PubMed

BMJ Open. 2024 Nov 21;14(11):e087684. doi: 10.1136/bmjopen-2024-087684.ABSTRACTINTRODUCTION: The gut microbiome plays an important role in maintaining both cognitive and physical functions in older adults, and gut dysbiosis is an important pathophysiological mechanism of mild cognitive impairment (MCI) in older adults. As a typical traditional Chinese mind-body exercise, regular Baduanjin training has been shown to improve cognitive function and modulate the gut microbiome in community-dwelling older adults. However, the potential role of the gut microbiome in the benefits of Baduanjin on cognitive function remains unclear. The aim of this study is to investigate the mediating effect of gut microbiome between regular Baduanjin training and improvement in cognitive function in community-dwelling older adults with MCI.METHODS AND ANALYSIS: This is a two-arm, randomised, parallel-controlled, single-blinded trial. Four residential communities (clusters) with a total of 64 eligible participants (16 participants in each residential community) will be randomised 1:1 to either the 24-week Baduanjin exercise intervention group (60 min per session, four sessions per week) or the no specific exercise intervention control group. Global cognitive function and the subdimensions of cognition including executive function, visuospatial function, language function and memory function will be assessed using the Montreal Cognitive Assessment Scale, Trail Making Test, Auditory Verbal Learning Test, Boston Naming Test-30 and Clock-Drawing Test, while the gut microbiome and its metabolomics will be detected using 16S rRNA and ultra-high-performance liquid chromatography-tandem mass spectrometry at baseline and at the end of 24-week intervention. The intervention effect of Baduanjin exercise and mediating role of gut microbiota will be analysed using linear mixed models and the bootstrapping method in the Hayes process.ETHICS AND DISSEMINATION: This study conforms to Declaration of Helsinki principles and relevant ethical guidelines. Ethical approval has been obtained from the Ethics Committee of the Shanghai University of Medicine and Health Sciences (approval number: 2023-GZR-011). Written informed consent will be obtained from all participants. Results will be disseminated to relevant groups in peer-reviewed journal(s), and at relevant international or national scientific conferences. Key findings will also be shared with social media, healthcare providers, participants or community-dwelling older adults to support access for non-research audiences.TRIAL REGISTRATION NUMBER: ChiCTR2300078147.PMID:39578030 | DOI:10.1136/bmjopen-2024-087684

Food Res Int. 2024 Dec;197(Pt 2):115231. doi: 10.1016/j.foodres.2024.115231. Epub 2024 Oct 29.ABSTRACTRice bran, a by-product of rice processing, is rich in various nutrients. As one of the main components of rice bran, dietary fiber has a variety of potential health benefits, especially its probiotic effects on gut health. This study involved the preparation and characterization of soluble rice bran dietary fibers (RB-SDF) and insoluble rice bran dietary fibers (RB-IDF), followed by an investigation into their gastrointestinal probiotic impact and principal metabolites. These results showed that rice bran dietary fiber could promote the production of short-chain fatty acids and the growth of probiotics during the fermentation in vitro. Specifically, RB-SDF significantly stimulated the growth of Bacteroides, Parabacteroides, and Acinetobacter, while RB-IDF encouraged the expansion of Tyzzerella, Pseudoflavonifractor, and Lachnospiraceae_UCG_004. Both dietary fibers could reduce the relative abundance of Escherichia_Shigella and Fusobacterium. The differential metabolites identified by untargeted metabolomics were l-pyroglutamic acid, d-(+)-tryptophan, indole-3-lactic acid, sulfolithocholic acid, 4-hydroxybenzaldehyde, indicating that different carbohydrates could significantly affect the metabolic profile of gut microbiota. Our finding indicated that rice bran dietary fiber can produce beneficial metabolites and modulate microbial ecosystems, which deserve further development for health applications.PMID:39577956 | DOI:10.1016/j.foodres.2024.115231

