This systematic review evaluates pneumolysin (PLY) as a target for new treatments against pneumococcal infections. Pneumolysin is one of the main virulence factors produced by all types of ...pneumococci. This toxin (53 kDa) is a highly conserved protein that binds to cholesterol in eukaryotic cells, forming pores that lead to cell destruction.
The databases consulted were MEDLINE, Web of Science, and Scopus. Articles were independently screened by title, abstract, and full text by two researchers, and using consensus to resolve any disagreements that occurred. Articles in other languages different from English, patents, cases report, notes, chapter books and reviews were excluded. Searches were restricted to the years 2000 to 2021. Methodological quality was evaluated using OHAT framework.
Forty-one articles describing the effects of different molecules that inhibit PLY were reviewed. Briefly, the inhibitory molecules found were classified into three main groups: those exerting a direct effect by binding and/or blocking PLY, those acting indirectly by preventing its effects on host cells, and those whose mechanisms are unknown. Although many molecules are proposed as toxin blockers, only some of them, such as antibiotics, peptides, sterols, and statins, have the probability of being implemented as clinical treatment. In contrast, for other molecules, there are limited studies that demonstrate efficacy in animal models with sufficient reliability.
Most of the studies reviewed has a good level of confidence. However, one of the limitations of this systematic review is the lack of homogeneity of the studies, what prevented to carry out a statistical comparison of the results or meta-analysis.
A panel of molecules blocking PLY activity are associated with the improvement of the inflammatory process triggered by the pneumococcal infection. Some molecules have already been used in humans for other purposes, so they could be safe for use in patients with pneumococcal infections. These patients might benefit from a second line treatment during the initial stages of the infection preventing acute respiratory distress syndrome and invasive pneumococcal diseases. Additional research using the presented set of compounds might further improve the clinical management of these patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The use and production of chemical compounds are subjected to strong legislative pressure. Chemical toxicity and adverse effects derived from exposure to chemicals are key regulatory aspects for a ...multitude of industries, such as chemical, pharmaceutical, or food, due to direct harm to humans, animals, plants, or the environment. Simultaneously, there are growing demands on the authorities to replace traditional in vivo toxicity tests carried out on laboratory animals (e.g., European Union REACH/3R principles, Tox21 and ToxCast by the U.S. government, etc.) with in silica computational models. This is not only for ethical aspects, but also because of its greater economic and time efficiency, as well as more recently because of their superior reliability and robustness than in vivo tests, mainly since the entry into the scene of artificial intelligence (AI)‐based models, promoting and setting the necessary requirements that these new in silico methodologies must meet. This review offers a multidisciplinary overview of the state of the art in the application of AI‐based methodologies for the fulfillment of regulatory‐related toxicological issues.
This article is categorized under:
Data Science > Chemoinformatics
Data Science > Artificial Intelligence/Machine Learning
Artificial Intelligence for Toxicological Predictions
Quantitative polymerase chain reaction (qPCR) is considered the gold standard for pathogen detection. However, improvement is still required, especially regarding the possibilities of ...decentralization. Apart from other reasons, infectious diseases demand on‐site analysis to avoid pathogen spreading and increase treatment efficacy. In this paper, the detection of SARS‐CoV‐2 is carried out by reverse transcription loop‐mediated isothermal amplification, which has the advantage of requiring simple equipment, easily adaptable to decentralized analysis. It is proposed, for the first time, the use of palladium nanoclusters (PdNCs) as indicators of the amplification reaction at end point. The pH of the medium decreases during the reaction and, in turn, a variation in the catalytic activity of PdNCs on the oxygen reduction reaction (ORR) can be electrochemically observed. For the detection, flexible and small‐size screen‐printed electrodes can be premodified with PdNCs, which together with the use of a simple and small electrochemical equipment would greatly facilitates their integration in field‐deployable devices. This would allow a faster detection of SARS‐CoV‐2 as well as of other future microbial threats after an easy adaptation.
In this article, authors propose an innovative methodology for electrochemical COVID‐19 diagnosis using palladium nanoclusters (PdNCs)‐based voltammetry. The product of the isothermal loop‐mediated amplification (LAMP) is transferred to a card with screen‐printed electrodes, previously modified with PdNCs. The change in the pH that occurs during a LAMP reaction produces a variation in the catalytic activity of PdNCs.
