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Topic Review
Structure and Aggregation Mechanisms in Amyloids
Functional amyloids can be found in bacteria, unicellular eukaryotes, fungi, plants, insects and vertebrates, playing roles as diverse as surface protection and modification, mediation of pathogen-host interactions, pigment biosynthesis, homeostasis control, hormone storage and release, signal transduction, among others. The aggregation of a polypeptide chain into amyloid fibrils and their accumulation and deposition into insoluble plaques and intracellular inclusions is the hallmark of several misfolding diseases known as amyloidoses. Alzheimer′s, Parkinson′s and Huntington’s diseases are some of the approximately 50 amyloid diseases described to date.
  • 1.0K
  • 23 Dec 2021
Topic Review
Ryanodine Receptor
The ryanodine receptor (RyR) is a Ca2+ release channel in the sarcoplasmic reticulum of skeletal and cardiac muscles and plays a key role in excitation–contraction coupling. The activity of the RyR is regulated by the changes in the level of many intracellular factors, such as divalent cations (Ca2+ and Mg2+), nucleotides, associated proteins, and reactive oxygen species. Since these intracellular factors change depending on the condition of the muscle, e.g., exercise, fatigue, or disease states, the RyR channel activity will be altered accordingly.
  • 1.0K
  • 20 Oct 2021
Topic Review
The Chemistry of Reactive Oxygen Species Revisited
Living species are continuously subjected to all extrinsic forms of reactive oxidants and others that are produced endogenously. There is extensive literature on the generation and effects of reactive oxygen species (ROS) in biological processes, both in terms of alteration and their role in cellular signaling and regulatory pathways. Cells produce ROS as a controlled physiological process, but increasing ROS becomes pathological and leads to oxidative stress and disease. The induction of oxidative stress is an imbalance between the production of radical species and the antioxidant defense systems, which can cause damage to cellular biomolecules, including lipids, proteins and DNA. Cellular and biochemical experiments have been complemented in various ways to explain the biological chemistry of ROS oxidants. However, it is often unclear how this translates into chemical reactions involving redox changes. 
  • 1.0K
  • 30 Sep 2022
Topic Review
Sophorolipids—Bio-Based Antimicrobial Formulating Agents
Sophorolipids are well-known glycolipid biosurfactants, produced mainly by non-pathogenic yeast species such as Candida bombicola with high yield. Its unique environmental compatibility and high biodegradable properties have made them a focus in the present review for their promising applications in diverse areas.
  • 1.0K
  • 27 Sep 2022
Topic Review
Biological Effects of Radiotherapy in Cancer Cells
Radiotherapy remains an effective conventional method of treatment for patients with cancer. However, the clinical efficacy of radiotherapy is compromised by the development of radioresistance of the tumor cells during the treatment. The main goal of radiotherapy is to destroy or slow tumor growth by using high-energy radiation, such as X-rays, gamma (γ) rays, electrons, protons, neutrons, and carbon ions. The efficacy of killing is influenced by a number of factors, including the type of radiation, the total dose, the fractionation rate, and the targeted organs.
  • 1.0K
  • 24 Oct 2022
Topic Review
Angiotensin II
Cardiovascular disease is the leading cause of morbidity and mortality in the western and developing world, and the incidence of cardiovascular disease is increasing with the longer lifespan afforded by our modern lifestyle.  Vascular diseases including coronary heart disease, high blood pressure, and stroke comprise the majority of cardiovascular disease and therefore represent a significant medical and socioeconomic burden on our society.  It is not be surprising that these conditions overlap and potentiate each other when we consider the many cellular and molecular similarities between them. At the molecular level, the vascular smooth muscle cell (VSMC) is the target, integrator, and effector cell of both atherogenic and the major effector protein of the hypertensive signal, Angiotensin II (Ang II).  Together, these signals can potentiate each other and prime the artery and exacerbate hypertension and atherosclerosis. Therefore, VSMC are the fulcrum in progression of these diseases and therefore, understanding the effects of atherogenic stimuli and Ang II on VSMC is  key to understanding and treating  atherosclerosis and hypertension.  In this review, we will examine studies in which hypertension and atherosclerosis intersect on the VSMC, and illustrate common pathways between these two diseases and vascular aging.
  • 1.0K
  • 07 Jul 2020
Topic Review
Spermine in Prostate Cancer
Spermine, a member of polyamines, exists in all organisms and is essential for normal cell growth and function. It is highly expressed in the prostate compared with other organs and is detectable in urine, tissue, expressed prostatic secretions, and erythrocyte. A significant reduction of spermine level was observed in prostate cancer (PCa) tissue compared with benign prostate tissue, and the level of urinary spermine was also significantly lower in men with PCa. Decreased spermine level may be used as an indicator of malignant phenotype transformation from normal to malignant tissue in prostate.
