PubMed

Allergy. 2024 Dec 21. doi: 10.1111/all.16450. Online ahead of print.NO ABSTRACTPMID:39707873 | DOI:10.1111/all.16450

J Sci Food Agric. 2024 Dec 21. doi: 10.1002/jsfa.14085. Online ahead of print.ABSTRACTBACKGROUND: α-Amylase (α-AMY) and α-glucosidase (α-GLU) inhibitors are important for controlling postprandial hyperglycemia (PHG). Bixa orellana (annatto) reported inhibitory activity against these enzymes because of its bioactive compound content. However, an understanding of its inhibitory mechanisms and metabolic profile is necessary to establish its therapeutic potential. The present study aimed to elucidate the inhibitory mechanisms of B. orellana extract (BOE) on α-AMY and α-GLU, identify and quantify its bioactive compounds using metabolomics (untargeted and targeted) analyses, and evaluate their interactions through in silico approaches.RESULTS: BOE exhibited IC50 values of 37.75 and 47.06 mg mL-1 for α-AMY and α-GLU, respectively, indicating mixed and competitive inhibition types. Thirty-six putative compounds were identified by untargeted metabolomics, mainly fatty acids (dethiobiotin, occidentalol, palmitic acid, norbixin, among others). The most significant biosynthetic pathways included secondary metabolites (unclassified), unsaturated fatty acids, phenylpropanoids and flavonoid metabolism. Eighteen compounds were identified and quantified by the targeted analysis, such as l-phenylalanine, gallic acid, protocatechuic acid and naringenin. In silico studies highlighted xanthoangelol, norbixin, myricetin and 26-hydroxybrassinolide as key compounds with the highest binding affinities to enzyme active sites.CONCLUSION: BOE effectively inhibited α-AMY and α-GLU, with gallic acid, naringenin, xanthoangelol, norbixin and 26-hydroxybrassinolide identified as key bioactive contributors. These findings provide molecular evidence of the inhibitory mechanisms of BOE and support its potential for PHG management and diabetes control. © 2024 Society of Chemical Industry.PMID:39707803 | DOI:10.1002/jsfa.14085

Microbiome. 2024 Dec 20;12(1):269. doi: 10.1186/s40168-024-01966-y.ABSTRACTBACKGROUND: Sheep coccidiosis is an infectious parasitic disease that primarily causes diarrhea and growth retardation in young animals, significantly hindering the development of the sheep breeding industry. Cereal grains and animal feeds are frequently contaminated with mycotoxins worldwide, with aflatoxin B1 (AFB1) being the most common form. AFB1 poses a serious threat to gastrointestinal health upon ingestion and affects the function of parenteral organs, thus endangering livestock health. However, the impact of the combined effects of coccidia and AFB1 on the reproductive system of sheep has not been reported. Therefore, this study utilized sheep as an animal model to investigate the mechanisms underlying the reproductive toxicity induced by the individual or combined effects of AFB1 and Eimeria ovinoidalis (E. ovinoidalis) on the gut-blood-reproductive axis.RESULTS: The results showed that AFB1 and coccidia adversely affect the reproductive system defense of sheep by altering uterine histopathology and hormone levels and triggering inflammation, which is associated with changes in the gut microbiota and metabolites. Moreover, co-exposure to AFB1 and coccidia disrupted the intestinal structure of the colon, resulting in reduced crypt depth. The impaired barrier function of the colon manifests primarily through the suppression of barrier protein expression, changes in the gut microbiome composition, and disruptions in gut metabolism. Importantly, the levels of blood inflammatory factors (IL-6, IL-10, TNF-α, and LPS) increased, suggesting that exposure to AFB1 and coccidia compromises the function of uterine organs in sheep by perturbing the gut-blood-reproductive axis. Blood metabolomics analysis further revealed that the differential metabolites predominantly concentrate in the amino acid pathway, particularly N-acetyl-L-phenylalanine. This metabolite is significantly correlated with IL-6, TNF-α, LPS, ERα, and ERβ, and it influences hormone levels while inducing uterine damage through the regulation of the downstream genes PI3K, AKT, and eNOS in the relaxin signaling pathway, as demonstrated by RNA sequencing.CONCLUSIONS: These findings reveal for the first time that the combined effects of AFB1 and E. ovinoidalis on sheep uterine function operate at the level of the gut-blood-reproductive axis. This suggests that regulating gut microbiota and its metabolites may represent a potential therapeutic strategy for addressing mycotoxins and coccidia-co-induced female reproductive toxicity.PMID:39707461 | DOI:10.1186/s40168-024-01966-y