Food Res Int. 2024 Dec;197(Pt 2):115309. doi: 10.1016/j.foodres.2024.115309. Epub 2024 Nov 2.ABSTRACTPost-harvest air exposure is unavoidable during oyster transportation and storage, yet the physiological tolerance limits and underlying metabolic responses of commercially important oyster species remain poorly understood. While previous studies have focused on immediate post-harvest quality changes, there is limited knowledge about the time-dependent metabolic adaptations that determine product quality during extended air exposure. This study investigated the physiological and metabolic responses of Crassostrea hongkongensis during air exposure at 4 °C, focusing on identifying the optimal period for quality preservation. Using a combination of survival analysis, enzyme activity assays, and metabolomic profiling, we examined oysters exposed to air for up to 18 days, with particular emphasis on the critical first three days. Survival analysis showed 100 % survival rate at 4 °C through day 7, with mortality beginning thereafter, compared to significant mortality observed at 25 °C (complete mortality by day 7) and 37 °C (complete mortality by day 2). Analysis of antioxidant enzyme activities revealed complex, time-dependent changes, with robust responses observed within the first three days, indicating effective stress management. Metabolomic analysis identified 38 differentially abundant metabolites throughout the exposure period. Notably, the metabolic profile at day 3 showed a tendency to revert towards the control state, suggesting a temporary adaptive response. Key findings included stability in total antioxidant capacity (T-AOC) levels during the initial three days and subtle changes in flavor-related compounds, such as slight decreases in glutamate and aspartate levels. Correlation analyses revealed intricate interactions between enzyme activities and metabolites, highlighting complex stress response mechanisms. The relationship between T-AOC and key osmolytes underscored their critical role in maintaining cellular redox balance during the initial exposure period. Our findings suggest that the optimal window for maintaining C. hongkongensis quality during air exposure at 4 °C is within the first three days. During this period, oysters demonstrate effective adaptive responses, maintaining key quality attributes and nutritional value. Beyond this timeframe, the risk of quality degradation increases significantly. These results have important implications for the oyster industry, providing evidence-based guidelines for post-harvest handling, transportation, and storage practices. We recommend limiting air exposure during cold storage to no more than 3 days to ensure optimal product quality and consumer satisfaction.PMID:39577954 | DOI:10.1016/j.foodres.2024.115309

Food Res Int. 2024 Dec;197(Pt 2):115304. doi: 10.1016/j.foodres.2024.115304. Epub 2024 Nov 6.ABSTRACTFermentation can enhance nutritional value and safety of insect protein, this study utilized probiotic Bacillus subtilis (B. subtilis) and complex enzyme containing chitinase and protease to ferment the paste of Black Soldier Fly larva (BSFL), decomposing anti-nutritional factor chitin and protein in paste while inhibiting the proliferation of harmful microorganisms. The result indicated a 40 % degradation of chitin after fermentation, accompanied by an increase in the variety and quantity of amino acids and peptides, functional substances such as raffinose and cucurbitacin significantly increased, while the levels of antibiotics such as erythromycin and ofloxacin had decreased; after fermentation, there is a significant difference in the microbial distribution between bacteria, co-fermentation and CK, the indigenous microbiota of BSF and pathogenic bacteria such as Klebsiella pneumoniae and Clostridiaceae bacteria were significantly inhibited, anaerobic bacteria, including Anaerosalibacter, Caldicoprobacter and Tissierella, exhibit a marked increase; significant changes are detected in the carbon sources, amino acids, and key enzymes related to other metabolic pathways of B. subtilis during the fermentation process. Overall, we have developed a method for fermenting BSFL paste, aiming at enhance its probiotic properties, nutritional value, and safety. This study provided groundwork for utilizing fermented insects as a novel protein source for food and fodder.PMID:39577953 | DOI:10.1016/j.foodres.2024.115304

