PubMed

Food Res Int. 2024 Jan;176:113810. doi: 10.1016/j.foodres.2023.113810. Epub 2023 Dec 5.ABSTRACTEighteen raw legs were evenly divided into two groups and salted with 100% NaCl and compound curing agent (60% NaCl + 40% KCl + 90 mg/kg NaNO2) to investigate the effect of compound curing agent on lipid metabolites and volatile flavor compounds in Nuodeng ham. The results of UHPLC-QE-MS and GC-IMS combined with multivariate statistical analysis showed that 27 lipid metabolites and 30 characteristic volatile flavor compounds were identified as characteristic markers in different treatment groups. The compound curing agent promoted the release of TG, SQDG, Hex1Cer, and LPC in Nuodeng ham, and accelerated the formation of volatile compounds such as 2-propanone, nonanal-d, gamma-butyrolactone, ethhyl acetate and benzeneacetaldehyde et al. Through correlation analysis, ketones were positively correlated with some PUFAs and negatively correlated with most MUFAs. Processing Nuodeng ham with compound curing agents has a positive effect on improving its quality. These findings provide a scientific theoretical basis for the development and utilization of compound curing agent.PMID:38163715 | DOI:10.1016/j.foodres.2023.113810

Plant Cell Rep. 2024 Jan 2;43(1):27. doi: 10.1007/s00299-023-03083-w.ABSTRACTIn this review, we made an attempt to create a holistic picture of plant response to a rising temperature environment and its impact by covering all aspects from temperature perception to thermotolerance. This comprehensive account describing the molecular mechanisms orchestrating these responses and potential mitigation strategies will be helpful for understanding the impact of global warming on plant life. Organisms need to constantly recalibrate development and physiology in response to changes in their environment. Climate change-associated global warming is amplifying the intensity and periodicity of these changes. Being sessile, plants are particularly vulnerable to variations happening around them. These changes can cause structural, metabolomic, and physiological perturbations, leading to alterations in the growth program and in extreme cases, plant death. In general, plants have a remarkable ability to respond to these challenges, supported by an elaborate mechanism to sense and respond to external changes. Once perceived, plants integrate these signals into the growth program so that their development and physiology can be modulated befittingly. This multifaceted signaling network, which helps plants to establish acclimation and survival responses enabled their extensive geographical distribution. Temperature is one of the key environmental variables that affect all aspects of plant life. Over the years, our knowledge of how plants perceive temperature and how they respond to heat stress has improved significantly. However, a comprehensive mechanistic understanding of the process still largely elusive. This review explores how an increase in the global surface temperature detrimentally affects plant survival and productivity and discusses current understanding of plant responses to high temperature (HT) and underlying mechanisms. We also highlighted potential resilience attributes that can be utilized to mitigate the impact of global warming.PMID:38163826 | DOI:10.1007/s00299-023-03083-w

Food Res Int. 2024 Jan;176:113834. doi: 10.1016/j.foodres.2023.113834. Epub 2023 Dec 7.ABSTRACTTrigonella foenum-graecum L. (Fenugreek) is an annual herb that belongs to Fabaceae family. The compositional make-up of microgreens depends on prevailing environmental conditions. So, Trigonella microgreens were cultivated under different photoperiod and temperature conditions and evaluated for plant height, total chlorophyll content (TCC), targeted compound analysis and non-targeted UHPLC-QTOF-IMS based metabolomic profile. The plant height and TCC of Trigonella microgreens increased by approximately 22 % and 20 %, respectively under T1 conditions (longer photoperiod of 22 h with 22 °C in light and 17 °C in dark). The targeted phenolic profile analysis revealed the dominant presence of gallic acid, p-coumaric acid and apigenin in Trigonella microgreens. Also, the concentration of p-coumaric acid concentration raised from 3.51 mg/g to 5.83 mg/g as a response of T1 conditions. The sugar profile revealed augmented concentration of myo-inositol, glucose, fructose, xylose, maltose, and sucrose in longer photoperiod with T1 conditions. The microgreens were also rich in amino acids like aspartic acid, glutamic acid, leucine, isoleucine, and phenylalanine. Notably, the concentration of proline increased from 10.40 mg/g to 16.92 mg/g as a response to T1 growth conditions. The concentration of these metabolites varied significantly under different photoperiod and temperature conditions. The comprehensive non-targeted UHPLC-QTOF-IMS analysis of microgreens revealed different class of metabolites like organic compounds, alkaloids, coumarin-derivatives, phenolic and flavonoid derivatives, terpenoids, sugars, amino acids and few nucleic acid derivatives. The multivariate PLS-DA explained different expression level of metabolites under different growing conditions. The T1 growing condition resulted in the increased biosynthesis of phenolic compounds and various metabolites. The expression level of terpenoid derivatives specifically of Trigonelloside C and Trigoneoside XIIa/b increased under T1 conditions. The substantial alteration in the metabolites due to growing conditions may alter the microgreen's dietary benefits. So, additional research may be warranted.PMID:38163730 | DOI:10.1016/j.foodres.2023.113834

