PubMed

Zhongguo Zhong Yao Za Zhi. 2024 Nov;49(22):5998-6007. doi: 10.19540/j.cnki.cjcmm.20240508.401.ABSTRACTPlant polysaccharides are effective components that widely present in traditional Chinese medicine(TCM), exhibiting rich biological activities. However, as most plant polysaccharides cannot be directly absorbed and utilized by the human digestive system, it is now believed that their mode of action mainly involves interaction with intestinal microbiota, leading to the production of functional small molecules. The efficacy of Astragalus polysaccharide(APS) is extensive, including weight loss, improvement of fatty liver, reduction of blood lipids, and enhancement of insulin sensitivity, which may also be related to the regulation of intestinal microbiota. Adipose tissue senescence is an important characteristic of the physiological aging process in the body, often occurring prior to the aging of other important organs. Its main features include the accumulation of senescent cells and exacerbation of inflammation within the tissue. Therefore, to explore the potential protective effects of APS on aging, the improvement of adipose tissue aging phenotype in naturally aging mice was observed using APS, and combined with metagenomic metabolomics, corresponding microbial metabolic functional molecules were identified. Furthermore, functional tests in cell aging models were conducted. The results showed that APS significantly improved the adipocyte aging characteristics of naturally aging mice: specifically reducing aging-induced adipocyte hypertrophy; decreasing the protein expression of aging markers cyclin-dependent kinase inhibitor p21(P21) and multiple tumor suppressor 1(P16); lowering the tissue inflammation reaction. Metagenomic metabolomic analysis of serum from mice in each group revealed that APS significantly increased the content of indole-3-lactic acid(ILA) in naturally aging mice. Further in vitro studies showed that ILA could improve the aging of 3T3-L1 mouse embryonic fibroblasts induced by bleomycin, reduce the protein expression of the aging marker P21, alleviate inflammation, and enhance the ability of preadipocytes to mature. Therefore, APS had the efficacy of protecting naturally aging mice, and its action may be related to the increase in the intestinal microbiota metabolite ILA. This study suggested that TCM may serve as an important entry point for explaining the mechanism of action of TCM by regulating intestinal microbiota and their functional metabolites.PMID:39701698 | DOI:10.19540/j.cnki.cjcmm.20240508.401

Zhongguo Zhong Yao Za Zhi. 2024 Nov;49(22):5988-5997. doi: 10.19540/j.cnki.cjcmm.20240611.708.ABSTRACTParabacteroides distasonis is a gram-negative bacterium initially isolated from a clinical specimen in the 1930s. The strain was re-classified to form the new genus Parabacteroides in 2006. P. distasonis can regulate intestinal barrier function and plays a key role in immune response and metabolic regulation of bodies. Traditional Chinese medicine(TCM) is closely related to the intestinal microbiota. Polysaccharides, saponins, and other ingredients of TCM can treat diseases by interacting with P. distasonis, but the specific mechanisms underlying these processes are still unclear, requiring further exploration. This study reviewed the roles and related mechanisms of P. distasonis in inflammatory-immune diseases, metabolic diseases, cardiovascular disease, neuropsychiatric diseases, cancer, and other diseases and summarized the relevant research results of TCM to prevent and treat diseases by regulating P. distasonis. This study provides a reference for subsequent exploration of P. distasonis and research on the interaction between TCM and intestinal microbiota.PMID:39701697 | DOI:10.19540/j.cnki.cjcmm.20240611.708

