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Topic Review
Large Rab GTPases
Rab GTPases are major coordinators of intracellular membrane trafficking, including vesicle transport, membrane fission, tethering, docking, and fusion events. Rab GTPases are roughly divided into two groups: conventional “small” Rab GTPases and atypical “large” Rab GTPases that have been recently reported. Some members of large Rab GTPases in mammals include Rab44, Rab45/RASEF, and Rab46. The genes of these large Rab GTPases commonly encode an amino-terminal EF-hand domain, coiled-coil domain, and the carboxyl-terminal Rab GTPase domain. A common feature of large Rab GTPases is that they express several isoforms in cells. For instance, Rab44’s two isoforms have similar functions, but exhibit differential localization. The long form of Rab45 (Rab45-L) is abundantly distributed in epithelial cells. The short form of Rab45 (Rab45-S) is predominantly present in the testes. Both Rab46 (CRACR2A-L) and the short isoform lacking the Rab domain (CRACR2A-S) are expressed in T cells, whereas Rab46 is only distributed in endothelial cells. Although evidence regarding the function of large Rab GTPases has been accumulating recently, there are only a limited number of studies. Here, we report the recent findings on the large Rab GTPase family concerning their function in membrane trafficking, cell differentiation, related diseases, and knockout mouse phenotypes.
  • 1.3K
  • 16 Aug 2021
Topic Review
PARP Inhibitors
 Poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPis) belong to a class of targeted drugs developed for the treatment of homologous recombination repair (HRR)-defective tumors. Preclinical and limited clinical data suggest that PARP inhibition is effective against prostate cancer (PC) in patients with HRR-deficient tumors and that PARPis can improve the mortality rate of PC in patients with BRCA1/2 mutations through a synthetic lethality. 
  • 1.3K
  • 24 May 2021
Topic Review
KRAS and the Inflammatory Tumor Microenvironment Modulation
The TME is a dynamic network composed, not only by tumor cells, but also by several non-tumor cell types, including stromal cells as immune cells (macrophages, neutrophils, dendritic and natural killer cells, myeloid-derived suppressor cells (MDSCs), B and T cells), fibroblasts, adipocytes, endothelial cells, neurons, osteoblasts, osteoclasts, and the extracellular matrix (ECM). This non-cellular component, together with the tumor and the non-tumor cells, establish a dynamic, challenging microenvironment that can be modulated, but especially modulates cancer cell activities, dictating the success of tumor progression. Inflammation has been gradually recognized as a key initiator and contributor for tumorigenesis by orchestrating the immune surveillance and the immune escape, but also by affecting treatment response. Interestingly, the concept of tumor-promoting inflammation has been tightly associated with KRAS mutations. In fact, in colorectal cancers, the majority of the cases with a high prevalence of KRAS mutations correlate with chronic inflammatory diseases. KRAS and its downstream interactors are described as capable of shaping the immune microenvironment through the induction of the nuclear factor kappa light chain enhancer of activated B cells (NF)-kB signaling, which in turn promotes the transcription of several cytokines and chemokines, including interleukin (IL)-1α/β, IL-6, tumor necrosis factor α (TNF-α), Cys-X-Cys Chemokine (CXCL)-1, 2, 5, and 8, monocyte chemoattractant protein 1 (MCP-1 or CCL2), inducible nitric oxide synthase (iNOS), intracellular adhesion molecule 1 (ICAM-1), and endothelial leukocyte adhesion molecule 1 (ELAM1). Independently of NF-kB, KRAS-downstream partners, such as RAF/MAPK and PI3K, may also induce IL-10, transforming growth factor β (TGF-β) and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression. Several studies already reported that KRAS mutations could drive the secretion of anti-inflammatory cytokines, such as IL-10 and TGF-β, with the ability to sustain an immunosuppressive TME, whereas other studies verified that KRAS mutations could interfere with the secretion of pro-inflammatory cytokines, such as ICAM-1, TNF-α, IL-1β, IL-6, and IL-18. Thus, KRAS seems to act as a modulator of both an anti-inflammatory and a pro-inflammatory TME.
