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
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

Ambient air pollution exposure, plasma metabolomic markers, and risk of type 2 diabetes: A prospective cohort study

Mon, 04/11/2024 - 12:00
J Hazard Mater. 2023 Oct 24;463:132844. doi: 10.1016/j.jhazmat.2023.132844. Online ahead of print.ABSTRACTBACKGROUND: Both air pollution (AP) and impaired lipid metabolism contribute to type 2 diabetes (T2D). However, little is known about the detailed associations of AP to lipidomic markers and the specific lipid metabolomic profile that mediates the impact of AP on incident T2D. We aimed to examine the associations between long-term AP exposure, plasma metabolomic markers, and incident T2D, and subsequently determine the lipid metabolomic profile that mediates the relationship between AP and T2D.METHODS: This prospective study included 82,548 participants from the UK Biobank without a history of T2D at baseline. Baseline plasma samples were analyzed using the nuclear magnetic resonance (NMR) metabolomic platform, which measured 168 metabolomic markers, including lipids, lipoprotein subclasses, and other circulating metabolites. Land Use Regression models were utilized to estimate annual average concentrations of PM2.5 and NO2. The associations among AP, metabolomic markers, and T2D were investigated using multivariable linear regressions and Cox proportional hazards models. Mediation analyses were performed to assess the role of each metabolomic marker in the AP-T2D relationship. Furthermore, principal component (PC) analysis was conducted on 168 metabolomic markers to extract metabolic patterns. These patterns were utilized to determine their associations with AP and T2D, as well as their mediating role in the AP-T2D relationship.RESULTS: We found that long-term AP exposure was associated with some lipid metabolites, including ApoA1, HDL concentration, HDL size, and lipid components within HDL, especially in very large, large, and medium HDL, as well as some other lipids, fatty acids, amino acids, glucose, and glycoprotein acetyls. In pairwise mediation analysis, these metabolites exhibited significant mediation effects in the AP-T2D relationship. We identified six PCS representing distinct metabolic patterns. Long-term exposure to PM2.5 and NO2 showed significantly negative associations with PC2 (characterized by high levels of ApoA1, larger HDL, other lipids, and low levels of larger VLDL). PC2 mediated 12.3% and 10.3% of the associations of PM2.5 and NO2 with incident T2D, respectively.CONCLUSIONS: This study revealed the associations of AP with various lipid metabolites. A lipid metabolomic profile characterized by ApoA1 and larger HDL may mediate the association between AP and incident T2D.PMID:39491993 | DOI:10.1016/j.jhazmat.2023.132844

The Sex Dependent and Independent Effects of Dietary Whey Proteins Are Passed from the Mother to the Offspring

Mon, 04/11/2024 - 12:00
Mol Nutr Food Res. 2024 Nov 3:e2400584. doi: 10.1002/mnfr.202400584. Online ahead of print.ABSTRACTSCOPE: The study assesses the metabolic impact of dietary whey proteins across generations.METHOD AND RESULTS: Virgin females are fed 20% energy whey proteins with 70% energy carbohydrates, which reduces body weight gain and visceral adipose compared to controls fed dietary casein. In contrast, the males are unresponsive. The effect is accentuated in reproductive females that also have reduced plasma levels of glucose. The responsive females have increased cecal levels of pyruvic and lactic acid, suggesting a greater catabolism of carbohydrates in the gut. While the male and female offspring born to mothers on whey proteins continue to reduce body weight gain, the female offspring further decreases the visceral and subcutaneous tissues and increases the gut capacity to breakdown dietary carbohydrates and proteins, whereas the male offspring are able to only decrease the visceral and increase protein catabolism in the gut. The ileum of male mice responded by reducing the gene expression for fibroblast growth factor 15 and increasing the expression of chymotrypsinogen B1.CONCLUSION: The effect of whey proteins on growth can be passed from the mother to the offspring without a sex preference, whereas the transmission of gut activity and adiposity are dependent on the sex of the offspring.PMID:39491812 | DOI:10.1002/mnfr.202400584

The Complement Factor H (Y402H) risk polymorphism for age-related macular degeneration affects metabolism and response to oxidative stress in the retinal pigment epithelium

