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Nature Metabolism Nov 2023Tumors are intrinsically heterogeneous and it is well established that this directs their evolution, hinders their classification and frustrates therapy. Consequently,...
Tumors are intrinsically heterogeneous and it is well established that this directs their evolution, hinders their classification and frustrates therapy. Consequently, spatially resolved omics-level analyses are gaining traction. Despite considerable therapeutic interest, tumor metabolism has been lagging behind this development and there is a paucity of data regarding its spatial organization. To address this shortcoming, we set out to study the local metabolic effects of the oncogene c-MYC, a pleiotropic transcription factor that accumulates with tumor progression and influences metabolism. Through correlative mass spectrometry imaging, we show that pantothenic acid (vitamin B) associates with MYC-high areas within both human and murine mammary tumors, where its conversion to coenzyme A fuels Krebs cycle activity. Mechanistically, we show that this is accomplished by MYC-mediated upregulation of its multivitamin transporter SLC5A6. Notably, we show that SLC5A6 over-expression alone can induce increased cell growth and a shift toward biosynthesis, whereas conversely, dietary restriction of pantothenic acid leads to a reversal of many MYC-mediated metabolic changes and results in hampered tumor growth. Our work thus establishes the availability of vitamins and cofactors as a potential bottleneck in tumor progression, which can be exploited therapeutically. Overall, we show that a spatial understanding of local metabolism facilitates the identification of clinically relevant, tractable metabolic targets.
Topics: Humans; Mice; Animals; Female; Breast Neoplasms; Pantothenic Acid; Proto-Oncogene Proteins c-myc; Transcription Factors; Vitamins
PubMed: 37946084
DOI: 10.1038/s42255-023-00915-7 -
ISME Communications Oct 2022Benthic organisms are the architectural framework supporting coral reef ecosystems, but their community composition has recently shifted on many reefs. Little is known...
Benthic organisms are the architectural framework supporting coral reef ecosystems, but their community composition has recently shifted on many reefs. Little is known about the metabolites released from these benthic organisms and how compositional shifts may influence other reef life, including prolific microorganisms. To investigate the metabolite composition of benthic exudates and their ecological significance for reef microbial communities, we harvested exudates from six species of Caribbean benthic organisms including stony corals, octocorals, and an invasive encrusting alga, and subjected these exudates to untargeted and targeted metabolomics approaches using liquid chromatography-mass spectrometry. Incubations with reef seawater microorganisms were conducted to monitor changes in microbial abundances and community composition using 16 S rRNA gene sequencing in relation to exudate source and three specific metabolites. Exudates were enriched in amino acids, nucleosides, vitamins, and indole-based metabolites, showing that benthic organisms contribute labile organic matter to reefs. Furthermore, exudate compositions were species-specific, and riboflavin and pantothenic acid emerged as significant coral-produced metabolites, while caffeine emerged as a significant invasive algal-produced metabolite. Microbial abundances and individual microbial taxa responded differently to exudates from stony corals and octocorals, demonstrating that exudate mixtures released from different coral species select for specific bacteria. In contrast, microbial communities did not respond to individual additions of riboflavin, pantothenic acid, or caffeine. This work indicates that recent shifts in benthic organisms alter exudate composition and likely impact microbial communities on coral reefs.
PubMed: 37938276
DOI: 10.1038/s43705-022-00184-7 -
The Veterinary Quarterly Dec 2023Epigallocatechin gallate (EGCG) is a main component in green tea extract, which possesses multiple bioactivities. The present research studied the effects of EGCG on the...
The effect of epigallocatechin gallate on laying performance, egg quality, immune status, antioxidant capacity, and hepatic metabolome of laying ducks reared in high temperature condition.
