Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Biological and Chemical Characterization of <em>Musa paradisiaca</em> Leachate

Fri, 27/10/2023 - 12:00
Biology (Basel). 2023 Oct 11;12(10):1326. doi: 10.3390/biology12101326.ABSTRACTThere is a growing demand for molecules of natural origin for biocontrol and biostimulation, given the current trend away from synthetic chemical products. Leachates extracted from plantain stems were obtained after biodegradation of the plant material. To characterize the leachate, quantitative determinations of nitrogen, carbon, phosphorus, and cations (K+, Ca2+, Mg2+, Na+), Q2/4, Q2/6, and Q4/6 absorbance ratios, and metabolomic analysis were carried out. The potential role of plantain leachates as fungicide, elicitor of plant defense, and/or plant biostimulant was evaluated by agar well diffusion method, phenotypic, molecular, and imaging approaches. The plant extracts induced a slight inhibition of fungal growth of an aggressive strain of Colletotrichum gloeosporioides, which causes anthracnose. Organic compounds such as cinnamic, ellagic, quinic, and fulvic acids and indole alkaloid such as ellipticine, along with some minerals such as potassium, calcium, and phosphorus, may be responsible for the inhibition of fungal growth. In addition, jasmonic, benzoic, and salicylic acids, which are known to play a role in plant defense and as biostimulants in tomato, were detected in leachate extract. Indeed, foliar application of banana leachate induced overexpression of LOXD, PPOD, and Worky70-80 genes, which are involved in phenylpropanoid metabolism, jasmonic acid biosynthesis, and salicylic acid metabolism, respectively. Leachate also activated root growth in tomato seedlings. However, the main impact of the leachate was observed on mature plants, where it caused a reduction in leaf area and fresh weight, the remodeling of stem cell wall glycopolymers, and an increase in the expression of proline dehydrogenase.PMID:37887036 | DOI:10.3390/biology12101326

An Integrated Multi-Omics and Artificial Intelligence Framework for Advance Plant Phenotyping in Horticulture

Fri, 27/10/2023 - 12:00
Biology (Basel). 2023 Sep 30;12(10):1298. doi: 10.3390/biology12101298.ABSTRACTThis review discusses the transformative potential of integrating multi-omics data and artificial intelligence (AI) in advancing horticultural research, specifically plant phenotyping. The traditional methods of plant phenotyping, while valuable, are limited in their ability to capture the complexity of plant biology. The advent of (meta-)genomics, (meta-)transcriptomics, proteomics, and metabolomics has provided an opportunity for a more comprehensive analysis. AI and machine learning (ML) techniques can effectively handle the complexity and volume of multi-omics data, providing meaningful interpretations and predictions. Reflecting the multidisciplinary nature of this area of research, in this review, readers will find a collection of state-of-the-art solutions that are key to the integration of multi-omics data and AI for phenotyping experiments in horticulture, including experimental design considerations with several technical and non-technical challenges, which are discussed along with potential solutions. The future prospects of this integration include precision horticulture, predictive breeding, improved disease and stress response management, sustainable crop management, and exploration of plant biodiversity. The integration of multi-omics and AI holds immense promise for revolutionizing horticultural research and applications, heralding a new era in plant phenotyping.PMID:37887008 | DOI:10.3390/biology12101298

Metabolic Basis of Circadian Dysfunction in Parkinson's Disease

Fri, 27/10/2023 - 12:00
Biology (Basel). 2023 Sep 28;12(10):1294. doi: 10.3390/biology12101294.ABSTRACTParkinson's disease (PD) is one of the most common neurodegenerative disorders. The management of PD is a challenging aspect for general physicians and neurologists. It is characterized by the progressive loss of dopaminergic neurons. Impaired α-synuclein secretion and dopamine release may cause mitochondrial dysfunction and perturb energy metabolism, subsequently altering the activity and survival of dopaminergic neurons, thus perpetuating the neurodegenerative process in PD. While the etiology of PD remains multifactorial, emerging research indicates a crucial role of circadian dysfunction in its pathogenesis. Researchers have revealed that circadian dysfunction and sleep disorders are common among PD subjects and disruption of circadian rhythms can increase the risk of PD. Hence, understanding the findings of circadian biology from translational research in PD is important for reducing the risk of neurodegeneration and for improving the quality of life. In this review, we discuss the intricate relationship between circadian dysfunction in cellular metabolism and PD by summarizing the evidence from animal models and human studies. Understanding the metabolic basis of circadian dysfunction in PD may shed light on novel therapeutic approaches to restore circadian rhythm, preserve dopaminergic function, and ameliorate disease progression. Further investigation into the complex interplay between circadian rhythm and PD pathogenesis is essential for the development of targeted therapies and interventions to alleviate the burden of this debilitating neurodegenerative disorder.PMID:37887004 | DOI:10.3390/biology12101294

Sample Preparation Method for MALDI Mass Spectrometry Imaging of Fresh-Frozen Spines