Zhongguo Zhong Yao Za Zhi. 2024 Sep;49(18):4913-4924. doi: 10.19540/j.cnki.cjcmm.20240615.101.ABSTRACTTo explore the difference in metabolism and transcription between seeds experiencing space flight and ground seeds after morphological post ripening, this study utilized ginseng seeds experiencing space flight and ground seeds as materials. Metabolomics and transcriptomics analyses were conducted using ultra-high performance liquid chromatography-mass spectrometry(UPLC-MS) and high-throughput transcriptome sequencing(RNA-seq) technologies, so as to identify differential terpenoid metabolites, differential endogenous hormones, and differentially expressed genes. The results showed that through metabolomics analysis, a total of 22 differential terpenoid metabolites were identified in the experimental and control groups, including chikusetsusaponin FK_7, ginsenoside F_2, ginseno-side K, majoroside R_1, ginsenoside Re_5, 12-hydroxyabietic acid, etc; through transcriptomics analysis, 15 differential terpenoid metabolism-related differentially expressed genes were identified in the experimental and control groups, including FCase, AACT, PMK, etc, and these genes were integrated into the pathway based on the MEP and MVA. At the same time, genes related to the seed germination process such as LEC2, PIPK, PUF, REC, QUD, and PIR were screened. In the detection of endogenous hormones, a total of 17 differential hormone metabolites were obtained, including IAA, CK, JA, ABA, GA, and SA. Among them, the content of CK increased in the SP group, while the content of GA and SA decreased in the SP group. Genes related to CK, GA, and SA were also screened. This study laid the foundation for further exploration of the biosynthesis of terpenoid metabolites in ginseng seeds and the key endogenous hormones and enzyme genes involved in the seed germination process, and it provided a reference for the application of space flight mutagenesis technology in ginseng.PMID:39701674 | DOI:10.19540/j.cnki.cjcmm.20240615.101

J Dairy Sci. 2024 Dec 17:S0022-0302(24)01390-0. doi: 10.3168/jds.2024-25784. Online ahead of print.ABSTRACTOne-carbon metabolism (OCM) is a series of connected pathways involving the methionine-folate cycles, transsulfuration, polyamine synthesis, nucleotide synthesis, free-radical scavenging, and energy metabolism. These pathways functionally depend upon amino acids (methionine, glycine, and serine), vitamins (folate, B2, B6, and B12), and minerals (sulfur, cobalt, and zinc). Growing bodies of research indicate that in beef cattle, physiological stage, nutritional plane, diet, species (Bos taurus vs. indicus), rumen protected vs. not, individual vs. combination supplementation and method of delivery all affect the efficacy of one-carbon metabolite supplementation. Infusion studies showed that supplementing methionine to growing steers improved N retention and altered hepatic activity of methionine synthase; however, only supplementing methionine without folate decreased folate concentrations in circulation. When heifers were supplemented with methionine, choline, folate, and B12 for the first 63 d of gestation, metabolomic analysis revealed increasing OCM analytes to the heifer, but a buffering effect to the fetus with minimal changes seen in hepatic metabolite abundance. Methionine supplementation to heifers during the periconceptual period increased circulating methionine but shifted fetal hepatic metabolism toward the transsulfuration pathway. Periconceptual methionine supplementation to cows increased gain and total-tract digestibility in calves post-weaning. In vitro supplementation of choline to beef cattle embryos results in calves of increased birth and weaning weight. Overall, these data demonstrate that OCM is altered in those cattle receiving one-carbon metabolites, and that a metabolic programming response is elicited in offspring receiving supplements in vitro or during early gestation. Research should be considered to maximize efficiency of beef cattle production at all stages by identifying limiting metabolites or enzymes to maximize efficiency of OCM in beef cattle, as well as to understand the concerted effects of multiple one-carbon metabolites to balance the stoichiometry of the pathway.PMID:39701525 | DOI:10.3168/jds.2024-25784

Contemp Clin Trials. 2024 Dec 17:107776. doi: 10.1016/j.cct.2024.107776. Online ahead of print.ABSTRACTINTRODUCTION: Effective spontaneous preterm birth (sPTB) prevention is an urgent unmet clinical need. Vaginal depletion of Lactobacillus crispatus is linked to sPTB. This trial will investigate impact of an oral Lactobacillus spp. probiotic product containing an L. crispatus strain with other Lactobacilli spp., on the maternal vaginal and gut microbiome in pregnancies high-risk for sPTB.METHODS: A double-blind, placebo-controlled, randomised trial will be performed at the National Maternity Hospital Dublin, Ireland. Inclusion criteria are women with history of sPTB or mid-trimester loss, cervical surgery (cone biopsy or two previous large-loop-excision-of-transformation-zone) or uterine anomaly. The intervention is oral supplementation for twelve weeks with probiotic or identical placebo. The probiotic will contains: ◦ 4 billion CFU Lactobacillus crispatus Lbv 88(2x109CFU/Capsule) ◦ 4 billion CFU Lactobacillus rhamnosus Lbv 96(2x109CFU/Capsule) ◦ 0.8 billion CFU Lactobacillus jensenii Lbv 116(0.4x109CFU/Capsule) ◦ 1.2 billion CFU Lactobacillus gasseri Lbv 150(0.6x109CFU/Capsule) Investigators and participants will be blinded to assignment.RESULTS: The primary outcome is detectable L. crispatus in the vaginal microbiome after twelve weeks of treatment, measured using high-throughput DNA sequencing. A total of 126 women are required to detect a 25 % increase in detectable L. crispatus. Secondary outcomes include impact of intervention on the gut microbiome and metabolome, rate of sPTB and mid-trimester loss, neonatal outcomes and maternal morbidity.CONCLUSIONS: This randomised trial will investigate ability of an oral probiotic containing L. crispatus to increase its abundance in the vaginal microbiome, both directly by horizontal transfer and indirectly via microbiome and metabolome of the gut.PMID:39701375 | DOI:10.1016/j.cct.2024.107776