Mon, 04/11/2024 - 12:00
Free Radic Biol Med. 2024 Nov 2:S0891-5849(24)01015-3. doi: 10.1016/j.freeradbiomed.2024.10.307. Online ahead of print.ABSTRACTAge-related macular degeneration (AMD), the leading cause of central vision loss in the elderly, involves death of the retinal pigment epithelium (RPE) and light-sensing photoreceptors. This multifactorial disease includes contributions from both genetic and environmental risk factors. The current study examined the effect of the Y402H polymorphism of Complement Factor H (CFH, rs1061170) and cigarette smoke, predominant genetic and environmental risk factors associated with AMD. We used targeted and discovery-based approaches to identify genotype-dependent responses to chronic oxidative stress induced by cigarette smoke extract (CSE) in RPE differentiated from induced pluripotent stem cells (iPSC) derived from human donors harboring either the low risk (LR) or high risk (HR) CFH genotype. Chronic CSE altered the metabolic profile in both LR and HR iPSC-RPE and caused a dose-dependent reduction in mitochondrial function despite an increase in mitochondrial content. Notably, cells with the HR CFH SNP showed a greater reduction in maximal respiration and ATP production. Significant genotype-dependent changes in the proteome were observed for HR RPE at baseline (cytoskeleton, MAPK signaling) and after CSE exposure, where a less robust upregulation of the antioxidants and significant downregulation in proteins involved in nucleic acid metabolism and membrane trafficking were noted compared to LR cells. In LR cells, uniquely upregulated proteins were involved in lipid metabolism and chemical detoxification. These genotype-dependent differences at baseline and in response to chronic CSE exposure suggest a broader role for CFH in modulating the response to oxidative stress in RPE and provides insight into the interaction between environmental and genetic factors in AMD pathogenesis.PMID:39491736 | DOI:10.1016/j.freeradbiomed.2024.10.307

Influenza A virus-induced glycolysis facilitates virus replication by activating ROS/HIF-1α pathway

Mon, 04/11/2024 - 12:00
Free Radic Biol Med. 2024 Nov 2:S0891-5849(24)01012-8. doi: 10.1016/j.freeradbiomed.2024.10.304. Online ahead of print.ABSTRACTAs a highly contagious acute respiratory disease, influenza A virus (A/WSN/1933) poses a huge threat to human health and public health. influenza A virus proliferation relies on glucose metabolism in host cells, yet the effects of influenza A virus on glucose metabolism and the underlying molecular mechanisms remain unclear. Here, we created models of WSN virus-infected mice and A549 cells, along with analyzing metabolomics and transcriptomics data, to investigate how WSN virus infection affects host cell glucose metabolism and specific mechanisms. Analysis of metabolites and gene expression showed that WSN virus infection triggers glycolysis in A549 cells, with notable upregulation of hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), hypoxia-inducible factor-1 alpha (HIF-1α), and elevated lactate levels. Additionally, it leads to mitochondrial impairment and heightened reactive oxygen species (ROS) generation. Elevated levels of glucose may enhance the replication of WSN virus, whereas inhibitors of glycolysis can reduce it. Enhancement of HIF-1α activation facilitated replication of WSN virus through stimulation of lactate synthesis, with the primary influence of glycolysis on WSN virus replication being mediated by ROS/HIF-1α signaling. Mice given HIF-1α inhibitor PTX-478 or glycolysis inhibitor 2-Deoxyglucose (2-DG) exhibited reduced lactate levels and decreased WSN virus replication, along with mitigated weight loss and lung damage. In summary, WSN virus-induced glycolysis has been demonstrated to enhance virus replication through the activation of the ROS/HIF-1α pathway, suggesting potential new targets for combating the virus.PMID:39491735 | DOI:10.1016/j.freeradbiomed.2024.10.304

(1)H NMR-Based Metabolomic Profiling and Comparison of Human Milk Across Different Lactation Stages in Secretors and Non-Secretors: A Study of Chinese Lactating Women

Mon, 04/11/2024 - 12:00
J Nutr. 2024 Nov 2:S0022-3166(24)01127-1. doi: 10.1016/j.tjnut.2024.10.050. Online ahead of print.ABSTRACTBACKGROUND: Human milk oligosaccharides (HMOs) and other milk-derived metabolites are crucial for infant health, influencing gut microbiota and overall development.OBJECTIVE: This study aims to uncover insights into the variations of HMOs and non-HMO metabolites based on secretor (Se) status, lactation time, mode of delivery, and infant sex.METHODS: An exploratory cross-sectional study was designed to compare the levels of HMOs and non-HMOs metabolites in milk samples from 129 lactating Chinese women within 1 year postpartum. Nuclear magnetic resonance analysis was employed for the identification and quantification of the metabolites. The metabolites measured were grouped into sugars, free amino acids, fatty acids, and metabolites related to energy metabolism. The influence of delivery mode and infant sex on milk metabolite composition were explored.RESULTS: Uniform Manifold Approximation and Projection (UMAP) analysis of HMOs profiles revealed distinct clustering based on Se status, with significant differences in 2'-FL and 3-FL levels observed between Se+ and Se- groups. A decreasing trend for 2'-FL and 6-'SL levels, along with an increase in 3-FL levels, was observed with increasing lactating period within 12 months postpartum. Non-HMOs metabolite analysis indicated that Se status only affected glutamate levels. An increase in glutamine levels was observed 3-9 months postpartum. A continuous increase in o-phosphocholine levels was noted in 12 months postpartum, along with reductions in citrate and sn-glycero-phosphocholine levels. Delivery mode and infant sex did not affect both HMOs and non-HMOs levels.CONCLUSIONS: Metabolomic analysis of human milk reveals significant variation of HMOs, but not in non-HMOs, based on Se status. Changes in certain HMOs and non-HMOs levels were also observed over the one year of lactation. Understanding how these metabolites change over time may influence recommendations for maternal diet, supplementation, and the timing of breastfeeding to ensure optimal nutrient delivery to the infant.PMID:39491676 | DOI:10.1016/j.tjnut.2024.10.050

