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Journal of Chromatography. A Oct 2023The value of the concept of retention indices (RI) to the practice of gas chromatography (GC) is highlighted, where the RI of a compound is one component of the strategy... (Review)
Review
The value of the concept of retention indices (RI) to the practice of gas chromatography (GC) is highlighted, where the RI of a compound is one component of the strategy to identify the compound. The widespread reliance on GC and then on mass spectrometry for 'identification', may result in inadequate confirmation of molecular identity. However, RI do provide a useful tentative indication of the possible molecule(s). Thus, the RI value is a useful first measure of the molecule identity, and shown here to be valuable provided limitations are recognised. An author has a responsibility to correctly calculate the index and then use the values for (tentative) identification. Tables of reference RI values are useful in this respect, but finding an 'exact match' RI value does not confirm the identity. Hence, it is necessary to understand how the RI value may be incorrectly used in this respect. The reviewer of written research is charged with ensuring the index values are applied in a rigorous manner. Selected case studies from our own work, support the care that must be exercised when reporting RI values. In terms of advanced GC operations, mention is made of multidimensional gas chromatography and comprehensive two-dimensional gas chromatography to acquire RI values on both the first and second columns in the two-column separation experiment.
Topics: Gas Chromatography-Mass Spectrometry; Mass Spectrometry; Reference Values
PubMed: 37717451
DOI: 10.1016/j.chroma.2023.464376 -
Biological Research Jul 2019In the growth condition(s) of plants, numerous secondary metabolites (SMs) are produced by them to serve variety of cellular functions essential for physiological... (Review)
Review
In the growth condition(s) of plants, numerous secondary metabolites (SMs) are produced by them to serve variety of cellular functions essential for physiological processes, and recent increasing evidences have implicated stress and defense response signaling in their production. The type and concentration(s) of secondary molecule(s) produced by a plant are determined by the species, genotype, physiology, developmental stage and environmental factors during growth. This suggests the physiological adaptive responses employed by various plant taxonomic groups in coping with the stress and defensive stimuli. The past recent decades had witnessed renewed interest to study abiotic factors that influence secondary metabolism during in vitro and in vivo growth of plants. Application of molecular biology tools and techniques are facilitating understanding the signaling processes and pathways involved in the SMs production at subcellular, cellular, organ and whole plant systems during in vivo and in vitro growth, with application in metabolic engineering of biosynthetic pathways intermediates.
Topics: Cell Culture Techniques; Gene Expression Regulation, Plant; Plant Growth Regulators; Plant Physiological Phenomena; Plant Roots; Plant Shoots; Plants; Secondary Metabolism; Signal Transduction; Stress, Physiological
PubMed: 31358053
DOI: 10.1186/s40659-019-0246-3 -
Toxicology in Vitro : An International... Feb 2024Phototoxicity, sometimes in the literature referred to as photo-irritation, is a chemically induced reaction requiring light. While it is generally accepted that...
Phototoxicity, sometimes in the literature referred to as photo-irritation, is a chemically induced reaction requiring light. While it is generally accepted that phototoxicity testing can be performed in the majority of cases in vitro (i.e. without the use of experimental animals), these tests may sometimes provide contradictory predictions. Understanding the mechanisms of initiating events based on the molecule's structure and its ability to reach the excited state and consequently generate ROS enables the creation of predictive QSAR for this adverse outcome. The ability to predict the phototoxicity potential via a QSAR model is beneficial in reducing the number of mechanical in vitro/in chemico tests needed to demonstrate absence of phototoxicity and it is very helpful in the overall safety assessment process. The QSAR prediction model presented here focused on developing a robust platform freely available on the web via the link http://mltox.online to provide interpretable predictions of the phototoxicity of tested molecules. Great attention was devoted to interpretability and explainability of the prediction results. The web application allows the user to input a chemical by CAS number, SMILES code or trivial name. The user can choose between simple prediction or advanced tools options. These extended tools include the artificial intelligence explainability of model prediction using XSMILES (interactive visualization technique to support the interpretation of SMILES) and SHAP values (impact each element on the prediction). The comprehensive tools in question allow the user to explore the properties of phototoxic substances and to understand the prediction outcomes better.