Int J Biol Macromol. 2024 Dec 17:138831. doi: 10.1016/j.ijbiomac.2024.138831. Online ahead of print.ABSTRACTHexokinase 2 (HK2) plays a vital role in mitochondrial homeostasis; however, the molecular mechanisms underlying its involvement in high-concentrate diet-induced damage in the ruminal epithelium of dairy cows are poorly understood. This study aimed to explore the regulatory role of HK2 in mitochondrial function and responses to inflammation in the rumen of dairy cows fed a high-concentrate diet. Our results showed that, compared with a low-concentrate (LC) diet, feeding a high-concentrate (HC) diet increased oxidative stress and reduced relative antioxidant gene expression levels and enzyme activities in the ruminal epithelium. Furthermore, the expression of genes related to mitochondrial biosynthesis and structure decreased in the HC group, concomitant with nuclear oligomerization domain (NOD)-like receptor 3 (NLRP3) signaling pathway activation, which compromised normal rumen epithelium function. Meanwhile, transcription results showed the same trend in HK2-knockout bovine rumen epithelial cells (HK2KO BRECs) related to wild-type (WT) BRECs. Notably, the knockout of HK2 aggravated mitochondrial dysfunction, resulting in the impairment of mitochondrial morphology and quality, a reduction in mitochondrial membrane potential (MMP), mitochondrial permeability transition pore (MPTP) opening, increased reactive oxygen species (ROS) generation, and decreased expression of antioxidant genes. These changes led to upregulating genes and proteins in the NLRP3 pathway and activating proinflammatory response. In addition, metabolomic results showed that knockout HK2 altered the glycerophospholipid metabolic pathway. This study provides new strategies for mitigating high-concentrate diet-induced injury in the ruminal epithelium of dairy cows.PMID:39701238 | DOI:10.1016/j.ijbiomac.2024.138831

Toxicol Appl Pharmacol. 2024 Dec 17:117203. doi: 10.1016/j.taap.2024.117203. Online ahead of print.ABSTRACTCadmium (Cd) is among the top seven most hazardous environmental contaminants. Minimal risk levels for daily exposure have been established, such as no observable adverse effect level (NOAEL) and lowest observable adverse effect level (LOAEL). Chronic exposure to Cd, at both NOAEL and LOAEL doses, causes toxicity in diverse tissues. However, Cd toxicity in adipose tissue, an endocrine and metabolic organ, remains relatively understudied. We aimed to investigate the potentially toxic effects of chronic Cd exposure (at NOAEL and LOAEL doses) on epidydimal adipose tissue of adult male Wistar rats. Ninety male Wistar rats were divided into three groups (n = 30): Control Cd-free, NOAEL, and LOAEL that received CdCl2 in drinking water for 15 days to 5 months. We evaluated over time zoometry, serum and adipose Cd concentration, redox balance, GLUT4 and Nrf2 expression, histology, leptin, adiponectin, adipose insulin resistance index, free fatty acids, and glucose tolerance. The higher dose group showed a more pronounced and sustained increase in serum and adipose tissue of Cd concentration. Zoometry was similarly affected in both Cd-exposed groups with adipocyte hypertrophy. The redox balance was maintained due to the augmenting of Nrf2 expression. Leptin concentration augmented, while adiponectin diminished. Adipose insulin resistance increased simultaneously to lipolysis and glucose intolerance despite high GLUT4 expression. In conclusion, this study provides strong evidence that chronic Cd exposure, even at minimal risk levels (LOAEL and NOAEL doses), has toxic effects, disrupting the function of epididymal adipose tissue and contributing to metabolic disorders.PMID:39701214 | DOI:10.1016/j.taap.2024.117203