BackgroundThis systematic review evaluates pneumolysin (PLY) as a target for new treatments against pneumococcal infections. Pneumolysin is one of the main virulence factors produced by all types of ...pneumococci. This toxin (53 kDa) is a highly conserved protein that binds to cholesterol in eukaryotic cells, forming pores that lead to cell destruction.MethodsThe databases consulted were MEDLINE, Web of Science, and Scopus. Articles were independently screened by title, abstract, and full text by two researchers, and using consensus to resolve any disagreements that occurred. Articles in other languages different from English, patents, cases report, notes, chapter books and reviews were excluded. Searches were restricted to the years 2000 to 2021. Methodological quality was evaluated using OHAT framework.ResultsForty-one articles describing the effects of different molecules that inhibit PLY were reviewed. Briefly, the inhibitory molecules found were classified into three main groups: those exerting a direct effect by binding and/or blocking PLY, those acting indirectly by preventing its effects on host cells, and those whose mechanisms are unknown. Although many molecules are proposed as toxin blockers, only some of them, such as antibiotics, peptides, sterols, and statins, have the probability of being implemented as clinical treatment. In contrast, for other molecules, there are limited studies that demonstrate efficacy in animal models with sufficient reliability.DiscussionMost of the studies reviewed has a good level of confidence. However, one of the limitations of this systematic review is the lack of homogeneity of the studies, what prevented to carry out a statistical comparison of the results or meta-analysis.ConclusionA panel of molecules blocking PLY activity are associated with the improvement of the inflammatory process triggered by the pneumococcal infection. Some molecules have already been used in humans for other purposes, so they could be safe for use in patients with pneumococcal infections. These patients might benefit from a second line treatment during the initial stages of the infection preventing acute respiratory distress syndrome and invasive pneumococcal diseases. Additional research using the presented set of compounds might further improve the clinical management of these patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
shows more than 90 capsular serotypes that can be distinguished by their reactivity against antisera. The main objective of this work was the development of a molecular method for serotyping without ...the use of antisera. A computer program containing an algorithm was used to search in a database for potentially useful enzymes for Restriction Fragment Length Polymorphism-RFLP typing, in order to maximize the discrimination between different serotypes. DNA sequences of 90 serotypes for the region between
B and
A genes were compiled, and a computer screening of restriction enzymes was performed. The
region and
9I restriction predicted unique PCR-RFLP patterns for 39 serotypes and eight serogroups. A second restriction enzyme resolved fragment specific patterns for 25 serotypes. The method was tested with 98 serotype-unknown clinical isolates. PCR-RFLP analysis deduced correct serotypes that were confirmed by Quellung reaction for 78.5% of the isolates.
To guarantee an adequate food supply for the world's growing population, intensive agriculture is necessary to ensure efficient food production. The use of pesticides helps maintain maximum ...productivity in intensive agriculture by minimizing crop losses due to pests. However, pesticide contamination of surface waters constitutes a major problem as they are resistant to degradation and soluble enough to be transported in water. In recent years, all groups of pesticides defined by the World Health Organization have increased their use and, therefore, their prevalence in the different environmental compartments that can have harmful effects. Despite this effort, there is no rigorous monitoring program that quantifies and controls the toxic effects of each pesticide. However, multiple scientific studies have been published by specialized research groups in which this information is disseminated. Therefore, any attempt to systematize this information is relevant. This review offers a current overview of the presence and distribution of the most widely-used pesticides (insecticides, herbicides, and fungicides) by crop type and an evaluation of the relationships between their uses and environmental implications in Spain. The data demonstrated that there are correlations between the presence of specific pesticides used in the main crops and their presence in the environmental compartments. We have found preliminary data pointing to existing associations between specific pesticides used in the main crops and their presence in environmental compartments within different geographical areas of Spain; this should be the subject of further investigation.
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•Factors influencing sustainable use of pesticides in Spanish agriculture.•Relationships between the uses of pesticides and their regional prevalence.•Current pesticide uses and prevalence relative to geographic area in Spain.•Sustainable pesticides usage to reduce the risks on human health and the environment.•Climatic changes and pesticide fluctuations association.