Food Res Int. 2024 Dec;197(Pt 2):115288. doi: 10.1016/j.foodres.2024.115288. Epub 2024 Nov 5.ABSTRACTTo achieve the triple purpose of enhancing lutein and protein contents as well as improving organoleptic properties in biomass of Auxenochlorella pyrenoidosa mutant as raw material of future food, a novel yellow mutant, CX41 strain, was successfully selected through atmospheric and room temperature plasma (ARTP) mutagenesis and norflurazon-based screening. CX41 strain exhibited a significantly increased lutein (0.86 mg/g) and protein (49.00 % DW) contents simultaneously, while higher levels of total (33.47 % DW) and essential amino acids (14.78 % DW) were achieved with higher amino acid score (86.49) than that of the original A4-1 strain, a yellow and high protein mutant bred previously. Sensory evaluation showed that CX41 biomass has more comparable to A4-1, while in comparison to the wild type (WT), it has a more inclination towards roasted, with a fainter grassy, woody, rancid and fishy odor, and a significant improvement in taste is reflected by a decrease of 8.40 % in sweetness, a reduction of 14.86 % in bitterness, and an increase of 5.93 % in umami intensity. Metabolome analysis revealed that the superior sensory profile was due to the significantly reduced relative odor activity of β-ionone (herbaceous odor) and substances such as 1-octene, hexanal, 1-octen-3-ol, and heptanal (fishy and rancid odors). The extensive enhancements demonstrated CX41 biomass as a highly promising raw material with high nutrients of lutein and protein as well as excellent taste and flavor for future food application.PMID:39577937 | DOI:10.1016/j.foodres.2024.115288

Food Res Int. 2024 Dec;197(Pt 2):115237. doi: 10.1016/j.foodres.2024.115237. Epub 2024 Oct 23.ABSTRACTIn the wine industry, Acetobacter sp. is a typical spoilage microorganism responsible for increased volatile acids and wine spoilage. This study investigated the impact of combined treatment using varying concentrations of resveratrol (RES) and pulsed electric field (PEF) on the bactericidal efficacy, intracellular enzyme activities, and cellular metabolism of Acetobacter sp. The results from the Weibull mathematical model revealed a notable enhancement in the bactericidal effectiveness of the RES and PEF treatments with increasing RES concentration. In addition, the synergies between RES and PEF might not only resulted in the deactivation of Alcohol dehydrogenase (ADH) and Aldehyde dehydrogenase (ALDH) of Acetobacter sp., but also induced modifications in the secondary and tertiary structures of intracellular enzymes as evidenced by fluorescence, ultraviolet, fourier transform infrared, and circular dichroism spectra. Furthermore, metabolomics results showed that 1,910 metabolites exhibited differential expression, with 1,118 metabolites being down-regulated and 792 metabolites being up-regulated. After the synergies between RES and PEF, 17 biochemical pathways were significantly changed, mainly involving amino acid metabolism, carbohydrate metabolism, cofactor and vitamin metabolism, nucleotide metabolism, etc. These findings demonstrated that the combined treatment of RES and PEF can effectively suppress the growth of Acetobacter sp. and the inactivation mechanism of Acetobacter sp. by PEF in conjunction with RES was revealed.PMID:39577929 | DOI:10.1016/j.foodres.2024.115237

Environ Res. 2024 Nov 20:120406. doi: 10.1016/j.envres.2024.120406. Online ahead of print.ABSTRACTElectronic waste dismantling has induced the surrounding agricultural soils suffered from combined contamination of heavy metals and organic pollutants. Lower efficiency and complex mechanisms of bioremediation remain to be resolved. Here, we adopted regulations to Sedum plumbizincicola cross aboveground and belowground scales to strengthen the bioremediation efficiency. Results showed that the S. plumbizincicola intercropping with the Astragalus sinicus L. that inoculated with Rhizobium had the highest performance in reduction of Cd, PBDEs and PCBs from soils by 0.11 mg/kg, 67.93 μg/kg and 38.91 μg/kg, respectively. Rhizosphere soil metabolomics analysis demonstrated that reductions in Cd and PBDEs significantly associated with 2-Methylhippuric acid and L-Saccharopine, which were involved in phenylalanine metabolism, biosynthesis of amino acids and lysine. Metagenomic analysis revealed that these functional pathways were mediated by Frankia, Mycobacterium, Blastococcus, etc. microbial taxa, which were also significantly altered by regulations. Moreover, regulation regimes significantly affected transcription genes of S. plumbizincicola. Functional annotation revealed that cross-scale regulations significantly improve bioremediation efficiency through microorganisms and metabolites in the rhizosphere and transcription genes of S. plumbizincicola, which were illustrated to promote plant growth and tolerance to environmental stress. Our integration of multi-omics provides comprehensive and deep insights into molecular mechanisms in the cross-scale regulations of S. plumbizincicola, which would favor remediation techniques advances for the soil contaminated by electronic waste dismantling.PMID:39577726 | DOI:10.1016/j.envres.2024.120406