Prog Neuropsychopharmacol Biol Psychiatry. 2024 Dec 17:111223. doi: 10.1016/j.pnpbp.2024.111223. Online ahead of print.ABSTRACT3,4-Methylenedioxymethamphetamine (MDMA; Ecstasy) is a widely abused recreational drug that has also gained interest for potential clinical applications in mental health. With the growing recognition of gut microbiota's role in mental health, this study examined whether repeated oral MDMA administration could affect gut microbiota in the small intestine, cecum, and colon of male rats. Repeated oral MDMA administration (10 mg/kg/day for 14 days) caused significant changes in the gut microbiota across these regions, with distinct effects observed in each. PICRUSt2 analysis revealed significant alterations in several metabolic pathways in these regions, indicating potential shifts in microbial functional capabilities associated with MDMA treatment. Untargeted metabolomics analysis revealed that MDMA significantly altered levels of two metabolites-ferulic acid and methylmalonic acid-in the colon, without changes in the blood, small intestine, or cecum. Notably, methylmalonic acid levels in the colon positively correlated with Lawsonibacter and Oscillibacter. These findings suggest that repeated oral MDMA treatment can alter gut microbiota composition across intestinal regions, potentially contributing to its pharmacological effects.PMID:39701173 | DOI:10.1016/j.pnpbp.2024.111223

NMR Biomed. 2025 Jan;38(1):e5299. doi: 10.1002/nbm.5299.ABSTRACTTo improve reliability of metabolite quantification at both, 3 T and 7 T, we propose a novel parametrized macromolecules quantification model (PRaMM) for brain 1H MRS, in which the ratios of macromolecule peak intensities are used as soft constraints. Full- and metabolite-nulled spectra were acquired in three different brain regions with different ratios of grey and white matter from six healthy volunteers, at both 3 T and 7 T. Metabolite-nulled spectra were used to identify highly correlated macromolecular signal contributions and estimate the ratios of their intensities. These ratios were then used as soft constraints in the proposed PRaMM model for quantification of full spectra. The PRaMM model was validated by comparison with a single-component macromolecule model and a macromolecule subtraction technique. Moreover, the influence of the PRaMM model on the repeatability and reproducibility compared with those other methods was investigated. The developed PRaMM model performed better than the two other approaches in all three investigated brain regions. Several estimates of metabolite concentration and their Cramér-Rao lower bounds were affected by the PRaMM model reproducibility, and repeatability of the achieved concentrations were tested by evaluating the method on a second repeated acquisitions dataset. Although the observed effects on both metrics were not significant, the fit quality metrics were improved for the PRaMM method (p ≤ 0.0001). Minimally detectable changes are in the range 0.5-1.9 mM, and the percentage coefficients of variations are lower than 10% for almost all the clinically relevant metabolites. Furthermore, potential overparameterization was ruled out. Here, the PRaMM model, a method for an improved quantification of metabolites, was developed, and a method to investigate the role of the MM background and its individual components from a clinical perspective is proposed.PMID:39701127 | DOI:10.1002/nbm.5299