A highly sensitive electrochemical methodology for end-point detection of loop-mediated isothermal nucleic acid amplification reactions was developed. It is based on the oxidation process of phenol ...red (PR), commonly used as a visual indicator. The dependence of its redox process on pH, which changes during amplification, allows performing quantitative measurements. Thus, the change in the oxidation potential of PR during the amplification is used, for the first time, as the analytical signal that correlates with the number of initial DNA copies. As a proof-of-concept, the amplification of the pneumolysin gene from Streptococcus pneumoniae, one of the main pathogens causing community-acquired pneumonia, is performed. Combination of isothermal amplification with electrochemical detection, performed on small-size flexible electrodes, allows easy decentralization. Adaptation to the detection of other pathogens causing infectious diseases would be very useful in the prevention of future epidemics.
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•A fast, sensitive, and simple on-site method is presented for COVID-19 diagnosis.•Electrochemical detection is combined with RT-LAMP for on-site SARS-CoV-2 detection.•Malachite green ...LAMP probe is monitored electrochemically for quantitative readout.•Electrochemical measurement of malachite green is presented for SARS-CoV-2 monitoring.•Dual visual/electrochemical LAMP detection is made using malachite green indicator.
Loop-mediated isothermal amplification (LAMP) has arisen as an outstanding molecular technique for the amplification of nucleic acids, becoming an important alternative to PCR due to its simplicity and high sensitivity. However, traditional visual readout used in LAMP only provides qualitative results and can thus not provide a precise quantification of the target DNA/RNA in the sample. To overcome this, electroactive reporters incorporated in the reaction mix can provide a subsequent quantitative result of the analysis. In this work, malachite green, a commonly used colorimetric LAMP indicator, is used as an electrochemical probe to obtain quantitative results. For this purpose, its optical and electrochemical behavior has been assessed for further use in LAMP detection. Using SARS-CoV-2 RNA as template, we have developed a quantitative detection method, proving the usefulness of this molecule as a dual optical/electrochemical indicator. Thereby, with the electrochemical detection using screen-printed electrodes on which a drop of the LAMP reaction is deposited, a calibration curve with a linear dynamic range comprised between 22 and 4296 copies/μL was achieved, with a practical limit of detection of 22 copies/µL. In this method, validated with clinical samples, malachite green is used, by the first time, as a dual visual electrochemical/visual probe that can provide both an initial visual qualitative assessment together with an electrochemical quantification.
Lateral flow immunoassays for detecting biomarkers in body fluids are simple, quick, inexpensive point-of-care tests widely used in disease surveillance, such as during the coronavirus disease 2019 ...(COVID-19) pandemic. Improvements in sensitivity would increase their utility in healthcare, food safety, and environmental control. Recently, biofunctional magnetic nanoclusters have been used to selectively label target proteins, which allows their detection and quantification with a magneto-inductive sensor. This type of detector is easily integrated with the lateral flow immunoassay format. Pneumolysin is a cholesterol-dependent cytolysin and one of the most important protein virulence factors of pneumonia produced by Streptococcus pneumoniae. It is recognized as an important biomarker for diagnosis in urine samples. Pneumonia is the infectious disease that causes the most deaths globally, especially among children under five years and adults over 65 years, most of them in low- and middle-income countries. There especially, a rapid diagnostic urine test for pneumococcal pneumonia with high sensitivity and specificity would be helpful in primary care. In this work, a lateral flow immunoassay with magnetic nanoclusters conjugated to anti-pneumolysin antibodies was combined with two strategies to increase the technique’s performance. First, magnetic concentration of the protein before the immunoassay was followed by quantification by means of a mobile telephone camera, and the inductive sensor resulted in detection limits as low as 0.57 ng (telephone camera) and 0.24 ng (inductive sensor) of pneumolysin per milliliter. Second, magnetic relocation of the particles within the test strip after the immunoassay was completed increased the detected signal by 20%. Such results obtained with portable devices are promising when compared to non-portable conventional pneumolysin detection techniques such as enzyme-linked immunosorbent assays. The combination and optimization of these approaches would have excellent application in point-of-care biodetection to reduce antibiotic misuse, hospitalizations, and deaths from community-acquired pneumonia.
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