BMC Musculoskelet Disord. 2024 Dec 20;25(1):1057. doi: 10.1186/s12891-024-08166-7.ABSTRACTBACKGROUND: The Intensive Diet and Exercise for Arthritis (IDEA) trial was a randomized trial conducted to evaluate the effects of diet and exercise on osteoarthritis (OA), the most prevalent form of arthritis. Various risk factors, including obesity and sex, contribute to OA's debilitating nature. While diet and exercise are known to improve OA symptoms, cellular and molecular mechanisms underlying these interventions, as well as effects of participant sex, remain elusive.METHODS: Serum was obtained at three timepoints from IDEA participants assigned to groups of diet, exercise, or combined diet and exercise (n = 10 per group). A randomly selected subset of serum samples were extracted and analyzed via liquid chromatography-mass spectrometry combined with metabolomic profiling to unveil mechanisms associated with types of intervention and disease. Extracted serum was pooled and fragmentation patterns were analyzed to identify metabolites that statistically differentially regulated between groups.RESULTS: Changes in metabolism across male and female IDEA participants after 18-months of diet, exercise, and combined diet and exercise intervention mapped to lipid, amino acid, carbohydrate, vitamin, and matrix metabolism. The diverse metabolic landscape detected across IDEA participants shows that intervention type differentially impacts the serum metabolome of OA individuals. Moreover, dissimilarities in the serum metabolome corresponded with participant sex.CONCLUSIONS: These findings suggest that intensive weight loss among males and females offers potential metabolic benefits for individuals with knee OA. This study provides a deeper understanding of dysregulation occurring during OA development in parallel with various interventions, potentially paving the way for improved interventions, treatments, and quality of life of those impacted by OA.TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT00381290, Registered, 9/25/2006.PMID:39707277 | DOI:10.1186/s12891-024-08166-7

BMC Genomics. 2024 Dec 20;25(1):1228. doi: 10.1186/s12864-024-11146-9.ABSTRACTPanax ginseng is an important medicinal plant in China and is classified into two types: cultivated ginseng (CFCG) and mountain-cultivated ginseng (MCG). The two types of genetic varieties are the same, but the growth environments and management practices are different, resulting in substantial differences in their taproot morphology. Currently, there is a paucity of research on the internal mechanisms that regulate the phenotypic differences between cultivated ginseng and mountain-cultivated ginseng. In this study, we explored the potential mechanisms underlying their phenotypic differences using transcriptomic and metabolomic techniques. The results indicate that the taproot thickening of CFCG was significantly greater than that of MCG. Compared with MCG-4, MCG-10, and MCG-18, the diameters of the taproots of CFCG-4 increased by 158.96, 81.57, and 43.21%, respectively. Additionally, the contents of sucrose and starch in the taproot, as well as TRA and DHZR, were markedly elevated. Transcriptome analysis revealed that compared with MCG of different age groups, genes associated with starch and sucrose metabolism pathways (PgSUS1, PgSPS1, PgSPS3, and PgglgC1) were significantly upregulated in CFCG-4, whereas genes involved in the phenylpropanoid biosynthesis pathway (PgPER3, PgPER51, and PgPER12) were significantly downregulated in CFCG-4. This imbalance in the metabolic pathways suggests that these genes play crucial roles in ginseng taproot thickening. PgbHLH130 and PgARF18 may be key regulators of transcriptional changes in these pathways. These findings elucidate the molecular mechanisms governing ginseng taproot thickening, and have important implications for enhancing the overall quality and value of ginseng.PMID:39707199 | DOI:10.1186/s12864-024-11146-9