Food Res Int. 2024 Jan;176:113789. doi: 10.1016/j.foodres.2023.113789. Epub 2023 Dec 3.ABSTRACTBlack sesame seeds (BSS) have been recognized as a functional food due to their nutritional and therapeutic value for many years. In China, BSS is traditionally processed and consumed through two methods, namely, nine steaming nine sun-drying and stir-frying. The present study aimed to evaluate the effects of these processing techniques on the antioxidant and anti-inflammatory activities of BSS. UPLC-QTOF/MS was used for untargeted metabolomics to analyze the composition changes. The results indicated that the different samples had good antioxidant and anti-inflammatory activities, but thermal treatment reduced their activities. Untargeted metabolomics identified a total of 196 metabolites. Molecular docking studies targeting proteins associated with inflammation (iNOS) demonstrated that compounds acting as inhibitors were significantly reduced under both treatments. These results indicate that both nine steaming nine sun-drying and stir-frying lead to substantial loss of antioxidant, anti-inflammatory, and bioactive metabolites in BSS, which provides an important reference for its rational utilization.PMID:38163704 | DOI:10.1016/j.foodres.2023.113789

J Ethnopharmacol. 2023 Dec 30:117647. doi: 10.1016/j.jep.2023.117647. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Huang-Qi-Ge-Gen decoction (HGD) is a traditional Chinese medicine prescription that has been used for centuries to treat "Xiaoke" (the name of diabetes mellitus in ancient China). However, the ameliorating effects of HGD on diabetic liver injury (DLI) and its mechanisms are not yet fully understood.AIM OF THE STUDY: To elucidate the ameliorative effect of HGD on DLI and explore its material basis and potential hepatoprotective mechanism.MATERIALS AND METHODS: A diabetic mice model was induced by feeding a high-fat diet and injecting intraperitoneally with streptozotocin (40 mg kg-1) for five days. After the animals were in confirmed diabetic condition, they were given HGD (3 or 12 g kg-1, i. g.) for 14 weeks. The effectiveness of HGD in treating DLI mice was evaluated by monitoring blood glucose and blood lipid levels, liver function, and pathological conditions. Furthermore, UPLC-MS/MS was used to identify the chemical component profile in HGD and absorption components in HGD-treated plasma. Network pharmacology and molecular docking were performed to predict the potential pathway of HGD intervention in DLI. Then, the results of network pharmacology were validated by examining biochemical parameters and using western blotting. Lastly, urine metabolites were analyzed by metabolomics strategy to explore the effect of HGD on the metabolic profile of DLI mice.RESULTS: HGD exerted therapeutic potential against the disorders of glucose metabolism and lipid metabolism, liver dysfunction, liver steatosis, and fibrosis in a DLI model mice induced by HFD/STZ. A total of 108 chemical components in HGD and 18 absorption components in HGD-treated plasma were preliminarily identified. Network pharmacology and molecular docking results of the absorbed components in plasma indicated PI3K/AKT as a potential pathway for HGD to intervene in DLI mice. Further experiments verified that HGD markedly reduced liver oxidative stress in DLI mice by modulating the PI3K/AKT/Nrf2 signaling pathway. Moreover, 19 differential metabolites between normal and DLI mice were detected in urine, and seven metabolites could be significantly modulated back by HGD.CONCLUSIONS: HGD could ameliorate diabetic liver injury by modulating the PI3K/AKT/Nrf2 signaling pathway and urinary metabolic profile.PMID:38163558 | DOI:10.1016/j.jep.2023.117647

