1 H Nuclear Magnetic Resonance Metabolomics of Plasma Unveils Liver Dysfunction in Dengue Patients (original) (raw)
Related papers
Acta Biochimica Polonica, 2017
Background: Dengue is one of the major public health problems in the world, affecting more than fifty million cases in tropical and subtropical region every year. The metabolome, as pathophysiological end-points, provide significant understanding of the mechanism and progression of dengue pathogenesis via changes in the metabolite profile of infected patients. Recent developments in diagnostic technologies provide metabolomics for the early detection of infectious diseases. Methods: The mid-stream urine was collected from 96 patients diagnosed with dengue fever at Penang General Hospital (PGH) and 50 healthy volunteers. Urine samples were analyzed with proton nuclear magnetic resonance (1H NMR) spectroscopy, followed by chemometric multivariate analysis. NMR signals highlighted in the orthogonal partial least square-discriminant analysis (OPLSDA) S-plots were selected and identified using Human Metabolome Database (HMDB) and Chenomx Profiler. A highly predictive model was constructe...
Serum Metabolomics Investigation of Humanized Mouse Model with Dengue Infection
Journal of virology, 2017
Dengue is an acute febrile illness caused by dengue virus (DENV) and a major cause of morbidity and mortality in tropical and subtropical regions of the world. The lack of an appropriate small-animal model of dengue infection has greatly hindered the study of dengue pathogenesis and the development of therapeutics. In this study, we conducted a mass spectrometry-based serum metabolic profiling from a humanized mice (humice) model with DENV serotype 2 infection at 0, 3, 7, 14 and 28 days post infection (dpi). Forty-eight differential metabolites were identified, including fatty acids, purines and pyrimidines, acylcarnitines, acylglycines, phospholipids, sphingolipids, amino acid and derivatives, free fatty acids, bile acid, etc. These metabolites showed a reversible change trend - most were significantly perturbed at 3 or 7 dpi and returned to control levels at 14 or 28 dpi, indicating that these metabolites might serve as prognostic markers of the disease in humice. Major perturbed ...
Metabolomics for characterization of gender differences in patients infected with dengue virus
Asian Pacific Journal of Tropical Medicine, 2015
To determine the metabolic response associate with dengue infection based on human gender metabolic differences by means of 1 H NMR-spectrometry. Methods: The mid-stream urine collected from both male and female patients diagnosed with dengue fever at Penang General Hospital and fourty-three healthy individuals were analyzed with 1 H NMR spectroscopy, followed by chemometric multivariate analysis. NMR signals which highlighted in the OPLS-DA S-plot were further selected and identified using Human Metabolome Database, Chenomx Profiler. Results: The results pointed out that NMR urine profiling was able to capture human gender metabolic differences that are important for the distinction of classes of individuals of similar physiological conditions; infected with dengue. Distinct differences between dengue infected patients versus healthy individuals and subtle differences in male versus female infected with dengue were found to be related to the metabolism of amino acid and tricarboxylic acid intermediates cycle. Conclusions: The 1 H NMR metabolomic investigation combined with appropriate algorithms and pattern recognition procedures, gave an evidence for the existence of distinct metabolic differentiation of individuals, according to their gender, modulates with the infection risk.
Jurnal Teknologi, 2015
Dengue is the most important human viral disease transmitted by arthropod vectors and over half of the world's populations live in areas at risk of infection. The severity of the infection depends on the form of the disease, which can be symptomatic or asymptomatic. Currently there is neither specific treatment nor vaccine to tackle this emerging disease. Metabolomics applied in this study, aimed to provide a global snapshot of all small-molecule metabolites in urine as biological sample of choice to more focused studies of metabolism to distinguish between healthy and dengue infected subjects. Fifty-two patients diagnosed with dengue fever at Penang General Hospital and fourty-three healthy individuals were recruited in this study. 1 H-nuclear magnetic resonance (NMR) spectroscopy combined with multivariate analysis (MVA) methods such as principal component analysis (PCA), partial least square discriminant analysis (PLS-DA) and orthogonal PLS-DA (OPLS-DA) were employed for statistical data exploration. The model score plot results showed that all three MVAs showed very good spatial distributions with clear clusters/grouping between healthy individuals and dengue infected individuals. Also, statistically, the PLS-DA and OPLS-DA models had high reproducibility and predictivity values, > 0.5. In conclusion, this study established the potential of using a combination of 1 H NMR spectroscopy and multivariate data analyses in differentiating healthy and non-healthy individuals, based on obtained score plots reflecting the metabolites pertubation, where spectral features contributing most to variation or separation are identified for further analysis.