BMC Plant Biol. 2024 Dec 20;24(1):1224. doi: 10.1186/s12870-024-05909-5.ABSTRACTBACKGROUND: Platostoma palustre is a kind of plant resource with medicinal and food value, which has been differentiated into many different varieties after a long period of breeding. The cultivars of Taiwan(TW) and Pingyuan(PY) are widely grown in Guangdong, but a clear basis for species differentiation has not yet been established, resulting in the mixing of different species which limits their production and application.RESULTS: Regarding leaf surface morphology, the TW exhibited greater leaf area, non-glandular hairs, and the number of stomata than the PY. Regarding chemical activities, the TW exhibited higher total flavonoid content and antioxidant activity than the PY. In metabolomics, a total of 85 DAMs were detected, among which four flavonoid DAMs were identified, all of which were up-regulated in TW expression. Transcriptome analysis identified 2503 DEGs, which were classified according to their functional roles. The results demonstrated that the DEGs were primarily involved in amino acid metabolism, carbohydrate metabolism, sorting and degradation. A total 536 transcription factors (TFs) were identified, of which bHLH and MYB were the top two most abundant TFs families. Combined analysis of metabolome and transcriptome indicated that the phenylpropanoid pathway plays a significant role in flavonoid synthesis. Furthermore, real-time fluorescence qrt-PCR validation demonstrated that the expression trend of 10 DEGs was consistent with the transcriptomics data.CONCLUSION: The phenylpropanoid pathway affects the synthesis of secondary metabolites, resulting in functional differences. In this study, metabolomic and transcriptomic analyses were performed to elucidate the regulatory mechanisms of flavonoid synthesis in P. palustre and to provide a theoretical basis for the identification, differentiation and breeding cultivation of different cultivars of P. palustre.PMID:39707195 | DOI:10.1186/s12870-024-05909-5

Mol Med. 2024 Dec 20;30(1):263. doi: 10.1186/s10020-024-01033-0.ABSTRACTBACKGROUND: Extensive research has underscored the criticality of preserving diversity and equilibrium within the gut microbiota for optimal human health. However, the precise mechanisms by which the metabolites and targets of the gut microbiota exert their effects remain largely unexplored. This study utilizes a network pharmacology methodology to elucidate the intricate interplay between the microbiota, metabolites, and targets in the context of DM, thereby facilitating a more comprehensive comprehension of this multifaceted disease.METHODS: In this study, we initially extracted metabolite information of gut microbiota metabolites from the gutMGene database. Subsequently, we employed the SEA and STP databases to discern targets that are intricately associated with these metabolites. Furthermore, we leveraged prominent databases such as Genecard, DisGeNET, and OMIM to identify targets related to diabetes. A protein-protein interaction (PPI) network was established to screen core targets. Additionally, we conducted comprehensive GO and KEGG enrichment analyses utilizing the DAVID database. Moreover, a network illustrating the relationship among microbiota-substrate-metabolite-target was established.RESULTS: We identified a total of 48 overlapping targets between gut microbiota metabolites and diabetes. Subsequently, we selected IL6, AKT1 and PPARG as core targets for the treatment of diabetes. Through the construction of the MSMT comprehensive network, we discovered that the three core targets exert therapeutic effects on diabetes through interactions with 8 metabolites, 3 substrates, and 5 gut microbiota. Additionally, GO analysis revealed that gut microbiota metabolites primarily regulate oxidative stress, inflammation and cell proliferation. KEGG analysis results indicated that IL-17, PI3K/AKT, HIF-1, and VEGF are the main signaling pathways involved in DM.CONCLUSION: Gut microbiota metabolites primarily exert their therapeutic effects on diabetes through the IL6, AKT1, and PPARG targets. The mechanisms of gut microbiota metabolites regulating DM might involve signaling pathways such as IL-17 pathways, HIF-1 pathways and VEGF pathways.PMID:39707185 | DOI:10.1186/s10020-024-01033-0

