In silico deconvolution of blood immune status to direct anti-malarial vaccination
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PROVIDER: PRJEB61727 | ENA |
REPOSITORIES: ENA
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Project description:Cerebral Malaria (HCM) is a serious neurological complication caused by Plasmodium falciparum infection. Currently the only treatment for HCM is the provision of anti-malarial drugs; however, such treatment by itself often fails to prevent death or development of neurological sequelae. To identify new potential adjunct treatments for HCM, we performed a non-biased whole brain transcriptomic time-course analysis of anti-malarial drug chemotherapy of murine experimental CM (ECM).
2018-07-03 | E-MTAB-6474 | biostudies-arrayexpress
Project description:BACKGROUND:Malaria is a parasitic disease that produces significant infection in red blood cells. The objective of this study is to investigate the relationships between factors affecting the penetration of currently available anti-malarials into red blood cells. METHODS:Fifteen anti-malarial drugs listed in the third edition of the World Health Organization malaria treatment guidelines were enrolled in the study. Relationship analysis began with the prioritization of the physicochemical properties of the anti-malarials to create a multivariate linear regression model that correlates the red blood cell penetration. RESULTS:It was found that protein binding was significantly correlated with red blood cell penetration, with a negative coefficient. The next step was repeated analysis to find molecular descriptors that influence protein binding. The coefficients of the number of rotating bonds and the number of aliphatic hydrocarbons are negative, as opposed to the positive coefficients of the number of hydrogen bonds and the number of aromatic hydrocarbons. The p-value was less than 0.05. CONCLUSIONS:Anti-malarials with a small number of hydrogen bonds and aromatic hydrocarbons, together with a high number of rotatable bonds and aliphatic hydrocarbons, may have a higher tendency to penetrate the red blood cells.
| S-EPMC7310442 | biostudies-literature
Project description:Tafenoquine , an anti-malarial agent, exhibited satisfactory antimicrobial efficacy against Staphylococcus aureus and its highly resistant phenotypes of biofilm and persister cells. Proteomic analysis of Staphylococcus aureus after treated with Tafenoquine was used to explore its underlying mechanisms.
2023-10-12 | PXD046080 |
Project description:Malaria continues to pose a significant public health threat, with millions of cases and hundreds of thousands of deaths reported annually, primarily in sub-Saharan Africa. The disease disproportionally affects children under five years of age residing in holoendemic Plasmodium falciparum transmission regions, who account for 94% of the cases and 80% of the mortality. Young children are highly vulnerable to developing life-threatening severe malarial anemia [SMA, hemoglobin (Hb)<5.0 g/dL]. The overall goal of the project was to identify critical gene pathways within the transcriptome that mediate disease severity and then target these specific genes with compounds that elicit expression profiles witnessed in children with milder forms of disease. To achieve this goal, we are investing the following specific aims: 1) Determine how changing temporal dynamics of gene pathways in the Malarial Immunity Transcriptome promote SMA during acute disease; 2) Determine how changes in gene pathways in the Malarial Immunity Transcriptome mediate malarial severity throughout the development of naturally acquired immunity; and 3) Identify immunotherapeutic targets in the Malarial Immunity Transcriptome that can be used to reduce malaria disease severity and improve clinical outcomes in future trials. To successfully complete these aims, we are determining how host profiles impact on acute disease over 14 days. We will utilize Ex vivo samples from the cohort to test the effect of immunotherapeutic compounds on host expression profiles. Accomplishing these goals will have broad reaching translational implications for: (1) identifying at-risk groups, and (2) prioritizing compounds that can be used to improve clinical outcomes in future immunotherapy trials.