Environ Int. 2023 Dec 22;183:108405. doi: 10.1016/j.envint.2023.108405. Online ahead of print.ABSTRACTPer- and polyfluoroalkyl substances (PFAS) can disrupt liver homeostasis. Studies have shown that a single exposure to PFAS may provoke abnormal liver function; however, few studies have investigated the overall effect of PFAS mixtures. We aimed to investigate associations between exposure to PFAS mixtures and liver function indices and explore the relevant mechanisms. This study included 278 adult males from Guangzhou, China. Serum metabolite profiles were analyzed using untargeted metabolomics. We applied weighted quantile sum (WQS) regression as well as Bayesian kernel machine regression (BKMR) to analyze the association of nine PFAS mixtures with 14 liver function indices. PFAS mixtures were positively associated with apolipoprotein B (APOB) and gamma-glutamyltransferase (GGT) and negatively associated with direct bilirubin (DBIL) and total bilirubin (TBIL) in both the WQS and BKMR analyses. In addition, Spearman's correlation test showed individual PFAS correlated with APOB, GGT, TBIL, and DBIL, while there's little correlation between individual PFAS and other liver function indices. In linear regression analysis, PFHxS, PFOS, PFHpS, PFNA, PFDA, and PFUdA were associated with APOB; PFOA, PFDA, PFOS, PFNA, and PFUdA were associated with GGT. Subsequently, a metabolome-wide association study and mediation analysis were combined to explore metabolites that mediate these associations. The mechanisms linking PFAS to APOB and GGT are mainly related with amino acid and glycerophospholipid metabolism. High-dimensional mediation analysis showed that glycerophospholipids are the main markers of the association between PFAS and APOB, and that (R)-dihydromaleimide, Ile Leu, (R)-(+)-2-pyrrolidone-5-carboxylic acid, and L-glutamate are the main markers of the association between PFAS and GGT. In summary, overall associations between PFAS and specific indices of liver function were found using two statistical methods; the metabolic pathways and markers identified here may serve to prompt more detailed study in animal-based systems, as well as a similar detailed analysis in other populations.PMID:38163401 | DOI:10.1016/j.envint.2023.108405

J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Dec 15;1233:123972. doi: 10.1016/j.jchromb.2023.123972. Online ahead of print.ABSTRACTThe accurate quantification of multiple vitamin D analogues simultaneously is challenging. This study set out to use liquid chromatography-tandem mass spectrometry (LC-MS/MS) to develop a method capable of measuring a comprehensive vitamin D profile, encompassing twelve vitamin D analogues (vitamin D2, D3, 25(OH)D2, 25(OH)D3, 1,25(OH)2D2, 1,25(OH)2D3, 24,25(OH)2D2, 24,25(OH)2D3, 3-epi-25(OH)D2, 3-epi-25(OH)D3, 7αC4 and1α(OH)D3) in a single run. Serum samples were prepared using double liquid-liquid extraction and analysed on an Agilent 6460 QQQ LC-MS/MS equipped with a Pursuit 3 Pentafluorophenyl (4.6 x 100 mm, 3 μm) column. Recovery rates for all analytes were above 95 % with a coefficient of variation (CV) below 10 %. The method exhibited good linearity (r > 0.995) and had a range of detection limits between 0.01 and 0.35 ng/mL and quantification limits between 0.15 and 0.96 ng/mL. Repeatability and within-lab precision were acceptable, with CV values below 10 % and 15 %, respectively. Method accuracy was excellent, with a systematic error below 6.60 %. additionally, all analytes-maintained stability for 48 h following sample preparation, and no interferences were observed among co-eluting analytes. Lastly, this method achieved "world-class" status according to the Sigma metric scale specifications, requiring minimal quality control to ensure data quality. This successfully validated method has the potential not only for improving vitamin D profiling procedures but also for aiding in the diagnosis of other genetic disorders where measuring beyond 25(OH)D is crucial.PMID:38163391 | DOI:10.1016/j.jchromb.2023.123972

J Vis Exp. 2023 Dec 15;(202). doi: 10.3791/65910.ABSTRACTLarge omics datasets are becoming increasingly available for research into human health. This paper presents DeepOmicsAE, a workflow optimized for the analysis of multi-omics datasets, including proteomics, metabolomics, and clinical data. This workflow employs a type of neural network called autoencoder, to extract a concise set of features from the high-dimensional multi-omics input data. Furthermore, the workflow provides a method to optimize the key parameters needed to implement the autoencoder. To showcase this workflow, clinical data were analyzed from a cohort of 142 individuals who were either healthy or diagnosed with Alzheimer's disease, along with the proteome and metabolome of their postmortem brain samples. The features extracted from the latent layer of the autoencoder retain the biological information that separates healthy and diseased patients. In addition, the individual extracted features represent distinct molecular signaling modules, each of which interacts uniquely with the individuals' clinical features, providing for a mean to integrate the proteomics, metabolomics, and clinical data.PMID:38163278 | DOI:10.3791/65910