Maternal Supplementation Spermidine During Gestation Improves Placental Angiogenesis and Reproductive Performance of High Prolific Sows

Mon, 04/11/2024 - 12:00
J Nutr Biochem. 2024 Nov 2:109792. doi: 10.1016/j.jnutbio.2024.109792. Online ahead of print.ABSTRACTSpermidine (SPD) is a widely recognized polyamine compound found in mammalian cells and plays a key role in various cellular processes. We propose that SPD may enhance placental vascular development in pregnant sows, leading to increased birth weight of piglets. Six hundred and nine sows at 60 days of gestation were randomly assigned into a basal diet (CON group), basal diet supplemented 10 mg/kg of SPD (SPD1 group), and basal diet supplemented 20 mg/kg of SPD (SPD2 group), respectively. Compared with the CON, SPD1 significantly increased the average number of healthy piglets per litter and the placental efficiency (P < 0.05), while the average number of mummified fetus per litter and the percentage of weak piglets significantly decreased (P < 0.05). In the plasma metabolomics, SPD content in plasma of sows (P = 0.075) and umbilical cord plasma of piglets (P = 0.078) had an increasing trend in response to SPD1. Furthermore, SPD1 increased the expression of the vascular endothelial cell marker protein, platelet endothelial cell adhesionmolecule-1 (PECAM-1/CD31) and the density of placental stromal vessels (P < 0.05). Moreover, as compared to CON, SPD2 significantly decreased the average number of mummified fetus per litter (P < 0.05), while the placental efficiency and the expression of amino acid transporter solute carrier (SLC) family 7, member7 (SLC7A7) and glucose transporters SLC2A2) and SLC5A4 in placental tissue significantly increased (P < 0.05). These results suggest that maternal supplementation of SPD during pregnancy increased healthy litter number, and promoted placental tissue development. Our findings provide evidence that maternal SPD has the potential to improve the production performance of sows.PMID:39491598 | DOI:10.1016/j.jnutbio.2024.109792

Decabromodiphenyl ethane (DBDPE) inhibited the growth and feeding by disrupting the gut and digestive gland homeostasis in octopus Amphioctopus fangsiao (Mollusca: Cephalopoda)

Mon, 04/11/2024 - 12:00
Sci Total Environ. 2024 Nov 2:177364. doi: 10.1016/j.scitotenv.2024.177364. Online ahead of print.ABSTRACTA novel brominated flame retardant decabromodiphenyl ethane (DBDPE) poses a potential threat to animals, but its effects on cephalopods remain unknown. In this study, Amphioctopus fangsiao, a common octopus in China, was exposed to DBDPE (0, 1, 50, 100, 300 μg/L) for 28 days. Chemical analysis revealed that the digestive gland bore a greater burden of DBDPE compared with other tissues. In addition, accumulated DBDPE could curb the growth and feeding performance of A. fangsiao. The potential effects on the "gut-digestive gland axis" were also elucidated. Specifically, DBDPE in the gut shifted the microorganisms toward a Bacteroidetes-dominated composition, and impaired the intestinal epithelial barrier, thereby triggering oxidative stress and inflammation. Excessive DBDPE also threatens the digestive gland function, including histological damage, immune reaction, oxidative stress, glucolipid metabolism dysfunction, and neurotoxicity. Metabolome plasticity enabled A. fangsiao to develop a DBDPE stress-adaptive metabolic profile via alteration of glucolipid metabolism, immunity, oxidative stress, and signaling molecules. Taken together, we identified a new detoxification mechanism linking the microbiota-gut-digestive gland axis with the growth and food intake of A. fangsiao, which is the first time it has been demonstrated in mollusks. These findings provided important clues for a further mechanism study and risk assessment of DBDPE.PMID:39491558 | DOI:10.1016/j.scitotenv.2024.177364

Microbial ecology and metabolite dynamics of backslopped triticale sourdough productions and the impact of scale

