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Topic Review
Chemical Enzymology of Monoamine Oxidase
Monoamine oxidase (E.C. 1.4.3.4) enzymes MAO A and MAO B are FAD-containing proteins located on the outer face of the mitochondrial inner membrane, retained there by hydrophobic interactions and a transmembrane helix. The redox co-factor (FAD) is covalently attached to a cysteine and buried deep inside the protein behind an aromatic cage that aligns substrates towards the flavin. MAO metabolizes neurotransmitters such as dopamine and serotonin in the nervous system so is a target for drugs to modify amine levels. MAO also metabolizes a wide range of biogenic amines in all tissues. Current accumulated evidence, particularly from theoretical modelling, supports hydride transfer as the chemical mechanism. The long active site cavity accommodates a wide chemical variety of small molecules designed as inhibitors, including coumarins, chromones, triazoles, and more. Inactivators that bind covalently to MAO include hydrazines, cyclopropylamines and propargylamines. This entry is an extract adapted from a review outlining the remaining uncertainties in the understanding of this key drug target.
  • 2.5K
  • 19 Oct 2021
Topic Review
LncRNA-Protein Interactions
LncRNA can act as gene regulators, and like other epigenetic mechanisms are involved in numerous biological processes. They achieve their regulatory function with their ability to interact with a wide range of biological molecules, such as other nucleic acids and proteins. These lncRNA-protein interactions (LPI) are involved in many biological pathways including development and disease. A variety of computational LPI predictors exist, each applying different strategies to achieve their goals, and are dependent on a few biological databases containing subsets of experimentally validated LPI. Most modern lncRNA-protein interaction (LPI) prediction algorithms use machine learning approaches, where algorithms are trained on large datasets with attributes of interest.
  • 2.5K
  • 05 Jul 2021
Topic Review
PDE4 as Therapeutic Targets in Different Diseases
Cyclic nucleotides (cAMP, cGMP) play a major role in normal and pathologic signaling. Beyond receptors, cyclic nucleotide phosphodiesterases; (PDEs) rapidly convert the cyclic nucleotide in its respective 5′-nucleotide to control intracellular cAMP and/or cGMP levels to maintain a normal physiological state. However, in many pathologies, dysregulations of various PDEs (PDE1-PDE11) contribute mainly to organs and tissue failures related to uncontrolled phosphorylation cascade. Among these, PDE4 represents the greatest family, since it is constituted by 4 genes with multiple variants differently distributed at tissue, cellular and subcellular levels, allowing different fine-tuned regulations.
  • 2.5K
  • 11 Oct 2022
Topic Review
Coriandrum sativum L.
Coriandrum sativum (C. sativum), belonging to the Apiaceae (Umbelliferae) family, is widely recognized for its uses in culinary and traditional medicine. C. sativum contains various phytochemicals such as polyphenols, vitamins, and many phytosterols, which account for its properties including anticancer, anti-inflammatory, antidiabetic, and analgesic effects.
  • 2.5K
  • 13 Jan 2022
Topic Review
Mitochondrial Heteroplasmy and Disease
Given the relevance of mitochondria in numerous physiological and pathological mechanisms, such as adenosine triphosphate (ATP) synthesis, apoptosis, metabolism, cancer progression, and drug resistance, mitochondrial genome (mtDNA) analysis has become of great interest in the study of human diseases, including cancer. A high number of variants and mutations have been identified in different types of tumors, which coexist with normal alleles, a phenomenon named heteroplasmy. This mechanism is considered an intermediate state between the fixation or elimination of the acquired mutations. It is suggested that mutations, which confer adaptive advantages to tumor growth and invasion, are enriched in malignant cells.
  • 2.5K
  • 09 Sep 2022
Topic Review
Clavulanic Acid
Clavulanic acid is an irreversible β-lactamase enzyme inhibitor with a weak antibacterial activity produced by the filamentous actinomycete Streptomyces clavuligerus (S. clavuligerus) and, in a lesser extent, by other streptomyces species. Clavulanic acid is typically co-formulated with broad-spectrum β‑lactam antibiotics such as amoxicillin and ticarcillin, conferring them high potential to treat infectious diseases caused by β‑lactam-resistant bacteria like Escherichia coli, Staphylococcus aureus, Neisseria gonorrhoeae and Streptococcus pneumonia.