BMC Genomics. 2024 Dec 20;25(1):1232. doi: 10.1186/s12864-024-11138-9.ABSTRACTBACKGROUND: In recent years, the total production of mud crab Scylla paramamosain has been declining, and the breeding areas are faced with land shortage and shortage of breeding production, which needs to be solved urgently. S. paramamosain can survive and grow in a wide range of salinities is an excellent variety suitable for saline-alkali water aquaculture. As a species with high economic value and strong adaptability to the environment, its cultivation under low salt conditions can not only improve the utilization efficiency of saline-alkali land, but also provide new possibilities for the sustainable development of aquaculture.RESULTS: A total of 248 different metabolites were identified by LC/GC-MS in the intestinal tract of S. paramamosain. These different metabolites were mainly concentrated in 'Lipids and lips-like molecules'. Among them, 112 metabolites are upregulated, and among these upregulated metabolites are mainly 'Fatty Acyls' and 'Glycerophospholipids'. The upregulation of these metabolites indicates an increase in lipid storage of S. paramamosain, which may increase the resistance of S. paramamosain to adverse environmental stress. Among them, 136 metabolic differentiates were down-regulated, mainly 'Carboxylic acids and derivatives'. The down-regulation of these organic acids may indicate that organic acids are used as energy sources for the immune response to long-term environmental stress.CONCLUSION: Under long-term chloride type low-salt saline-alkali water stress, S. paramamosain will shift to another homeostasis for development.PMID:39707184 | DOI:10.1186/s12864-024-11138-9

Mol Med. 2024 Dec 20;30(1):250. doi: 10.1186/s10020-024-01046-9.ABSTRACTBACKGROUND: Diabetic ketoacidosis (DKA) is a serious complication of type 1 diabetes (T1D), arising from relative insulin deficiency and leading to hyperglycemia, ketonemia, and metabolic acidosis. Early detection and treatment are essential to prevent severe outcomes. This pediatric case-control study utilized plasma metabolomics to explore metabolic alterations associated with DKA and to identify predictive metabolite patterns.METHODS: We examined 34 T1D participants, including 17 patients admitted with severe DKA and 17 age- and sex-matched individuals in insulin-controlled states. A total of 215 plasma metabolites were analyzed using proton nuclear magnetic resonance and direct-injection liquid chromatography/mass spectrometry. Multivariate statistical methods, machine learning techniques, and bioinformatics were employed for data analysis.RESULTS: After adjusting for multiple comparisons, 65 metabolites were found to differ significantly between the groups (28 increased and 37 decreased). Metabolomics profiling demonstrated 100% accuracy in differentiating severe DKA from insulin-controlled states. Random forest analysis indicated that classification accuracy was primarily influenced by changes in ketone bodies, acylcarnitines, and phosphatidylcholines. Additionally, groups of metabolites (ranging in number from 8 to 18) correlated with key clinical and biochemical variables, including pH, bicarbonate, glucose, HbA1c, and Glasgow Coma Scale scores.CONCLUSIONS: These findings underscore significant metabolic disturbances in severe DKA and their associations with critical clinical indicators. Future investigations should explore if metabolic alterations in severe DKA can identify patients at increased risk of complications and/or guide future therapeutic interventions.PMID:39707182 | DOI:10.1186/s10020-024-01046-9

Biol Trace Elem Res. 2024 Dec 21. doi: 10.1007/s12011-024-04496-8. Online ahead of print.ABSTRACTSelenium (Se) is a trace element that is essential for health. Organic Se created by Se-enriched microorganisms has the characteristics of low toxicity, high bioavailability, and regulation of physiological functions. Here, the regulatory effect of Se-enriched Aspergillus oryzae A02 on the reproductive function of male mice and its potential molecular mechanism was studied. Specifically, twenty-four male mice were randomly divided into a control group and a Se-enriched A. oryzae A02 (Nano-Se) (daily gavage of 0.5 mg/kg, dissolved in saline) for an 8-week experiment. The results showed that Nano-Se intervention did not affect body weight and testicular index, but increased sperm concentration and seminiferous epithelium height in experimental mice, indicating that Nano-Se has the potential to improve the reproductive performance of male mice. Mechanistically, Nano-Se intervention increased the levels of antioxidant-related indicators catalase (CAT) and glutathione peroxidase (GSH-Px) in mouse serum, and increased the relative mRNA expression of GSH-Px, heme oxygenase-1 (HO-1), and NADPH quinine oxidoreductase-1 (NQO-1) in testicular tissues. We identified 9,10,13-trihydroxyoctadecenoic acids (TriHOMEs), stearidonic acid and selenomethionine linked with alpha-linolenic acid metabolism, selenocompound metabolism, folate biosynthesis, ubiquinone, and other terpenoid-quinone biosynthesis and biosynthesis of cofactors. In addition, Nano-Se did not influence the fecal bacterial alpha and beta diversity (P > 0.05), but increased the abundance of the Actinobacteriota and Proteobacteria phyla and the Staphylococcus and Corynebacterium genera, and lowered the abundance of the Bacteroidota phylum and the Lactobacillus and norank_f_Muribaculaceae genera. Nano-Se is considered a novel and promising nutritional regulator to improve reproductive function.PMID:39707080 | DOI:10.1007/s12011-024-04496-8