Heliyon. 2023 Dec 2;10(1):e22963. doi: 10.1016/j.heliyon.2023.e22963. eCollection 2024 Jan 15.ABSTRACTZanthoxylum motuoense (Tibetan prickly ash, MTHJ), different from the Chinese prickly ash species, is distributed only in the Tibet. Now the chemical characterization and antibacterial activity of MTHJ extracts were analyzed for the first time. As a result, Schinifoline (12), γ-Fagarine (8), (2E,7E,9E)-6 S-Hydroxy-N-(2-methylpropyl)-11-oxo-2, 7, 9-Dodecatrienamide (6), and Neoechinulin A (17) were found to be the major different factors by untarget LC-MS metabolomics together with quantitative analysis on target. These four compounds were also the major antibacterial constituents. Then, the antimicrobial activity of MTHJ fractions was evaluated with colony forming units (CFU), fluorescence microscopy imaging, SEM and investigating the potential food preservation. Nutritional composition, colour and sensory evaluation of extract-treated samples were evaluated along storage time. The results suggested the MTHJ may be used for meat products preservation, and the scores were significantly higher for its unique flavor, which offered a promising choice for food safety, preservation and reducing foodborne illness.PMID:38163185 | PMC:PMC10755585 | DOI:10.1016/j.heliyon.2023.e22963

Front Microbiol. 2023 Dec 13;14:1280628. doi: 10.3389/fmicb.2023.1280628. eCollection 2023.ABSTRACTOBJECTIVES: Periodontitis is associated with benign prostatic hyperplasia (BPH), whether it related to gut floramicrobiota and metabonomics is unclear.METHODS: We established ligature-induced periodontitis (EP), testosterone-induced BPH, and composite rat models. Fecal samples were collected to detect gut microbiota by 16S rDNA sequencing and metabonomics were detected by liquid chromatography tandem mass spectrometry (LC-MS/MS).RESULTS: Sequencing results revealed differential gut floramicrobiota composition between EP+BPH group and other three groups. The abundances of Ruminococcus flavefaciens were significantly increased in EP+BPH group compared with other groups. Tenericutes, Mollicutes, RF39 and Ruminococcus gnavus were significantly decreased in EP+BPH group compared with BPH group, while Ruminococcus callidus and Escherichia were significantly decreased compared with EP group. For gut metabonomics, LC-MS/MS showed that fecal metabolites and seven metabolic pathways were changed in EP+BPH group, such as biosynthesis of unsaturated fatty acids, steroid hormone biosynthesis. Correlation analysis showed that the alterations of gut metabolism were significantly correlated with differential gut floramicrobiota, such as Ruminococcus callidus and Ruminococcus flavefaciens.CONCLUSION: Our study highlights the relationship of periodontitis and BPH, the alterations of gut floramicrobiota and metabolites may be involved in two diseases, which provides new idea for prevention and treatment of patients with periodontitis concurrent BPH.PMID:38163068 | PMC:PMC10756679 | DOI:10.3389/fmicb.2023.1280628

Curr Dev Nutr. 2023 Nov 20;7(12):102038. doi: 10.1016/j.cdnut.2023.102038. eCollection 2023 Dec.ABSTRACTBACKGROUND: The effects of supplementation with L-arginine (L-arg), the precursor of nitric oxide (NO), on vascular and cardiometabolic health have largely been explored. Whether other mechanisms of the action of L-arg exist remains unknown, as arginine metabolism is complicated.OBJECTIVE: We aimed to characterize the effect of low dose L-arg supplementation on overall human metabolism both in a fasting state and in response to an allostatic stress.METHODS: In a randomized, double-blind, crossover study, 32 healthy overweight adults (mean age 45 y) with cardiometabolic risk (fasting plasma triglycerides >150 mg/dL; waist circumference >94 cm [male] or >80 cm [female]) were treated with 1.5 g sustained-release L-arg 3 times/d (4.5 g/d) or placebo for 4 wk. On the last day of treatment, volunteers consumed a high-fat meal challenge (900 kcal, 80% as fat, 13% as carbohydrate, and 7% as protein). Plasma was collected at fasting, 2, 4, and 6 h after the challenge, and the metabolome was analyzed by high-resolution liquid chromatography-mass spectrometry. Metabolic profiles were analyzed using linear mixed models-principal component analysis.RESULTS: The challenge meal explained most of the changes in the metabolome. The overall effect of L-arg supplementation significantly explained 0.5% of the total variance, irrespective of the response to the challenge meal (P < 0.05). Among the metabolites that explain most of the L-arg effect, we found many amino acids, including branched-chain amino acids, that were decreased by L-arg supplementation. L-arg also decreased trimethylamine N-oxide (TMAO). Other changes suggest that L-arg increased methyl demand.CONCLUSIONS: Analysis of the effect of 4 wk of L-arg supplementation on the metabolome reveals important effects on methyl balance and gut microbiota activity, such as a decrease in TMAO. Further studies are needed to investigate those mechanisms and the implications of these changes for long-term health.This trial was registered at clinicaltrials.gov as NCT02354794.PMID:38162999 | PMC:PMC10754708 | DOI:10.1016/j.cdnut.2023.102038

