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Topic Review
Angiopoietin-like Proteins
Angiopoietin-like proteins (ANGPTLs) are a family of eight proteins with a diversity of applications, including pro- and anti-angiogenic properties.
  • 1.4K
  • 25 Aug 2021
Topic Review
Abscisic Acid (ABA)
Abscisic acid (ABA) is a significant regulator of numerous flexible traits of plant developmental improvements, including embryo maturation, germination, seed dormancy, floral initiation, and root growth.
  • 1.4K
  • 25 Aug 2021
Topic Review
Ovarian Cancer Peritoneal Metastasis: Exosomes and Mesothelial-to-Mesenchymal Transition
Most patients with ovarian cancer (OvCA) present peritoneal disseminated disease at the time of diagnosis. During peritoneal metastasis, cancer cells detach from the primary tumor and disseminate through the intraperitoneal fluid. The peritoneal mesothelial cell (PMC) monolayer that lines the abdominal cavity is the first barrier encountered by OvCA cells. Subsequent progression of tumors through the peritoneum leads to the accumulation into the peritoneal stroma of a sizeable population of carcinoma-associated fibroblasts (CAFs), which is mainly originated from a mesothelial-to-mesenchymal transition (MMT) process. A common characteristic of OvCA patients is the intraperitoneal accumulation of ascitic fluid, which is composed of cytokines, chemokines, growth factors, miRNAs, and proteins contained in exosomes, as well as tumor and mesothelial suspended cells, among other components that vary in proportion between patients. Exosomes are small extracellular vesicles that have been shown to mediate peritoneal metastasis by educating a pre-metastatic niche, promoting the accumulation of CAFs via MMT, and inducing tumor growth and chemoresistance. This review summarizes and discusses the pivotal role of exosomes and MMT as mediators of OvCA peritoneal colonization and as emerging diagnostic and therapeutic targets.
  • 1.4K
  • 11 Nov 2021
Topic Review
Molecular Basis of Soybean Cold Tolerance
Cold stress is a major factor influencing the geographical distribution of soybean growth and causes immense losses in productivity. Understanding the molecular mechanisms that the soybean has undergone to survive cold temperatures will have immense value in improving soybean cold tolerance. Cold-tolerant quantitative trait loci (QTLs) were found to be overlapped with the genomic region of maturity loci of E1, E3, E4, pubescence color locus of T, stem growth habit gene locus of Dt1, and leaf shape locus of Ln, indicating that pleiotropic loci may control multiple traits, including cold tolerance. The C-repeat responsive element binding factors (CBFs) are evolutionarily conserved across species. The expression of most GmDREB1s was upregulated by cold stress and overexpression of GmDREB1B;1 in soybean protoplast, and transgenic Arabidopsis plants can increase the expression of genes with the DRE core motif in their promoter regions under cold stress. Other soybean cold-responsive regulators, such as GmMYBJ1, GmNEK1, GmZF1, GmbZIP, GmTCF1a, SCOF-1 and so on, enhance cold tolerance by regulating the expression of COR genes in transgenic Arabidopsis. CBF-dependent and CBF-independent pathways are cross-talking and work together to activate cold stress gene expression. 
  • 1.4K
  • 02 Feb 2023
Topic Review
Oleuropein in Non-Communicable Diseases
Growing scientific literature data suggest that the intake of natural bioactive compounds plays a critical role in preventing or reducing the occurrence of human chronic non-communicable diseases (NCDs), such as neuro- and cardiovascular diseases, diabetes mellitus and cancer. Oleuropein, the main phenolic component of Olea europaea L., has attracted scientific attention for its several health beneficial properties such as antioxidant, anti-inflammatory, cardio- and neuro-protective, and anti-cancer. This entry contains data from the current literature concerning the effect of oleuropein in NCDs not only due to its putative antioxidant and anti-inflammatory activities, but also to its other peculiar actions such as autophagy inducer and amyloid fibril growth inhibitor and, finally, as anti-cancer agent. Despite the increasing number of published studies, looking at the health effects of oleuropein, there is limited clinical evidence focused on the benefits of this polyphenol as a nutraceutical product in humans, and many problems are still to be resolved about its bioavailability, bioaccessibility, and dosage. Thus, future clinical randomized trials are needed to establish the relation between the beneficial effects and the mechanisms of action occurring in the human body in response to the intake of oleuropein.
