Screening and identification of potential novel biomarker for diagnosis of complicated Plasmodium vivax malaria

Kaur, Harpreet; Sehgal, Rakesh; Kumar, Archit; Sehgal, Alka; Bansal, Devendra; Sultan, Ali A.

doi:10.1186/s12967-018-1646-9

Cited by 29 publications

(27 citation statements)

References 61 publications

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“…Still, some issues remain, including the lack of a standardized protocol regarding specimen collection, handling, and analysis. Plasmodium vivax miR-451, miR-16 ↓ Chamnanchanunt and colleagues [248] miR-7977 ↑ Kaur and colleagues [249]…”

Section: Mirnas In Sepsismentioning

confidence: 99%

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Condrat

Thompson

Barbu

et al. 2020

Cells

919

583

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MicroRNAs (miRNAs) represent a class of small, non-coding RNAs with the main roles of regulating mRNA through its degradation and adjusting protein levels. In recent years, extraordinary progress has been made in terms of identifying the origin and exact functions of miRNA, focusing on their potential use in both the research and the clinical field. This review aims at improving the current understanding of these molecules and their applicability in the medical field. A thorough analysis of the literature consulting resources available in online databases such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate was performed. There is promising evidence that in spite of the lack of standardized protocols regarding the use of miRNAs in current clinical practice, they constitute a reliable tool for future use. These molecules meet most of the required criteria for being an ideal biomarker, such as accessibility, high specificity, and sensitivity. Despite present limitations, miRNAs as biomarkers for various conditions remain an impressive research field. As current techniques evolve, we anticipate that miRNAs will become a routine approach in the development of personalized patient profiles, thus permitting more specific therapeutic interventions.Biogenesis of miRNA begins in the nucleus, where the transcription of its precursor, primary miRNA or pri-miRNA takes place under the influence of RNA polymerases II and III [11,12]. The resulting molecule is a hairpin-like structure, which contains a loop at one end [11]. This primordial mi-RNA precursor that is usually made up of hundreds of nucleotides is then processed consecutively by two RNase III enzymes [13][14][15]. The first enzyme to act upon the pri-miRNA, which still resides in the nucleus, is called Drosha or DCGR8, and turns it into a new hairpin-like structure of approximately 70 nucleotides, the Precursor-miRNA or pre-miRNA. The latter is then transported to the cytoplasm, with the help of Exportin-5, where it is cleaved again by the Ago2/Dicer complex leading to the short, mature miRNA double strands [16].Further on, one of the strands, usually known as the guide strand, will be integrated into the RNA-induced silencing complex (RISC), while the other one, known as the passenger strand, is going to be degraded, even though in some occasions it has been found to be also functional [17]. In most cases, the strand that contains the less stable 5 end or a uracil at the beginning is more likely to be selected as the guide strand [18][19][20]. In those situations, where the passenger strand is not degraded and both get incorporated into the miRISC complex, the mature miRNA in the guide strand will be the dominant one [21,22].The main role of miRNA in the human body is gene regulation [23] by mediating the degradation of mRNA and also by regulating transcription and translation through canonical and non-canonical mechanisms [4]. The canonical mechanism means that the miRISC complex containing the miRNA guide strand is exerting its action by binding to the targ...

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Section: Mirnas In Sepsismentioning

confidence: 99%

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Condrat

Thompson

Barbu

et al. 2020

Cells

919

583

View full text Add to dashboard Cite

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“…The hsa-miR-15b-5p and hsa-miR-150-5p were up-regulated in the plasma-derived EVs from P. vivaxinfected patients but not in the P. falciparum-infected patients. An analysis of miRNAs from whole blood of adult imported falciparum malaria showed a down regulation of hsa-miR-150-5p [48]. Kaur et al have identi ed a potential biomarker for differential diagnosis between uncomplicated and complicated P. vivax malaria infection, hsa-miR-7977.…”

Section: Discussionmentioning

confidence: 99%

“…Kaur et al have identi ed a potential biomarker for differential diagnosis between uncomplicated and complicated P. vivax malaria infection, hsa-miR-7977. In addition, an increase in this miRNA was predicted to be involved in malaria pathogenesis through the transforming growth factor beta (TGF-β) signaling pathway [48].…”

Section: Discussionmentioning

confidence: 99%

“…By studying the EV compartment as a whole the chances of nding differences in miRNA expression between the groups would be increased. Five miRNA were selected based on previous in vitro, animal model, or clinical studies that suggested these miRNAs had a potential involvement in malaria, namely: hsa-miR-451a, hsa-miR-150-5p, hsa-miR-15b-5p, hsa-let-7a, and hsa-miR-16-5p [37][38][39][41][42][43][44]48]. This study provides novel insight about circulating EVs-derived miRNAs in human malaria.…”

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confidence: 99%

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The characterization of extracellular vesicles-derived microRNAs in Thai malaria patients

