A blood RNA transcriptome signature for COVID-19.

BACKGROUND: COVID-19 is a respiratory viral infection with unique features including a more chronic course and systemic disease manifestations including multiple organ involvement; and there are differences in disease severity between ethnic groups. The immunological basis for disease has not been fully characterised. Analysis of whole-blood RNA expression may provide valuable information on disease pathogenesis. METHODS: We studied 45 patients with confirmed COVID-19 infection within 10 days from onset of illness and a control group of 19 asymptomatic healthy volunteers with no known exposure to COVID-19 in the previous 14 days. Relevant demographic and clinical information was collected and a blood sample was drawn from all participants for whole-blood RNA sequencing. We evaluated differentially-expressed genes in COVID-19 patients (log2 fold change ≥ 1 versus healthy controls; false-discovery rate < 0.05) and associated protein pathways and compared these to published whole-blood signatures for respiratory syncytial virus (RSV) and influenza. We developed a disease score reflecting the overall magnitude of expression of internally-validated genes and assessed the relationship between the disease score and clinical disease parameters. RESULTS: We found 135 differentially-expressed genes in the patients with COVID-19 (median age 35 years; 82% male; 36% Chinese, 53% South Asian ethnicity). Of the 117 induced genes, 14 were found in datasets from RSV and 40 from influenza; 95 genes were unique to COVID-19. Protein pathways were mostly generic responses to viral infections, including apoptosis by P53-associated pathway, but also included some unique pathways such as viral carcinogenesis. There were no major qualitative differences in pathways between ethnic groups. The composite gene-expression score was correlated with the time from onset of symptoms and nasal swab qPCR CT values (both p < 0.01) but was not related to participant age, gender, ethnicity or the presence or absence of chest X-ray abnormalities (all p > 0.05). CONCLUSIONS: The whole-blood transcriptome of COVID-19 has overall similarity with other respiratory infections but there are some unique pathways that merit further exploration to determine clinical relevance. The approach to a disease score may be of value, but needs further validation in a population with a greater range of disease severity.

Polyphenol-rich curry made with mixed spices and vegetables benefits glucose homeostasis in Chinese males (Polyspice Study): a dose-response randomized controlled crossover trial.

PURPOSE: To investigate acute effects of two doses of a polyphenol-rich curry made with seven different spices and four base vegetables, eaten with white rice, on 24 h glucose response, postprandial insulinemia, triglyceridemia and 24 h urinary total polyphenol excretion (TPE). METHODS: Randomized, controlled, dose-response crossover trial in healthy, Chinese men [n = 20, mean ± standard deviation (SD) age 23.7 ± 2.30 years, BMI 23.0 ± 2.31 kg/m2] who consumed test meals matched for calories, macronutrients and total vegetables content, consisting either Dose 0 Control (D0C) or Dose 1 Curry (D1C) or Dose 2 Curry (D2C) meal. 24 h glucose concentration was measured using continuous glucose monitoring (CGM), together with postprandial plasma insulin and triglyceride for up to 7 h. Total polyphenol content (TPC) of test meals and urinary TPE were measured using the Folin-Ciocalteu assay. RESULTS: TPC for D0C, D1C and D2C were 130 ± 18, 556 ± 19.7 and 1113 ± 211.6 mg gallic acid equivalent (GAE) per portion served, respectively (p < 0.0001). Compared with D0C meal, we found significant linear dose-response reductions in the 3-h postprandial incremental AUC (iAUC) for CGM glucose of 19% and 32% during D1C and D2C meals respectively (p < 0.05) and non-significant linear dose response reductions in iAUC of insulin (p = 0.089). Notably, we found significant dose-dependent increases in postprandial triglyceride with increasing curry doses (p < 0.01). Significant increases in TPE with increasing curry doses were also observed (p < 0.01). CONCLUSION: Polyphenol-rich curry intake can improve postprandial glucose homeostasis. The longer term effects remain to be established.

Dose-Dependent Increase in Unconjugated Cinnamic Acid Concentration in Plasma Following Acute Consumption of Polyphenol Rich Curry in the Polyspice Study.