  • 1.4K
  • 27 Sep 2021
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
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
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
Metabolic Action of Metformin
Metformin, a cheap and safe biguanide derivative, due to its ability to influence metabolism, is widely used as a first-line drug for type 2 diabetes (T2DM) treatment. 
  • 1.4K
  • 08 Jul 2022
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
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
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
miRNA Therapeutics
The discovery of the link between microRNAs (miRNAs) and a myriad of human diseases, particularly various cancer types, has generated significant interest in exploring their potential as a novel class of drugs. This has led to substantial investments in interdisciplinary research fields such as biology, chemistry, and medical science for the development of miRNA-based therapies. Furthermore, the recent global success of SARS-CoV-2 mRNA vaccines against the COVID-19 pandemic has further revitalized interest in RNA-based immunotherapies, including miRNA-based approaches to cancer treatment. Consequently, RNA therapeutics have emerged as highly adaptable and modular options for cancer therapy.
  • 1.4K
  • 30 Jan 2024
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
ROR and Melatonin Nuclear Receptor
Retinoic acid-related orphan receptor (ROR)  is implicated in modulating a variety of physiological processes, including cerebellar development, lymphoid tissue development, retinal development, bone formation, lipid metabolism, circadian rhythm, oxidative stress, and inflammation suppression. Furthermore, ROR is also a promising therapeutic target for autoimmune diseases, tumours, obesity, diabetes, and other diseases. Melatonin (N-acetyl-5-methoxytryptamine) is an evolutionary molecule found in bacteria, fungi, algae, plants, invertebrates, and vertebrates. It regulates multiple functions that have developed along the evolutionary timescale. In humans, melatonin is pleiotropic [5]. Melatonin modulates sleep-wake rhythms, reproduction, and bone metabolism; it also affects the immune, neurological, cardiovascular, digestive, urinary, and endocrine systems. Moreover, it exhibits anti-inflammatory, antioxidant, anti-infective, and anti-tumour properties while also being a potential therapeutic agent for obesity, cardiovascular diseases, and neurodegenerative disorders.  A debate is ongoing on whether ROR is a nuclear receptor of melatonin. 
  • 1.4K
  • 27 May 2021
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
Sphingosine 1-phosphate
The breakdown of the endothelial cell (EC) barrier contributes significantly to sepsis mortality. Sphingosine 1-phosphate (S1P) is one of the most effective EC barrier-stabilizing signaling molecules. Stabilization is mainly transduced via the S1P receptor type 1 (S1PR1). Here, we demonstrate that S1P was autonomously produced by ECs. S1P secretion was significantly higher in primary human umbilical vein endothelial cells (HUVEC) compared to the endothelial cell line EA.hy926. Constitutive barrier stability of HUVEC, but not EA.hy926, was significantly compromised by the S1PR1 antagonist W146 and by the anti-S1P antibody Sphingomab. HUVEC and EA.hy926 differed in the expression of the S1P-transporter Spns2, which allowed HUVEC, but not EA.hy926, to secrete S1P into the extracellular space. Spns2 deficient mice showed increased serum albumin leakage in bronchoalveolar lavage fluid (BALF). Lung ECs isolated from Spns2 deficient mice revealed increased leakage of fluorescein isothiocyanate (FITC) labeled dextran and decreased resistance in electric cell-substrate impedance sensing (ECIS) measurements. Spns2 was down-regulated in HUVEC after stimulation with pro-inflammatory cytokines and lipopolysaccharides (LPS), which contributed to destabilization of the EC barrier. Our work suggests a new mechanism for barrier integrity maintenance. Secretion of S1P by EC via Spns2 contributed to constitutive EC barrier maintenance, which was disrupted under inflammatory conditions via the down-regulation of the S1P-transporter Spns2.
  • 1.4K
  • 30 Oct 2020
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
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
Mammalian Zona Pellucida Glycoproteins
Zona pellucida (ZP) plays an important role in the oocyte lifespan providing mechanical protection and defense against polyspermic fertilization by directly modulating sperm function.
  • 1.4K
  • 27 May 2021
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