Ketprasit

Cheng

Deutsch

et al. 2020

Preprint

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Background Extracellular vesicles (EVs) have been broadly studied in malaria for nearly a decade. These vesicles carry various functional biomolecules including RNA families such as microRNAs (miRNA). These EVs-derived microRNAs have numerous roles in host-parasite interactions and are considered promising biomarkers for disease severity. However, this field lacks clinical studies of malaria-infected samples. In this study, EV specific miRNAs were isolated from the plasma of patients from Thailand infected with Plasmodium vivax and Plasmodium falciparum. In addition, it is postulated that these miRNAs were differentially expressed in these groups of patients and had a role in disease onset through the regulation of specific target genes.Methods EVs were purified from the plasma of Thai P. vivax-infected patients (n=19), P. falciparum-infected patients (n=18) and uninfected individuals (n=20). EV-derived miRNAs were then prepared and abundance of hsa-miR-15b-5p, hsa-miR-16-5p, hsa-let-7a-5p and hsa-miR-150-5p was assessed in these samples. Quantitative polymerase chain reaction was performed, and relative expression of each miRNA was calculated using hsa-miR-451a as endogenous control. Then, the targets of up-regulated miRNAs and relevant pathways were predicted by using bioinformatics. Receiver Operating Characteristic with Area Under the Curve (AUC) was then calculated to assess their diagnostic potential.Results The relative expression of hsa-miR-150-5p and hsa-miR-15b-5p was higher in P. vivax-infected patients compared to uninfected individuals, but hsa-let-7a-5p was up-regulated in both P. vivax-infected patients and P. falciparum-infected patients. Bioinformatic analysis revealed that these miRNAs might regulate genes involved in the malaria pathway including the adherens junction and the transforming growth factor-β pathways. All up-regulated miRNAs could potentially be used as disease biomarkers as determined by AUC; however, the sensitivity and specificity require further investigation.Conclusion An upregulation of hsa-miR-150-5p and hsa-miR-15b-5p was observed in P. vivax-infected patients while hsa-let-7a-5p was up-regulated in both P. vivax-infected and P. falciparum-infected patients. These findings will require further validation in larger cohort groups of malaria patients to fully understand the contribution of these EVs miRNAs to malaria detection and biology.

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“…To account for these characteristics, the successful entrepreneurship requires several experimental stages, from basic research towards final clinical validations. Initial steps for biomarker selection can be pursued using bioinformatic strategies, with large databases of the -omics providing valid alternatives [45,46]. Genome-wide translation dynamics studies as revealed by RP, and in contrast to transcriptomic approaches, offer a precise approximation for the P. falciparum proteome [8].…”

Section: Discussionmentioning

confidence: 99%

DNA aptamers for the recognition of HMGB1 from Plasmodium falciparum

Joseph

Nakamoto

Ruiz

et al. 2019

Preprint

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21 Rapid Diagnostic Tests (RDTs) for malaria are restricted to a few biomarkers and antibody-22 mediated detection. However, the expression of commonly used biomarkers varies 23 geographically and the sensibility of immunodetection can be affected by batch-to-batch 24 differences or limited thermal stability. In this study we aimed to overcome these limitations 25 by identifying a potential biomarker and by developing molecular sensors based on aptamer 26 technology. Using gene expression databases, ribosome profiling analysis, and structural 27 modeling, we find that the High Mobility Group Box 1 protein (HMGB1) of Plasmodium 28 falciparum is highly expressed, structurally stable and steadily present along all blood-stages 29 of P. falciparum infection. To develop biosensors, we used in vitro evolution techniques to 30 produce DNA aptamers for the recombinantly expressed HMG-box, the conserved domain 31 of HMGB1. An evolutionary approach for evaluating the dynamics of aptamer populations 32 suggested three predominant aptamer motifs. Representatives of the aptamer families were 33 tested for binding parameters to the HMG-box domain using microscale thermophoresis and 34 rapid kinetics. Dissociation constants of the aptamers varied over two orders of magnitude 35 between nano-and micromolar ranges while the aptamer-HMG-box interaction occurred in 36 less than 30 seconds. The specificity of aptamer binding to the HMG-box of P. falciparum 37 compared to its human homolog depended on pH conditions. Altogether, our study proposes 38 HMGB1 as a potential biomarker and a set of sensing aptamers that can be further developed 39 into rapid diagnostic tests for P. falciparum detection. 40 41 42 3 43 44 45 46 47 Malaria is an infectious disease that affects animals and humans, caused by protozoans of the 48 genus Plasmodium. Malaria remains the cause of 435,000 deaths worldwide, with 219 49 million cases reported during 2017 [1]. Accurate treatment requires the identification of the 50 parasite of the genus Plasmodium, in addition to the species causing the disease. Currently, 51 there are several methods to diagnose malaria, such as PCR-based, Giemsa microscopy, and 52 Rapid Diagnostic Tests (RDTs). Among these options, the last two appear to be suitable for 53 low-income and mostly affected countries; nonetheless, they also present certain limitations 54 [2]. 55 Giemsa microscopy is inexpensive to perform, can differentiate malaria species and stages, 56 and can quantify the parasites [2]. However, well-trained personnel is required and, 57 frequently unavailable in low-income countries [2]. RDTs, on the other hand, 58 detect Plasmodium spp. biomarker antigens in a small amount of blood using immobilized 59 antibodies. The two most used biomarkers are histidine-rich protein 2 (HRP-2) and lactate 60 dehydrogenase (LDH), which have been shown of high sensitivity and specificity for 61 detecting P. falciparum [3]. However, P. falciparum strains lacking the HRP-2 and HRP-3 62 genes have appeared, increasing false negative re...

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Screening and identification of potential novel biomarker for diagnosis of complicated Plasmodium vivax malaria

Cited by 29 publications

References 61 publications

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

The characterization of extracellular vesicles-derived microRNAs in Thai malaria patients

DNA aptamers for the recognition of HMGB1 from Plasmodium falciparum

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