Epigallocatechin gallate (EGCG) is a main component in green tea extract, which possesses multiple bioactivities. The present research studied the effects of EGCG on the laying performance, egg quality, immune status, antioxidant capacity, and hepatic metabolome of laying ducks reared under high temperature. A total of 180 42-w-old healthy laying ducks were allocated into control or EGCG-treated groups. Each treatment had 6 replicates with 15 ducks in each replicate. Diets for the two groups were basal diets supplemented with 0 or 300 mg/kg EGCG, respectively. All ducks were raised in the high temperature condition (35 ± 2 °C for 6 h from 10:00 to 16:00, and 28 ± 2 °C for the other 18 h from 16:00 to 10:00 the next day) for 21 days. Results showed that EGCG increased the egg production rate ( = 0.014) and enhanced the immunocompetence by improving serum levels of immunoglobulin A ( = 0.008) and immunoglobulin G ( = 0.006). EGCG also fortified the antioxidant capacity by activating superoxide dismutase ( = 0.012), catalase ( = 0.009), and glutathione peroxidase ( = 0.021), and increasing the level of heat-shock protein 70 ( = 0.003) in laying ducks' liver. At the same time, hepatic metabolomics result suggested that EGCG increased the concentration of several key metabolites, such as spermidine ( = 0.031), tetramethylenediamine ( = 0.009), hyoscyamine ( = 0.026), β-nicotinamide adenine dinucleotide phosphate ( = 0.038), and pantothenic acid ( = 0.010), which were involved in the metabolic pathways of glutathione metabolism, arginine and proline metabolism, β-alanine metabolism, and tropane, piperidine, and pyridine alkaloid biosynthesis. In conclusion, 300 mg/kg dietary EGCG showed protection effects on the laying ducks reared in high temperature by improving the immune and antioxidant capacities, which contributed to the increase of laying performance of ducks. The potential mechanism could be that EGCG modulate the synthesis of key metabolites and associated metabolic pathways.
Topics: Animals; Antioxidants; Ducks; Temperature; Dietary Supplements; Diet; Liver; Metabolome; Animal Feed
PubMed: 37921498
DOI: 10.1080/01652176.2023.2280041 -
Dermatopathology (Basel, Switzerland) Sep 2023Lactic acid bacteria consumption serves several health benefits to humans. However, their effect on natural skin aging is still unclear.
BACKGROUND
Lactic acid bacteria consumption serves several health benefits to humans. However, their effect on natural skin aging is still unclear.
METHODS
This study examined the effects of skin naturalization (particularly skin drying) by administering a spore-bearing lactic acid bacteria () in mice for 2 years.
RESULTS
administration improved the natural skin of mice and significantly increased proportions of the genera and , among other intestinal bacteria. As metabolites, increases in nicotinic acid, putrescin, and pantothenic acid levels and a decrease in choline levels were observed. Increased hyaluronic acid, interleukin-10, and M2 macrophage levels indicate aging-related molecules in the skin. Intestinal permeability was also suppressed. Thus, these changes together improved natural skin aging.
CONCLUSIONS
This study revealed that administration improved the natural skin aging in mice. This enhancement might be induced by the interaction of alterations in intestinal flora, metabolites, or inflammatory substances.
PubMed: 37873804
DOI: 10.3390/dermatopathology10040037 -
Animals : An Open Access Journal From... Sep 2023The gut microbiota plays an important role in the physiological activities of the host and affects the formation of important economic traits in livestock farming. The...
The gut microbiota plays an important role in the physiological activities of the host and affects the formation of important economic traits in livestock farming. The effects of cecal microbiota on chicken weights were investigated using the Guizhou yellow chicken as a model. Experimental cohorts from chickens with high- (HC, = 16) and low-market-weights (LC, = 16) were collected. Microbial 16S rRNA gene sequencing and non-targeted serum metabolome data were integrated to explore the effect and metabolic mechanism of cecal microbiota on market weight. The genera , , , , and were enriched in the HC group, while was enriched in the LC group ( < 0.05). Metabolomic analysis determined that pantothenic acid (vitamin B5), luvangetin (2-1-benzopyran-6-acrylic acid), and menadione (vitamin K3) were significantly higher in HC serum, while beclomethasone dipropionate (a glucocorticoid) and chlorophene (2-benzyl-4-chlorophenol) were present at higher levels in the LC group. The microbes enriched in HC were significantly positively correlated with metabolites, including pantothenic acid and menadione, and negatively correlated with beclomethasone dipropionate and chlorophene. These results indicated that specific cecal bacteria in Guizhou yellow chickens alter the host metabolism and growth performance. This study provides a reference for revealing the mechanism of cecal microbe actions that affect chicken body weight.
PubMed: 37835639
DOI: 10.3390/ani13193034 -
Life Science Alliance Dec 2023The tumor microenvironment is a dynamic network of stromal, cancer, and immune cells that interact and compete for resources. We have previously identified the Vanin1...