Environ Pollut. 2024 Nov 20:125338. doi: 10.1016/j.envpol.2024.125338. Online ahead of print.ABSTRACTDaily dietary intake inevitably exposes individuals to various natural toxins, which may pose potential health threats. Focusing only on specific toxins could underestimate dietary risks. Therefore, we have developed a suspect and nontarget method based on ultrahigh-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) to screen both known and unknown natural toxins in various foodstuffs. An in-house database containing 2952 natural toxins including fungal toxins, phytotoxins, animal toxins and cyanotoxins was established, facilitating suspect screening. Predicted retention time and mass spectrometry data were employed to enhance the confidence levels. Subsequently, Nontarget screening method was conducted based on molecular network analysis, annotating the edges and nodes through modified types and fragmentation characteristics. Finally, we analyzed 102 foodstuff samples and identified a total of 90 natural toxins, including mycotoxins and phytotoxins, with 65 identified by suspect screening and 25 by nontarget screening. Based on measured concentrations, the daily per capita dietary intake of total natural toxins was estimated, it was below risk doses for natural toxins with available reference values. Overall, this work established a novel method for the comprehensive identification of natural toxins in foodstuffs and emphasized the importance of dietary risk assessment for natural toxins.PMID:39577611 | DOI:10.1016/j.envpol.2024.125338

Sci Total Environ. 2024 Nov 20:177681. doi: 10.1016/j.scitotenv.2024.177681. Online ahead of print.ABSTRACTDespite the knowledge of the effects of contaminants on periphyton, information is limited about their natural fluctuations in sensitivity to chemical stress between various months. In particular, the molecular and biochemical mechanisms associated with sensitivity of photosynthesis and its fluctuations remain poorly described. To tackle this lack of knowledge, meta-metabolomics offers a comprehensive picture of the sensitive molecular response preceding the physiological impact. This study aimed to describe changes in the sensitivity of periphyton to chemical stress at different months over one year and a half period, at both the physiological and molecular levels by measuring photosynthetic yield and meta-metabolome responses (targeted and untargeted approaches). Periphyton was colonized for four weeks and then exposed to a range of terbuthylazine concentrations (0.3-30 μg L-1) under controlled conditions for 4 h. Sensitivity was assessed by determining the benchmark doses for the meta-metabolome and photosynthesis, along with the cumulative distribution of aggregated metabolomics signals. The results showed a strong sensitivity shift in the meta-metabolome compared to a smaller shift in photosynthetic yield at different months. This study also confirmed the high sensitivity of the meta-metabolome, as most signals responded before photosynthesis. The annotation highlighted the discrepancies in the molecular response to TBA between the months in terms of metabolite classes (e.g. amino acids, alkaloids, and lipids), their sensitivity, and trends in common classes across months, and correlation to photosynthesis inhibition, notably oxylipins. Overall, this study highlights that the molecular response of the periphyton to chemical stress, and thus toxicity pathways, may differ between the months but can still lead to similar physiological responses.PMID:39577586 | DOI:10.1016/j.scitotenv.2024.177681

Curr Biol. 2024 Nov 19:S0960-9822(24)01495-7. doi: 10.1016/j.cub.2024.10.068. Online ahead of print.ABSTRACTThe tri-trophic interaction of plants, insect herbivores, and entomoviruses is an important topic in ecology and pest control. The susceptibility of insect herbivores to entomoviruses (e.g., nucleopolyhedroviruses) is influenced by host plants; however, the role of plant secondary metabolites in determining such susceptibility is poorly understood. Metabolomic analyses of Brassica oleracea, Glycine max, and Ipomoea aquatica plants, which differ in how they affect the susceptibility of Spodoptera exigua to nucleopolyhedroviruses among 14 plants, suggested that the plant secondary metabolites genistein, kaempferol, quercitrin, and coumarin play a role in influencing nucleopolyhedroviruses susceptibility. Subsequently, transcriptomic analysis of caterpillars, treated with nucleopolyhedroviruses alone or with one of these four phenolics, identified four genes (CYP340K4, CXE18, GSTe, and GSTe1) that were significantly downregulated by the phenolics. Functional characterization of these genes suggested that their downregulation significantly increased larval sensitivity to nucleopolyhedroviruses and altered aspects of the immune response. Our findings provide new insight into the role of plant defense metabolites in influencing the interactions between insect herbivores and entomopathogens and identify plant secondary metabolites as potential synergists of viral agents for the control of agricultural pests.PMID:39577425 | DOI:10.1016/j.cub.2024.10.068