J Pharm Biomed Anal. 2024 Dec 16;255:116638. doi: 10.1016/j.jpba.2024.116638. Online ahead of print.ABSTRACTUnderstanding the pharmacodynamics of ritonavir through metabolomics offers insights into its side effects and helps in the development of safer therapies. This study aimed to investigate the effects of ritonavir treatment on the metabolic profiles of rabbits via a metabolomics approach, with the objective of elucidating its impact on various biochemical pathways and identifying relevant biomarkers. The rabbits were divided into control and ritonavir-treated groups, and their plasma samples were analyzed via ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF/MS/MS). Metabolites were identified on the basis of the masscharge ratio (m/z) and validated via XCMS software. Metabolites with a fold change ≥ 1.5 and P ≤ 0.01 were analyzed via principal component analysis (PCA) and orthogonal partial least squares discrimination analysis (OPLS-DA) to distinguish between the groups. MetaboAnalyst 6.0 was used for pathway analysis to identify metabolic pathways affected by ritonavir. The PCA and OPLS-DA models revealed clear separation between the control and ritonavir-treated groups, with high R² and Q² values indicating robust model performance. Pathway analysis revealed that ritonavir treatment significantly affected several metabolic pathways, including those related to ether lipid, phenylalanine, sphingolipid, and glycerophospholipid metabolism. Particularly significant changes were observed in metabolites related to lipid metabolism, oxidative stress responses and cellular signaling. Ritonavir significantly impacts metabolic pathways, particularly those involved in lipid metabolism, and oxidative stress responses, which may influence immune responses and drug interactions. This study also highlights the potential of integrating metabolomics with personalized medicine approaches to optimize ritonavir treatment strategies and reduce adverse effects. These findings indicate that ritonavir significantly influences cellular homeostasis and metabolic processes in addition to its antiviral properties. This highlights the necessity of comprehending the metabolic effects of ritonavir to enhance its clinical application, especially in the management of COVID-19. Further research is warranted to explore these alterations and their implications for therapeutic strategies.PMID:39700866 | DOI:10.1016/j.jpba.2024.116638

Food Chem. 2024 Dec 14;468:142492. doi: 10.1016/j.foodchem.2024.142492. Online ahead of print.ABSTRACTAstragali radix (HQ) is a herb with rich medicinal and edible value. Wild-simulated HQ (FYS) and Transplanted HQ (PZ) are its currently two primary forms available in the market. Metabolomics was employed to investigate their intricate metabolic variations under various cultivation methods and growth years. Notable similarities were observed in their metabolic changes across various growth years. Specifically, saponins was higher in the early growth phase, while flavonoids increased in the later. Additionally, comparative analysis of HQ samples from different cultivation methods indicated that FYS generally exhibited different chemical characteristics compared to PZ within the same market circulation period, and Calycosin-7-O-Glc-6"-O-acetate and Cycloastragenol-H2O might be used to discriminant them (the content of Calycosin-7-O-Glc-6"-O-acetate and Cycloastragenol-H2O was higher in FYS than in PZ). This approach elucidates the dynamic change pattern of characteristic metabolites and pinpoints potential biomarkers for both FYS and PZ, thereby enhancing our understanding of these medicinal materials.PMID:39700793 | DOI:10.1016/j.foodchem.2024.142492

Comp Biochem Physiol Part D Genomics Proteomics. 2024 Dec 13;54:101401. doi: 10.1016/j.cbd.2024.101401. Online ahead of print.ABSTRACTHypoxia disrupts multiple physiological processes, including metabolism, immunity, and reproduction in teleosts. The brain plays a critical role in adapting to environmental changes, regulating the endocrine system, and controlling reproduction. The present study investigated the sex-specific cerebral responses to chronic hypoxia through an integrated analysis of the transcriptome, proteome, and metabolome of yellow catfish. Common cerebral responses in both females and males included activation of the HIF signaling pathway, angiogenesis, and improved oxygen delivery by red blood cells. Reproductive defects were indicated by the downregulation of gh1, cga, and tshb in both sexes. Thyroid hormone homeostasis was more severely disrupted by hypoxia in females than in males, accompanied by a significant decrease in the level of VTG in the female brain. Damaged brain function was evidenced by the highly enriched pathways of "cytokine-cytokine receptor interaction" and "ECM-receptor interaction," and the blood-brain barrier (BBB) also appeared to be disrupted in female fish. In the male brain, reproductive-related genes or proteins, including prl, lepr, and AVP, were specifically decreased. Dysfunction in the male brain was also indicated by the enrichment of pathways such as "cytokine-cytokine receptor interaction" and "neuroactive ligand-receptor interaction," based on differentially expressed genes (DEGs) and proteins (DEPs). Additionally, chronic hypoxia appeared to inhibit cerebral amino acid metabolism in males. In summary, our results offer insight into understanding the sex-specific cerebral responses induced by chronic hypoxia in teleosts.PMID:39700741 | DOI:10.1016/j.cbd.2024.101401

