This study combined high resolution mass spectrometry (HRMS), advanced chemometrics and pathway enrichment analysis to analyse the blood metabolome of patients attending the memory clinic: cases of ...mild cognitive impairment (MCI; n = 16), cases of MCI who upon subsequent follow-up developed Alzheimer's disease (MCI_AD; n = 19), and healthy age-matched controls (Ctrl; n = 37). Plasma was extracted in acetonitrile and applied to an Acquity UPLC HILIC (1.7μm x 2.1 x 100 mm) column coupled to a Xevo G2 QTof mass spectrometer using a previously optimised method. Data comprising 6751 spectral features were used to build an OPLS-DA statistical model capable of accurately distinguishing Ctrl, MCI and MCI_AD. The model accurately distinguished (R2 = 99.1%; Q2 = 97%) those MCI patients who later went on to develop AD. S-plots were used to shortlist ions of interest which were responsible for explaining the maximum amount of variation between patient groups. Metabolite database searching and pathway enrichment analysis indicated disturbances in 22 biochemical pathways, and excitingly it discovered two interlinked areas of metabolism (polyamine metabolism and L-Arginine metabolism) were differentially disrupted in this well-defined clinical cohort. The optimised untargeted HRMS methods described herein not only demonstrate that it is possible to distinguish these pathologies in human blood but also that MCI patients 'at risk' from AD could be predicted up to 2 years earlier than conventional clinical diagnosis. Blood-based metabolite profiling of plasma from memory clinic patients is a novel and feasible approach in improving MCI and AD diagnosis and, refining clinical trials through better patient stratification.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Previous studies have demonstrated that SARS-CoV-2 is stable on surfaces for extended periods under indoor conditions. In the present study, simulated sunlight rapidly inactivated SARS-CoV-2 ...suspended in either simulated saliva or culture media and dried on stainless steel coupons. Ninety percent of infectious virus was inactivated every 6.8 minutes in simulated saliva and every 14.3 minutes in culture media when exposed to simulated sunlight representative of the summer solstice at 40°N latitude at sea level on a clear day. Significant inactivation also occurred, albeit at a slower rate, under lower simulated sunlight levels. The present study provides the first evidence that sunlight may rapidly inactivate SARS-CoV-2 on surfaces, suggesting that persistence, and subsequently exposure risk, may vary significantly between indoor and outdoor environments. Additionally, these data indicate that natural sunlight may be effective as a disinfectant for contaminated nonporous materials.
This study provides the first evidence that sunlight may rapidly inactivate SARS-CoV-2 on surfaces, suggesting that persistence, and subsequently exposure risk, may vary significantly between indoor and outdoor environments.
Abstract
Aerosols represent a potential transmission route of COVID-19. This study examined effect of simulated sunlight, relative humidity, and suspension matrix on stability of SARS-CoV-2 in ...aerosols. Simulated sunlight and matrix significantly affected decay rate of the virus. Relative humidity alone did not affect the decay rate; however, minor interactions between relative humidity and other factors were observed. Mean decay rates (± SD) in simulated saliva, under simulated sunlight levels representative of late winter/early fall and summer were 0.121 ± 0.017 min−1 (90% loss, 19 minutes) and 0.306 ± 0.097 min−1 (90% loss, 8 minutes), respectively. Mean decay rate without simulated sunlight across all relative humidity levels was 0.008 ± 0.011 min−1 (90% loss, 286 minutes). These results suggest that the potential for aerosol transmission of SARS-CoV-2 may be dependent on environmental conditions, particularly sunlight. These data may be useful to inform mitigation strategies to minimize the potential for aerosol transmission.
This study demonstrates that simulated sunlight rapidly inactivates SARS-CoV-2 in small-particle aerosols, suggesting that exposure risk may vary significantly across different environmental conditions.
The World Cancer Research Fund (WCRF) 2007 stated that the consumption of processed meat is a convincing cause of colorectal cancer (CRC), and therefore, the public should avoid it entirely. Sodium ...nitrite has emerged as a putative candidate responsible for the CRC-inducing effects of processed meats. Sodium nitrite is purported to prevent the growth of
and other food-spoiling bacteria, but recent, contradictory peer-reviewed evidence has emerged, leading to media reports questioning the necessity of nitrite addition. To date, eleven preclinical studies have investigated the effect of consuming nitrite/nitrite-containing meat on the development of CRC, but the results do not provide an overall consensus. A sizable number of human clinical studies have investigated the relationship between processed meat consumption and CRC risk with widely varying results. The unique approach of the present literature review was to include analysis that limited the human studies to those involving only nitrite-containing meat. The majority of these studies reported that nitrite-containing processed meat was associated with increased CRC risk. Nitrite consumption can lead to the formation of N-nitroso compounds (NOC), some of which are carcinogenic. Therefore, this focused perspective based on the current body of evidence links the consumption of meat containing nitrites and CRC risk.
•Neuron-specific knock-in of human BACE1 age-dependently affects the brain metabolome.•More brain metabolites were significantly altered in ‘old’ PLB4 mice than ‘young’.•Leucine, creatinine, ...putrescine, various acylcarnitines and phospholipids were affected.•Compared with other AD models (e.g., APP/PS1) fewer metabolites were affected.•Oligomer versus plaque Aβ pathology may have divergent effects on some metabolites.