Fri, 27/10/2023 - 12:00
Anal Chem. 2023 Oct 27. doi: 10.1021/acs.analchem.3c03672. Online ahead of print.ABSTRACTTechnologies assessing the lipidomics, genomics, epigenomics, transcriptomics, and proteomics of tissue samples at single-cell resolution have deepened our understanding of physiology and pathophysiology at an unprecedented level of detail. However, the study of single-cell spatial metabolomics in undecalcified bones faces several significant challenges, such as the fragility of bone, which often requires decalcification or fixation leading to the degradation or removal of lipids and other molecules. As such, we describe a method for performing mass spectrometry imaging on undecalcified spine that is compatible with other spatial omics measurements. In brief, we use fresh-frozen rat spines and a system of carboxyl methylcellulose embedding, cryofilm, and polytetrafluoroethylene rollers to maintain tissue integrity while avoiding signal loss from variations in laser focus and artifacts from traditional tissue processing. This reveals various tissue types and lipidomic profiles of spinal regions at 10 μm spatial resolutions using matrix-assisted laser desorption/ionization mass spectrometry imaging. We expect this method to be adapted and applied to the analysis of the spinal cord, shedding light on the mechanistic aspects of cellular heterogeneity, development, and disease pathogenesis underlying different bone-related conditions and diseases. This study furthers the methodology for high spatial metabolomics of spines and adds to the collective efforts to achieve a holistic understanding of diseases via single-cell spatial multiomics.PMID:37886878 | DOI:10.1021/acs.analchem.3c03672

Time-Resolved Concentrations of Serum Amino Acids, One-carbon Metabolites, and B-vitamin Biomarkers during the Postprandial and Fasting State: The Postprandial Metabolism in Healthy Young Adults (PoMet) study

Fri, 27/10/2023 - 12:00
Br J Nutr. 2023 Oct 27:1-42. doi: 10.1017/S0007114523002490. Online ahead of print.ABSTRACTMetabolomics has been utilized in epidemiological studies to investigate biomarkers of nutritional status and metabolism in relation to non-communicable diseases. However, little is known about the effect of prandial status on several biomarker concentrations. Therefore, the aim of this intervention study was to investigate the effect of a standardized breakfast meal followed by food abstinence for 24 h on serum concentrations of amino acids, one-carbon metabolites, and B-vitamin biomarkers. 34 healthy subjects (18 males and 16 females) aged 20-30 years were served a breakfast meal (∼500 kcal) after which they consumed only water for 24 hours. Blood samples were drawn before, and at 13 standardized timepoints after the meal. Circulating concentrations of most amino acids and metabolites linked to one-carbon metabolism peaked within the first three hours after the meal. The branched-chain amino acids steadily increased from six or eight hours after the meal, while proline decreased in the same period. Homocysteine and cysteine concentrations immediately decreased after the meal but steadily increased from three and four hours until 24 hours. Flavin mononucleotide and riboflavin fluctuated immediately after the meal but increased from 6 hours, while folate increased immediately after the meal and remained elevated during the 24 hours. Our findings indicate that accurate reporting of time since last meal is crucial when investigating concentrations of certain amino acids and one-carbon metabolites. Our results suggest a need for caution when interpretating studies which utilize such biomarkers, but do not strictly control for time since the last meal.PMID:37886826 | DOI:10.1017/S0007114523002490

Cross-sectional association between plasma biomarkers and multimorbidity patterns in older adults

Fri, 27/10/2023 - 12:00
J Gerontol A Biol Sci Med Sci. 2023 Oct 27:glad249. doi: 10.1093/gerona/glad249. Online ahead of print.ABSTRACTMultimorbidity is the simultaneous presence of two or more chronic conditions. Metabolomics could identify biomarkers potentially related to multimorbidity. We aimed to identify groups of biomarkers and their association with different multimorbidity patterns. Cross-sectional analyses were conducted within the Seniors-ENRICA-2 cohort in Spain, with information from 700 individuals aged ≥65 years. Biological samples were analyzed using high-throughput proton nuclear magnetic resonance metabolomics. Biomarkers groups were identified with exploratory factor analysis, and multimorbidity was classified into three types: cardiometabolic, neuropsychiatric, and musculoskeletal. Logistic regression was used to estimate the association between biomarkers groups and multimorbidity patterns, after adjusting for potential confounders including sociodemographics, lifestyle, and body mass index. Three factors were identified: the "lipid metabolism" mainly reflected biomarkers related to lipid metabolism, such as very-low-density lipoprotein and low-density lipoprotein cholesterol; the "high-density lipoprotein cholesterol" mainly included high-density lipoprotein cholesterol subclasses and other lipids not included in the first factor; and the "amino acid/glycolysis/ketogenesis", composed of some amino acids, glycolysis-related metabolites and ketone bodies. Higher scores in the "lipid metabolism" factor were associated with a higher likelihood of cardiometabolic multimorbidity, odds ratio for tertile 3 vs. tertile 1 was 1.79 (95% confidence interval: 1.17-2.76). The "high-density lipoprotein cholesterol" factor was associated with lower odds of cardiometabolic multimorbidity [0.51 (0.32-0.82)], and the "amino acid/glycolysis/ketogenesis" factor was associated with more frequent cardiometabolic multimorbidity [1.85 (1.18-2.90)]. Different metabolomic biomarkers are associated with different multimorbidity patterns, therefore multiple biomarker measurements are needed for a complete picture of the molecular mechanisms of multimorbidity.PMID:37886823 | DOI:10.1093/gerona/glad249