Aquat Toxicol. 2024 Nov 18;278:107168. doi: 10.1016/j.aquatox.2024.107168. Online ahead of print.ABSTRACTNanopolystyrene (NP) pollution in aquatic environments has become an increasing concern. Phoxim (PHO), one of the major organophosphorus pesticides, has also been detected in aquatic environments, posing serious health risks to crustaceans. This study aimed to assess the detrimental effects of NP and/or PHO exposure at environmentally relevant concentrations on the intestinal histopathology, intestinal microbiota, and metabolome of adult crabs (Eriocheir sinensis) for 21 days. Our study revealed significant histopathological abnormalities in the intestines. In all the exposure groups, there was a discovery of vacuolar degeneration occurring in epithelial cells. Additionally, the peritrophic membrane exhibited thinning after NP or PHO single exposure, while thickening was observed after co-exposure. Exposure to NP and/or PHO disrupted the intestinal microbiota homeostasis, as evidenced by the proliferation of pathogenic bacteria and suppression of beneficial bacteria. Notably, PHO exposure resulted in increased abundance of pathogenic bacteria (Spiroplasma and Arcobacter) and decreased abundance of beneficial bacteria (Bacteroides). Analysis of the metabolome revealed that exposure to NP and/or PHO led to alterations in the metabolic profile as well as several critical pathways. Among these, the upregulation of arachidonic acid metabolism, ABC transporters, and biosynthesis of amino acids was observed in both NP single exposure and co-exposure, while PHO single exposure downregulated these pathways. Additionally, NP and/or PHO exposure downregulated neuroactive ligand-receptor interaction. Spearman correlation analysis revealed that the significant reduction of some differentially expressed metabolites (DEMs) was potentially regulated by the low-abundance bacterial genera following exposure to NP and/or PHO. And these DEMs have a role in anti-inflammatory or antioxidant properties. Collectively, our results offer novel perspectives on the intestinal toxicity of crustaceans by NP and/or PHO at environmentally relevant concentrations.PMID:39577361 | DOI:10.1016/j.aquatox.2024.107168

Anim Reprod Sci. 2024 Nov 14;272:107643. doi: 10.1016/j.anireprosci.2024.107643. Online ahead of print.ABSTRACTEfficient and sustainable reproduction and production of cattle and goats are vitally important for ensuring global food security. There is a need for potent biomarkers to accurately evaluate semen quality and predict male fertility. Although there is a reasonable set of biomarkers identified in bull sperm, there is a significant lack of such information in buck sperm along with a lack of transfer of proven technologies in goat reproductive biotechnology. These gaps are important problems because they are preventing advances in fundamental andrology and applied science of goat production. Both cattle and goats are ruminants, and they share significant similarities in their genetics and physiology although subtle differences do exist. This review harnesses the power of utilizing the knowledge developed in bull sperm to generate information on buck sperm fertility markers. These include genomic, functional genomic, epigenomic fertility markers. Revealing molecular underpinnings of such similarity and diversity using systems biology is expected to advance both fundamental and applied andrology of livestock and endangered species.PMID:39577268 | DOI:10.1016/j.anireprosci.2024.107643

Food Chem. 2024 Nov 15;465(Pt 2):142068. doi: 10.1016/j.foodchem.2024.142068. Online ahead of print.ABSTRACTFollowing our previous discovery that Lactiplantibacillus plantarum LCC-605 secreted spherical exopolysaccharide nanoparticles (EPS-605 NPs), which may contribute to the quality, function, and stability of the fermented yoghurt. We thus prepared the fermented skim milk with strain LCC-605 (Y-605) and investigated the functions and metabolic changes of Y-605. Y-605 showed excellent antioxidant activities with DPPH, ABTS+, and hydroxyl scavenging ability of 90.6 ± 0.1 %, 96.1 ± 0.2 %, and 99.3 ± 0.4 %, respectively, and cholesterol-lowering ability up to 39.9 %. After storage for 7 days, the bacterial count reached 10.9 log CFU/mL. EPS production significantly improved the water holding capacity (71.7 ± 0.5 %), and the texture of the yoghurt. Untargeted metabolomic analysis further revealed significant metabolomic differences between skim milk and Y-605, validating the beneficial mechanism of Y-605. This study develops a novel probiotic for producing functional yoghurts and provides the basis for understanding the beneficial mechanism of Y-605.PMID:39577262 | DOI:10.1016/j.foodchem.2024.142068