Spices that are rich in polyphenols are metabolized to a convergent group of phenolic/aromatic acids. We conducted a dose-exposure nutrikinetic study to investigate associations between mixed spices intake and plasma concentrations of selected, unconjugated phenolic/aromatic acids. In a randomized crossover study, 17 Chinese males consumed a curry meal containing 0 g, 6 g, and 12 g of mixed spices. Postprandial blood was drawn up to 7 h at regular intervals and plasma phenolic/aromatic acids were quantified via liquid chromatography tandem mass spectrometry (LC-MS/MS). Cinnamic acid (CNA, p < 0.0001) and phenylacetic acid (PAA, p < 0.0005) concentrations were significantly increased with mixed spices consumption, although none of the other measured phenolic/aromatic acids differ significantly between treatments. CNA displayed a high dose-exposure association (R² > 0.8, p < 0.0001). The adjusted mean area under the plasma concentration-time curve until 7 h (AUC0⁻7 h) for CNA during the 3 increasing doses were 8.4 ± 3.4, 376.1 ± 104.7 and 875.7 ± 291.9 nM.h respectively. Plasma CNA concentration may be used as a biomarker of spice intake.

Effects of Two Doses of Curry Prepared with Mixed Spices on Postprandial Ghrelin and Subjective Appetite Responses-A Randomized Controlled Crossover Trial.

Spices are known to provide orosensory stimulation that can potentially influence palatability, appetite, and energy balance. Previous studies with individual spices have shown divergent effects on appetite and energy intake measures. In a real-life context, however, several spices are consumed in combinations, as in various forms of curries. Therefore, we investigated changes in postprandial appetite and plasma ghrelin in response to the intake of two doses of curry prepared with mixed spices. The study was undertaken in healthy Chinese men, between 21 and 40 years of age and body mass index ≤27.5 kg/m². Appetite was measured using visual analogue scales (VAS) and plasma ghrelin was measured using multiplex assay. Compared with the control meal (Dose 0 Control (D0C), 0 g mixed spices), we found significantly greater suppression in 'hunger' (both p < 0.05, after Bonferroni adjustments) as well in 'desire to eat' (both p < 0.01) during the Dose 1 Curry (D1C, 6 g mixed spices) and Dose 2 Curry (D2C, 12 g mixed spices) intake. There were no differences, however, in plasma ghrelin or in other appetite measures such as in 'fullness' or in 'prospective eating' scores. Overall, the results of our study indicate greater inter-meal satiety due to mixed spices consumption, independent of any changes in plasma ghrelin response.

Polyphenol-rich curry made with mixed spices and vegetables increases postprandial plasma GLP-1 concentration in a dose-dependent manner.

Glucagon-like peptide-1 (GLP-1) plays an important role in glucose homeostasis. Evidence is emerging that dietary bioactive phytochemicals such as polyphenols can increase GLP-1 concentration in vivo. Spices are rich in polyphenols and have oro-sensory properties, both of which can increase GLP-1 secretion. We therefore investigated the effects of mixed spices intake on postprandial GLP-1 concentration. Using a randomised, controlled, dose-response crossover trial in 20 young, healthy, Chinese men, volunteers were served white rice with 3 doses of curry made with mixed spices and vegetables. These test meals were isocaloric and macronutrient matched. Plasma total GLP-1 concentrations were measured before (baseline) and for up to 3 h after the consumption of test meals. We found a significant dose dependent increase in total AUC of plasma GLP-1 concentrations, adjusted for baseline, with increasing mixed spice doses [adjusted mean (±SEM) of 10568.3 ± 1267.9, 12391.8 ± 1333.94, and 13905.1 ± 1267.6 pg ml-1.min for Dose 0 Control, Dose 1 Curry and Dose 2 Curry respectively (p = 0.019)]. Consumption of polyphenol rich mixed spices and vegetables can therefore increase in vivo GLP-1 concentration.

Reductions in Postprandial Plasma Allantoin Concentrations With Increasing Doses of Polyphenol Rich Curry Intake - A Randomized Crossover Trial.