Intestinal Pgc1α ablation protects from liver steatosis and fibrosis

Fri, 27/10/2023 - 12:00
JHEP Rep. 2023 Jul 19;5(11):100853. doi: 10.1016/j.jhepr.2023.100853. eCollection 2023 Nov.ABSTRACTBACKGROUND & AIMS: The gut-liver axis modulates the progression of metabolic dysfunction-associated steatotic liver disease (MASLD), a spectrum of conditions characterised by hepatic steatosis and a progressive increase of inflammation and fibrosis, culminating in metabolic dysfunction-associated steatohepatitis. Peroxisome proliferator-activated receptor-gamma coactivator 1α (Pgc1α) is a transcriptional co-regulator of mitochondrial activity and lipid metabolism. Here, the intestinal-specific role of Pgc1α was analysed in liver steatosis and fibrosis.METHODS: We used a mouse model in which Pgc1α was selectively deleted from the intestinal epithelium. We fed these mice and their wild-type littermates a Western diet to recapitulate the major features of liver steatosis (after 2 months of diet) and metabolic dysfunction-associated steatohepatitis (after 4 months of diet). The chow diet was administered as a control diet.RESULTS: In humans and mice, low expression of intestinal Pgc1α is inversely associated with liver steatosis, inflammation, and fibrosis. Intestinal disruption of Pgc1α impairs the transcription of a wide number of genes, including the cholesterol transporter Niemann-Pick C1-like 1 (Npc1l1), thus limiting the uptake of cholesterol from the gut. This results in a lower cholesterol accretion in the liver and a decreased production of new fatty acids, which protect the liver from lipotoxic lipid species accumulation, inflammation, and related fibrotic processes.CONCLUSIONS: In humans and mice, intestinal Pgc1α induction during Western diet may be another culprit driving hepatic steatosis and fibrosis. Here, we show that enterocyte-specific Pgc1α ablation protects the liver from steatosis and fibrosis by reducing intestinal cholesterol absorption, with subsequent decrease of cholesterol and de novo fatty acid accumulation in the liver.IMPACT AND IMPLICATIONS: Liver diseases result from several insults, including signals from the gut. Although the incidence of liver diseases is continuously increasing worldwide, effective drug therapy is still lacking. Here, we showed that the modulation of an intestinal coactivator regulates the liver response to a Western diet, by limiting the uptake of dietary cholesterol. This results in a lower accumulation of hepatic lipids together with decreased inflammation and fibrosis, thus limiting the progression of liver steatosis and fibrosis towards severe end-stage diseases.PMID:37886435 | PMC:PMC10597770 | DOI:10.1016/j.jhepr.2023.100853

Aspartate metabolic flux promotes nitric oxide to eliminate both antibiotic-sensitive and -resistant <em>Edwardsiella tarda</em> in zebrafish

Fri, 27/10/2023 - 12:00
Front Immunol. 2023 Oct 11;14:1277281. doi: 10.3389/fimmu.2023.1277281. eCollection 2023.ABSTRACTINTRODUCTION: Metabolic reprogramming potentiates host protection against antibiotic-sensitive or -resistant bacteria. However, it remains unclear whether a single reprogramming metabolite is effective enough to combat both antibiotic-sensitive and -resistant bacteria. This knowledge is key for implementing an antibiotic-free approach.METHODS: The reprogramming metabolome approach was adopted to characterize the metabolic state of zebrafish infected with tetracycline-sensitive and -resistant Edwardsiella tarda and to identify overlapping depressed metabolite in dying zebrafish as a reprogramming metabolite.RESULTS: Aspartate was identify overlapping depressed metabolite in dying zebrafish as a reprogramming metabolite. Exogenous aspartate protects zebrafish against infection caused by tetracycline-sensitive and -resistant E. tarda. Mechanistically, exogenous aspartate promotes nitric oxide (NO) biosynthesis. NO is a well-documented factor of promoting innate immunity against bacteria, but whether it can play a role in eliminating both tetracycline-sensitive and -resistant E. tarda is unknown. Thus, in this study, aspartate was replaced with sodium nitroprusside to provide NO, which led to similar aspartate-induced protection against tetracycline-sensitive and -resistant E. tarda.DISCUSSION: These findings support the conclusion that aspartate plays an important protective role through NO against both types of E. tarda. Importantly, we found that tetracycline-sensitive and -resistant E. tarda are sensitive to NO. Therefore, aspartate is an effective reprogramming metabolite that allows implementation of an antibiotic-free approach against bacterial pathogens.PMID:37885884 | PMC:PMC10598754 | DOI:10.3389/fimmu.2023.1277281