Beta secretase 1 (BACE1) is an enzyme involved in the pathogenesis of Alzheimer’s disease (AD). PLB4 mice are a neuron-specific human BACE1 knock-in mouse model characterized by the accumulation of extracellular Aβ and an AD-like phenotype. In this investigation brain hemispheres from ‘young’ (4–6 months) and ‘old’ (8 months) female PLB4 mice and age-matched wild-type littermates underwent targeted LC-MS/MS metabolomic profiling. Powdered lyophilized brain tissue was extracted in ethanol:PBS 85%:15% (v/v)) and a total of 187 metabolites were quantified using a targeted metabolomics methodology. Multivariate statistical analysis produced models distinguished PLB4 from wild type (WT) mice regardless of their age group. Univariate analysis (t-test) found that more brain metabolites were perturbed in ‘old’ PLB4 mice than ‘young’. Carnosine and 8 phosphatidylcholine species were significantly decreased (p < 0.05) in ‘young’ PLB4 mouse brain. In ‘old’ PLB4 mice a total of 21 metabolites were perturbed including: leucine, creatinine, putrescine and species of acylcarnitines, lysophosphatidylcholines, phosphatidylcholines and sphingomyelin. Within the PLB4 genotype there were a range of age-dependent increases in metabolites. This study indicates that gender-specific responses occur in models of AD-like pathology, but importantly, when changes in PLB4 mice (where Aβ oligomers predominate) are compared with APP/PS1 mice (where Aβ plaques predominate) there are consistent and also divergent effects on the brain metabolome.
Rice is a globally important staple consumed by billions of people, and recently there has been considerable interest in promoting the consumption of wholegrain brown rice (WBR) due to its obvious ...advantages over polished rice in metabolically protective activities. This work highlights the effects of innovative processing technologies on the quality and functional properties of WBR in comparison with traditional approaches; and it is aimed at establishing a quantitative and/or qualitative link between physicochemical changes and high-efficient processing methods. Compared with thermal treatments, applications of innovative nonthermal techniques, such as high hydrostatic pressure (HHP), pulsed electric fields (PEF), ultrasound and cold plasma, are not limited to modifying physicochemical properties of WBR grains, since improvements in nutritional and functional components as well as a reduction in anti-nutritional factors can also be achieved through inducing related biochemical transformation. Much information about processing methods and parameters which influence WBR quality changes has been obtained, but simultaneously achieving the product stabilization and functionality of processed WBR grains requires a comprehensive evaluation of all the quality changes induced by different processing procedures as well as quantitative insights into the relationship between the changes and processing variables.
•Casein proteins are not detrimental to enteroendocrine cells.•Beta casein significantly stimulated enteroendocrine cell proliferation.•Most caseins were potent glucagon-like peptide-1 ...secretagogues.•Glucagon-like peptide-1 secretory activity of caseins was mostly reduced when hydrolysed with enzymes.•Moderate pepsin hydrolysis of beta casein increases potency of the protein.
Previous studies suggest that casein exerts various anti-diabetic effects. However, it is not known which casein proteins are bioactive, nor their effects on enteroendocrine cells. This study evaluated the effects of intact whole casein, intact individual proteins (alpha, beta and kappa casein) and hydrolysates on an enteroendocrine cell line. High content analysis accurately monitored changes in cell health and intracellular glucagon-like peptide-1 (GLP-1) content. Cheese ripening duration and GLP-1 secretory responses were also considered. Beta casein significantly stimulated enteroendocrine cell proliferation and all caseins were potent GLP-1 secretagogues (except kappa casein). Interestingly the GLP-1 secretory activity was almost always lost or significantly reduced upon hydrolysis with proteolytic enzymes. Only pepsin-derived beta casein hydrolysates had significantly increased potency compared with the intact protein, but this was diminished with prolonged hydrolysis. In conclusion casein proteins are not detrimental to enteroendocrine cells, and alpha and beta casein are particularly beneficial stimulating proliferation and GLP-1 secretion.
•Report of a Phase I clinical trial to assess a malaria transmission blocking vaccine.•P. falciparum Pfs25 virus-like particle produced under cGMP in a plant-based system.•The vaccine candidate ...displays an acceptable safety and tolerability profile.•The vaccine candidate induced Pfs25-specific IgG in a dose dependent manner.•However, low transmission reducing activity implies need for an improved formulation.
Malaria continues to be one of the world’s most devastating infectious tropical diseases, and alternative strategies to prevent infection and disease spread are urgently needed. These strategies include the development of effective vaccines, such as malaria transmission blocking vaccines (TBV) directed against proteins found on the sexual stages of Plasmodium falciparum parasites present in the mosquito midgut. The Pfs25 protein, which is expressed on the surface of gametes, zygotes and ookinetes, has been a primary target for TBV development. One such vaccine strategy based on Pfs25 is a plant-produced malaria vaccine candidate engineered as a chimeric non-enveloped virus-like particle (VLP) comprising Pfs25 fused to the Alfalfa mosaic virus coat protein. This Pfs25 VLP-FhCMB vaccine candidate has been engineered and manufactured in Nicotiana benthamiana plants at pilot plant scale under current Good Manufacturing Practice guidelines. The safety, reactogenicity and immunogenicity of Pfs25 VLP-FhCMB was assessed in healthy adult volunteers. This Phase 1, dose escalation, first-in-human study was designed primarily to evaluate the safety of the purified plant-derived Pfs25 VLP combined with Alhydrogel® adjuvant. At the doses tested in this Phase 1 study, the vaccine was generally shown to be safe in healthy volunteers, with no incidence of vaccine-related serious adverse events and no evidence of any dose-limiting or dose-related toxicity, demonstrating that the plant-derived Pfs25 VLP-FhCMB vaccine had an acceptable safety and tolerability profile. In addition, although the vaccine did induce Pfs25-specific IgG in vaccinated patients in a dose dependent manner, the transmission reducing activity of the antibodies generated were weak, suggesting the need for an alternative vaccine adjuvant formulation.
This study was registered at www.ClinicalTrials.gov under reference identifier NCT02013687.
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