  • 1.0K
  • 25 May 2021
Topic Review
Saffron for the Treatment of Human Diseases
Saffron (Crocus sativus L.) is a medicinal plant, originally cultivated in the East and Middle East, and later in some Mediterranean countries. Saffron is obtained from the stigmas of the plant. Currently, the use of saffron is undergoing a revival. The medicinal virtues of saffron, its culinary use and its high added value have led to the clarification of its phytochemical profile and its biological and therapeutic characteristics. Saffron is rich in carotenoids and terpenes. The major products of saffron are crocins and crocetin (carotenoids) deriving from zeaxanthin, pirocrocin and safranal, which give it its taste and aroma, respectively. Saffron and its major compounds have powerful antioxidant and anti-inflammatory properties in vitro and in vivo. Anti-tumor properties have also been described. 
  • 1.0K
  • 18 Feb 2022
Topic Review
Leaf Molecular and Hormonal Regulation
Shoot apical meristems (SAM) are tissues that function as a site of continuous organogenesis, which indicates that a small pool of pluripotent stem cells replenishes into lateral organs. The coordination of intercellular and intracellular networks is essential for maintaining SAM structure and size and also leads to patterning and formation of lateral organs. Leaves initiate from the flanks of SAM and then develop into a flattened structure with variable sizes and forms. This process is mainly regulated by the transcriptional regulators and mechanical properties that modulate leaf development. Leaf initiation along with proper orientation is necessary for photosynthesis and thus vital for plant survival. Leaf development is controlled by different components such as hormones, transcription factors, miRNAs, small peptides, and epigenetic marks. Moreover, the adaxial/abaxial cell fate, lamina growth, and shape of margins are determined by certain regulatory mechanisms. The over-expression and repression of various factors responsible for leaf initiation, development, and shape have been previously studied in several mutants. However, in this review, we collectively discuss how these factors modulate leaf development in the context of leaf initiation, polarity establishment, leaf flattening and shape.
  • 1.0K
  • 27 Oct 2020
Topic Review
Protein Glutathionylation and Glutaredoxin in Neurodegenerative Diseases
The brain is highly sensitive to oxidative stress due to its high oxygen consumption, abundance of unsaturated fatty acids which are prone to oxidation, and low antioxidant levels. It is a metabolically active and a high energy demanding organ that relies heavily on mitochondria for its energy needs. Majority of oxygen consumed by mitochondria during oxidative phosphorylation is coupled to ATP synthesis while ~4% contributes to the generation of superoxides which are further metabolized to reactive oxygen species (ROS). ROS modify proteins causing functional and structural damage to biomolecules. Prolonged exposure to reactive oxygen species (ROS) also damages DNA, mitochondrial membranes, and lipids, impairing its metabolic functions including synthesis of ATP, fatty acid oxidation and metabolism of essential biomolecules.
  • 1.0K
  • 16 Dec 2022
Topic Review
Software for Mass Spectrometry-based Lipidomics
Mass spectrometry (MS) is a state-of-the-art analytical technology, which enables the rapid and consistent identification and quantification of lipids in lipidomics, metabolites in metabolomics and proteins in proteomics for biomedical and biochemical research purposes.
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  • 01 Jul 2022
Topic Review
Tumor Cell Infiltration into the Brain in Glioblastoma
Glioblastoma is the most common and malignant primary brain tumor, defined by its highly aggressive nature. Despite the advances in diagnostic and surgical techniques, and the development of novel therapies in the last decade, the prognosis for glioblastoma is still extremely poor. One major factor for the failure of existing therapeutic approaches is the highly invasive nature of glioblastomas. The extreme infiltrating capacity of tumor cells into the brain parenchyma makes complete surgical removal difficult; glioblastomas almost inevitably recur in a more therapy-resistant state, sometimes at distant sites in the brain. Therefore, there are major efforts to understand the molecular mechanisms underpinning glioblastoma invasion; however, there is no approved therapy directed against the invasive phenotype as of now.
  • 1.0K
  • 07 Feb 2022
Topic Review
Lipid Phosphate Phosphatases
Lipid phosphate phosphatases (LPPs) consist of three enzymes (LPP1–3), which have been classified as phospholipid phosphatases (PLPP). The LPPs dephosphorylate a wide spectrum of bioactive lipid phosphates, among which lysophosphatidate (LPA) and sphingosine 1-phosphate (S1P) are two important extracellular signaling molecules. The LPPs are integral membrane proteins, which are partly localized on plasma membranes. These activities participate in regulating the concentrations of extracellular LPA and S1P and thus signaling through their families of G protein coupled receptors. The expression of the LPPs on intracellular membranes, including endoplasmic reticulum and Golgi net work, are thought to attenuate signaling downstream of the activation of LPA and protease activates receptors. The LPPs differentially regulate signal transduction in cancer cells. LPP1 and LPP3 have decreased expressions in several caners and this is associated with increased tumor growth and metastasis.  Conversely, LPP2 activity is increased in these cancers and this accelerates progression through the cell cycle. Increasing the relative activities of LPP1 and LPP3 and decreasing LPP2 activity, therefore, provides a novel approach to treating some cancers.