Food Chem. 2024 Nov 16;465(Pt 2):141995. doi: 10.1016/j.foodchem.2024.141995. Online ahead of print.ABSTRACTEgg yolk granules (EYGs) are water-insoluble components of egg yolk that are rich in protein and phospholipids. Improving the solubility of EYGs is crucial for their development and utilization. The solubilization of EYGs in a weak alkaline environment (pH 7.5-8.5) was investigated through physicochemical properties, microstructure analysis, and metabolomics. The results reveal a significant reduction in the average particle size of EYGs, ranging from 70.49 to 91.28 nm in weakly alkaline conditions. Microstructure and spectroscopic analyses indicate conformational changes in EYGs under these conditions, facilitating the solubilization of proteins, calcium, phosphorus and other components. Furthermore, metabolomics analyses confirms that depolymerization of EYGs promotes the release of glycerophospholipids. These findings underscore the beneficial effects of weakly alkaline conditions on the solubility of EYGs.PMID:39577258 | DOI:10.1016/j.foodchem.2024.141995

J Psychosom Res. 2024 Nov 19;188:111994. doi: 10.1016/j.jpsychores.2024.111994. Online ahead of print.ABSTRACTOBJECTIVE: Type D (Distressed) personality combines negative affectivity (NA) and social inhibition (SI) and is associated with an increased risk of cardiometabolic diseases. Here, we examined the association of Type D traits with 230 (predominantly) lipid metabolites and metabolite ratios.METHODS: Four Dutch cohorts were included, comprising 10,834 individuals. Type D personality traits were measured by self-report questionnaires. A proton nuclear magnetic resonance (NMR) metabolomics platform provided 149 absolute measures (98 belonging to lipoprotein subclasses) and 81 derived ratios. For all, linear regression analyses were performed within each cohort, followed by random-effects meta-analyses. A per-measure FDR q-value<0.05 was set as a study-wise significant association.RESULTS: SI was significantly associated with a lower omega-3 fatty acids to total fatty acids (FAw3.FA%) ratio, and a lower free cholesterol to total lipids ratio in very small VLDL (XS.VLDL.FC%). FAw3.FA% was also associated to NA (no study-wise significance though). NA showed a suggestive replication (p-value<.05) of the previous reported associations with depression for 5 out of 18 metabolites from the same metabolomics platform: triglycerides in HDL, serum total triglycerides, VLDL cholesterol, mean diameter for VLDL particles and VLDL triglycerides.CONCLUSIONS: In this large meta-analysis, SI was associated with omega-3 fatty acids to total fatty acids ratio, which is suggestive of lower omega-3 fatty acid intake. Only some metabolite biomarkers showed tentative links to Type D and NA. In sum, it seems that there are no major alterations in lipid metabolism associated with Type D traits.PMID:39577138 | DOI:10.1016/j.jpsychores.2024.111994

