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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
Antioxidant Potential of Psychotropic Drugs
Due to high oxygen consumption, the brain is particularly vulnerable to oxidative stress, which is considered an important element in the etiopathogenesis of several mental disorders, including schizophrenia, depression and dependencies. Despite the fact that it is not established yet whether oxidative stress is a cause or a consequence of clinic manifestations, the intake of antioxidant supplements in combination with the psychotropic therapy constitutes a valuable solution in patients’ treatment. When the psychoactive compounds possess themselves antioxidant capacity, this is an added-value for the therapy.
  • 1.3K
  • 12 Oct 2020
Topic Review
PPAR Alpha
Peroxisome proliferator-activated receptor α is a potent regulator of systemic and cellular metabolism and energy homeostasis, but it also suppresses various inflammatory reactions.
  • 1.3K
  • 19 Oct 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
CLMS application for protein interfaces
The fundamentals of how protein–protein/RNA/DNA interactions influence the structures and functions of the workhorses from the cells have been well documented in the 20th century. A diverse set of methods exist to determine such interactions between different components, particularly, the mass spectrometry (MS) methods, with its advanced instrumentation, has become a significant approach to analyze a diverse range of biomolecules, as well as bring insights to their biomolecular processes. Cross-linking mass spectrometry (CLMS) holds promise to identify interaction sites in larger and more complex biological systems.
  • 1.3K
  • 16 Mar 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
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
FTO Dioxygenase
The FTO (FaT mass and Obesity-associated) protein is an alpha-ketoglutarate and iron dependent dioxygenase, a member of ALKBH family proteins. FTO removes the methyl groups from modified nucleotides on single stranded DNA or RNA with N6-methyladenozine in the mRNA removed most efficiently. It is engaged in wide range of key physiological processes such as adipogenesis, cell cycle progression, heart remodelling, neural development and osteogenesis. Impairments of FTO activity is lethal or leads to serious developmental disorders. It is also one of the factors responsible for development and maintenance of many type of cancers. FTO acts in cooperation with other proteins e.g. CaMKII, MRS, SFPQ or XPO2. Similarly to other dioxygenases, it shows ability to form homodimer. Recently, it was shown that FTO interacts with the calmodulin (CaM) in Ca2+ dependent manner.
  • 1.3K
  • 26 Oct 2021
Topic Review
Protein Tertiary Structure Prediction
The prediction of three-dimensional (3D) protein structure from amino acid sequences has stood as a significant challenge in computational and structural bioinformatics for decades. The widespread integration of artificial intelligence (AI) algorithms has substantially expedited advancements in protein structure prediction, yielding numerous significant milestones. In particular, the end-to-end deep learning method AlphaFold2 has facilitated the rise of structure prediction performance to new heights, regularly competitive with experimental structures in the 14th Critical Assessment of Protein Structure Prediction (CASP14). 
  • 1.3K
  • 26 Feb 2024
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
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
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
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
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
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
Hydroxy Fatty Acid
Fatty acid esters of hydroxy fatty acids (FAHFAs) are a new class of endogenous lipids with interesting physiological functions in mammals. Despite their structural diversity and links with nuclear factor erythroid 2-related factor 2 (NRF2) biosynthesis, FAHFAs are less explored as NRF2 activators. 
  • 1.3K
  • 06 Aug 2021
Topic Review
Microvesicles
Extracellular vesicles (EV) are secreted by all cell types in a tumor and its microenvironment (TME) and play an essential role in intercellular communication and the establishment of a TME favorable for tumor invasion and metastasis. They encompass a variety of vesicle populations, among them the well-known endosomal-derived small exosomes (Exo), but also larger vesicles (diameter >100 nm) that are shed directly from the plasma membrane, the so-called microvesicles (MV). Increasing evidence suggests that MV, although biologically different, share the tumor-promoting features of Exo in the TME. Due to their larger size, they can be readily harvested from patients’ blood and characterized by routine methods such as conventional flow cytometry exploiting the plethora of molecules expressed on their surface. In this review we summarize the current knowledge about the biology and the composition of MV as well as their role within the TME. We highlight not only the challenges and potential of MV as novel biomarkers for cancer, but also discuss their possible use for therapeutic intervention.
  • 1.3K
  • 05 Nov 2020
Topic Review
Iron Oxide Nanoparticles in Cancer Diagnostics and Therapy
Cancer theranostics remains a vital research niche as a result of the rising mortality rates caused by various cancers globally. This is excarcebated by challenges related to conventional therapies. Iron-oxide-based NPs that possess characteristically large surface areas, small particle sizes, and superparamagnetism have been cited in applications geared towards diagnosis, and targeted drug delivery. When an external magnetic field is applied to superparamagnetic iron oxide NPs (SPIONs), the domains are aligned to the field. Once the field is removed, they return to a non-magnetic state. The NP magnetic moments turn to flip in the direction of the applied field. This flipping of the magnetic moments generates heat, which forms the basis of tumour ablation therapy through hyperthermia. Substituted iron-oxides or ferrites (MFe2O4) have emerged as interesting magnetic NPs due to their unique and attractive properties such as size and magnetic tunability, ease of synthesis, and manipulatable properties. In recent years, they have been explored for use in targeted therapy and drug delivery for anti-cancer treatment.
  • 1.3K
  • 27 May 2022
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