Comparison of Significance of Lipid Profile with Liver Function Tests in Dengue Fever
Journal of Evolution of Medical and Dental Sciences, 2019
BACKGROUND Dengue is the most prevalent mosquito borne viral infection with rapidly changing epidemiology over the last few years. Lipoproteins play a pathophysiological role in the hosts immune response to severe infection. The need to know the lipoprotein status in dengue fever, find its correlation with severity, liver function tests, and clinical outcome are the objectives of this study. METHODS This prospective observational study was taken up involving 50 adults diagnosed with dengue fever between December 2013 to December 2014 in Mysore Medical College. Patients were classified based on severity of dengue fever (DF), dengue haemorrhagic fever (DHF), dengue shock syndrome (DSS). Fasting lipid profile, liver function test (LFT), complete blood count were estimated on day 1 and day 5 of admission. RESULTS The study population comprised of 50 dengue sero positive cases. The total cholesterol was greatly reduced and LFT alterations were seen highest in DSS group. During admission, serum cholesterol and liver enzymes showed statistically significant difference in their mean concentrations in the three groups of dengue infection. The spearman correlation analysis shows that AST and total cholesterol had negative correlation (r=-0.782; p <0.01), whereas ALT and cholesterol also showed similar correlation (r=-0.738; p< 0.01). CONCLUSIONS Total cholesterol, HDL and LDL of dengue fever cases were significantly reduced at admission in comparison to the second estimation on day 5. Mean cholesterol, triglyceride and LDL levels showed statistically significant (p value <0.05) changes with severity of dengue. LFT was correlated with the severity of dengue fever. These abnormal values may serve as indicators for recognizing patients at increased risk for DHF and DSS, thus serving as prognostic markers of the dengue infected individuals.
IOSR Journals , 2019
Introduction: Dengue is an acute viral infection hyper-endemic in tropics where significant population isat risk. The World Health Organization (WHO) estimated that 50 million dengue infections occur annually, making it as the most rapidly spreading arbo viral infection Materials and Methods: This prospective observational study was taken up involving 40 adults diagnosed with dengue fever and admitted to Maheswara Medical College between December 2017 to December 2018. Patients were classified according to WHO criteria based on the severity of presentation and were grouped as: Group 1 Dengue fever (DF), Group 2 Dengue Haemorrhagic Fever (DHF), Group 3 Dengue Shock Syndrome (DSS). All patients were included into the study after obtaining written informed patient consent Ethical clearance was obtained from the Institutional Ethics Committee. Sample size has been taken based on the convenience of the study Results: The study population comprised of 40 Dengue seropositive cases amongst whom 21 were females and 19 males. The average age of the cases was 55 ± 15 years. The study subjects were divided into 3 groups: Group I 14 cases of dengue fever, Group II 17 cases of dengue haemorrhagic fever, Group III 9 cases of dengue shock syndrome. The cholesterol reduced with increasing severity of infection and on subsequent estimation, the serum total cholesterol levels showed improvement signifying recovery of the patient. The liver functions especially the liver enzymes were altered during admission and improved on day 5. This was statistically significant change in all 3 groups. The total protein and albumin showed statistically significant changes in dengue fever and dengue haemorrhagic fever as compared to dengue shock syndrome. This signifies that extent of damage is more in group three and thus the recovery is slow. Conclusion: Lipid profile changes accompany dengue infection, some of which may indicate severity and guide therapy. Consecutive estimation of the same parameters on day five of hospitalization showed statistically significant differences in total cholesterol levels across the three groups. The lipid profile of subjects showcased the tendency to approach normal levels during recovery phase. This reversible trend suggests dengue fever as a potential cause for lipid alteration. These abnormal values may serve as indicators for recognition of patients at increased risk for DHF and DSS, thus serving as prognostic markers of the dengue infected individuals.