Environ Int. 2024 Dec 11;195:109180. doi: 10.1016/j.envint.2024.109180. Online ahead of print.ABSTRACTOrganic fertilizer application promotes the prevalence of antibiotic resistance genes (ARGs), yet the factors driving temporal differences in ARG abundance under long-term organic fertilizer application remain unclear. This study investigated the temporal dynamics of ARG diversity and abundance in both bulk and rhizosphere soils over 17 years (2003-2019), and explored microbial evolution strategies, ARG hosts succession and the influence of root exudates on ARGs regulation. The results showed that the ARGs abundance in rhizosphere soil was lower than that in bulk soil under long-term fertilization, and ARGs abundance exhibited a decrease and then remained stable in rhizosphere soil over time. There was a strong association between host bacteria and dominant ARGs (p < 0.05). Structural equations demonstrated that bacterial community had a most pronounced influence on ARGs (p < 0.05), and metabolites exhibited an important mediation effect on bacterial community (p < 0.05), thereby impacting ARGs. The metabolome analysis evidenced that significant correlations were found between defensive root exudates and most ARGs abundance (p < 0.05), like, luteolin-7-glucoside was negatively correlated with tetA(58). These findings provide deeper insights into the dynamics of soil ARGs under long-term fertilization, and identify critical factors that influence ARGs colonization in soils, providing support for controlling the spread of ARGs in agriculture soils.PMID:39700687 | DOI:10.1016/j.envint.2024.109180

Poult Sci. 2024 Nov 10;104(1):104506. doi: 10.1016/j.psj.2024.104506. Online ahead of print.ABSTRACTThe use of bio-enzyme as feed additives holds significant potential. This study aimed to evaluate the impact of a kind of compound bio-enzyme supplementation (the main functional components are probiotics and astragalus polysaccharides) on the production performance, serum immunity, and intestinal health of Pekin ducks. A total of 126 male Pekin ducks were randomly assigned to three groups: a control group (CG, no additive), a low-dose group (LG, 0.1 % bio-enzyme), and a high-dose group (HG, 0.2 % bio-enzyme), with 6 replicates per group. Ducks were raised until 35 days of age, with weekly measurements of growth performance. At day 35, serum immunoglobulins were measured, carcass traits were recorded, and cecal contents were analyzed using 16S rRNA sequencing and metabolomics. Results indicated a significant increase in ADG (P = 0.049) and a decrease in feed-to-gain ratio (F:G) (P = 0.020) in LG and HG compared to CG during rearing. The HG showed a notable improvement in half eviscerated yield (HEY) (P = 0.023) and full eviscerated yield (FEY) (P = 0.008). No substantial changes were observed in immunological parameters (P > 0.05). The jejunal villus height to crypt depth ratio (VH/CD) significantly increased (P < 0.001) in LG, with notable improvements in duodenal (P = 0.001) and jejunal (P < 0.001) VH/CD in HG. The Shannon index (P = 0.042) and Pielou index (P = 0.038) of cecal microbiota were markedly lower in HG. Notable changes in the relative abundance of Firmicutes and Bacteroidota were observed in LG and HG. Differential bacteria and metabolites among the treatments were identified, and their correlations were analyzed. KEGG enrichment pathways of the metabolites were also identified. In conclusion, this bio-enzyme can improve production performance, intestinal wall structure, and microbiota in Pekin ducks. A 0.1 % concentration of this bio-enzyme is optimal for Pekin duck production.PMID:39700598 | DOI:10.1016/j.psj.2024.104506

J Exp Bot. 2024 Dec 19:erae506. doi: 10.1093/jxb/erae506. Online ahead of print.ABSTRACTUnderstanding how crop varieties acclimate to elevated temperatures is key to priming them for future climates. Here, we exposed two genotypes of Sorghum bicolor (one sensitive to heat shock (Sen) and one tolerant (Tol)) from multiple growth temperatures to a six-day heat shock (reaching 45°C), carrying out a suite of measurements before and during heat shock. Sen consistently reduced photosynthetic functioning during heat shock, while Tol increased its photosynthetic rate. Higher abundance of heat shock protein transcripts and metabolites related to heat tolerance were noted for Tol when compared to Sen both before and during heat shock, which can be attributed to constitutive and inducible responses to elevated temperatures. In addition, important changes in metabolic pathways were clearly identified for Tol during heat shock (including upregulation of raffinose family oligosaccharides and downregulation of the GABA catalytic pathway), even as the concentration of hexose sugars became depleted. We infer Tol was able to tolerate elevated temperatures due to an upregulation of osmoprotectants, chaperones and reactive oxygen species scavengers and by the suppression of SnRK1 via transcripts and metabolites during heat shock. Our results highlight potential targets for attributes of high temperature tolerance which can be utilised in future breeding trials.PMID:39700407 | DOI:10.1093/jxb/erae506