Topics: Animals; Artificial Intelligence; Dermatitis, Phototoxic; Software
PubMed: 37820749
DOI: 10.1016/j.tiv.2023.105701 -
Angewandte Chemie (International Ed. in... Nov 2020A significant amount of attention has been given to the design and synthesis of co-crystals by both industry and academia because of its potential to change a molecule's...
A significant amount of attention has been given to the design and synthesis of co-crystals by both industry and academia because of its potential to change a molecule's physicochemical properties. Yet, difficulties arise when searching for adequate combinations of molecules (or coformers) to form co-crystals, hampering the efficient exploration of the target's solid-state landscape. This paper reports on the application of a data-driven co-crystal prediction method based on two types of artificial neural network models and co-crystal data present in the Cambridge Structural Database. The models accept pairs of coformers and predict whether a co-crystal is likely to form. By combining the output of multiple models of both types, our approach shows to have excellent performance on the proposed co-crystal training and validation sets, and has an estimated accuracy of 80 % for molecules for which previous co-crystallization data is unavailable.
PubMed: 32797658
DOI: 10.1002/anie.202009467 -
Critical Reviews in Therapeutic Drug... 2023Cyclosporine (CsA) stays the most intangible molecule holding a good history for treating several ophthalmic conditions and it even attributes to multiple off-label... (Review)
Review
Cyclosporine (CsA) stays the most intangible molecule holding a good history for treating several ophthalmic conditions and it even attributes to multiple off-label uses. Topical delivery of CsA is the most preferred route but owing to the molecule's physicochemical properties such as poor aqueous solubility and high molecular weight as well as its encounter with multiple barriers of eye causes hindrance for proper delivery of the molecule to the site of action. However, Restasis®, Cequa®, and Verkazia® are the marketed formulations that have been approved by U.S. Food and Drug Administration, whereas Cyclokat® and Ikervis® by the European Medicines Agency. Although these medications are in use, they are associated with severe discomfort and poor patient compliance. This review gives an overview regarding current formulations available in the market, the products in pipeline and the recent advances undertaken for improving ocular delivery of CsA for various ophthalmic indications.
Topics: Humans; Cyclosporine; Immunosuppressive Agents; Eye; Eye Diseases; Drug Delivery Systems; Excipients; Administration, Ophthalmic
PubMed: 37522548
DOI: 10.1615/CritRevTherDrugCarrierSyst.2022043085 -
Functional & Integrative Genomics Jun 2023Introgression of disease resistance genes (R-genes) to fight against an array of phytopathogens takes several years using conventional breeding approaches. Pathogens... (Review)
Review
Introgression of disease resistance genes (R-genes) to fight against an array of phytopathogens takes several years using conventional breeding approaches. Pathogens develop mechanism(s) to escape plants immune system by evolving new strains/races, thus making them susceptible to disease. Conversely, disruption of host susceptibility factors (or S-genes) provides opportunities for resistance breeding in crops. S-genes are often exploited by phytopathogens to promote their growth and infection. Therefore, identification and targeting of disease susceptibility genes (S-genes) are gaining more attention for the acquisition of resistance in plants. Genome engineering of S-genes results in targeted, transgene-free gene modification through CRISPR-Cas-mediated technology and has been reported in several agriculturally important crops. In this review, we discuss the defense mechanism in plants against phytopathogens, tug of war between R-genes and S-genes, in silico techniques for identification of host-target (S-) genes and pathogen effector molecule(s), CRISPR-Cas-mediated S-gene engineering, its applications, challenges, and future prospects.
Topics: Plant Diseases; Genome, Plant; Crops, Agricultural; Plants, Genetically Modified; CRISPR-Cas Systems; Plant Breeding
PubMed: 37338599
DOI: 10.1007/s10142-023-01133-w -
Frontiers in Oncology 2019Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumour in humans and has a very poor prognosis. The existing treatments have had... (Review)
Review
Glioblastoma multiforme (GBM) is the most common and aggressive malignant primary brain tumour in humans and has a very poor prognosis. The existing treatments have had limited success in increasing overall survival. Thus, identifying and understanding the key molecule(s) responsible for the malignant phenotype of GBM will yield new potential therapeutic targets. The treatment of brain tumours faces unique challenges, including the presence of the blood brain barrier (BBB), which limits the concentration of drugs that can reach the site of the tumour. Nevertheless, several promising treatments have been shown to cross the BBB and have shown promising pre-clinical results. This review will outline the status of several of these promising targeted therapies.