The tumor microenvironment is a dynamic network of stromal, cancer, and immune cells that interact and compete for resources. We have previously identified the Vanin1 pathway as a tumor suppressor of sarcoma development via vitamin B5 and coenzyme A regeneration. Using an aggressive sarcoma cell line that lacks Vnn1 expression, we showed that the administration of pantethine, a vitamin B5 precursor, attenuates tumor growth in immunocompetent but not nude mice. Pantethine boosts antitumor immunity, including the polarization of myeloid and dendritic cells towards enhanced IFNγ-driven antigen presentation pathways and improved the development of hypermetabolic effector CD8 T cells endowed with potential antitumor activity. At later stages of treatment, the effect of pantethine was limited by the development of immune cell exhaustion. Nevertheless, its activity was comparable with that of anti-PD1 treatment in sensitive tumors. In humans, expression correlates with improved survival and immune cell infiltration in soft-tissue sarcomas, but not in osteosarcomas. Pantethine could be a potential therapeutic immunoadjuvant for the development of antitumor immunity.
Topics: Humans; Mice; Animals; CD8-Positive T-Lymphocytes; Coenzyme A; Pantothenic Acid; Sarcoma; Tumor Microenvironment
PubMed: 37833072
DOI: 10.26508/lsa.202302200 -
Molecular Plant Pathology Jan 2024Root-knot nematodes (RKNs) inflict extensive damage to global agricultural production. Intercropping has been identified as a viable agricultural tool for combating...
Metabolic variations in root tissues and rhizosphere soils of weak host plants potently lead to distinct host status and chemotaxis regulation of Meloidogyne incognita in intercropping.
Root-knot nematodes (RKNs) inflict extensive damage to global agricultural production. Intercropping has been identified as a viable agricultural tool for combating RKNs, but the mechanisms by which intercropped plants modulate RKN parasitism are still not well understood. Here, we focus on the cucumber-amaranth intercropping system. We used a range of approaches, including the attraction assay, in vitro RNA interference (RNAi), untargeted metabolomics, and hairy root transformation, to unveil the mechanisms by which weak host plants regulate Meloidogyne incognita chemotaxis towards host plants and control infection. Amaranth roots showed a direct repellence to M. incognita through disrupting its chemotaxis. The in vitro RNAi assay demonstrated that the Mi-flp-1 and Mi-flp-18 genes (encoding FMRFamide-like peptides) regulated M. incognita chemotaxis towards cucumber and controlled infection. Moreover, M. incognita infection stimulated cucumber and amaranth to accumulate distinct metabolites in both root tissues and rhizosphere soils. In particular, naringenin and salicin, enriched specifically in amaranth rhizosphere soils, inhibited the expression of Mi-flp-1 and Mi-flp-18. In addition, overexpression of genes involved in the biosynthesis of pantothenic acid and phloretin, both of which were enriched specifically in amaranth root tissues, delayed M. incognita development in cucumber hairy roots. Together, our results reveal that both the distinct host status and disruption of chemotaxis contribute to M. incognita inhibition in intercropping.
Topics: Animals; Tylenchoidea; Soil; Chemotaxis; Rhizosphere; Plants
PubMed: 37823341
DOI: 10.1111/mpp.13396 -
Heliyon Oct 2023Wheat bread is among stable foods that are nutritionally imbalanced, thus enrichment is crucial. We evaluated the nutritional impact of high-valued wheat bread enriched...
Wheat bread is among stable foods that are nutritionally imbalanced, thus enrichment is crucial. We evaluated the nutritional impact of high-valued wheat bread enriched with varying levels of meat powder from hen fed diet with insect ()-based meal. Crude protein and ash in bread increased with increasing inclusion of meat powder. Limiting amino acids like lysine and threonine in enriched bread products increased by 3.0-4.5 and 1.8-3.1-folds, respectively. Omega 3 fatty acids were significantly enhanced in bread fortified with meat powder. Vitamins (retinol, nicotinic acid, and pantothenic acid) were significantly increased in supplemented bread products. Iron, zinc, and calcium increased by 1.1, 1.2 and 3.0-folds in enriched bread with 30% meat powder. Colour, flavour and overall acceptability of breads prepared with 25 and 30% meat powder were highly ranked. Our findings demonstrate that meat powder (i.e., from hen fed insect-based diets) enrichment would provide added health and nutritional benefits to bread products without having adverse effects on any functional or sensory properties. Thus, this could be a novel strategy and trend for improving bread products, that might generate increasing demand for a healthier consumer-oriented lifestyle.