Metabolomics. 2024 Dec 20;21(1):12. doi: 10.1007/s11306-024-02213-z.NO ABSTRACTPMID:39707079 | DOI:10.1007/s11306-024-02213-z

Biomarkers. 2024 Dec 20:1-17. doi: 10.1080/1354750X.2024.2445258. Online ahead of print.ABSTRACTBackgroundAt present, there is a lack of efficient biomarkers for the diagnosis of thyroid cancer, and the influence of natural factors such as high iodine exposure on the expression of biomarkers remains unclear.MethodsSerum samples from papillary thyroid cancer (PTC) and non-cancer controls matched 1:1 in different iodine nutritional regions were analyzed metabolomically using an ultra-high performance liquid chromatography-Orbitrap Exploris mass spectrometry (UHPLC-OE-MS) platform. Then the data were randomly divided into training and test sets in a 1:1 ratio according to the different iodine nutritional regions and different PTC status. In the training set, differential metabolites were selected by multivariate statistical analysis methods, and the prediction models were then built using Random forest (RF), Gradient boosting machine (GBM), and Support vector machine (SVM) models. At last, their diagnostic effects were examined in the test set.ResultsPTCs were significantly separated from non-cancer samples, and a total of 37 differentially expressed metabolites were selected. The results of pathway analysis showed that the PTC-related differential metabolites were mainly involved in the sphingolipid metabolism and glycerophosphate metabolism. The prediction models constructed by the 6 screened potential biomarkers could all better identify PTCs in the test set. The metabolomic fingerprinting between PTC and non-cancer groups in different water iodine regions did not show significant disturbance. However, high iodine exposure would effect on the expression of six metabolites, reflecting in a significantly different diagnostic efficacy in different water iodine regions.ConclusionSerum metabolites have potential value as biomarkers of PTC, and iodine status affects the expression and even diagnostic levels of certain serum metabolites.PMID:39706815 | DOI:10.1080/1354750X.2024.2445258

Anal Chem. 2024 Dec 20. doi: 10.1021/acs.analchem.4c04263. Online ahead of print.ABSTRACTPatients with epidermal growth factor receptor mutant nonsmall cell lung cancer (NSCLC) often fail to treat gefitinib because of secondary drug resistance. The development of tumor drug resistance is closely related to variations in cancer cell metabolism. Single-cell metabolomics analysis can provide unique information about tumor drug resistance. Herein, we constructed a platform to study the secondary resistance of tumor cells based on single-cell metabolomics (sSRTC-scM). A gefitinib-resistant NSCLC cell line (PC9GR) was constructed by increasing the dose step by step. The metabolic profiles of parental PC9 cells and PC9GR cells with different drug resistance levels were detected by intact living-cell electrolaunching ionization mass spectrometry at the single-cell level. The data were analyzed by statistical methods such as t-SNE, variance, volcano plot, heat map, and metabolic pathway analysis. Using this platform, we found that the metabolic fingerprints of PC9GR cells can evaluate drug resistance degrees. The metabolic fingerprints continue to be altered with the increase of drug resistance. We revealed 19 metabolic markers of secondary resistance by variance analysis and clarified that the glycerophospholipid metabolic pathway of PC9GR cells changed significantly. In addition, we found that with the increase in drug resistance levels, the heterogeneity of single-cell metabolism became greater and the number of cells with weak drug resistance gradually decreased. This phenomenon can be utilized to illustrate the drug resistance degrees of PC9GR cells. This study provides diagnostic markers for evaluating the drug resistance of tumors and gives new insight into overcoming the secondary resistance of tumors.PMID:39706799 | DOI:10.1021/acs.analchem.4c04263

