon, branched isoprenic chains derived from isopentenyl pyrophosphate (IPP) and its isomer, dimethylallyl pyrophosphate (DMAPP). Isoprene units are consecutively condensed to form longer structures such as farnesyl and geranylgeranyl pyrophosphate (FPP and GGPP, respectively), necessary for the biosynthesis of several metabolites. Polyprenyl transferases and synthases use polyprenyl pyrophosphates as their natural substrates; however, it is known that free polyprenols, such as farnesol (FOH), and geranylgeraniol (GGOH) can be incorporated into prenylated proteins, ubiquinone, cholesterol, and dolichols. Furthermore, FOH and GGOH have been shown to block the effects of isoprenoid biosynthesis inhibitors such as fosmidomycin, bisphosphonates, or statins in several organisms.
  • 1.4K
  • 13 Dec 2022
Topic Review
Circadian Rhythms and Glioblastomas
Gliomas are solid tumors of the central nervous system (CNS) that originated from different glial cells. The World Health Organization (WHO) classifies these tumors into four groups (I–IV) with increasing malignancy. Glioblastoma (GBM) is the most common and aggressive type of brain tumor classified as grade IV. GBMs are resistant to conventional therapies with poor prognosis after diagnosis even when the Stupp protocol that combines surgery and radiochemotherapy is applied. Nowadays, few novel therapeutic strategies have been used to improve GBM treatment, looking for higher efficiency and lower side effects, but with relatively modest results. The circadian timing system temporally organizes the physiology and behavior of most organisms and daily regulates several cellular processes in organs, tissues, and even in individual cells, including tumor cells.
  • 1.4K
  • 15 Aug 2021
Topic Review
Oxidative Stress in Cancer Cell Metabolism
Reactive oxygen species (ROS) are important in regulating normal cellular processes whereas deregulated ROS leads to the development of a diseased state in humans including cancers. Several studies have been found to be marked with increased ROS production which activates pro-tumorigenic signaling, enhances cell survival and proliferation and drives DNA damage and genetic instability. However, higher ROS levels have been found to promote anti-tumorigenic signaling by initiating oxidative stress-induced tumor cell death. Tumor cells develop a mechanism where they adjust to the high ROS by expressing elevated levels of antioxidant proteins to detoxify them while maintaining pro-tumorigenic signaling and resistance to apoptosis. Therefore, ROS manipulation can be a potential target for cancer therapies as cancer cells present an altered redox balance in comparison to their normal counterparts.
  • 1.4K
  • 11 May 2022
Topic Review
Tuning between Nuclear Organization and Functionality in Health
The organization of eukaryotic genome in the nucleus, a double-membraned organelle separated from the cytoplasm, is highly complex and dynamic. The functional architecture of the nucleus is confined by the layers of internal and cytoplasmic elements, including chromatin organization, nuclear envelope associated proteome and transport, nuclear–cytoskeletal contacts, and the mechano-regulatory signaling cascades. The size and morphology of the nucleus could impose a significant impact on nuclear mechanics, chromatin organization, gene expression, cell functionality and disease development. The maintenance of nuclear organization during genetic or physical perturbation is crucial for the viability and lifespan of the cell. Abnormal nuclear envelope morphologies, such as invagination and blebbing, have functional implications in several human disorders, including cancer, accelerated aging, thyroid disorders, and different types of neuro-muscular diseases. 
  • 1.4K
  • 07 Mar 2023
Topic Review
Histone-lysine N-methyltransferase Subclass Complexes
KMT2 (histone-lysine N-methyltransferase subclass 2) complexes methylate lysine 4 on the histone H3 tail at gene promoters and gene enhancers. H3K4 methylation mark allows to control gene transcription. The KMT2s function in large multi-subunit complexes, which, in vertebrates, are often referred to as COMPASS or COMPASS-like complexes (COMplex of Proteins ASsociated with Set1). These complexes contain an enzyme (KMT2A or KMT2B, KMT2C or KMT2D, KMT2F or KMT2G), common core subunits (WDR5, RBBP5, ASH2L, DPY30) and unique interacting proteins, which are different for each of the three KMT2 groups (A/B, C/D and F/G). Also, the KMT2 complexes dynamically interact with many transcription factors.