PubMed: 31616641
DOI: 10.3389/fonc.2019.00963 -
Acta Tropica Jul 2021Podoconiosis is a non-filarial and non-communicable disease leading to lymphedema of the lower limbs. Worldwide, 4 million individuals live with podoconiosis, which is... (Review)
Review
Podoconiosis is a non-filarial and non-communicable disease leading to lymphedema of the lower limbs. Worldwide, 4 million individuals live with podoconiosis, which is accompanied by disability and painful intermittent acute inflammatory episodes that attribute to significant disability adjusted life years (DALYs). Different risk factors like contact with volcanic red clay soil, high altitude (above 1000 m), high seasonal rainfall (above 1000 mm/year) and occupation (e.g., subsistence farmer) are associated with the risk of podoconiosis. Although podoconiosis was described to be endemic in 32 countries in Africa, parts of Latin America and South East Asia, knowledge about related genetics, pathophysiology, immunology and especially the causing molecule(s) in the soil remain uncertain. Thus, podoconiosis can be considered as one of the most neglected diseases. This review provides an overview about this non-filarial related geochemical disease and aim to present perspectives and future directions that might be important for better understanding of the disease, prospect for point-of-care diagnosis, achieving protection and developing novel treatment strategies.
Topics: Elephantiasis; Humans; Risk Factors; Soil
PubMed: 33839086
DOI: 10.1016/j.actatropica.2021.105918 -
Biochemistry Apr 2020Messenger RNA degradation is an important component of overall gene expression. During the final step of eukaryotic mRNA degradation, exoribonuclease 1 (Xrn1) carries...
Messenger RNA degradation is an important component of overall gene expression. During the final step of eukaryotic mRNA degradation, exoribonuclease 1 (Xrn1) carries out 5' → 3' processive, hydrolytic degradation of RNA molecules using divalent metal ion catalysis. To initiate studies of the 5' → 3' RNA decay machinery in our lab, we expressed a C-terminally truncated version of Xrn1 and explored its enzymology using a second-generation, time-resolved fluorescence RNA degradation assay. Using this system, we quantitatively explored Xrn1's preference for 5'-monophosphorylated RNA substrates, its pH dependence, and the importance of active site mutations in the molecule's conserved catalytic core. Furthermore, we explore Xrn1's preference for RNAs containing a 5' single-stranded region both in an intermolecular hairpin structure and in an RNA-DNA hybrid duplex system. These results both expand and solidify our understanding of Xrn1, a centrally important enzyme whose biochemical properties have implications in numerous RNA degradation and processing pathways.
Topics: Exoribonucleases; Hydrogen-Ion Concentration; Models, Molecular; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins
PubMed: 32251580
DOI: 10.1021/acs.biochem.9b01035 -
Journal of Natural Products Jun 2023Fungal metabolites represent an underutilized resource in the development of novel anticancer drugs. This review will focus on the promising fungal nephrotoxin... (Review)
Review
Fungal metabolites represent an underutilized resource in the development of novel anticancer drugs. This review will focus on the promising fungal nephrotoxin orellanine, found in mushrooms including (Fools webcap). Emphasis will be placed on its historical significance, structural features, and associated toxicomechanics. Chromatographic methods for analysis of the compound and its metabolites, its synthesis, and chemotherapeutic potential are also discussed. Although orellanine's exceptional selectivity for proximal tubular cells is well documented, the mechanics of its toxicity in kidney tissue remains disputed. Here, the most commonly proposed hypotheses are detailed in the context of the molecule's structure, the symptoms seen following ingestion, and its characteristic prolonged latency period. Chromatographic analysis of orellanine and its related substances remains challenging, while biological evaluation of the compound is complicated by uncertainty regarding the role of active metabolites. This has limited efforts to structurally refine the molecule; despite numerous established methods for its synthesis, there is minimal published material on how orellanine's structure might be optimized for therapeutic use. Despite these obstacles, orellanine has generated promising data in preclinical studies of metastatic clear cell renal cell carcinoma, leading to the early 2022 announcement of phase I/II trials in humans.
Topics: Humans; Mycotoxins; Neoplasms; 2,2'-Dipyridyl; Agaricales
PubMed: 37308446
DOI: 10.1021/acs.jnatprod.2c01068