PLoS One. 2024 Dec 19;19(12):e0315330. doi: 10.1371/journal.pone.0315330. eCollection 2024.ABSTRACTMembrane transporters are responsible for moving a wide variety of molecules across biological membranes, making them integral to key biological pathways in all organisms. Identifying all membrane transporters within a (meta-)proteome, along with their specific substrates, provides important information for various research fields, including biotechnology, pharmacology, and metabolomics. Protein datasets are frequently annotated with thousands of molecular functions that form complex networks, often with partial or full redundancy and hierarchical relationships. This complexity, along with the low sample count for more specific functions, makes them unsuitable as classes for supervised learning methods, meaning that the creation of an optimal subset of annotations is required. However, selection of this subset requires extensive manual effort, along with knowledge about the biology behind the respective functions. Here, we present an automated pipeline to address this problem. Unlike previous approaches for reducing redundancy in GO datasets, we employ machine learning to identify a subset of functional annotations in a training dataset. Classes in the resulting predictive model meet four essential criteria: sufficient sample size for training predictive models, minimal redundancy, strong class separability, and relevance to substrate transport. Furthermore, we implemented a pipeline for creating training datasets of transmembrane transporters that cover a wide range of organisms, including plants, bacteria, mammals, and single-cell eukaryotes. For a dataset containing 98.1% of transporters from S. cerevisiae, the pipeline automatically reduced the number of functional annotations from 287 to 11 GO terms that could be classified with a median pairwise F1 score of 0.87±0.16. For a meta-organism dataset containing 96% of all transport proteins from S. cerevisiae, A. thaliana, E. coli and human, the number of classes was reduced from 695 to 49, with a median F1 score of 0.92±0.10 between pairs of GO terms. When lowering the percentage of covered proteins down to 67%, the pipeline found a subset of 30 GO terms with a median F1 score of 0.95±0.06.PMID:39700222 | DOI:10.1371/journal.pone.0315330

J Cell Mol Med. 2024 Dec;28(24):e70277. doi: 10.1111/jcmm.70277.ABSTRACTLipid reprogramming in carcinoma is reported to have a role in carcinogenesis, prognosis and therapy response. The lipid reprogramming could be contributed by either autonomous or nonautonomous resources. Since the nonautonomous lipid resources contributed by lipoproteins and their receptors have been reported in epithelial ovarian cancer (EOC), the impact of autonomous lipid metabolites was unknown. This report revealed a unique lipid class, ether-linked phosphatidyl-ethanolamine (PE O-), which enhances chemo-insensitivity and progression in EOC and potentially cross carcinomas. Analysis of CCLEC/GDSCC database and in-house cell line lipidomes identified PE O- as the major lipid associated with cisplatin/paclitaxel sensitivity. In the testing of PE O- effect on cancer phenotypes, it enhanced cell growth, migratory activities and promoted cisplatin/paclitaxel insensitivity. In addition, treating AGPS inhibitor-sensitised chemo-cytotoxic upon cisplatin/paclitaxel treatments. Treating PE O- could reverse AGPS inhibitor chemosensitisation effect on EOC cells. At last, using TCGA-EOC transcriptome database, the PE O- related gene expressions were positive correlated with patient prognosis in general, or in whom were treated with platin- or taxel-based chemotherapies. The expressions of genes for the synthesis of PE O- aggravates therapy response in EOC patients. PE O- facilitates human carcinoma cell line growth, mobility and chemo-insensitivity.PMID:39700026 | DOI:10.1111/jcmm.70277