  • 2.4K
  • 22 Sep 2021
Topic Review
Cannabis and Male Reproductive Health
Cannabis sativa is a cheap hallucinating agent used in different parts of the world from time unknown as a part of various religious as well as social practices. Cannabis which is a special type of Marijuana can provide temporary relief from analgesia, body pain and in some other clinical conditions. But, impacts of Cannabis on reproductive health of males and females are multi-faceted and differentially fatal. In males, Cannabis can cause changes in testicular morphology, sperm parameters (in terms of semen quality, sperm morphology, sperm mortality and sperm motility), male reproductive hormones and finally causing reduced libido. In females, Cannabis can reduce female fertility by disrupting hypothalamic release of gonadotropin releasing hormone (GnRH), leading to reduced estrogen and progesterone production and anovulatory menstrual cycles.  Current research suggest that cannabis may negatively impact on male and female fertility conditions. However, male sterility considering the Cannabis impact is totally lacking in human as well as in sub-human primates. However, very limited studies are available on Cannabis effect on primate female reproduction considering Rhesus monkeys. Hence, further studies are needed to validate that robust findings in animal models will carry over into human experience.
  • 2.4K
  • 18 Sep 2021
Topic Review
Chitin and Chitin Biosynthesis in Filamentous Fungi
Chitin, a major structural component of the fungal cell wall, synthesized via the activityof the enzyme chitin synthase (chs), has become a high-profifile target for investigating the effect on morphology, development and pathogenicity of filamentous fungi. Besides, disruption of chitin biosynthesis can modify the mycelial morphology of filamentous fungi and regulate the biosynthesis of the target metabolites during submerged fermentation. Thus, we summarize the classifification, structure and function of chs enzymes, the biosynthetic pathway of chitin of filamentous fungi. 
  • 2.4K
  • 15 May 2023
Topic Review
Sirtuins
The sirtuin system consists of seven highly conserved regulatory enzymes responsible for metabolism, antioxidant protection, and cell cycle regulation. The great interest in sirtuins is associated with the potential impact on life extension. 
  • 2.4K
  • 05 Jan 2023
Topic Review
Bile Acids
Bile acids (BAs) are facial amphiphiles synthesized in the body of all vertebrates.
  • 2.4K
  • 18 Mar 2021
Topic Review
Bone Morphogenetic Protein-2
Bone morphogenetic proteins (BMPs) are multi-functional growth factors belonging to the Transforming Growth Factor-Beta (TGF-β) superfamily. These proteins are essential to many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis. Specifically, within the BMP family, Bone Morphogenetic Protein-2 (BMP-2) was the first BMP to be characterized and has been well-studied. BMP-2 has important roles during embryonic development, as well as bone remodeling and homeostasis in adulthood. Some of its specific functions include digit formation and activating osteogenic genes, such as Runt-Related Transcription Factor 2 (RUNX2). Because of its diverse functions and osteogenic potential, the Food and Drug Administration (FDA) approved usage of recombinant human BMP-2 (rhBMP-2) during spinal fusion surgery, tibial shaft repair, and maxillary sinus reconstructive surgery. However, shortly after initial injections of rhBMP-2, several adverse complications were reported, and alternative therapeutics have been developed to limit these side-effects.
  • 2.4K
  • 26 Oct 2020
Topic Review
Ras-Associated Protein 1 in Cancer
Metastasis is known as the most life-threatening event in cancer patients. In principle, the immune system can prevent tumor development. However, dysfunctional T cells may fail to eliminate the tumor cells effectively and provide additional survival advantages for tumor proliferation and metastasis. Constitutive activation of Ras-associated protein1 (Rap1) has not only led to T cell anergy, but also inhibited autophagy and supported cancer progression through various oncogenic events. Inhibition of Rap1 activity with its negative regulator, Rap1GAP, impairs tumor progression. However, active Rap1 reduces tumor invasion in some cancers, indicating that the pleiotropic effects of Rap1 signaling in cancers could be cancer-specific. All in all, targeting Rap1 signaling and its regulators could potentially control carcinogenesis, metastasis, chemoresistance and immune evasion. Rap1GAP could be a promising therapeutic target in combating cancer. 
  • 2.4K
  • 23 Sep 2020
Topic Review
Kinesin-1
The most of the transportations in cells are realized through a kind of proteins, the molecular motor. Molecular motor can be classed into three families, myosin, kinesin and dynein. Kinesin-1 (also called conventional kinesin) is the founding member of the kinesin family and mainly exists in the nerve axons to transport membranous organelles along the microtubule lattice. By using the energy stored in the ATP molecule, kinesin-1 can “walk” along the microtubule lattice in a hand-over-hand manner. In the walking process of the kinesin-1, the conformational changes of the compact motor domain transmit and amplify the small changes of the nucleotide-binding site to the force-generation element to produce the processive movement. The chemical cycle and mechanical cycle of kinesin-1 are highly coupled to ensure the processivity of the kinesin-1 and to avoid the futile ATP hydrolysis.