  • 1.4K
  • 23 Dec 2020
Topic Review
Type-2 Diabetes Mellitus and Dementia
Dementia is reported to be common in those with type 2 diabetes mellitus. Type 2 diabetes contributes to common molecular mechanisms and an underlying pathology with dementia. Brain cells becoming resistant to insulin leads to elevated blood glucose levels, impaired synaptic plasticity, microglial overactivation, mitochondrial dysfunction, neuronal apoptosis, nutrient deprivation, TAU (Tubulin-Associated Unit) phosphorylation, and cholinergic dysfunction.
  • 1.4K
  • 30 Nov 2022
Topic Review
DNA Manipulation and Single-Molecule Imaging
DNA replication, repair, and recombination in the cell play a significant role in the regulation of the inheritance, maintenance, and transfer of genetic information. To elucidate the biomolecular mechanism in the cell, some molecular models of DNA replication, repair, and recombination have been proposed. These biological studies have been conducted using bulk assays, such as gel electrophoresis. Because in bulk assays, several millions of biomolecules are subjected to analysis, the results of the biological analysis only reveal the average behavior of a large number of biomolecules. Therefore, revealing the elementary biological processes of a protein acting on DNA (e.g., the binding of protein to DNA, DNA synthesis, the pause of DNA synthesis, and the release of protein from DNA) is difficult. Single-molecule imaging allows the analysis of the dynamic behaviors of individual biomolecules that are hidden during bulk experiments. Thus, the methods for single-molecule imaging have provided new insights into almost all of the aspects of the elementary processes of DNA replication, repair, and recombination. However, in an aqueous solution, DNA molecules are in a randomly coiled state. Thus, the manipulation of the physical form of the single DNA molecules is important. 
  • 1.4K
  • 01 Apr 2021
Topic Review
Targeting Tyrosine Kinases in ccRCC
Clear cell renal cell carcinoma (ccRCC) is the seventh most frequently diagnosed tumor in adults in Europe and represents approximately 2.5% of cancer deaths. Currently, there are multiple therapeutic drugs available for advanced disease, including therapies against VEGFR with successful results in patients´ survival. Other tyrosine kinases’ pathways, including PDGFR, Axl or MET have emerged as key signaling pathways involved in RCC biology. 
  • 1.4K
  • 08 Jun 2021
Topic Review
LSEC in Post-Hepatectomy Liver Regeneration/Failure
Liver sinusoids are lined by liver sinusoidal endothelial cells (LSEC), which represent approximately 15 to 20% of the liver cells, but only 3% of the total liver volume. LSEC have unique functions, such as fluid filtration, blood vessel tone modulation, blood clotting, inflammatory cell recruitment, and metabolite and hormone trafficking. Different subtypes of liver endothelial cells are also known to control liver zonation and hepatocyte function. The liver has the exceptional ability to regenerate from small remnants. The past decades have seen increasing awareness in the role of non-parenchymal cells in liver regeneration despite not being the most represented population. While a lot of knowledge has emerged, clarification is needed regarding the role of LSEC in sensing shear stress and on their participation in the inductive phase of regeneration by priming the hepatocytes and delivering mitogenic factors. It is also unclear if bone marrow-derived LSEC participate in the proliferative phase of liver regeneration. Similarly, data are scarce as to LSEC having a role in the termination phase of the regeneration process. Here, we review what is known about the interaction between LSEC and other liver cells during the different phases of liver regeneration. We next explain extended hepatectomy and small liver transplantation, which lead to “small for size syndrome” (SFSS), a lethal liver failure. SFSS is linked to endothelial denudation, necrosis, and lobular disturbance. Using the knowledge learned from partial hepatectomy studies on LSEC, we expose several techniques that are, or could be, used to avoid the “small for size syndrome” after extended hepatectomy or small liver transplantation. 