Chemosphere. 2024 Dec 18:143998. doi: 10.1016/j.chemosphere.2024.143998. Online ahead of print.ABSTRACTMetabolomics is a valuable tool to assess glyphosate exposure and its potential impact on human health. However, few studies have used metabolomics to evaluate human exposure to glyphosate or glyphosate-based herbicides (GBHs). In this study, an untargeted and targeted metabolomics approach was applied to human skin fibroblasts exposed to the GBH Roundup (GLYP-R). Cytotoxicity, cell death, and oxidative stress assays were performed to evaluate potential damage caused by GLYP-R in fibroblasts. The herbicide showed a cytotoxic effect at concentrations above 100.0 mg L-1, with IC50 = 164.2 ± 8.7 mg L-1, inducing significant reactive oxygen species (ROS) production and necrosis. A GC×GC/Q-TOFMS method using derivatization with propyl chloroformate/propanol was developed for untargeted analysis, allowing the identification of 400 metabolites of different classes in the samples. The most significant compounds in the discrimination and classification of the samples were fatty acids and amino acids (AA). Based on the relevance of AA in untargeted analysis, a targeted analysis of 21 AA was performed using the same validated GC×GC method. Metabolomic analyses allowed the construction of two biomarker models with performance evaluated by receiver operating characteristic (ROC) curves: an untargeted model formed by four metabolites (methylcysteine, N-acetyl-L-methionine, methyl stearate, and linoleic acid) and a targeted model formed by three AA (L-glutamic acid, L-cysteine, and γ-aminobutyric acid). This study is the first to report the use of metabolomics to evaluate human skin cells exposed to GLYP-R, contributing to the toxicological research on glyphosate.PMID:39706496 | DOI:10.1016/j.chemosphere.2024.143998

Int J Biol Macromol. 2024 Dec 18:138782. doi: 10.1016/j.ijbiomac.2024.138782. Online ahead of print.ABSTRACTCannabis sativa L. (hemp) seeds are increasingly recognized as a promising food source rich in phytochemicals that support inflammatory and immunological reactions. This study investigates whether fermentation with Lactiplantibacillus plantarum can further enhance these functional properties, paving the way for hemp seeds to be developed into potent functional food ingredients. Aqueous, 70 % ethanol, and ethyl acetate extracts from both L. plantarum-fermented (FHS) and unfermented hemp seeds (HS) were evaluated for their anti-inflammatory activities using cell-based assays. The 70 % ethanol extract of FHS exhibited marked inhibitory effects on cytokines, including TNF-α, IL-1β, and IL-10, with fermentation significantly enhancing these effects by 25 %, 39.3 %, and 29.6 %, respectively, compared to the unfermented extracts. Additionally, mRNA expression analysis confirmed the strong immunomodulatory potential of the fermented extracts. Intracellular metabolomic analysis revealed that the 'antifolate resistance', 'nicotine addiction', 'aminoacyl-tRNA biosynthesis', and 'D-amino acid metabolism' are highlighted in the reasons for this enhancement. Furthermore, FHS significantly prolonged the survival of C. elegans exposed to pathogens, with gene expression analysis indicating modulation of the innate immune system via regulation of genes such as gcs-1, lys-1, dbl-1, pmk-1, elt-2, and dod-22. A comprehensive metabolomic and correlation analysis identified five novel bioactive peptides (AAELIGVP, AAVPYPQ, VFPEVAP, DVIGVPLG, PVPKVL) and bioactive acids (indoleacetic acid and homovanillic acid) that were enriched during fermentation, which are strongly linked to the enhanced anti-inflammatory and immunomodulatory effects observed. These findings suggest that L. plantarum-fermented hemp seeds hold significant promise as functional ingredients in anti-inflammatory and immunomodulatory food products, with potential applications in health and wellness industries.PMID:39706455 | DOI:10.1016/j.ijbiomac.2024.138782