PubMed: 37810857
DOI: 10.1016/j.heliyon.2023.e20506 -
Heliyon Sep 2023A feeding trial was conducted to investigate the effect of fermented soybean meal with bacteria on growth performance, feed utilization, carcass composition, and...
A feeding trial was conducted to investigate the effect of fermented soybean meal with bacteria on growth performance, feed utilization, carcass composition, and hematological, and histological section of the liver and intestine of Nile tilapia fingerlings. Commercial soybean meal (SBM) containing 44% Crude Protein (CP) was fermented using the solid-state fermentation method which depended on autoclaving of SBM, then bacterial treatment injection by , and finally incubation at 40C for 72 h then autoclaved to stop the growth of bacteria. Five isonitrogenous (25% crude protein) and isocaloric (4.4 kcal\g gross energy) experimental fish meal-free diets were formulated to compare with a common control diet containing fishmeal and unfermented soybean meal. Diets without fish meal contain fermented soybean meal (FSM) as a sole protein, FSM with corn gluten (CG), FSM with free amino acid methionine (Meth), FSM with corn gluten and methionine, and unfermented soybean meal. Eighteen glass aquaria, 80-L net volume, were used to stock 10 fingerlings (10.0 ± 0.1 g/fish) in each aquarium in the replicates group. The feed amount was given three times daily, six days a week throughout the 98 days experimental period. Fish were weighed biweekly and feed amounts were adjusted based on the new fish weight. Bacterial fermentation enhanced the protein content of commercial soybean meals by 6%. The crude protein of fermented soybean meal increased from 43.44% to 50.67%. Used of FSM as a sole dietary protein source resulted in a decrease in growth rate and feed utilization. However, the incorporation of FSM with corn gluten, and/or methionine amino acid led to an improvement in the performance of fish. Finally, the best final body weight, weight gain, specific growth rate, protein efficiency ratio, and protein productive value were recorded by a fish-fed mixed plant protein diet (FSM + CG + Meth). Also, Hematocrit and red blood cells were not significantly affected including the FSM.
PubMed: 37809758
DOI: 10.1016/j.heliyon.2023.e19602 -
BMC Nutrition Sep 2023Present study aimed to assess potential health risk in Slovenian adolescents due to inadequate diet and/or dietary supplement (DS) use.
OBJECTIVE
Present study aimed to assess potential health risk in Slovenian adolescents due to inadequate diet and/or dietary supplement (DS) use.
METHODS
Data on DS use, micronutrient intake (24-h recall), eating habits (FFQ), body height and mass were collected within ACDSi (Analysis of Children's Development in Slovenia) cross-sectional study conducted in 2014. Adolescents enrolled in first year of 15 secondary schools (average (SD) age: 15.4 (0.7) years, N = 342) were included in the sample.
RESULTS
Adolescents' use of DS (especially multivitamins ingested as a popular drink (60%), magnesium (16%), and vitamin C (10%)) significantly contributed to their absolute intake of vitamins/minerals, resulting in higher percentage of DS users meeting reference values proposed by the nutrition societies of Germany, Austria, and Switzerland (D-A-CH recommendation). Simultaneously, DS users did not exceed the upper tolerable level proposed by the European Food Safety Authority for daily intake. With diet alone, adolescents consumed less than recommended amounts of the following vitamins/minerals: the intake was lowest for fat-soluble vitamins A, D, and E; water-soluble vitamins folate, biotin, and pantothenic acid; and minerals fluoride, iodine, chromium, and molybdenum. Suboptimal intake was due to the fact that around ¾ of adolescents consumed less than 54% of the recommended amounts (according to Optimized Mixed Diet (OMD) recommendations) for fruits, vegetables, milk/dairy products, fish, and cereals/cereal products. In contrast, the diet contributed to the consumption of 200-300% of D-A-CH minimum value for sodium. Furthermore, almost ¾ of adolescents exceeded the recommended amount for meat/meat products (320% of OMD) and sweet/salty snacks (453% of OMD).
CONCLUSIONS
Although DS use improved micronutrient intake in adolescents (especially vitamin C and magnesium), activities on public-health interventions should be focus to improve their diets, especially to achieve increased intakes of fruits, vegetables, cereals/cereal products and milk/dairy products, and to reduce consumption of sweet/salty snacks and meat products.
PubMed: 37770942
DOI: 10.1186/s40795-023-00768-z