Protective effect and mechanism of procyanidin B2 against hypoxic injury of cardiomyocytes

Fri, 27/10/2023 - 12:00
Heliyon. 2023 Oct 20;9(11):e21309. doi: 10.1016/j.heliyon.2023.e21309. eCollection 2023 Nov.ABSTRACTBACKGROUND: Cardiomyocyte ischemia and hypoxia are important causes of oxidative stress damage and cardiomyocyte apoptosis in coronary heart disease (CHD). Epidemiological investigation has shown that eating more plant-based foods, such as vegetables and fruits, may significantly decrease the risk of CHD. As natural antioxidants, botanicals have fewer toxic side effects than chemical drugs and have great potential for development. Procyanidin B2 (PB2) is composed of flavan-3-ol and epicatechin and has been reported to have antioxidant and anti-inflammatory effects. However, whether PB2 exerts protective effects on hypoxic cardiomyocytes has remained unclear. This study aimed to explore the protective effect of PB2 against cardiomyocyte hypoxia and to provide new treatment strategies and ideas for myocardial ischemia and hypoxia in CHD.METHODS AND RESULTS: A hypoxic cardiomyocyte model was constructed, and a CCK-8 assay proved that PB2 had a protective effect on cardiomyocytes in a hypoxic environment. DCFH fluorescence staining, DHE staining, and BODIPY lipid oxidation assessment revealed that PB2 reduced the oxidative stress levels of cardiomyocytes under hypoxic conditions. TUNEL staining, Annexin V/PI fluorescence flow cytometry, and Western blot analysis of the expression of the apoptosis marker protein cleaved caspase-3 confirmed that PB2 reduced cardiomyocyte apoptosis under hypoxic conditions. JC-1 staining indicated that PB2 reduced the mitochondrial membrane potential of cardiomyocytes under hypoxia. In addition, transcriptomic analysis proved that the expression of 158 genes in cardiomyocytes was significantly changed after PB2 was added during hypoxia, of which 53 genes were upregulated and 105 genes were downregulated. GO enrichment analysis demonstrated that the activity of cytokines, extracellular matrix proteins and other molecules was changed significantly in the biological process category. KEGG enrichment analysis showed that the IL-17 signaling pathway and JAK-STAT signaling pathway underwent significant changes. We also performed metabolomic analysis and found that the levels of 51 metabolites were significantly changed after the addition of PB2 to cardiomyocytes during hypoxia. Among them, 39 metabolites exhibited increased levels, while 12 metabolites exhibited decreased levels. KEGG enrichment analysis showed that cysteine and methionine metabolism, arginine and proline metabolism and other metabolic pathways underwent remarkable changes.CONCLUSION: This study proves that PB2 can reduce the oxidative stress and apoptosis of cardiomyocytes during hypoxia to play a protective role. Transcriptomic and metabolomic analyses preliminarily revealed signaling pathways and metabolic pathways that are related to its protective mechanism. These findings lay a foundation for further research on the role of PB2 in the treatment of CHD and provide new ideas and new perspectives for research on PB2 in the treatment of other diseases.PMID:37885736 | PMC:PMC10598540 | DOI:10.1016/j.heliyon.2023.e21309

Study on the metabolic process of phthalic acid driven proliferation of <em>Rhizoctonia solani</em>

Fri, 27/10/2023 - 12:00
Front Plant Sci. 2023 Oct 11;14:1266916. doi: 10.3389/fpls.2023.1266916. eCollection 2023.ABSTRACTINTRODUCTION: Continuous cropping obstacle seriously affects the quality and yield of Salvia miltiorrhiza, and the synergistic effect of root exudates and rhizosphere pathogenic microorganisms may be an important cause of continuous cropping obstacle. This study aimed to explore the effects of representative organic acids on the growth and metabolism of specific microorganisms in the S. miltiorrhiza rhizosphere soil under continuous cropping, and clarify its mechanism.METHODS: The effect of phthalic acid (PA) on the growth and metabolism of Rhizoctonia solani was evaluated by mycelial growth inhibition method. Ultra-high performance liquid chromatography and tandem mass spectrometry were used to identify the differential metabolites of R. solani induced by exogenous PA.RESULTS: PA exerted a concentration-dependent effect on mycelial growth, biomass, intracellular polysaccharides con-tent, and total protein content in R. solani. A total of 1773 metabolites and 1040 differential metabolites were identified in the blank medium (CK), Fungi (CK + fungi), and PA-Fungi (CK + fungi + acid) groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the differential metabolites were mainly involved in the sugar, lipid, and protein metabolic pathways related to stable membrane structure and cell growth.DISCUSSION: The proliferation and metabolism network of R. solani induced by PA was proposed, and the enhancement of sugar, lipid, and amino acid metabolism was presumed to be related to the active resistance of cells to organic acid stress. These results offer new in-sights into the effects of PA metabolism on promoting R. solani proliferation, and provide theoretical support for further optimizing the rhizosphere microecological environment of Salvia miltiorrhiza continuous cropping soil and reducing continuous cropping obstacle.PMID:37885668 | PMC:PMC10598758 | DOI:10.3389/fpls.2023.1266916