Int J Biol Macromol. 2024 Dec 18:138526. doi: 10.1016/j.ijbiomac.2024.138526. Online ahead of print.ABSTRACTAcute kidney injury (AKI) is a common and serious clinical complication with high incidence. Polysaccharides extracted from Flammulina velutipes (FVPs) have been proven to possess anti-inflammatory and antioxidant properties. The present study aimed to investigate the ameliorative effect and mechanism of FVPs on cisplatin (CDPP)-induced AKI. The results of our study revealed that FVPs improved CDPP-induced AKI in mice as indicated by decreasing serum creatinine and urea levels and down-regulating the mRNA expression of IL-6 and TNF-α. Moreover, FVPs modified the composition of gut microorganisms and increased the content of short-chain fatty acids (SCFAs). Additionally, kidney metabolomics analysis demonstrated enrichment of the ferroptosis metabolic pathway. Furthermore, FVPs suppressed ferroptosis as shown by increasing levels of GSH, GPX4, and SLC7A11, while reducing the arachidonic acid level. In conclusion, FVPs were confirmed to ameliorate CDPP-induced AKI in the present study. FVPs can modify the composition of the gut microbiota to promote the production of SCFAs, as well as modulate renal metabolism and inhibit ferroptosis.PMID:39706410 | DOI:10.1016/j.ijbiomac.2024.138526

Int J Biol Macromol. 2024 Dec 18:138944. doi: 10.1016/j.ijbiomac.2024.138944. Online ahead of print.ABSTRACTFoliar fertilizers quickly replenish nutrients for plant growth, boosting production and quality. However, how this affects metabolite accumulation in fruits is unclear. In this study, the metabolome and transcriptome of Torreya grandis seeds were investigated after five different foliar fertilizer treatments. Based on the results, foliar fertilizer treatments significantly altered the visual properties and nutritional quality of T. grandis seeds. According to the transcriptome and metabolome data, the differential metabolites and genes in T. grandis seeds were enriched in the sugar/starch and lipid metabolism-related pathways. Correlation analysis revealed that TgVIN1 and TgPEPCK play key roles in sugar/starch and lipid metabolism pathways, respectively. A dual-luciferase analysis and yeast one-hybrid assay were used to examine the regulation of candidate transcription factors on TgVIN1 and TgPEPCK expression. The results showed that TgHDZIP1 and TgMYB7 could directly bind to the TgVIN1 promoter and activate TgVIN1 expression. Similarly, TgIWS1 could directly bind to the TgPEPCK promoter. Transient overexpression of TgVIN1 increased the contents of fructose, soluble sugar and starch in and TgPEPCK significantly increased the C16:1 content in tobacco leaves, respectively. Our results contribute to the mechanisms underlying sucrose/starch and lipid metabolism as affected by foliar fertilizer treatments.PMID:39706403 | DOI:10.1016/j.ijbiomac.2024.138944

Int J Biol Macromol. 2024 Dec 18:138975. doi: 10.1016/j.ijbiomac.2024.138975. Online ahead of print.ABSTRACTA heteropolysaccharide (IHP3) with a molecular weight of 22.0 kDa was isolated from Inonotus hispidus (Bull.: Fr.) P. Karst using column chromatography purification from water extraction. Its backbone was predominantly composed of →6)-α-D-Galp-(1→, →2,6)-α-D-Galp-(1→,→6)-α-D-O-Me-Galp-(1→, →3)-α-D-Manp-(1→, and →3,4,6) -β-D-Galp-(1 → residues, branched at C2 of partial α-D-Galp, or C3 and C4 of β-D-Galp, and terminated by α-D-Manp, and α-L-Fucp. In high-fat diet (HFD)-fed obese mice, IHP3 effectively suppressed body weight and plasma glucose gain, decreased fat accumulation, ameliorated lipid metabolism, and protected liver function from HFD-induced damage. Combining the analysis of gut microbiota metabolomics, hepatic proteomics and biochemical detection revealed, IHP3 significantly altered cecum fecal metabolite abundances, inhibited the phosphorylation of peroxisome proliferator-activated receptor gamma, and promoted the browning of white adipose tissue and the activation of brown adipose tissue. These changes collectively contributed to alleviating obesity symptoms by suppressing the interleukin (IL)-17-mediated inflammatory response in obese mice. Therefore, these findings suggest that IHP3 could be a potential candidate for the development of anti-obesity drugs.PMID:39706397 | DOI:10.1016/j.ijbiomac.2024.138975