While dietary or supplementary antioxidants are thought to inhibit or delay oxidation of biological molecules, their utility in vivo has been marred by equivocal evidence. Consumption of polyphenol rich foods has been thought to alleviate postprandial oxidative stress and/or improve endothelial function. Although, previous studies suggested the utility of allantoin as a biomarker of oxidative stress, controlled dose response studies with dietary antioxidants to test this in humans have been limited. We therefore investigated the effects of 2 doses of polyphenol rich curry consumption on postprandial plasma concentrations of allantoin, allantoin to uric acid ratio, F2-isoprostanes using liquid chromatography-tandem mass spectrometry (LCMS-MS) and measured endothelial function using peripheral arterial tonometry (endoPAT). In a randomized controlled crossover trial in 17 non-smoking, healthy, Chinese men, aged 23.7 ± 2.4 years and BMI 23.1 ± 2.3 kg/m2, the volunteers consumed 3 test meals in a random order, consisting of either non-curry Dose 0 Control (D0C, 0 g spices), or Dose 1 Curry (D1C, 6 g spices) or Dose 2 Curry (D2C, 12 g spices), after overnight fast. There were significant reductions in postprandial allantoin concentrations (p < 0.001) and allantoin to uric acid ratio (p < 0.001) at 2 h and 3 h following test meal consumption, indicating improvements in postprandial redox balance with increasing curry doses, although there were no differences between treatments on F2-isoprostane concentrations or on RHI (measured at 2 h only). Allantoin may have a utility as a biomarker of redox balance, in an acute setting. The study was registered at www.clinicaltrials.gov (Identifier No. NCT02599272).

Fatty acid and vitamin interventions in adults with schizophrenia: a systematic review of the current evidence.

Current psychopharmacological approaches to reduce psychotic phenomenology in schizophrenia are associated with adverse effects including extrapyramidal and metabolic side effects. In view of the emerging data on nutritional supplementation interventions in schizophrenia which are not entirely consistent, we aimed to review existent studies focusing on fatty acid and vitamin interventions and summarise current evidence on such nutritional supplementations in schizophrenia. We searched the digital databases (ScienceDirect, Scopus, SpringerLINK, PubMed/Medline) for relevant studies pertaining to fatty acid and vitamin supplementation interventions in the management of psychotic symptoms in schizophrenia up to February 2015. Overall, there were more studies conducted on fatty acid over vitamin supplementations in patients with schizophrenia. There were more positive findings in support of fatty acid supplementation compared with vitamin supplementation in the context of specific intervention features (dose of nutrient supplementation, single versus combination nutritional interventions, specific antipsychotic), subject features (older age, long duration of illness, baseline polyunsaturated fatty acid levels) and clinical outcomes (improvements of psychotic symptoms and/or extrapyramidal side effects from antipsychotics). However, investigations of both supplementation modalities were limited by relatively small study sample sizes, short study duration, which precluded further segmentation of impact on more diverse patient subtypes and symptom profiles. Future studies may consider examining larger samples over a longer time period, recruiting younger subjects with shorter duration of illness, examination of different clinical features including specific cognitive domains, and use of single versus combination nutritional interventions.

Body Composition in Asians and Caucasians: Comparative Analyses and Influences on Cardiometabolic Outcomes.

Within the last four decades Asia has witnessed major transformation in its population demographics, which gave rise to changes in food availability, food habits and lifestyle. A significant consequence of these changes has been the continuing rise in overweight and obesity across Asia. In parallel, there has been a significant rise in Asians in the incidence of the major chronic diseases, particularly in cardiometabolic disorders such as metabolic syndrome, type 2 diabetes, hypertension, and other cardiovascular diseases. Given that the majority of the evidence, to date, investigating the associations between adiposity and cardiometabolic disorder risk have been obtained from studies undertaken either in European or in North American Caucasians, in this chapter, we have reviewed differences in body fat content and distribution between East Asians, South Asians, and Caucasians. The evidence is consistent that the content and distribution of body fat are markedly different between the various ethnic groups. We found that Asians have a greater predisposition towards adiposity at higher BMI than in Caucasians. Moreover, at any given level of adiposity, Asians have a much greater predisposition to risk of cardiometabolic disorders than Caucasians. We therefore strongly endorse the need for different adiposity cutoffs in Asians as compared to the Caucasians. We have also reviewed the predictive abilities of the various body composition/adiposity measures in determining risk of cardiometabolic disorders in Asians.