Mon, 04/11/2024 - 12:00
Int J Food Microbiol. 2023 Oct 18;408:110445. doi: 10.1016/j.ijfoodmicro.2023.110445. Online ahead of print.ABSTRACTTriticale (X Triticosecale Wittmack) is a hybrid of wheat (Triticum aestivum L.) and rye (Secale cereale L.), combining the positive attributes of both cereals. However, it has not been exploited for sourdough production yet. Further, the effect of scale on sourdough production has not been investigated systematically up to now. The aims of the present study were to assess the microbial ecology and metabolomic output of eleven spontaneously fermented, backslopped sourdough productions made with triticale flour on a scale of 100, 200, 500, and 1000 g. The acidification profile [pH and total titratable acidity (TTA)], microbial diversity (culture-dependent and culture-independent), metabolite dynamics, and appropriate correlations were determined. After ten fermentation steps, different species of Lactobacillaceae were prevalent in the mature sourdoughs, in particular Latilactobacillus curvatus, Limosilactobacillus fermentum, and Pediococcus pentosaceus. The microbial diversity could be traced back to the grains and was also present in the milling fractions (flour, bran, and shorts). Furthermore, thanks to the use of Illumina-based high-throughput sequencing and an amplicon sequence variant (ASV) approach, the presence of undesirable bacterial groups (bacilli, clostridia, and enterobacteria) during the initial steps of the backslopping cycle was revealed, as well as a finetuned taxonomic diversity of the LAB genera involved. Small sourdough productions (100 and 200 g) selected for a lower species diversity and reached a stable consortium faster than large ones (500 and 1000 g). Although a comparable final pH of 3.6-4.0 was obtained, the TTA of small sourdoughs was lower than that of large ones. Regarding the metabolic output, the simultaneous production of mannitol and erythritol, beyond ethanol and glycerol, could be linked to sourdoughs in which Liml. fermentum was the sole LAB species present. Further, the use of the arginine deiminase pathway by P. pentosaceus and Liml. fermentum was obvious. An appropriate extraction method followed by liquid injection gas chromatography coupled to triple quadrupole tandem mass spectrometry allowed the quantification of interesting volatile organic compounds, such as ethyl lactate. These findings support the inclusion of triticale as a viable alternative to wheat or rye for the production of sourdoughs that can be integrated into bread-making production schemes.PMID:39491387 | DOI:10.1016/j.ijfoodmicro.2023.110445

Insights into major pigment accumulation and (non)enzymatic degradations and conjugations to characterized flavors during intelligent black tea processing

Mon, 04/11/2024 - 12:00
Food Chem. 2023 Oct 27;437(Pt 1):137860. doi: 10.1016/j.foodchem.2023.137860. Online ahead of print.ABSTRACTIntelligently processed black teas (BT) possess premium quality but there is a lack in comprehensive understanding of flavor formation mechanism. In this study, the accumulation of carotenoids, flavonoids, and Maillard products and (non)enzymatic degradations and conjugations to characterized flavors were comprehensively studied. Significant decrease was observed that flava-3-ols were heavily oxidised from > 240 mg·g-1 in fresh leaves (FL) to < 30 mg·g-1, while other 21 flavonoids decreased by < 30% in BT, accompanied by a sweet aftertaste. Carotenes and xanthophylls, significantly accumulated during withering compared to FL (from 641 ± 39.7 μg·g-1 to 728 ± 44.9 μg·g-1) but decreased in BT. Strong correlations were confirmed between the 218 primary metabolites, carotenoids, and flavonoids, and their contributions to BT sweet tastes were elucidated. Furthermore, 45 floral/sweet volatiles with VIP > 1 originating from carotenoids, lipids, and amino acids were screened. An integrated illustration of pigments thermal- and enzymatic-dominated contributions to BT flavour was comprehensively conducted.PMID:39491256 | DOI:10.1016/j.foodchem.2023.137860

Tire rubber-derived contaminant 6PPD had the potential to induce metabolism disorder in early developmental stage of zebrafish

Mon, 04/11/2024 - 12:00
Comp Biochem Physiol C Toxicol Pharmacol. 2024 Oct 25:110062. doi: 10.1016/j.cbpc.2024.110062. Online ahead of print.ABSTRACTThe increasing release of tire-derived particles, particularly those containing N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD), into the environment has raised concerns regarding their ecological impact. This study aims to elucidate the toxicological effects of 6PPD on the metabolism in early developmental stage of zebrafish. Larval zebrafish were exposed to 10 and 100 μg/L 6PPD, and some endpoints in biochemical parameters, gene expression, and metabolism were analyzed. The results showed that 6PPD exposure disrupted glucolipid metabolism in zebrafish larvae, evidenced by increased triglyceride (TG) levels and decreased glucose content. Nile red staining indicated significant lipid accumulation in the liver and intestines. Additionally, RT-qPCR analysis revealed the upregulation of genes involved in lipid synthesis and metabolism, such as ppar-γ and fas, and downregulation of glycolysis-related genes like pk and gk. Furthermore, the untargeted metabolomics technique was used to identify a total of 220 differentially expressed metabolites (DEMs) with changes in amino acid metabolism, lipid metabolism, and the TCA cycle. KEGG pathway enrichment analysis highlighted disruptions mainly in Taurine and hypotaurine metabolism, Arginine and proline metabolism, and Histidine metabolism, which played very important roles on energy metabolism in zebrafish. The results provided some critical insights into the ecological risks associated with 6PPD.PMID:39490946 | DOI:10.1016/j.cbpc.2024.110062