Comprehensive insights into herbicide resistance mechanisms in weeds: a synergistic integration of transcriptomic and metabolomic analyses

Fri, 27/10/2023 - 12:00
Front Plant Sci. 2023 Oct 11;14:1280118. doi: 10.3389/fpls.2023.1280118. eCollection 2023.ABSTRACTOmics techniques, including genomics, transcriptomics, proteomics, and metabolomics have smoothed the researcher's ability to generate hypotheses and discover various agronomically relevant functions and mechanisms, as well as their implications and associations. With a significant increase in the number of cases with resistance to multiple herbicide modes of action, studies on herbicide resistance are currently one of the predominant areas of research within the field of weed science. High-throughput technologies have already started revolutionizing the current molecular weed biology studies. The evolution of herbicide resistance in weeds (particularly via non-target site resistance mechanism) is a perfect example of a complex, multi-pathway integration-induced response. To date, functional genomics, including transcriptomic and metabolomic studies have been used separately in herbicide resistance research, however there is a substantial lack of integrated approach. Hence, despite the ability of omics technologies to provide significant insights into the molecular functioning of weeds, using a single omics can sometimes be misleading. This mini-review will aim to discuss the current progress of transcriptome-based and metabolome-based approaches in herbicide resistance research, along with their systematic integration.PMID:37885667 | PMC:PMC10598704 | DOI:10.3389/fpls.2023.1280118

<em>Corylus avellana</em> "Nocciola Piemonte": metabolomics focused on polar lipids and phenolic compounds in fresh and roasted hazelnuts

Fri, 27/10/2023 - 12:00
Front Plant Sci. 2023 Oct 11;14:1252196. doi: 10.3389/fpls.2023.1252196. eCollection 2023.ABSTRACTThe common hazel plant (Corylus avellana L., Betulaceae) is one of the most popular tree nuts widespread in Europe and Asia. In Italy, there are different cultivars among which the cultivar affording the valuable hazelnut "Tonda Gentile Trilobata," also known as "Tonda Gentile delle Langhe," covered by the Protected Geographical Indication (PGI) label "Nocciola Piemonte" (NP), known for its sweetness, cooked-bread aroma, and the low intensity of the burnt aroma. In order to obtain a detailed and in-depth characterization of the polar fraction of fresh (NPF) and roasted (NPR) kernels of NP the analysis of the n-butanol extracts by liquid chromatography coupled to electrospray ionization and high-resolution mass spectrometry (LC-ESI/HRMS) was carried out. Moreover, to evaluate the quantitative distribution of the most representative polar lipids in NPF and NPR, the analysis by liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) was performed. To unambiguously identify the phenolic compounds highlighted by the LC-ESI/HRMS profiles, they were isolated from the n-butanol extract and characterized by Nuclear Magnetic Resonance (NMR) experiments. Finally, the ability of the isolated compounds to exert radical scavenging activity and to inhibit the lipid peroxidation induced by H2O2 or H2O2/Fe2+ was tested by Trolox Equivalent Antioxidant Capacity (TEAC) and thiobarbituric acid reactive substances (TBARS) assays, respectively. The LC-ESI/HRMS allowed to ascertain the presence of phenolic compounds and multiple classes of polar lipids including phospholipids, glycolipids, sphingolipids, and oxylipins. The quantitative analysis highlighted in NPR fraction a lipid content three times higher than in NPF, evidencing lyso-phospholipids and phospholipids as the most represented lipid classes in both NPF and NPR, together accounting for 94 and 97% of the considered lipids, respectively. Furthermore, phytochemical analysis permitted to identify flavonoid and diarylheptanoid derivatives. In particular, quercetin 3-O-β-D-galactopyranosyl-(1→2)-β-D-glucopyranoside and myricetin-3-O-α-L-rhamnopyranoside showed the highest antioxidant activity, exhibiting TEAC values similar to that of quercetin, used as reference compound (2.00 ± 0.03 and 2.06 ± 0.03 mM vs 2.03 ± 0.03 mM, respectively). Moreover, most of the tested compounds were found to reduce lipid peroxidation induced by H2O2 and H2O2/Fe2+ more than curcumin used as positive control, with myricetin-3-O-α-L-rhamnopyranoside determining 44.4 % and 34.1 % inhibition percentage, respectively.PMID:37885660 | PMC:PMC10598857 | DOI:10.3389/fpls.2023.1252196

Chronic supplementation of a multi-ingredient herbal supplement increases speed of cognitive task performance alongside changes in the urinary metabolism of dopamine and the gut microbiome in cognitively intact older adults experiencing subjective...