Front Physiol. 2023 Dec 7;14:1308777. doi: 10.3389/fphys.2023.1308777. eCollection 2023.ABSTRACTThe Manila clam (Ruditapes philippinarum), as one of the shellfish living in the intertidal zone, is known for its strong ability to withstand air exposure. Sodium nitroprusside (SNP), a donor of nitric oxide (NO), has been shown to be useful for antioxidant and immune regulation in aquatic animals. In this study, an untargeted metabolomics (LC-MS/MS) technique was employed for the first time in Manila clam to analyze the metabolic and histological impacts after air exposure and the positive effects of SNP pretreatment. During air exposure, a significant increase in taurine, L-glutamate, and several polyunsaturated fatty acids in clams was detected, which indicates that clams may experience inflammatory reactions, oxidative stress, and an increase in blood ammonia content. When clams were exposed to SNP for 6 h, arginine, spermine, L-glutamic acid, and glutathione content were all upregulated, indicating that the SNP exposure induced NO production and improved antioxidant capacity in clams. When the clams were exposed to air after SNP pretreatment, there were no significant differences in the levels of taurine, L-glutamate, or aliphatic acids between the experimental and control groups. Gill tissue was more severely damaged in clams directly exposed to air than in those that experienced air exposure after SNP pretreatment, especially in clams exposed to air for a long time (72 h). Both metabolomics and tissue section structure indicated that SNP pretreatment decreased the stress responses caused by air exposure in R. philippinarum. These findings provided fresh insights and a theoretical foundation for understanding the tolerance to air exposure and physiological functions of SNP (or NO) in R. philippinarum.PMID:38162826 | PMC:PMC10756084 | DOI:10.3389/fphys.2023.1308777

J Diabetes Res. 2023 Dec 23;2023:8810106. doi: 10.1155/2023/8810106. eCollection 2023.ABSTRACTNephropathy injury is a prevalent complication observed in individuals with diabetes, serving as a prominent contributor to end-stage renal disease, and the advanced glycation products (AGEs) are important factors that induce kidney injury in patients with diabetes. Addressing this condition remains a challenging aspect in clinical practice. The aim of this study was to explore the effects of Lactiplantibacillus plantarum NKK20 strain (NKK20) which protects against diabetic kidney disease (DKD) based on animal and cell models. The results showed that the NKK20 can significantly reduce renal inflammatory response, serum oxidative stress response, and AGE concentration in diabetic mice. After treatment with NKK20, the kidney damage of diabetic mice was significantly improved, and more importantly, the concentration of butyrate, a specific anti-inflammatory metabolite of intestinal flora in the stool of diabetic mice, was significantly increased. In addition, nontargeted metabolomics analysis showed a significant difference between the metabolites in the mouse serum contents of the NKK20 administration group and those in the nephropathy injury group, in which a total of 24 different metabolites that were significantly affected by NKK20 were observed, and these metabolites were mainly involved in glycerophospholipid metabolism and arachidonic acid metabolism. Also, the administration of butyrate to human kidney- (HK-) 2 cells that were stimulated by AGEs resulted in a significant upregulation of ZO-1, Occludin, and E-cadherin gene expressions and downregulation of α-SMA gene expression. This means that butyrate can maintain the tight junction structure of HK-2 cells and inhibit fibrosis. Butyrate also significantly inhibited the activation of PI3K/Akt pathway. These results indicate that NKK20 can treat kidney injury in diabetic mice by reducing blood glucose and AGE concentration and increasing butyrate production in the intestine. By inhibiting PI3K pathway activation in HK-2 cells, butyrate maintains a tight junction structure of renal tubule epithelial cells and inhibits renal tissue fibrosis. These results suggest that NKK20 is helpful to prevent and treat the occurrence and aggravation of diabetic kidney injury.PMID:38162631 | PMC:PMC10757665 | DOI:10.1155/2023/8810106