Low molecular fucoidan alleviated alcohol-induced liver injury in BALB/c mice by regulating the gut microbiota-bile acid-liver axis

Sun, 03/11/2024 - 12:00
Int J Biol Macromol. 2024 Oct 25:136930. doi: 10.1016/j.ijbiomac.2024.136930. Online ahead of print.ABSTRACTFucoidan has attracted significant attention owing to its remarkable bioactivities, but the effect of molecular weight (Mw) on its activities in the context of alcoholic liver diseases (ALD) is poorly understood. In this study, low Mw fucoidan (OSLF) was prepared, and its protective effect against alcohol-induced liver injury was assessed in a mouse model. OSLF increased weight gain and colon length, improved lipid disorders, and reduced oxidative stress in mice exposed to alcohol, alleviating liver injury. OSLF alleviated inflammation in the liver by inhibiting alcohol-activated NF-κB and MAPK pathways. The underlying mechanism can be attributed to the improvement of alcohol-induced dysbiosis of the gut microbiota, including a decrease in Proteobacteria and Bacteroidetes and an increase in microbiota diversity, as well as the abundances of Parabacteroides, Bacteroides, and Faecalibaculum. Metabolomics results showed that OSLF improved alcohol-induced abnormalities of microbiota metabolites, primarily involving amino acid metabolism and short chain fatty acids production. In addition, OSLF ameliorated bile acid metabolism in the gut and regulated the expression of bile acid-associated genes in the liver, affecting bile acid synthesis, regulation, and transport. It suggested that OSLF had the potential for the management of ALD by regulating the gut microbiota-bile acid-liver axis.PMID:39490864 | DOI:10.1016/j.ijbiomac.2024.136930

Biochanin-A co-crystal formulation improves bioavailability and ameliorates cerulein-induced pancreatitis by attenuating the inflammation

Sun, 03/11/2024 - 12:00
Int J Pharm. 2024 Oct 26:124874. doi: 10.1016/j.ijpharm.2024.124874. Online ahead of print.ABSTRACTCo-crystallization of a therapeutic ingredient with an appropriate co-former is a powerful technique to augment the physicochemical and pharmacokinetic properties and the effectiveness of Active Pharmaceutical Ingredients (APIs). Biochanin A (BCA), a flavonoid with medicinal potential, is limited by poor solubility and low oral bioavailability. This study aimed to design and develop a novel BCA-nicotinamide cocrystal as BCC to enhance BCA's oral bioavailability and explore its therapeutic potential for ameliorating cerulein-induced acute pancreatitis (CIAP) by elucidating the target identification utilizing tissue/serum metabolite profiles. The cocrystal was designed by the supramolecular synthon approach and characterized by single-crystal X-ray diffraction that confirms a robust three-dimensional hydrogen-bonded network of BCA and Nicotinamide (NCT) in the crystal. FT-IR and DSC were used to analyze the cocrystal's intermolecular interactions and thermal behavior. BCC exhibited enhanced solubility and drug release compared to BCA alone, resulting in enhanced oral bioavailability and pancreatic tissue concentration. Comparing BCC to BCA in the CIAP model, BCC therapy remarkably reduced cerulein-induced pancreatitis, evidenced by significant reductions in inflammation, acinar cell atrophy, and amylase levels in pancreatic tissues. Further, the cocrystal formulation also down-regulated the oxidative stress markers, inflammatory cytokines and macrophage-related proteins. The study has identified distinct metabolomic signatures linked with AP with the help of Orbitrap Exploris mass spectrometry, which could pave the way for creating focused diagnostic tools for a better prognosis. In conclusion, these results offer new insights into exploring mechanistic pathways associated with specific biomarkers and underscore BCC cocrystals as a promising approach to enhance BCA's therapeutic potential.PMID:39490549 | DOI:10.1016/j.ijpharm.2024.124874

Scutellarein inhibits lung cancer growth by inducing cell apoptosis and inhibiting glutamine metabolic pathway