  • 1.4K
  • 17 Aug 2021
Topic Review
Phosphate in Vascular Calcification
Inorganic phosphate is essential for a variety of cellular processes, such as energy metabolism, bone formation, and synthesis of biomolecules, including phospholipids and nucleic acids. However, elevated serum phosphorus has emerged as a key risk factor for vascular calcification.
  • 1.4K
  • 21 Dec 2021
Topic Review
Nanobody in CAR-T Therapy
Chimeric antigen receptor (CAR) T therapy represents a form of immune cellular therapy with clinical efficacy and a specific target. A typical chimeric antigen receptor (CAR) construct consists of an antigen binding domain, a transmembrane domain, and a cytoplasmic domain. Nanobod-ies have been widely applied as the antigen binding domain of CAR-T due to their small size, optimal stability, high affinity, and manufacturing feasibility. The nanobody-based CAR struc-ture has shown a proven function in more than ten different tumor-specific targets. After being transduced in Jurkat cells, natural killer cells, or primary T cells, the resulting nanobody-based CAR-T or CAR-NK cells demonstrate anti-tumor effects both in vitro and in vivo. Interestingly, anti-BCMA CAR-T modulated by a single nanobody or bi-valent nanobody displays comparable clinical effects with that of single-chain variable fragment (scFv)-modulated CAR-T. The applica-tion of nanobodies in CAR-T therapy has been well demonstrated from bench to bedside and displays great potential in forming advanced CAR-T for more challenging tasks.
  • 1.4K
  • 21 Feb 2021
Topic Review Video
Transgenerational-Epigenetic Inheritance and Immune System
Epigenetic modifications cause heritable changes in gene expression which are not due to alterations in underlying DNA sequence. Inside the eukaryotic nucleus, there is condense packing of DNA around histone proteins to constitute chromatin structure. Epigenetic modifications are caused by factors that alter chromatin structure. Some epigenetic factors are enzymes that regulate DNA methylation and histone modifications, non-coding RNA, and prions. An offspring inherits parental epigenetic modifications but most of them are deleted and reset during early developmental stages. Some epigenetic modifications are retained and persist across multiple generations. If any epigenetic modification is the result of a stimulus or immune response in one generation, such that the modification continues to be inherited in subsequent generations which are not subjected to the stimulus; and the inheritance continues beyond the 3rd generation in the female germline and 2nd generation in male, then the phenomenon is called transgenerational epigenetic inheritance (TGEI). This entry is focused on a review which discusses some examples of TGEI that are reported in association with  immune system development and disorders.
  • 1.4K
  • 22 May 2021
Topic Review
Redox Potential Features of Laccase
Laccase, one of the metalloproteins, belongs to the multicopper oxidase family. It oxidizes a wide range of substrates and generates water as a sole by-product. The engineering of laccase is important to broaden their industrial and environmental applications. The general assumption is that the low redox potential of laccases is the principal obstacle, as evidenced by their low activity towards certain substrates. Therefore, the primary goal of engineering laccases is to improve their oxidation capability, thereby increasing their redox potential. Even though some of the determinants of laccase are known, it is still not entirely clear how to enhance its redox potential. However, the laccase active site has additional characteristics that regulate the enzymes’ activity and specificity. These include the electrostatic and hydrophobic environment of the substrate binding pocket, the steric effect at the substrate binding site, and the orientation of the binding substrate with respect to the T1 site of the laccase. 
  • 1.4K
  • 01 Sep 2023
Topic Review
Activity-Dependent Neuroprotective Protein
The activity-dependent neuroprotective protein (ADNP), a double-edged sword, sex-dependently regulates multiple genes and was previously associated with the control of early muscle development and aging.
  • 1.4K
  • 12 Jul 2021
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