Front Cell Infect Microbiol. 2023 Dec 13;13:1295311. doi: 10.3389/fcimb.2023.1295311. eCollection 2023.ABSTRACTBiofilm is a structured community of bacteria encased within a self-produced extracellular matrix. When bacteria form biofilms, they undergo a phenotypic shift that enhances their resistance to antimicrobial agents. Consequently, inducing the transition of biofilm bacteria to the planktonic state may offer a viable approach for addressing infections associated with biofilms. Our previous study has shown that the mouse antimicrobial peptide CRAMP-34 can disperse Pseudomonas aeruginosa (P. aeruginosa) biofilm, and the potential mechanism of CRAMP-34 eradicate P. aeruginosa biofilms was also investigated by combined omics. However, changes in bacterial extracellular metabolism have not been identified. To further explore the mechanism by which CRAMP-34 disperses biofilm, this study analyzed its effects on the extracellular metabolites of biofilm cells via metabolomics. The results demonstrated that a total of 258 significantly different metabolites were detected in the untargeted metabolomics, of which 73 were downregulated and 185 were upregulated. Pathway enrichment analysis of differential metabolites revealed that metabolic pathways are mainly related to the biosynthesis and metabolism of amino acids, and it also suggested that CRAMP-34 may alter the sensitivity of biofilm bacteria to antibiotics. Subsequently, it was confirmed that the combination of CRAMP-34 with vancomycin and colistin had a synergistic effect on dispersed cells. These results, along with our previous findings, suggest that CRAMP-34 may promote the transition of PAO1 bacteria from the biofilm state to the planktonic state by upregulating the extracellular glutamate and succinate metabolism and eventually leading to the dispersal of biofilm. In addition, increased extracellular metabolites of myoinositol, palmitic acid and oleic acid may enhance the susceptibility of the dispersed bacteria to the antibiotics colistin and vancomycin. CRAMP-34 also delayed the development of bacterial resistance to colistin and ciprofloxacin. These results suggest the promising development of CRAMP-34 in combination with antibiotics as a potential candidate to provide a novel therapeutic approach for the prevention and treatment of biofilm-associated infections.PMID:38162583 | PMC:PMC10757720 | DOI:10.3389/fcimb.2023.1295311

Front Plant Sci. 2023 Dec 15;14:1340039. doi: 10.3389/fpls.2023.1340039. eCollection 2023.ABSTRACTFlowering time, plays a crucial role in tobacco ecological adaptation besides its substantial influence on tobacco production and leaf quality. Meanwhile, it is sensitive to biotic or abiotic challenges. The plant hormones Gibberellins (GAs), controlling a number of metabolic processes, govern plants growth and development. In this study, we created a late flowering mutant HG14 through knocking out NtGA3ox1 by CRISPR/Cas9. It took around 13.0 and 12.1 days longer to budding and flowering compared to wild type Honghuadajinyuan. Nearly all of the evaluated agronomic characters deteriorated in HG14, showing slower growth and noticeably shorter and narrower leaves. We found that NtGA3ox was more prevalent in flowers through quantitative reverse transcription PCR analysis. Transcriptome profiling detected 4449, 2147, and 4567 differently expressed genes at the budding, flowering, and mature stages, respectively. The KEGG pathway enrichment analysis identified the plant-pathogen interaction, plant hormone signal transduction pathway, and MAPK signaling pathway are the major clusters controlled by NtGA3ox1 throughout the budding and flowering stages. Together with the abovementioned signaling pathway, biosynthesis of monobactam, metabolism of carbon, pentose, starch, and sucrose were enriched at the mature stage. Interestingly, 108 up- and 73 down- regulated DEGs, impairing sugar metabolism, diterpenoid biosynthesis, linoleic and alpha-linolenic acid metabolism pathway, were continuously detected accompanied with the development of HG14. This was further evidenced by the decreasing content of GA metabolites such as GA4 and GA7, routine chemicals, alkaloids, amino acids, and organic acids Therefore, we discovered a novel tobacco flowering time gene NtGA3ox1 and resolved its regulatory network, which will be beneficial to the improvement of tobacco varieties.PMID:38162297 | PMC:PMC10754988 | DOI:10.3389/fpls.2023.1340039

Cardiovasc Diagn Ther. 2023 Dec 15;13(6):1043-1055. doi: 10.21037/cdt-23-183. Epub 2023 Nov 7.ABSTRACTBACKGROUND: Aortic dissection (AD) is a serious aortic disease. Although current imaging methods can provide accurate diagnosis for AD, they do not include essential biological information. The aim of this study is to identify plasma metabolites for the risk and severity of type B AD (TBAD).METHODS: In this cross-sectional study, we enrolled 16 hypertensive patients with TBAD and 7 hypertensive patients without TBAD in Jieyang People's Hospital between December 2021 and April 2022. After plasma metabolomics analysis, a metabolites risk score (MRS) model was conducted through logistic regression and least absolute shrinkage and selection operator (LASSO) regression to predict the risk of TBAD. Subsequently, TBAD group was divided into uncomplicated and complicated TBAD subgroups for further screening for metabolites related to the severity of TBAD.RESULTS: Three metabolites, including 1,5-anhydro-D-glucitol, D-(+)-sucrose and PC(O-16:0/0:0) were related to the risk of TBAD. Compared to hypertensive patients without TBAD, the abundance of 1,5-anhydro-D-glucitol and D-(+)-sucrose were significantly increased while PC(O-16:0/0:0) was significantly reduced in hypertensive patients with TBAD (P<0.001). We subsequently built an MRS model based on these three metabolites. Furthermore, we found that hydrocinnamic acid (r=0.741, P<0.001) was independently correlated with the TBAD severity, while glycine deoxycholic acid (r=-0.538, P=0.008) and glycochenodeoxycholic acid (r=-0.538, P=0.008) were inversely correlated with the TBAD severity independently.CONCLUSIONS: The present study screened out three plasma metabolites associated with the risk of TBAD, constructed an MRS model, and identified three metabolites that were independently associated with the severity of TBAD. These findings may serve to identify more TBAD-related biomarkers and shed light on exploring potential mechanisms of TBAD.PMID:38162108 | PMC:PMC10753243 | DOI:10.21037/cdt-23-183