Sun, 03/11/2024 - 12:00
J Ethnopharmacol. 2024 Oct 26:118999. doi: 10.1016/j.jep.2024.118999. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Scutellaria baicalensis Georgi, a widely used Chinese medicinal herb, has shown effectiveness against lung cancer. Scutellarein, a key component of Scutellaria baicalensis, also demonstrates anticancer properties in lung cancer. However, the underlying mechanisms have not yet been clarified.AIM OF THE STUDY: This study aimed to investigate the effects of scutellarein in the treatment of NSCLC and its underlying mechanisms.METHODS: This study explored the effects of scutellarein on non-small cell lung cancer (NSCLC) and its mechanisms. A Lewis lung cancer mouse model was established to assess scutellarein's anticancer activity in vivo. Additionally, the compound's effects on cell proliferation, colony formation, migration, and apoptosis were evaluated in vitro using A549 and H1299 lung cancer cells. Metabolomics analysis was conducted to identify changes in cellular metabolism due to scutellarein, while molecular docking and western blotting techniques were employed to elucidate the molecular mechanisms of its anti-lung cancer effects.RESULTS: Scutellarein significantly inhibited lung cancer xenograft tumor growth. In vitro studies showed that scutellarein suppressed migration and colony formation in A549 and H1299 cells, induced cell cycle arrest, and triggered cell apoptosis. Notably, scutellarein profoundly altered amino acid metabolism, particularly affecting glutamine metabolites. It affected key glutamine transporters ASCT2 and LAT1, as well as glutaminase GLS1, leading to their reduced expression.CONCLUSION: Scutellarein effectively inhibits lung cancer growth both in vivo and in vitro by inducing cell apoptosis and downregulating the glutamine metabolic pathway.PMID:39490431 | DOI:10.1016/j.jep.2024.118999

Metabolomic characterization of MC3T3-E1pre-osteoblast differentiation induced by ipriflavone-loaded mesoporous nanospheres

Sun, 03/11/2024 - 12:00
Biomater Adv. 2024 Oct 23;166:214085. doi: 10.1016/j.bioadv.2024.214085. Online ahead of print.ABSTRACTThis study reports on the metabolic changes accompanying the differentiation of MC3T3-E1 osteoprogenitor cells induced by mesoporous bioactive glass nanospheres (nMBG) loaded with ipriflavone (nMBG-IP). Ipriflavone (IP) is a synthetic isoflavone known for inhibiting bone resorption, maintaining bone density, and preventing osteoporosis. Delivering IP intracellularly is a promising strategy to modulate bone remodeling at significantly lower doses compared to free drug administration. Our results demonstrate that nMBG are efficiently internalized by pre-osteoblasts and, when loaded with IP, induce their differentiation. This differentiation process is accompanied by pronounced metabolic alterations, as monitored by NMR analysis of medium supernatants and cell extracts (exo- and endo-metabolomics, respectively). The main effects include an early-stage intensification of glycolysis and changes in several metabolic pathways, such as nucleobase metabolism, osmoregulatory and antioxidant pathways, and lipid metabolism. Notably, the metabolic impacts of nMBG-IP and free IP were very similar, whereas nMBG alone induced only mild changes in the intracellular metabolic profile without affecting the cells' consumption/secretion patterns or lipid composition. This finding indicates that the observed effects are primarily related to IP-induced differentiation and that nMBG nanospheres serve as convenient carriers with both efficient internalization and minimal metabolic impact. Furthermore, the observed link between pre-osteoblast differentiation and metabolism underscores the potential of utilizing metabolites and metabolic reprogramming as strategies to modulate the osteogenic process, for instance, in the context of osteoporosis and other bone diseases.PMID:39490191 | DOI:10.1016/j.bioadv.2024.214085

Individual and combined effects of sodium dichloroisocyanurate and isothiazolinone on the cyanobacteria-Vallisneria natans-microbe aquatic ecosystem

Sun, 03/11/2024 - 12:00
J Hazard Mater. 2024 Oct 22;480:136229. doi: 10.1016/j.jhazmat.2024.136229. Online ahead of print.ABSTRACTThe use of algaecides to control high-density cyanobacterial blooms is often complicated by secondary pollution and the toxicity to non-target organisms. This study investigates the individual and combined effects of sodium dichloroisocyanurate (NaDCC, 5, 50, and 100 mg/L) and isothiazolinone (0.1, 0.5, and 1.5 mg/L) on a cyanobacteria-Vallisneria natans-microbe aquatic ecosystem, focusing on their interactions and ecological impacts. Results indicate that NaDCC could achieve a higher algae removal rate than isothiazolinone within 15 days, but has a greater negative effect on Vallisneria natans. Both algaecides disrupt nutrient and secondary metabolite balances at low and high concentrations, increasing nutrient loads and harmful substances. Optimal results were obtained with low concentrations of NaDCC (5 mg/L) and isothiazolinone (0.1 mg/L), effectively controlling cyanobacteria while minimizing harm to Vallisneria natans and reducing nutrient loads and microcystin accumulation. Algaecide application enhanced microbial diversity in water and leaves, shifting the dominant community from cyanobacteria to organisms adapted to the post-cyanobacterial decay environment. Metabolomic analysis indicated increased secretion of lipids and organic acids by cyanobacteria in response to algaecide stress. High concentrations of NaDCC and isothiazolinone disrupted nitrogen metabolism in cyanobacteria and induced ROS overproduction, affecting unsaturated fatty acid synthesis and other metabolic pathways. These findings highlight the importance of exploring different combinations of algaecides to reduce their concentrations, balance algal control with ecological stability, and offer insights for effective eutrophication management.PMID:39490170 | DOI:10.1016/j.jhazmat.2024.136229