Fri, 27/10/2023 - 12:00
Front Nutr. 2023 Oct 10;10:1257516. doi: 10.3389/fnut.2023.1257516. eCollection 2023.ABSTRACTBACKGROUND: The effects of herbs on brain function are often investigated in isolation, yet herbal preparations are often complex combinations of phytochemicals, designed to target widespread mechanisms.OBJECTIVE: To assess the effects of chronic, 12 weeks, supplementation of a multi-ingredient herbal supplement (containing Bacopa monnieri, Gotu kola leaf, Turmeric whole powder, Reishi full spectrum, Rosemary, Cardamom, Holy Basil, Turmeric Wholistic™ extract, Green Tea & Seagreens) on cognitive function in older adults with subjective memory decline. Secondly, to investigate whether effects are underpinned by shifts in microbial composition and/or metabolism of the herbs.METHODS: Male and female participants (N = 128) aged between 55-75 years completed lab-based cognitive assessments, and provided stool and urine samples, at baseline and then following 90 days of multi-ingredient herb, or placebo, supplementation.RESULTS: Deficits in memory were observed in response to 90 days of multi-ingredient herbal supplement supplementation but the positive effects were all focused on speed of cognitive task performance, with an additional improvement in the false alarm rate on the rapid visual information processing task. These improvements coincided with an increased presence of tyrosine in the urinary metabolome and this may implicate the role of dopamine in these processing and/or motor speed increases. Finally, multi-ingredient herbal supplementation significantly reduced levels of 3 bacterial species in the gut microbiome and one of these, Sutterella, coincides with lower levels of constipation reported in the multi-ingredient herbal supplement condition.CONCLUSION: A multi-ingredient herbal supplement increases speed of cognitive task performance and increased metabolism of tyrosine suggests that this is modulated by increased dopaminergic activity. Reduced levels of Sutterella in the gut is associated with improved bowel movements of participants. Interpretation of the negative effects on memory are, however, stymied by an unequal randomization of participants into treatment groups pre- and post-COVID 19.Clinical trial registration: identifier NCT05504668.PMID:37885445 | PMC:PMC10598389 | DOI:10.3389/fnut.2023.1257516

Comprehensive improvement of nutrients and volatile compounds of black/purple rice by extrusion-puffing technology

Fri, 27/10/2023 - 12:00
Front Nutr. 2023 Oct 11;10:1248501. doi: 10.3389/fnut.2023.1248501. eCollection 2023.ABSTRACTINTRODUCTION: Black/purple rice is a pigmented rice variety that contains high levels of anthocyanins, flavonoids, and other valuable bioactive compounds. Owing to its robust anti-inflammatory and antioxidant properties, black/purple rice exerts a beneficial effect on human health. Extrusion puffing technology has emerged as a promising means of improving rice flavor with lesser effect on nutrient content. In this study, metabolomics approach was used to conduct comprehensive metabolomics analyses aimed at examining the impact of extrusion puffing on black/purple rice nutritional value and flavor.METHODS: Firstly, the basic nutrient composition contents and extrudate characteristics of black/purple rice and Extrusion puffed black/purple rice were conducted. Then metabolomics profiling analyses of black/purple rice samples were performed to explore the impact of the extrusion puffing process on nutrient content and bioactive properties, in which we quantitatively determined the flavonoids and evaluated relative contents of volatile compounds.RESULTS: These analyses revealed that following extrusion puffing, black/purple rice exhibited significant improvements in the content of nutrients including flavonoids, minerals, and proteins together. Extrusion puffing additionally increased the diversity of volatile compounds within black/purple rice.DISCUSSION: These results suggest that extrusion puffing represents an effective means of substantially improving the functional and nutritional properties of black/purple rice, offering beneficial effects on consumer health. Overall, these data provide novel insights into the quality of extrusion puffed black/purple rice that will guide future efforts to establish how extrusion puffing can alter the nutrient content in a range of foods, thereby supporting the further development of a range of healthy food products.PMID:37885443 | PMC:PMC10598597 | DOI:10.3389/fnut.2023.1248501

Using the power of innate immunoprofiling to understand vaccine design, infection, and immunity