  • 2.4K
  • 27 Oct 2020
Topic Review
RNA-Targeting CRISPR–Cas Systems
Many CRISPR–Cas systems have been used as a backbone for the development of potent research tools, with Cas9 being the most widespread. While most of the utilized systems are DNA-targeting, recently more and more attention is being gained by those that target RNA. Their ability to specifically recognize a given RNA sequence in an easily programmable way makes them ideal candidates for developing new research tools. 
  • 2.4K
  • 23 Dec 2020
Topic Review
The Role of Cytochromes P450 in Plants
Cytochromes P450 are ancient enzymes diffused in organisms belonging to all kingdoms of life, including viruses, with the largest number of P450 genes found in plants. The functional characterization of cytochromes P450 has been extensively investigated in mammals, where these enzymes are involved in the metabolism of drugs and in the detoxification of pollutants and toxic chemicals.
  • 2.4K
  • 29 Mar 2023
Topic Review
1,3,4-Oxadiazole
Compounds containing 1,3,4-oxadiazole ring in their structure are characterised by multidirectional biological activity.
  • 2.4K
  • 13 Sep 2021
Topic Review
Hydrogen Peroxide Formation and Elimination in Mammalian Cells
Hydrogen peroxide (H2O2) is a compound involved in some mammalian reactions and processes. It modulates and signals the redox metabolism of cells by acting as a messenger together with hydrogen sulfide (H2S) and the nitric oxide radical (•NO), activating specific oxidations that determine the metabolic response. 
  • 2.4K
  • 29 Sep 2022
Topic Review
Nanopore Sequencing
Nanopore sequencing is a third generation approach used in the sequencing of biopolymers — specifically, polynucleotides in the form of DNA or RNA. Using nanopore sequencing, a single molecule of DNA or RNA can be sequenced without the need for PCR amplification or chemical labeling of the sample. Nanopore sequencing has the potential to offer relatively low-cost genotyping, high mobility for testing, and rapid processing of samples with the ability to display results in real-time. Publications on the method outline its use in rapid identification of viral pathogens, monitoring ebola, environmental monitoring, food safety monitoring, human genome sequencing, plant genome sequencing, monitoring of antibiotic resistance, haplotyping and other applications.
  • 2.4K
  • 16 Nov 2022
Topic Review
The Autophagic Pathway
Autophagy is a catabolic pathway that accounts for degradation and recycling of cellular components to extend cell survival under stress conditions. In addition to this prominent role, recent evidence indicates that autophagy is crucially involved in the regulation of the inflammatory response, a tightly controlled process aimed at clearing the inflammatory stimulus and restoring tissue homeostasis. To be efficient and beneficial to the host, inflammation should be controlled by a resolution program, since uncontrolled inflammation is the underlying cause of many pathologies. Resolution of inflammation is an active process mediated by a variety of mediators, including the so-called specialized pro-resolving lipid mediators (SPMs), a family of endogenous lipid autacoids known to regulate leukocyte infiltration and activities, and counterbalance cytokine production. Recently, regulation of autophagic mechanisms by these mediators has emerged, uncovering unappreciated connections between inflammation resolution and autophagy. Here, we summarize mechanisms of autophagy and resolution, focusing on the contribution of autophagy in sustaining paradigmatic examples of chronic inflammatory disorders. Then, we discuss the evidence that SPMs can restore dysregulated autophagy, hypothesizing that resolution of inflammation could represent an innovative approach to modulate autophagy and its impact on the inflammatory response.
  • 2.4K
  • 09 Nov 2020
Topic Review
Endocytosis in Health and Disease
Endocytosis is a mechanistic process, associated with internalization of the extracellular materials such as microbes, cellular components, nutrients, or macromolecules. Conventionally, eukaryotic cells use the endocytosis process for the absorption of molecules and secretion of signaling transmitters (hormones and cytokines) to maintain cellular homeostasis. Endocytosis machinery is a well-conserved physiological process in lower to higher organisms, which has been frequently acquired for cellular defense, immune responses, uptake, and energy metabolism. 
  • 2.4K
  • 13 Feb 2023
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