Anal Chem. 2024 Dec 19. doi: 10.1021/acs.analchem.4c04060. Online ahead of print.ABSTRACTMethods for assessing compound identification confidence in metabolomics and related studies have been debated and actively researched for the past two decades. The earliest effort in 2007 focused primarily on mass spectrometry and nuclear magnetic resonance spectroscopy and resulted in four recommended levels of metabolite identification confidence─the Metabolite Standards Initiative (MSI) Levels. In 2014, the original MSI Levels were expanded to five levels (including two sublevels) to facilitate communication of compound identification confidence in high resolution mass spectrometry studies. Further refinement in identification levels have occurred, for example to accommodate use of ion mobility spectrometry in metabolomics workflows, and alternate approaches to communicate compound identification confidence also have been developed based on identification points schema. However, neither qualitative levels of identification confidence nor quantitative scoring systems address the degree of ambiguity in compound identifications in the context of the chemical space being considered. Neither are they easily automated nor transferable between analytical platforms. In this perspective, we propose that the metabolomics and related communities consider identification probability as an approach for automated and transferable assessment of compound identification and ambiguity in metabolomics and related studies. Identification probability is defined simply as 1/N, where N is the number of compounds in a database that matches an experimentally measured molecule within user-defined measurement precision(s), for example mass measurement or retention time accuracy, etc. We demonstrate the utility of identification probability in an in silico analysis of multiproperty reference libraries constructed from a subset of the Human Metabolome Database and computational property predictions, provide guidance to the community in transparent implementation of the concept, and invite the community to further evaluate this concept in parallel with their current preferred methods for assessing metabolite identification confidence.PMID:39699939 | DOI:10.1021/acs.analchem.4c04060

Nat Prod Res. 2024 Dec 19:1-6. doi: 10.1080/14786419.2024.2443490. Online ahead of print.ABSTRACTPhanera vahlii (Wight & Arn.) Benth., leaves are used traditionally in variety of diseases. Chemical examination of the leaves yielded Davinvolunol B (1) and Quercetin-3-O-rhamnoside (2). Compared with the other extracts, the aqueous methanol extract significantly inhibited Streptococcus aureus with an IC50 of 8 µg/mL. In the anticancer activity assay, the ethyl acetate extract was effective against HeLa cells (IC50 19 µg/mL), the methanol extract was effective against A549 cells (IC50 of 19 µg/mL), the aqueous methanol extract was effective against PANC-1 cells (IC50 of 17 µg/mL) and the chloroform extract was effective against HT1080 cells (IC50 of 19 µg/mL). The polar extracts which showed good antioxidant activity exhibited strong bioactivity. This finding was supported by untargeted phytometabolite profiling of extracts using UPLC-ESI-Q-TOF-MSE. The PCA score plot and the Ven diagram revealed that the extracts had a distinctive and adequate number of polar molecules that likely contributed to their observed inhibitory activity.PMID:39699566 | DOI:10.1080/14786419.2024.2443490

Food Funct. 2024 Dec 19. doi: 10.1039/d4fo04301d. Online ahead of print.ABSTRACTObesity-related metabolic syndrome is intimately associated with infiltrated adipose tissue macrophages (ATMs), gut microbiota, and metabolic disorders. Pediococcus acidilactici holds the potential to mitigate obesity; however, there exist strain-specific functionalities and diverse mechanisms, which deserve extensive exploration. This study aims to explore the potential of P. acidilactici Y01, isolated from traditional sour whey, in alleviating HFD-induced metabolic syndrome in mice and elucidating its underlying mechanism. The results showed that P. acidilactici Y01 could inhibit the increase of body weight gain, the deposition of fat, lipid disorders and chronic low-grade inflammation, improve glucose tolerance and insulin resistance, and could reduce adipose tissue inflammation by decreasing M1-type ATMs and increasing M2-type ATMs. Meanwhile, P. acidilactici Y01 significantly increased the abundance of potentially beneficial intestinal bacteria, such as Akkermansia, Alistipes, Bifidobacterium, Lachnospiraceae_NK4A136_group, Lactobacillus, norank_f__Muribaculaceae, and Parabacteroides, and partially restored the levels of metabolites, such as phosphatidylcholines, glycerophosphocholines, sphingolipids and unsaturated fatty acids. The fecal microbiota transplantation experiment demonstrated that P. acidilactici Y01 ameliorated obesity-related metabolic syndrome by modulating the polarization of M1/M2 ATMs mediated by gut microbiota. Overall, as a dietary supplement, P. acidilactici Y01 has good potential in the prevention and treatment of obesity.PMID:39699275 | DOI:10.1039/d4fo04301d