Fri, 27/10/2023 - 12:00
Hum Vaccin Immunother. 2023 Dec 15;19(3):2267295. doi: 10.1080/21645515.2023.2267295. Epub 2023 Oct 26.ABSTRACTIn the field of immunology, a systems biology approach is crucial to understanding the immune response to infection and vaccination considering the complex interplay between genetic, epigenetic, and environmental factors. Significant progress has been made in understanding the innate immune response, including cell players and critical signaling pathways, but many questions remain unanswered, including how the innate immune response dictates host/pathogen responses and responses to vaccines. To complicate things further, it is becoming increasingly clear that the innate immune response is not a linear pathway but is formed from complex networks and interactions. To further our understanding of the crosstalk and complexities, systems-level analyses and expanded experimental technologies are now needed. In this review, we discuss the most recent immunoprofiling techniques and discuss systems approaches to studying the global innate immune landscape which will inform on the development of personalized medicine and innovative vaccine strategies.PMID:37885158 | DOI:10.1080/21645515.2023.2267295

An Aphid-Transmitted Virus Reduces the Host Plant Response to Its Vector to Promote Its Transmission

Fri, 27/10/2023 - 12:00
Phytopathology. 2023 Oct 26:PHYTO12220454FI. doi: 10.1094/PHYTO-12-22-0454-FI. Online ahead of print.ABSTRACTThe success of virus transmission by vectors relies on intricate trophic interactions between three partners, the host plant, the virus, and the vector. Despite numerous studies that showed the capacity of plant viruses to manipulate their host plant to their benefit, and potentially of their transmission, the molecular mechanisms sustaining this phenomenon has not yet been extensively analyzed at the molecular level. In this study, we focused on the deregulations induced in Arabidopsis thaliana by an aphid vector that were alleviated when the plants were infected with turnip yellows virus (TuYV), a polerovirus strictly transmitted by aphids in a circulative and nonpropagative mode. By setting up an experimental design mimicking the natural conditions of virus transmission, we analyzed the deregulations in plants infected with TuYV and infested with aphids by a dual transcriptomic and metabolomic approach. We observed that the virus infection alleviated most of the gene deregulations induced by the aphids in a noninfected plant at both time points analyzed (6 and 72 h) with a more pronounced effect at the later time point of infestation. The metabolic composition of the infected and infested plants was altered in a way that could be beneficial for the vector and the virus transmission. Importantly, these substantial modifications observed in infected and infested plants correlated with a higher TuYV transmission efficiency. This study revealed the capacity of TuYV to alter the plant nutritive content and the defense reaction against the aphid vector to promote the viral transmission.PMID:37885045 | DOI:10.1094/PHYTO-12-22-0454-FI

Anti-aging activities of Rehmannia glutinosa Libosch. crude polysaccharide in Caenorhabditis elegans based on gut microbiota and metabonomic analysis

Thu, 26/10/2023 - 12:00
Int J Biol Macromol. 2023 Oct 24:127647. doi: 10.1016/j.ijbiomac.2023.127647. Online ahead of print.ABSTRACTAging is a degenerative progress, accompanied by oxidative damage, metabolic disorders and intestinal flora imbalance. Natural macromolecular polysaccharides have shown excellent anti-aging and antioxidant properties, while maintaining metabolic and intestinal homeostasis. The molecular weight, monosaccharide composition, infrared spectrum and other chemical structure information of four Rehmannia glutinosa polysaccharides (RG50, RG70, RG90, RGB) were determined, and their free radical scavenging ability was assessed. Molecular weight and monosaccharide composition analysis exhibited that RG50 (2-72 kDa), RG70 (3.2-37 kDa), RG70 (3-42 kDa), and RGB (3.1-180 kDa) were heteropolysaccharide with significant different monosaccharide species and molar ratios. We found that RG70 had the best antioxidant activity in vitro and RG70 could enhance the antioxidant enzyme system of Caenorhabditis elegans, diminished lipofuscin and reactive oxygen species levels, up-regulate the expression of daf-16, skn-1 and their downstream genes, and down-regulate the expression of age-1. Metabolomics results showed that RG70 mainly influenced glycine, serine and threonine metabolism and citric acid cycle. 16S rRNA sequencing showed that RG70 significantly up-regulated the abundance of Lachnospiraceae_NK4B4_group, which were positively correlated with amino acid metabolism and energy cycling. These results suggest that RG70 may delay aging by enhancing antioxidant effects, affecting probiotics and regulating key metabolic pathways.PMID:37884235 | DOI:10.1016/j.ijbiomac.2023.127647

Podophyllotoxin-mediated neurotoxicity via the microbiota-gut-brain axis in SD rats based on the toxicological evidence chain (TEC) concept