Scientific Reports, 2016
Chikungunya and dengue are arboviral infections with overlapping clinical symptoms. A subset of chikungunya infection occurs also as co-infections with dengue, resulting in complications during diagnosis and patient management. The present study was undertaken to identify the global metabolome of patient sera infected with chikungunya as mono infections and with dengue as coinfections. Using nuclear magnetic resonance (NMR) spectroscopy, the metabolome of sera of three disease conditions, namely, chikungunya and dengue as mono-infections and when co-infected were ascertained and compared with healthy individuals. Further, the cohorts were analyzed on the basis of age, onset of fever and joint involvement. Here we show that many metabolites in the serum are significantly differentially regulated during chikungunya mono-infection as well as during chikungunya co-infection with dengue. We observed that glycine, serine, threonine, galactose and pyrimidine metabolisms are the most perturbed pathways in both mono and co-infection conditions. The affected pathways in our study correlate well with the clinical manifestation like fever, inflammation, energy deprivation and joint pain during the infections. These results may serve as a starting point for validations and identification of distinct biomolecules that could be exploited as biomarker candidates thereby helping in better patient management. Dengue (DEN) and chikungunya (CHIK) are among the most important vector borne diseases, together affecting about 40 million people globally 1-3. Dengue is an acute systemic viral disease that has established itself globally in both endemic and epidemic transmission cycles 4. With more than one-third of the world population living in areas at risk of this infection, dengue virus is a leading cause of illness and death in the tropics and subtropics 5. Global distribution map of dengue has estimated and predicted India to be the worst affected 6. In India dengue contributes about 34% of the total global infections making it a transmission hub 7. Known to occur as either single infections or as co-infections with dengue 8,9 , Chikungunya virus (CHIKV) poses a serious threat to public health 10 with spread to many parts of the globe 11. In the Indian sub-continent, while as many as 1.2 million individuals were affected by CHIK in 2006 12 , recent trends have shown it be declining though numbers are still large 13. One of the main challenges that clinicians face during diagnosis of CHIK and DEN are overlapping symptoms of these two infections resulting in gross misdiagnosis and patient mismanagement 14. Recent studies have shown that almost ten percent of suspected dengue cases are in fact co-infected with chikungunya virus making it imperative to distinguish the difference between the two infections for better patient management 15. Additionally, misdiagnosis also obstructs the true incidence of chikungunya within a region thereby providing incorrect information of epidemiology of the disease and evolution of the virus. There are infection associated independent
Metabolomics as a powerful tool for diagnostic, pronostic and drug intervention analysis in COVID-19
Frontiers in Molecular Biosciences
COVID-19 currently represents one of the major health challenges worldwide. Albeit its infectious character, with onset affectation mainly at the respiratory track, it is clear that the pathophysiology of COVID-19 has a systemic character, ultimately affecting many organs. This feature enables the possibility of investigating SARS-CoV-2 infection using multi-omic techniques, including metabolomic studies by chromatography coupled to mass spectrometry or by nuclear magnetic resonance (NMR) spectroscopy. Here we review the extensive literature on metabolomics in COVID-19, that unraveled many aspects of the disease including: a characteristic metabotipic signature associated to COVID-19, discrimination of patients according to severity, effect of drugs and vaccination treatments and the characterization of the natural history of the metabolic evolution associated to the disease, from the infection onset to full recovery or long-term and long sequelae of COVID.
The role of lipids in the inception, maintenance and complications of dengue virus infection
Scientific reports, 2018
Dengue fever is a viral condition that has become a recurrent issue for public health in tropical countries, common endemic areas. Although viral structure and composition have been widely studied, the infection phenotype in terms of small molecules remains poorly established. This contribution providing a comprehensive overview of the metabolic implications of the virus-host interaction using a lipidomic-based approach through direct-infusion high-resolution mass spectrometry. Our results provide further evidence that lipids are part of both the immune response upon Dengue virus infection and viral infection maintenance mechanism in the organism. Furthermore, the species described herein provide evidence that such lipids may be part of the mechanism that leads to blood-related complications such as hemorrhagic fever, the severe form of the disease.
Profiling metabolites and lipoproteins in COMETA, an Italian cohort of COVID-19 patients
PLOS Pathogens
Metabolomics and lipidomics have been used in several studies to define the biochemical alterations induced by COVID-19 in comparison with healthy controls. Those studies highlighted the presence of a strong signature, attributable to both metabolites and lipoproteins/lipids. Here, 1H NMR spectra were acquired on EDTA-plasma from three groups of subjects: i) hospitalized COVID-19 positive patients (≤21 days from the first positive nasopharyngeal swab); ii) hospitalized COVID-19 positive patients (>21 days from the first positive nasopharyngeal swab); iii) subjects after 2–6 months from SARS-CoV-2 eradication. A Random Forest model built using the EDTA-plasma spectra of COVID-19 patients ≤21 days and Post COVID-19 subjects, provided a high discrimination accuracy (93.6%), indicating both the presence of a strong fingerprint of the acute infection and the substantial metabolic healing of Post COVID-19 subjects. The differences originate from significant alterations in the concentra...