Sichuan Da Xue Xue Bao Yi Xue Ban. 2023 Nov 20;54(6):1219-1226. doi: 10.12182/20231160601.ABSTRACTOBJECTIVE: To analyze the plasma metabolomic features of patients suffering from acute diquat (DQ) poisoning and to explore the molecular mechanism and potential biomarkers of DQ poisoning.METHODS: A total of 7 patients suffering from acute DQ poisoning were enrolled in the DQ poisoning group. The poisoning of these patients occurred within a 12-h window at the time of enrollment. Meanwhile, 7 healthy immediate family members of the patients were enrolled as the normal controls. Liquid chromatography-mass spectrometry (LC-MS) was used to perform non-targeted metabolomic profiling of the plasma samples and to screen and identify differential metabolites and metabolic pathways.RESULTS: A total of 104 metabolites were screened and identified (P<0.05 and the variable importance in the projection [VIP]>1). Compared with those of the control group, 61 metabolites, such as sorbitol and galactitol, were up-regulated, and 43 metabolites, such as myo-inositol and gamma-glutamylcysteine, were down-regulated in the DQ poisoning group. Pathway enrichment analysis revealed changes in 11 metabolic pathways, including those for galactose metabolism and linoleic acid metabolism (P<0.05).CONCLUSION: Metabolomics analysis of plasma samples from DQ poisoning patients shows that DQ mainly interferes with the metabolism of energy, amino acids, and lipids, thus causing metabolic disorders. Some potential biomarkers closely associated with oxidative stress and organ damage of the liver, kidney, and nervous system have been identified.PMID:38162068 | PMC:PMC10752779 | DOI:10.12182/20231160601

Sichuan Da Xue Xue Bao Yi Xue Ban. 2023 Nov 20;54(6):1112-1120. doi: 10.12182/20231160208.ABSTRACTOBJECTIVE: To investigate the renoprotective effects of a Sichuan dark tea-based medicated dietary formula (alternatively referred to as Qing, or clarity in Chinese) on mice with diet-induced obesity (DIO) and to explore the specific mechanisms involved.METHODS: Male C57BL/6 mice were randomly assigned to three groups, a control group, a DIO group, and a Qing treatment group, or the Qing group, with 8 mice in each group. The mice in the control group were given normal maintenance feed and purified water, and the other two groups were fed a high-fat diet for 12 weeks to establish the DIO model. After that, high-fat diet continued in the DIO group, while the Qing group was given Qing at the same time for 12 weeks, during which period the weight of the mice was monitored and recorded every week. The mice were sacrificed after 12 weeks. Serum samples were collected and the levels of triglyceride (TG), total cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin were measured to evaluate liver function. In addition, renal lipids were extracted to determine the levels of TG and TC in the kidney and periodic acid-Schiff (PAS) and oil red O stainings were performed to evaluate kidney pathological injury. Western blot was performed to determine the phosphorylated AMPK (pAMPK)/AMPK ratio in the kidney tissue. RT-qPCR and Western blot were used to determine the expression of proteins related to fatty acid oxidation, including acetyl-CoA carboxylase 1 (ACC1), carnitine acyltransferase 1 (CTP1), peroxisome proliferators-activated receptor γ (PPARγ), peroxisome proliferators-activated receptor-1 α (PPAR1α), sterol-regulatory element binding proteins (SREBP-1), and key proteins related to lipid synthesis, including fatty acid synthase (FASN) and stearoyl-coenzyme A desaturase 1 (stearoyl-CoA desaturase) in the kidney tissue. 16SrRNA and metabolomics were applied to analyze the gut microbiota in the intestinal contents and its metabolites.RESULTS: Compared with those of the control group, the levels of liver mass (P=0.0003), serum ALT (P<0.0001) and AST (P=0.0001), and kidney TC (P=0.0191) and TG (P=0.0101) of the DIO group were significantly increased and there was lipid deposition in the kidney. Compared with those of the DIO group, mice in the Qing group showed effective reduction in liver mass (P=0.0316) and improvements in the abnormal serum levels of AST (P=0.0012) and ALT (P=0.0027) and kidney TC (P=0.0200) and TG (P=0.0499). In addition, mice in the Qing group showed significant improvement in lipid deposition in the kidney. Qing group showed increased pAMPK/AMPK ratio in comparison with that of the DIO group. In comparison with those of the control group, mice in the DIO group had upregulated expression of lipid synthesis-related genes and proteins (SREBP-1, FASN, and SCD1). As for the fatty acid oxidation-related genes and proteins, DIO mice showed upregulated expression of ACC1 and downregulated expression of CPT1A, PPARγ, and PGC1α in comparison with those of the control group. In the Qing goup, improvements in regard to all these changes were observed. The Qing group demonstrated improvement in the disrupted homeostasis of the gut microbiota. Short-chain fatty acids in the cecal contents, especially isovaleric acid and propionic acid, were also restored.CONCLUSION: Sichuan dark tea-based medicated dietary formula may improve renal lipid metabolism by regulating gut microbiota and the levels of intestinal short-chain fatty acids, thereby protecting obesity-related kidney injury. Isovaleric acid and propionic acid may be the metabolites key to its regulation of gut microbiota.PMID:38162058 | PMC:PMC10752792 | DOI:10.12182/20231160208