Thu, 26/10/2023 - 12:00
Sci Total Environ. 2023 Oct 24:168106. doi: 10.1016/j.scitotenv.2023.168106. Online ahead of print.ABSTRACTPodophyllotoxin (PPT) is a naturally occurring aryltetralin lignan. However, its clinical application has been limited due to its neurotoxicity, the mechanism of which remains unclear. This study aimed to investigate the potential involvement of the microbiota-gut-brain (MGB) axis in PPT-induced neurotoxicity using the toxicological evidence chain concept. Our approach included behavioral testing in rats, evaluation of colon and hippocampal pathological changes, examination of proinflammatory factors, brain-gut peptides, and an in-depth analysis of gut microbiome and metabolic profiles. Our results demonstrated that PPT exposure compromised cognitive functions, induced damage to the colon and hippocampus, and increased intestinal permeability in rats. Furthermore, it elevated proinflammatory factors, particularly TNF-α and IL-6, while causing disruptions in the gut microbiota, favoring Escherichia-Shigella over Lactobacillus. Significant alterations in metabolic profiles in feces, serum, and hippocampus, particularly in tryptophan metabolism with a correlation to inflammatory factors and Escherichia-Shigella, were also observed. Our findings suggest that PPT promotes the enrichment of Escherichia-Shigella leading to inflammatory factor production and alterations in kynurenine metabolism in the hippocampus, potentially contributing to neurotoxicity. The study provides novel insights into the mechanistic pathways of PPT-induced neurotoxicity, emphasizing the role of the MGB axis and offering avenues for therapeutic interventions.PMID:37884145 | DOI:10.1016/j.scitotenv.2023.168106

Comparison of the metabolite profile of donkey and horse seminal plasma and its relationship with sperm viability and motility

Thu, 26/10/2023 - 12:00
Res Vet Sci. 2023 Oct 12;165:105046. doi: 10.1016/j.rvsc.2023.105046. Online ahead of print.ABSTRACTPrevious research revealed that several seminal plasma (SP) metabolites are related to sperm functionality, fertility, and preservation. While it is understood that variations between species exist, whether the SP metabolome differs between donkeys and horses has not been previously investigated. The aim of this work, therefore, was to characterize and compare donkey and horse SP metabolites using nuclear magnetic resonance (NMR) spectroscopy, and relate them to sperm viability and motility. For this purpose, ejaculates from 18 different donkeys and 18 different horses were collected and separated into two aliquots: one for harvesting the SP by centrifugation and obtaining the metabolic profile through NMR, and the other for evaluating sperm viability and motility. Based on total motility and sperm viability, samples were classified as with good (GQ) or poor (PQ) quality. The metabolomic profile of donkey and horse SP revealed the presence of 28 metabolites, which coincided in the two species. Yet, differences between horses and donkeys were observed in the concentration of 18 of these 28 metabolites, as well as between ejaculates classified as GQ or PQ and in the relationship of metabolites with sperm motility and viability. These findings suggest that sperm from donkeys and horses differ in their metabolism and energetic requirements, and that the concentration of specific SP metabolites may be related to sperm functionality. Further research should shed light on the metabolic needs of donkey and horse sperm, and evaluate how the knowledge collected from the contribution of these metabolites can help improve semen preservation in the two species.PMID:37883856 | DOI:10.1016/j.rvsc.2023.105046

Paralemnalia thyrsoides-associated fungi: phylogenetic diversity, cytotoxic potential, metabolomic profiling and docking analysis

Thu, 26/10/2023 - 12:00
BMC Microbiol. 2023 Oct 26;23(1):308. doi: 10.1186/s12866-023-03045-y.ABSTRACTBACKGROUND: Cancer continues to be one of the biggest causes of death that affects human health. Chemical resistance is still a problem in conventional cancer treatments. Fortunately, numerous natural compounds originating from different microbes, including fungi, possess cytotoxic characteristics that are now well known. This study aims to investigate the anticancer prospects of five fungal strains that were cultivated and isolated from the Red Sea soft coral Paralemnalia thyrsoides. The in vitro cytotoxic potential of the ethyl acetate extracts of the different five isolates were evaluated using MTS assay against four cancer cell lines; A549, CT-26, MDA-MB-231, and U87. Metabolomics profiling of the different extracts using LC-HR-ESI-MS, besides molecular docking studies for the dereplicated compounds were performed to unveil the chemical profile and the cytotoxic mechanism of the soft coral associated fungi.RESULTS: The five isolated fungal strains were identified as Penicillium griseofulvum (RD1), Cladosporium sphaerospermum (RD2), Cladosporium liminiforme (RD3), Penicillium chrysogenum (RD4), and Epicoccum nigrum (RD5). The in vitro study showed that the ethyl acetate extract of RD4 exhibited the strongest cytotoxic potency against three cancer cell lines A549, CT-26 and MDA-MB-231 with IC50 values of 1.45 ± 8.54, 1.58 ± 6.55 and 1.39 ± 2.0 µg/mL, respectively, also, RD3 revealed selective cytotoxic potency against A549 with IC50 value of 6.99 ± 3.47 µg/mL. Docking study of 32 compounds dereplicated from the metabolomics profiling demonstrated a promising binding conformation with EGFR tyrosine kinase that resembled its co-crystallized ligand albeit with better binding energy score.CONCLUSION: Our results highlight the importance of soft coral-associated fungi as a promising source for anticancer metabolites for future drug discovery.PMID:37884900 | DOI:10.1186/s12866-023-03045-y

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