  • 1.3K
  • 22 Feb 2022
Topic Review
Roles of LacdiNAc Group on N- and O-glycans
The GalNAcβ1→4GlcNAc (LacdiNAc) group is widely expressed on N- and O-glycans in invertebrates, in particular, parasitic helminths. An increasing number of studies have shown that the disaccharide GalNAcβ1→4GlcNAc (LacdiNAc) group bound to N- and O-glycans in glycoproteins is expressed in a variety of mammalian cells. Biosynthesis of the LacdiNAc group was well studied, and two β4-N-acetylgalactosaminyltransferases, β4GalNAcT3 and β4GalNAcT4, have been shown to transfer N-acetylgalactosamine (GalNAc) to N-acetylglucosamine (GlcNAc) of N- and O-glycans in a β-1,4-linkage. The LacdiNAc group is often sialylated, sulfated, and/or fucosylated, and the LacdiNAc group, with or without these modifications, is recognized by receptors and lectins and is thus involved in the regulation of several biological phenomena, such as cell differentiation.
  • 1.3K
  • 23 May 2022
Topic Review
Innate Immunity to Tick-Borne Pathogens
Tick borne pathogens, such as Anaplasma spp., Ehrlichia spp., Rickettsia spp., Babesia and Theileria sensu stricto species, cause infectious diseases both in animals and humans. Different types of immune effector mechanisms could be induced in hosts by these microorganisms. The components of innate immunity, such as natural killer cells, complement proteins, macrophages, dendritic cells and tumor necrosis factor alpha, cause a rapid and intense protection for the acute phase of infectious diseases. Moreover, the onset of a pro-inflammatory state occurs upon the activation of the inflammasome, a protein scaffold with a key-role in host defense mechanism, regulating the action of caspase-1 and the maturation of interleukin-1β and IL-18 into bioactive molecules. Innate immunity is activated immediately after the infection and inflammasome-mediated changes in the pro-inflammatory cytokines at systemic and intracellular levels can be detected as early as on days 2–5 after tick bite. The knowledge of the innate immunity mechanisms could lead to the development of new methods of emergency diagnosis and prevention of tick-borne infections.
  • 1.3K
  • 18 Dec 2020
Topic Review
Talazoparib and Niraparib
Niraparib (MK-4827) inhibits PARP1 and PARP2. It was approved by the U.S. Food and Drug Administration (FDA) in March 2017 indicated for the therapy of adult patients with ovarian, fallopian tube and peritoneal neoplasms. Talazoparib (BMN 673) is a potent and selective inhibitor of PARP1 and PARP2 used at lower concentrations than previous generations of PARP inhibitors. The FDA approved Talazoparib in October 2018 for patients with germline BRCA-mutated, HER2-negative breast cancer. Poly (ADP-ribose) polymerases (PARP) play an essential role in different cellular processes, including several pathways of DNA repair. PARP inhibitors (PARPi) are able to impair DNA damage repair by non-homologous end joining (NHEJ). This effect depends on the cell´s ability to compensate for the inhibition of PARP-mediated pathways by other repair pathways. PARPi especially induce cell death in cancer cells with a lack of PARP-independent DNA repair pathways.
  • 1.3K
  • 25 Jun 2021
Topic Review
Tellurium: Its Influence on Organisms
Tellurium (Te) is a member of the chalcogen group, which includes oxygen, sulphur, selenium (Se) and polonium . The first three members of the chalcogen group have crucial functions in biochemistry, biology and medicine, whereas Te is a strange element with no apparent role in biological systems. Moreover, it belongs to the group of very few elements in the Periodic Table that have been almost completely ignored.
  • 1.3K
  • 09 Jul 2021
Topic Review
Vitamin D and Primary Ciliary Dyskinesia
Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormalities in ciliary structure/function. Low plasmatic level of this vitamin is present in the PCD population. The utility of vitamin D supplementation may be essential in this group of individuals.
  • 1.3K
  • 04 Nov 2021
Topic Review
Main Characteristics of CircRNAs
Circular RNAs (circRNAs) represent a category of non-coding RNAs (ncRNAs) and constitute functional RNAs that are predetermined not to be translated, but transcribed. CircRNAs are characterized by single-stranded closed-loop structures without 5′-3′-polarity or a polyadenylated tail. The term “circRNA” was first used by Sanger et al. when identifying the structure of viroids.
  • 1.3K
  • 06 Jan 2022
Topic Review
MicroRNAs-dysregulation and mitochondrial-dysfunction in neurodegenerative-diseases
       Neurodegenerative diseases are debilitating and currently incurable conditions causing severe cognitive and motor impairments, defined by the progressive deterioration of neuronal structure and function, eventually causing neuronal loss. Understand the molecular and cellular mechanisms underlying these disorders are essential to develop therapeutic approaches. MicroRNAs (miRNAs) are short non-coding RNAs implicated in gene expression regulation at the post-transcriptional level. Moreover, miRNAs are crucial for different processes, including cell growth, signal transmission, apoptosis, cancer and aging-related neurodegenerative diseases. Altered miRNAs levels have been associated with the formation of reactive oxygen species (ROS) and mitochondrial dysfunction. Mitochondrial dysfunction and ROS formation occur in many neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases. The crosstalk existing among oxidative stress, mitochondrial dysfunction and miRNAs dysregulation plays a pivotal role in the onset and progression of neurodegenerative diseases.