Advanced metabolomics-based approach to reveal new insights into Bisphenol A metabolism and its presence in human excreta and water bodies in Taiwan

Sun, 03/11/2024 - 12:00
Ecotoxicol Environ Saf. 2024 Oct 26;286:117236. doi: 10.1016/j.ecoenv.2024.117236. Online ahead of print.ABSTRACTBisphenol A (BPA) is an environmental contaminant and can be detected in foodstuffs. Hence, investigating BPA metabolism in humans is crucial because certain BPA metabolites may exhibit similar or even greater be toxicity than does the parent compound. In this study, we used an advanced metabolomics-based data processing approach along with ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) to identify BPA metabolites in human liver enzyme incubation samples, and those metabolites were further detected in human excreta and water body samples in Taiwan. The first stage involved converting full-scan MS files from the incubation samples into feature information; this stage revealed 1056 and 2472 features with dose-response relationships in the BPA and isotopically labeled BPA incubation datasets, respectively. The second stage involved using stable isotope tracing to identify isotopic pairs from the two datasets; this stage revealed 190 isotopic pairs. An additional dose-response experiment was conducted to confirm that all these features with isotopic pairs also exhibited a dose-response relationship. To focus on the primary BPA metabolite features, we excluded those with low intensities (below 50,000). This left us with 86 features, which we then used for our analysis. To confirm these features as possible BPA metabolites, we compared the tandem MS (MS/MS) spectra between BPA and isotopically labeled BPA incubation samples. The results revealed 75 isotopic pairs with matching isotopically labeled MS/MS spectra. Among these identified features, one feature's m/z value matched to that of a previously reported BPA metabolite, and the other 74 features were novel. However, only 9 of them had proposed structures. We further investigated whether these features could be detected in humans or Taiwanese water bodies. Furthermore, 10 and 2 novel metabolites were identified in human urine and fecal samples, respectively; 17 novel metabolites were identified in the water samples. These findings indicate some of these novel metabolites are present not only in humans but also in various water bodies across Taiwan. These identified metabolites are phase I BPA metabolites, suggesting they may have toxic properties. Further research is warranted to investigate the structures of these newly discovered metabolites and assess their potential human health risks.PMID:39490109 | DOI:10.1016/j.ecoenv.2024.117236

Seasonal influence on tomato fruit metabolome profile: Implications for ABA signaling in multi-stress resilience

Sun, 03/11/2024 - 12:00
Plant Physiol Biochem. 2024 Oct 24;217:109234. doi: 10.1016/j.plaphy.2024.109234. Online ahead of print.ABSTRACTThe increasing effects of climate change are leading to an increase in the number and intensity of extreme events, making it essential to study how plants respond to various stresses occurring simultaneously. A crucial regulator of plant responses to abiotic stress is abscisic acid (ABA), as its accumulation in response to stress leads to transcriptomic and metabolomic changes that contribute to plant stress tolerance. In the present study, we investigated how ABA, stress conditions (salinity, water deficit and their combination) and seasons (autumn-winter and spring-summer) regulate tomato fruit yield and metabolism using tomato wild type (WT) and the ABA-deficient flacca mutant (flc) under stress conditions in cold and warm seasons. Our results showed that the applied stresses did not have the same effect in the warm season as in the cold season. In WT plants, the levels of other flavonoids, lignans and other polyphenols were higher in summer fruits, whereas the levels of anthocyanins, flavanols, flavonols, phenolic acids and stilbenes were higher in winter fruits. Furthermore, the significant increase in anthocyanins and flavonols was associated with the combination of salinity + water deficit in both seasons. Additionally, under certain conditions, flc mutants showed an enrichment of the superclasses of benzenoids and organosulphur compounds. The synthesis of phenolic compounds in flc fruits was also significantly different compared to WT plants. Thus, the metabolic profile of tomato fruits varies significantly with endogenous ABA levels, season of cultivation and applied stress treatments, highlighting the multifactorial nature of plant responses to combined environmental factors.PMID:39490099 | DOI:10.1016/j.plaphy.2024.109234

Co-selective effect of dissolved organic matter and chlorine on the bacterial community and their antibiotic resistance in biofilm of drinking water distribution pipes