J Clin Transl Hepatol. 2023 Dec 28;11(7):1498-1507. doi: 10.14218/JCTH.2023.00069. Epub 2023 Sep 15.ABSTRACTNonalcoholic fatty liver disease (NAFLD) particularly affects patients with type 2 diabetes and obesity. The incidence of NAFLD has increased significantly over the last decades and is now pandemically across the globe. It is a complex systemic disease comprising hepatic lipid accumulation, inflammation, lipotoxicity, gut dysbiosis, and insulin resistance as main features and with the potential to progress to cirrhosis and hepatocellular carcinoma (HCC). In numerous animal and human studies the gut microbiota plays a key role in the pathogenesis of NAFLD, NAFLD-cirrhosis and NAFLD-associated HCC. Lipotoxicity is the driver of inflammation, insulin resistance, and liver injury. Likewise, western diet, obesity, and metabolic disorders may alter the gut microbiota, which activates innate and adaptive immune responses and fuels hereby hepatic and systemic inflammation. Indigestible carbohydrates are fermented by the gut microbiota to produce important metabolites, such as short-chain fatty acids and succinate. Numerous animal and human studies suggested a pivotal role of these metabolites in the progression of NAFLD and its comorbidities. Though, modification of the gut microbiota and/or the metabolites could even be beneficial in patients with NAFLD, NAFLD-cirrhosis, and NAFLD-associated HCC. In this review we collect the evidence that exogenous and endogenous hits drive liver injury in NAFLD and propel liver fibrosis and the progressing to advanced disease stages. NAFLD can be seen as the product of a complex interplay between gut microbiota, the immune response and metabolism. Thus, the challenge will be to understand its pathogenesis and to develop new therapeutic strategies.PMID:38161503 | PMC:PMC10752805 | DOI:10.14218/JCTH.2023.00069

iScience. 2023 Nov 29;27(1):108590. doi: 10.1016/j.isci.2023.108590. eCollection 2024 Jan 19.ABSTRACTSkeletal muscle is a highly plastic organ that adapts to different metabolic states or functional demands. This study explored the impact of permanent glucose restriction (GR) on skeletal muscle composition and metabolism. Using Glut4m mice with defective glucose transporter 4, we conducted multi-omics analyses at different ages and after low-intensity treadmill training. The oxidative fibers were significantly increased in Glut4m muscles. Mechanistically, GR activated AMPK pathway, promoting mitochondrial function and beneficial myokine expression, and facilitated slow fiber formation via CaMK2 pathway. Phosphorylation-activated Perm1 may synergize AMPK and CaMK2 signaling. Besides, MAPK and CDK kinases were also implicated in skeletal muscle protein phosphorylation during GR response. This study provides a comprehensive signaling network demonstrating how GR influences muscle fiber types and metabolic patterns. These insights offer valuable data for understanding oxidative fiber formation mechanisms and identifying clinical targets for metabolic diseases.PMID:38161415 | PMC:PMC10755363 | DOI:10.1016/j.isci.2023.108590