  • 1.0K
  • 11 Sep 2020
Topic Review
HER2-Positive Breast Cancer
Up to one-third of all breast cancers are classified as the aggressive HER2-positive subtype, which is associated with a higher risk of recurrence compared to HER2-negative breast cancers. The HER2 hyperactivity associated with this subtype drives tumor growth by up-regulation of mTOR pathways and metabolic adaptation. Combination therapies that simultaneously target HER2 and mTOR improve clinical outcomes compared with HER2 inhibition alone. Drugs that mimic glucose deprivation in HER2-positive breast cancer patients have not been evaluated; however, preclinical studies have shown that the growth of HER2-positive breast tumors is reduced in response to combining the glycolytic inhibitor 2-DG with mTOR inhibitors.
  • 1.0K
  • 02 Jul 2021
Topic Review
Endoplasmic Reticulum's Applications in Mitochondrial Proteins
Most mitochondrial proteins are synthesized in the cytosol and targeted to the mitochondrial surface in a post-translational manner. The surface of the endoplasmic reticulum (ER) plays an active role in this targeting reaction. ER-associated chaperones interact with certain mitochondrial membrane protein precursors and transfer them onto receptor proteins of the mitochondrial surface in a process termed ER-SURF.
  • 1.0K
  • 26 Oct 2021
Topic Review
Mitochondrial Genetic and Epigenetic Regulations in Cancer
Mitochondria are dynamic organelles managing crucial processes of cellular metabolism and bioenergetics. Enabling rapid cellular adaptation to altered endogenous and exogenous environments, mitochondria play an important role in many pathophysiological states, including cancer. Being under the control of mitochondrial and nuclear DNA (mtDNA and nDNA), mitochondria adjust their activity and biogenesis to cell demands. In cancer, numerous mutations in mtDNA have been detected, which do not inactivate mitochondrial functions but rather alter energy metabolism to support cancer cell growth. Increasing evidence suggests that mtDNA mutations, mtDNA epigenetics and miRNA regulations dynamically modify signalling pathways in an altered microenvironment, resulting in cancer initiation and progression and aberrant therapy response. 
  • 1.0K
  • 10 Aug 2022
Topic Review
The PINK1/Parkin Pathway
The process by which dysfunctional mitochondria are selectively targeted for lysosome-mediated degradation otherwise known as mitophagy, requires the serine/threonine kinase PINK1 and the E3 ubiquitin ligase Parkin to occur. In the last decade the PINK1/Parkin pathway received great attention due to its importance in many physiological and pathological processes. Understanding the mechanisms by which mitochondria are selectively recognized and targeted for degradation is thus fundamental to understand and to develop therapies for many devastating diseases. Here the mechanisms at the basis of the PINK1/Parkin-mediated degradation of dysfunctional mitochondria are described.
  • 1.0K
  • 27 Oct 2020
Topic Review
Nucleotide Sugars
Nucleotide sugars have essential roles in every living creature. They are the building blocks of the biosynthesis of carbohydrates and their conjugates and their biological reaction pathways are potential targets of drug development. Information on the chemical and biological reactions supports the development of synthetic and analytic methods required.
  • 1.0K
  • 16 Dec 2020
Topic Review
Replication Protein A
Replication protein A (RPA) is a heterotrimeric protein complex and the main single-stranded DNA (ssDNA)-binding protein in eukaryotes. RPA has key functions in most of the DNA-associated metabolic pathways and DNA damage signalling. Its high affinity for ssDNA helps to stabilise ssDNA structures and protect the DNA sequence from nuclease attacks. RPA consists of multiple DNA-binding domains which are oligonucleotide/oligosaccharide-binding (OB)-folds that are responsible for DNA binding and interactions with proteins. These RPA–ssDNA and RPA–protein interactions are crucial for DNA replication, DNA repair, DNA damage signalling, and the conservation of the genetic information of cells. Proteins such as ATR use RPA to locate to regions of DNA damage for DNA damage signalling.
  • 1.0K
  • 18 Feb 2024
Topic Review
Benchmarking Data Sets
Developing realistic data sets for evaluating virtual screening methods is a task that has been tackled by the cheminformatics community for many years. Numerous artificially constructed data collections were developed, such as DUD, DUD-E, or DEKOIS. However, they all suffer from multiple drawbacks, one of which is the absence of experimental results confirming the impotence of presumably inactive molecules, leading to possible false negatives in the ligand sets. In light of this problem, the PubChem BioAssay database, an open-access repository providing the bioactivity information of compounds that were already tested on a biological target, is now a recommended source for data set construction. Nevertheless, there exist several issues with the use of such data that need to be properly addressed. In this article, an overview of benchmarking data collections built upon experimental PubChem BioAssay input is provided, along with a thorough discussion of noteworthy issues that one must consider during the design of new ligand sets from this database. The points raised in this review are expected to guide future developments in this regard, in hopes of offering better evaluation tools for novel in silico screening procedures.
  • 1.0K
  • 26 Oct 2020
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