J Ethnopharmacol. 2024 Dec 18:119223. doi: 10.1016/j.jep.2024.119223. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Huangkui capsule (HKC), a patent traditional Chinese medicine, has shown significant efficacy in managing chronic kidney disease (CKD), particularly diabetic nephropathy (DN). Previous studies have shown that HKC can alleviate kidney damage in DN. However, the exact mechanisms through which it exerts its effects remain unclear.AIM OF THE STUDY: This study aimed to elucidate the potential molecular mechanisms of HKC in treating kidney injury in type 1 diabetic nephropathy (T1DN) models through serum metabolomics, Chinmedomics, and molecular docking techniques.MATERIALS AND METHODS: T1DN mouse models were induced by intraperitoneal injection of streptozotocin (STZ), resulting in the ACR value ten times that of the control group. The efficacy of HKC on T1DN was comprehensively evaluated in general conditions, renal coefficient, histopathology, and related biochemical indicators. UPLC-Q-TOF-MS/MS based serum metabolomics was employed to identify biomarkers of T1DN and evaluate the effects of HKC. Relevant pathways were analyzed, and followed by Protein-Protein Interaction network analysis to screen for key enzymes. By integrating the Chinmedomics strategy and molecular docking the relationship between these targets and active components was elucitaed.RESULTS: HKC resulted in a significant reduction in renal inflammation and fibrosis, as evidenced by the decreased levels of urinary ACR, blood TG, T-CHO, BUN, and renal TNF-α and VEGF-A, along with a reduction in the positive area of COL-1. Palmitic acid, stearic acid, arachidonic acid, pantothenic acid, and sphingosine-1-phosphate serve as key serum metabolite biomarkers for T1DN, involved in the biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, pantothenate and CoA biosynthesis, and sphingolipid metabolism. FASN, Cyp2e1, and Cyp4a32 are the key enzymes in the treatment of T1DN with HKC. Additionally, 8 key active components were identified in the serum of HKC-H, including quercetin, myricetin, isoquercitrin, hyperoside, hibifolin, gentisic acid 5-O-β-glucoside, floramanoside F, and quercetin-4'-O-glucoside, which are believed to interact with key enzymes.CONCLUSIONS: The active components of HKC influence Fasn, Cyp2e1, and Cy4a32, improving renal injury in T1DN. These findings provide new molecular insights for the future clinical application and research of HKC in treating T1DN.PMID:39706356 | DOI:10.1016/j.jep.2024.119223

Chem Biol Interact. 2024 Dec 18:111360. doi: 10.1016/j.cbi.2024.111360. Online ahead of print.ABSTRACTPodophyllotoxin (PPT) is a lignan isolated from the traditional Chinese medicine Dysosma Versipellis, with significant anti-tumor activity. However, its cardiotoxicity restricts its clinical application. This study aims to investigate the cardiotoxicity of PPT in mice and its underlying mechanisms based on the concept of toxicological evidence chain (TEC). In this study, alterations in body weight, behavior, and the levels of myocardial enzymes and histopathology in mice were observed. Additionally, microbiome and metabolome were integrated to identify potential microorganisms, metabolic markers and major pathways with correlation analysis. The results indicated that PPT induced pathological changes in mice, including weight loss, diarrhea, alopecia and dehydration accompanied by increased levels of serum myocardial enzymes. The results of microbiome showed that PPT altered the gut microbiota composition, changing the abundance of microbial community. The results of metabolome studies indicated total of 55 differential metabolites were involved in glycine, serine, and threonine metabolism, alanine, glutamate, and aspartate metabolism, purine, pyrimidine metabolism, and steroid hormone metabolism. Integrating the results of microbiome and metabolome, it was concluded that PPT remodeled the gut microbiota composition, which in turn modified the gut microbiota metabolism, affecting amino acid metabolisms, nucleotide metabolism, and steroid hormone metabolism in the heart, potentially leading to energy metabolism disorders, apoptosis, and oxidative stress, ultimately inducing cardiotoxicity.PMID:39706312 | DOI:10.1016/j.cbi.2024.111360