J Reprod Immunol. 2024 Nov 19;166:104397. doi: 10.1016/j.jri.2024.104397. Online ahead of print.ABSTRACTINTRODUCTION: Higher maternal body mass index (BMI) is associated with metabolic disturbances and pregnancy complications. We aimed to examine whether metabolic profiles in early pregnancy were associated with metabolic pregnancy complications in women with obesity (BMI ≥ 30 kg/m2).MATERIAL AND METHODS: Nested cohort study from a prospective longitudinal cohort (n = 1031) of women who were healthy prior to pregnancy and gave birth at Oslo University Hospital from 2002-2008. The sample comprised 81 women with obesity. Metabolic pregnancy complications included gestational diabetes mellitus, gestational hypertension and preeclampsia. In plasma samples from gestational weeks 14-16, 91 metabolites were analyzed by nuclear magnetic resonance spectroscopy. We performed a principal component analysis to reduce the metabolic dimensions. Logistic regression models were fitted to estimate crude and adjusted odds ratios (ORs) of metabolic pregnancy complications.RESULTS: Twenty-four out of 81 women developed metabolic pregnancy complications (gestational hypertension, preeclampsia, and/or gestational diabetes). Two of five principal components (80 % explained variance) were significantly associated with metabolic pregnancy complications. The ratio of monounsaturated to total fatty acids increased the risk of metabolic pregnancy complications (OR 2.09, 95 % confidence interval [CI] 1.25-3.75), while the ratio of polyunsaturated to monounsaturated fatty acids decreased the risk (OR 0.54, 95 % CI 0.30-0.89). The ratio of omega-3 to total fatty acids (OR 0.59, 95 % CI 0.34-0.98) and the ratio of docosahexaenoic acid to total fatty acids (OR 0.57, 95 % CI 0.31-0.97) also decreased the risk of metabolic pregnancy complications.CONCLUSION: Metabolic profile in early pregnancy was associated with risk of metabolic pregnancy complications in women with obesity. We observed the strongest associations between fatty acid composition and metabolic pregnancy complications.PMID:39577057 | DOI:10.1016/j.jri.2024.104397

Biomaterials. 2024 Nov 19;315:122971. doi: 10.1016/j.biomaterials.2024.122971. Online ahead of print.ABSTRACTAbnormal tumor metabolism leads to tumor growth, metastasis, and recurrence, reprogramming tumor metabolism and activating potent anti-tumor immune response have been demonstrated to have good therapeutic effects on tumor elimination. Copper-based nanomaterials involved in cuproptosis show great prospects in these two aspects, but their efficiency is restricted by Cu homeostasis and the toxicity of the chelator. Here, the pH-responsive AuNRs@Cu2O core-shell plasmonic hybrid nanorods (ACNRs) have been successfully fabricated to realize microenvironment-controlled release at the tumor site for the combined therapy of cuproptosis and photothermal treatment. The AuNRs core exhibited excellent NIR-II photothermal property, which boost the intracellular concentration of copper to trigger severe cuproptosis and induce immunogenic cell death of tumor cells. In vivo studies demonstrated the ACNR exhibited efficient tumor therapy for primary, metastatic, and recurrent tumors. ACNRs-induced cuproptosis and PTT were capable of reprogramming energy metabolism, leading to a decreased production of lactic acid. This potential of metabolic reprogramming assisted in reshaping the immunosuppressive tumor microenvironment to facilitate the infiltration of immune cells and boost the immune responses triggered by PTT. The therapeutic mechanism was further verified by metabolomics analysis, which indicated that ACNRs + PTT treatment led to the inhibition of the Pentose Phosphate Pathway and Glycolysis pathways in tumor cells. The suppression of glycolytic reduced ATP synthesis, thereby hindering energy-dependent copper efflux, which in turn promoted cuproptosis. Taken together, this study offers promising insights for cuproptosis-based cancer treatment and sheds new light on nanomedicine-mediated metabolic modulation for future tumor therapy.PMID:39577035 | DOI:10.1016/j.biomaterials.2024.122971

Metab Brain Dis. 2024 Nov 22;40(1):37. doi: 10.1007/s11011-024-01427-3.ABSTRACTOBJECTIVES: Given the unclear etiology and treatment mechanisms of depression, we aim to explore the metabolic differences between patients with major depressive disorder (MDD) and the healthy population, as well as before and after treatment with escitalopram (ESC).METHODS: Recruit first-episode drug-naïve MDD (DN-MDD) patients and healthy controls (HCs). Clinical data and serum samples from all subjects were collected at baseline and patients' samples were collected again after ESC monotherapy for four weeks. Perform non-targeted metabolomic analysis and apply MetaboAnalyst 5.0 to identify differential metabolites and execute KEGG pathway enrichment.RESULTS: Through metabolomic analysis of serum samples, 904 differential metabolites were identified in the DN-MDD group compared to the HCs, and 455 metabolites in treated patients compared to DN-MDD patients. In the pathway analysis, DN-MDD state regulated functions of histidine, beta-alanine, aspartate, and tryptophan metabolism, while ESC treatment produced an influence on the biological process of aspartate and sphingolipid.CONCLUSION: We respectively depicted metabolism-related biomolecular changes in the serum of patients suffering from MDD and undergoing ESC treatment. Multiple amino acid metabolism pathways were adjusted in MDD patients, and levels of aspartate, arginine and sphingolipids were regulated after ESC monotherapy. These biomolecular changes may bring new insights into the biology and treatment of MDD from the perspective of the serum metabolites.PMID:39576355 | DOI:10.1007/s11011-024-01427-3