Sun, 03/11/2024 - 12:00
Water Res. 2024 Oct 19;268(Pt A):122664. doi: 10.1016/j.watres.2024.122664. Online ahead of print.ABSTRACTThe proliferation of pathogenic bacteria and antibiotic resistance genes (ARGs) in the biofilm of drinking water distribution pipes poses a serious threat to human health. This work adopted 15 polyethylene (PE) pipes to study the co-selective effect of dissolved organic matter (DOM) and chlorine on the bacterial community and their antibiotic resistance in biofilm. The results indicated that ozone and granular activated carbon (O3-GAC) filtration effectively removed lignins and proteins from DOM, and chlorine disinfection eliminated carbohydrate and unsaturated hydrocarbons, which both contributed to the inhibition of bacterial growth and biofilm formation. After O3-GAC and disinfection treatment, Porphyrobacter, unclassified_d_bacteria, and Sphingopyxis dominated in the biofilm bacterial community. Correspondingly, the bacterial metabolism pathways, including the phosphotransferase system, phenylalanine, tyrosine and tryptophan biosynthesis, ABC transporters, and starch and sucrose metabolism, were downregulated significantly (p < 0.05), compared to the sand filtration treatment. Under such a situation, extracellular polymeric substances (EPS) secretion was inhibited in biofilm after O3-GAC and disinfection treatment, postponing the interaction between EPS protein and pipe surface, preventing bacteria, especially pathogens, from adhering to the pipe surface to form biofilm, and restraining the spread of ARGs. This study revealed the effects of various water filtration and disinfection processes on bacterial growth, metabolism, and biofilm formation on a molecular level, and validated that the O3-GAC filtration followed by chlorine disinfection is an effective and promising pathway to control the microbial risk of drinking water.PMID:39490093 | DOI:10.1016/j.watres.2024.122664

Diagnosis of systemic lupus erythematosus using cross-modal specific transfer fusion technology based on infrared spectra and metabolomics

Sun, 03/11/2024 - 12:00
Anal Chim Acta. 2024 Nov 22;1330:343302. doi: 10.1016/j.aca.2024.343302. Epub 2024 Oct 4.ABSTRACTBACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Currently, the medical diagnosis of SLE mainly relies on the clinical experience of physicians, and there is no universally accepted objective method for diagnosing SLE. Therefore, there is an urgent need to design an intelligent approach to accurately diagnose SLE to assist physicians in formulating appropriate treatment plans. With the rapid development of intelligent medical diagnostic technology, medical data is becoming increasingly multimodal. Multimodal data fusion can provide richer information than single-modal data, and the fusion of multiple modalities can effectively enhance the richness of data features to improve modeling performance.RESULTS: In this paper, a cross-modal specific transfer fusion technique based on infrared spectra and metabolomics is proposed to effectively integrate infrared spectra and metabolomics by fully exploiting the intrinsic relationships between features across different modalities, thus achieving the diagnosis of SLE. In this research, a Decision Level Fusion module is also proposed to fuse the representations of two specific transfers further, obtaining the final prediction scores. Comprehensive experimental results demonstrate that the proposed method significantly improves the performance of SLE prediction, with accuracy and Area Under Curve (AUC) reaching 94.98 % and 97.13 %, respectively, outperforming existing methods.SIGNIFICANCE: Our framework effectively integrates infrared spectra and metabolomics to achieve a more accurate prediction of SLE. Our research indicates that prediction methods based on different modalities outperform those using single-modality data. The Cross-modal Specific Transfer Fusion module effectively captures the complex relationships within each single modality and models the complex relationships between different modalities.PMID:39489981 | DOI:10.1016/j.aca.2024.343302

Effect of rapamycin on hepatic metabolomics of non-alcoholic fatty liver rats based on non-targeted platform

Sun, 03/11/2024 - 12:00
J Pharm Biomed Anal. 2024 Oct 22;253:116541. doi: 10.1016/j.jpba.2024.116541. Online ahead of print.ABSTRACTRapamycin (Rapa) is an inhibitor of mTOR complex, and its therapeutic effect on liver function was examined in non-alcoholic fatty liver disease (NAFLD) rats here. And the possible mechanism of Rapa in NAFLD was preliminarily elucidated based on the non-targeted metabolomics analysis. Adult male SD rats were fed with a high-fat and high-cholesterol diet (HFD) to establish NAFLD model. For Rapa group, 0.8 mg/(kg.d) Rapa was given to the HFD rats. Ultra-performance liquid chromatography and Q-Tof-mass spectrometry (UPLC and Q-TOF/MS) analysis were applied for the identification of metabolites in the serum of rats, which were annotated using Kyoto Encyclopedia of Genes and Genomes (KEGG). NAFLD rats presented with disturbed liver function, lipid metabolism and oxidative stress, but Rapa exerted a mitigating influence on the disorders. The metabolite profile data identified 579 metabolites that varied remarkably between the Rapa and HFD groups, with the main classes of amino acids and peptides, benzene, lipids and fatty acids. The differential metabolites were mainly involved in biosynthesis of cofactors, bile secretion, and glycerophospholipid metabolism were mainly enriched. In conclusion, Rapa has a potential protective effect against HFD-induced NAFLD, its hepatoprotective effect may achieved through mediating bile secretion and glycerophospholipid metabolism.PMID:39489928 | DOI:10.1016/j.jpba.2024.116541

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