  • 1.3K
  • 01 Sep 2020
Topic Review
Hepatitis B Virus Cure
Hepatitis B virus (HBV) is a small, enveloped, and partially double-stranded DNA virus of the Hepadnaviridae family that infects hepatocytes, establishes its replication cycle, and persists in the nucleus.
  • 1.3K
  • 18 Mar 2021
Topic Review
Bile Salt Hydrolases
Bile salt hydrolase (BSH; EC 3.5.1.24) is an enzyme produced by the intestinal microbiota that catalyzes the hydrolysis of amide bonds in conjugated BAs, resulting in the release of free amino acids. These enzymes belong to the N-terminal nucleophilic (Ntn) hydrolase superfamily and share a similar αββα-core structure to an N-terminal catalytic cysteine residue. This residue is critical to the catalysis mechanism and acts both as a nucleophile and a proton donor. The N-terminal amino group serves as the proton acceptor and activates the nucleophilic thiol group of the cysteine side chain. Besides the cysteine residue, other amino acids conserved in most BSHs are also relevant to the catalytic reaction, including Arg18, Asp21, Asn82, Asn175, and Arg228.
  • 1.3K
  • 27 May 2021
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. 
  • 1.3K
  • 07 Mar 2023
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. 
  • 1.3K
  • 01 Sep 2023
Topic Review
Biopesticides
Biopesticides are a type of pesticides derived from natural materials including plants and bacteria. In this entry, we reviewed the structural and biological features of Jaburetox and Soyuretox, two plant urease-derived recombinant peptides that present entomotoxic and fungitoxic effects without harming beneficial species or the environment. We also discussed other bioactive peptides in the context of their action mechanism.
  • 1.3K
  • 15 Dec 2020
Topic Review
Molecular Mechanisms of Eosinophilic Esophagitis
Eosinophilic esophagitis is a recently recognized allergic-mediated disease with eosinophil-predominant esophagus inflammation. Its pathogenesis is a complicated network of interactions and signaling between epithelial, mesenchymal, and immune cells on molecular and intercellular levels.
  • 1.3K
  • 15 Dec 2021
Topic Review
Deep Learning Architectures from A Genomic Perspective
The data explosion driven by advancements in genomic research, such as high-throughput sequencing techniques, is constantly challenging conventional methods used in genomics. In parallel with the urgent demand for robust algorithms, deep learning has succeeded in various fields such as vision, speech, and text processing.
  • 1.3K
  • 08 Nov 2023
Topic Review
CD38–Cyclic ADP-Ribose Signal System
Calcium (Ca2+) is a ubiquitous and fundamental signaling component that is utilized by cells to regulate a diverse range of cellular functions, such as insulin secretion from pancreatic β-cells of the islets of Langerhans. Cyclic ADP-ribose (cADPR), synthesized from NAD+ by ADP-ribosyl cyclase family proteins, such as the mammalian cluster of differentiation 38 (CD38), is important for intracellular Ca2+ mobilization for cell functioning. cADPR induces Ca2+ release from endoplasmic reticulum via the ryanodine receptor intracellular Ca2+ channel complex, in which the FK506-binding protein 12.6 works as a cADPR-binding regulatory protein.
  • 1.3K
  • 20 Apr 2022
Topic Review
Tau protein Interaction Partners
Tau protein belongs to the family of microtubule-associated proteins (MAPs) and can influence axonal transport and growth, neuronal polarization, and thus the normal function of neurons and the brain.
  • 1.3K
  • 15 Dec 2021
Topic Review
Omega-3 Fatty Acids on Insulin Resistance
Insulin resistance is a critical pathophysiological process in the onset and advancement of type 2 diabetes mellitus. It is well-recognized that alterations in the metabolism of lipids and aberrant fat buildup effectively trigger the development of resistance to insulin. Adjusting one’s eating habits and managing weight appropriately are crucial for treating, controlling, and reducing the risk of T2DM because obesity and a lack of physical exercise are the primary factors responsible for the worldwide rise in T2DM. Omega-3 fatty acid is one of the polyunsaturated fatty acids (PUFA) that include long-chain omega-3 fatty acids such as eicosapentaenoic acid and docosahexaenoic acid, commonly found in fish oils.
  • 1.3K
  • 21 Jun 2023
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