Org Biomol Chem. 2024 Nov 22. doi: 10.1039/d4ob01395f. Online ahead of print.ABSTRACTRibosomally synthesized and post-translationally modified peptides (RiPPs) are intriguing compounds with potential pharmacological applications. While many RiPPs are known as antimicrobial agents, a limited number of RiPPs with anti-proliferative effects in cancer cells are available. Here we report the discovery of nostatin A (NosA), a highly modified RiPP belonging among nitrile hydratase-like leader peptide RiPPs (proteusins), isolated from a terrestrial cyanobacterium Nostoc sp. Its structure was established based on the core peptide sequence encoded in the biosynthetic gene cluster recovered from the producing strain and subsequent detailed nuclear magnetic resonance and high-resolution mass spectrometry analyses. NosA, composed of a 30 amino-acid peptide core, features a unique combination of moieties previously not reported in RiPPs: the simultaneous presence of oxazole/thiazole heterocycles, dehydrobutyrine/dehydroalanine residues, and a sactionine bond. NosA includes an isobutyl-modified proline residue, highly unusual in natural products. NosA inhibits proliferation of multiple cancer cell lines at low nanomolar concentration while showing no hemolysis. It induces cell cycle arrest in S-phase followed by mitochondrial apoptosis employing a mechanism different from known tubulin binding and DNA damaging compounds. NosA also inhibits Staphylococcus strains while it exhibits no effect in other tested bacteria or yeasts. Due to its novel structure and selective bioactivity, NosA represents an excellent candidate for combinatorial chemistry approaches leading to development of novel NosA-based lead compounds.PMID:39576263 | DOI:10.1039/d4ob01395f

mBio. 2024 Nov 22:e0334323. doi: 10.1128/mbio.03343-23. Online ahead of print.ABSTRACTIn a new respiratory virus pandemic, optimizing allocation of scarce medical resources becomes an urgent challenge. Infection prognosis takes on particular importance when allocating scarce antiviral antibodies and drugs, which are most effective when administered before the onset of severe disease. During arrival of the COVID-19 pandemic to the United States in 2020, we conducted a prognostic biomarker discovery and validation effort based upon metabolomic profiling with a liquid-chromatography-mass spectrometer (LC-MS) type used clinically for rapid toxicology. We obtained urine specimens from 163 patients presenting for evaluation. We obtained LC-MS profiles in the initial cohort and used machine learning methods to define a simplified urine metabolomic signature associated with respiratory failure or death by 90 days. This signature was composed of three metabotypes linked to intestinal microbiome metabolism and anticonvulsant use, with a receiver-operator characteristic area under the curve (ROC AUC) of 89.4%. Blinded application of this signature to the subsequent validation cohort yielded a ROC AUC of 81.2%. A model trained on the two baseline metabotypes present before intubation exhibited similar performance in the validation cohort. This study demonstrates the plausibility and promise of rapid metabolome-based prognostic discovery and validation in the opening wave of a pandemic. The approach used here could be used to inform therapeutic and resource allocation decisions early in a future epidemic.IMPORTANCEIn a new respiratory virus pandemic, the ability to identify patients at greatest risk for severe disease is essential to direct scarce medical resources to those most likely to benefit from them. Tools to predict disease severity are best developed early in a pandemic, but laboratory-based resources to develop these may be limited by available technology and by infection precautions. Here, we show that an accessible metabolic profiling approach could identify a prognostic signature of severe disease in the initial wave of COVID-19, when patients presenting for care often exceeded the available doses of convalescent plasma and remdesivir. In a future pandemic, this approach, alongside efforts to identify clinical disease severity predictors, could improve patient outcomes and facilitate therapeutic trials by identifying individuals at high risk for severe disease.PMID:39576111 | DOI:10.1128/mbio.03343-23