2024-04-16 | GSE255403 | GEO
Project description:Cardiac magnetic resonance myocardial perfusion imaging can detect coronary artery disease and is an alternative to single-photon emission computed tomography or positron emission tomography. However, the complex, non-linear MR signal and the lack of robust quantification of myocardial blood flow have hindered its widespread clinical application thus far. Recently, a new Bayesian approach was developed for brain imaging and evaluation of perfusion indexes (Kudo et al., 2014). In addition to providing accurate perfusion measurements, this probabilistic approach appears more robust than previous approaches, particularly due to its insensitivity to bolus arrival delays. We assessed the performance of this approach against a well-known and commonly deployed model-independent method based on the Fermi function for cardiac magnetic resonance myocardial perfusion imaging. The methods were first evaluated for accuracy and precision using a digital phantom to test them against the ground truth; next, they were applied in a group of coronary artery disease patients. The Bayesian method can be considered an appropriate model-independent method with which to estimate myocardial blood flow and delays. The digital phantom comprised a set of synthetic time-concentration curve combinations generated with a 2-compartment exchange model and a realistic combination of perfusion indexes, arterial input dynamics, noise and delays collected from the clinical dataset. The myocardial blood flow values estimated with the two methods showed an excellent correlation coefficient (r 2 > 0.9) under all noise and delay conditions. The Bayesian approach showed excellent robustness to bolus arrival delays, with a similar performance to Fermi modeling when delays were considered. Delays were better estimated with the Bayesian approach than with Fermi modeling. An in vivo analysis of coronary artery disease patients revealed that the Bayesian approach had an excellent ability to distinguish between abnormal and normal myocardium. The Bayesian approach was able to discriminate not only flows but also delays with increased sensitivity by offering a clearly enlarged range of distribution for the physiologic parameters.
| S-EPMC8072361 | biostudies-literature
Project description:Global changes in murine liver and kidney transcriptome were analyzed following different levels of malarial parasite infection.Known levels of parasites were injected in mice and transcriptomic changes were recorded with comparison to control non infected healthy mice.
2012-08-01 | GSE31686 | GEO
Project description:MARCH1 regulates anti-malarial immunity through interferon signaling and T cell activation
| PRJNA490750 | ENA
Project description:ATAC-seq of monocytes from patients before and after anti-malarial treatment
| PRJEB52334 | ENA
Project description:Increasing evidence suggests the liver as to be an effector against blood-stage malaria. Vaccination induces changes in the liver and survival of otherwise lethal blood-stage malaria of Plasmodium chabaudi which is associated with changes in the liver. Here, the time-course of expression of erythroid genes is investigated during infections with P. chabaudi in the liver of vaccination-protected and unprotected non-vaccinated mice.
2020-02-10 | GSE129133 | GEO
Project description:BackgroundThe critically important issue on emergence of drug-resistant malarial parasites is compounded by cross resistance, where resistance to one drug confers resistance to other chemically similar drugs or those that share mode of action. This aspect requires discovery of new anti-malarial compounds or formulation of new combination therapy. The current study attempts to contribute towards accelerating anti-malarial drug development efforts, by exploring the potential of existing FDA-approved drugs to target proteins of Plasmodium falciparum.MethodsUsing comparative sequence and structure analyses, FDA-approved drugs, originally developed against other pathogens, were identified as potential repurpose-able candidates against P. falciparum. The rationale behind the undertaken approach is the likeliness of small molecules to bind to homologous targets. Such a study of evolutionary relationships between established targets and P. falciparum proteins aided in identification of approved drug candidates that can be explored for their anti-malarial potential.ResultsSeventy-one FDA-approved drugs were identified that could be repurposed against P. falciparum. A total of 89 potential targets were recognized, of which about 70 are known to participate in parasite housekeeping machinery, protein biosynthesis, metabolic pathways and cell growth and differentiation, which can be prioritized for chemotherapeutic interventions. An additional aspect of prioritization of predicted repurpose-able drugs has been explored on the basis of ability of the drugs to permeate cell membranes, i.e., lipophilicity, since the parasite resides within a parasitophorous vacuole, within the erythrocyte, during the blood stages of infection. Based on this consideration, 46 of 71 FDA-approved drugs have been identified as feasible repurpose-able candidates against P. falciparum, and form a first-line for laboratory investigations. At least five of the drugs identified in the current analysis correspond to existing antibacterial agents already under use as repurposed anti-malarial agents.ConclusionsThe drug-target associations predicted, primarily by taking advantage of evolutionary information, provide a valuable resource of attractive and feasible candidate drugs that can be readily taken through further stages of anti-malarial drug development pipeline.
| S-EPMC5516367 | biostudies-literature