PubMed
Functional role of DFR genes in various blue Iris for the regulation of delphinidin synthesis
Plant Physiol Biochem. 2024 Nov 27;219:109355. doi: 10.1016/j.plaphy.2024.109355. Online ahead of print.ABSTRACTFlowers belonging to the Iris genus, with a predominant display of blue hues, showcase a variety of blue polymorphisms across different species. This study focused on analyzing the L∗, a∗, and b∗ color values of Iris typhifolia, I. lactea, I. laevigata, and I. sanguinea. Notably, I. lactea exhibited the highest L∗ value, indicating a brighter hue, while I. typhifolia and I. laevigata displayed larger a∗ values, suggesting a shift towards a reddish tone. I. sanguinea, conversely, presented the most profound blue with the lowest b∗ value. Our research delved into understanding the influence of anthocyanin components on these color variations and explored the regulatory role of the dihydroflavonol-4-reductase (DFR) gene. The findings underscore delphinidin as the primary blue pigment, with the additional presence of petunidin in I. typhifolia and I. laevigata introducing a purplish-red hue. Flavonoids were identified as contributors to enhancing the brightness of I. lactea's color. The study elucidates that blue polymorphism predominantly arises from varying proportions of delphinidin pigments, closely linked to substrate selection by Asp type DFRs. Following the expression of different DFR genes from the two blue Iris species, significant substrate selection differences were observed. These findings lay a foundation for future efforts to enhance flower colors in Irises and other related species by offering DFR as a target candidate gene.PMID:39708701 | DOI:10.1016/j.plaphy.2024.109355
A cell-based exploration of environmental and health impacts of food waste digestate for its sustainable reutilization
J Environ Manage. 2024 Dec 20;373:123795. doi: 10.1016/j.jenvman.2024.123795. Online ahead of print.ABSTRACTAnaerobic digestion of food waste is increasingly utilized for bioenergy generation, producing a byproduct known as food waste digestate (FWD), which has potential applications as a fertilizer within the circular economy. However, accumulating numerous pollutants in FWD poses significant challenges to environmental management and human health. The complex nature of these pollutants complicates both targeted and non-targeted chemical analyses, making safety evaluations difficult. To address this, we developed a toxicity evaluation protocol based on comprehensive cellular effects to assess the safety profile of FWD. Our study found that human FHC cells were significantly more sensitive to FWD solutions, with 1.2-, 1.8-, and 1.7-fold greater sensitivity than GES-1, HepG2, and HEK293 cells. We identified oxidative stress levels and the activation of the NF-κB signaling pathway as crucial and sensitive indicators of FWD-induced toxicity. Metabolomics analysis revealed that FWD triggered the activation of the inflammatory mediator regulation of the transient receptor potential channels pathway, indicating a cellular response aimed at mitigating damage through immune repair mechanisms. By comprehensively assessing these cellular and molecular indicators, we can better predict the potential human and environmental risks associated with FWD. This knowledge is essential for establishing safety guidelines and appropriate dilution ratios for FWD reutilization, enhancing environmental management practices within a circular economy framework.PMID:39708690 | DOI:10.1016/j.jenvman.2024.123795
Unraveling key non-volatiles responsible for taste differences of Pixian broad bean paste based on sensory analysis and untargeted metabolomics
Food Chem. 2024 Dec 18;469:142565. doi: 10.1016/j.foodchem.2024.142565. Online ahead of print.ABSTRACTBesides aroma, the tastes of Pixian Broad Bean Paste (PBBP) are also important, however, they have not yet been thoroughly elucidated. Therefore, this study employed sensory and untargeted metabolomics approaches to investigate taste characteristics, molecular basis and their metabolic pathways of PBBP from three different manufacturers and two grades. Results showed PBBP was predominantly characterized by strong sour, umami and salty tastes, and significant differences were observed in samples from different manufacturers and grades (p < 0.05), especially higher sourness, saltiness and umami in premium PBBP. Based on non-volatiles, 55 key differential metabolites were identified through orthogonal partial least square discriminant analysis (OPLS-DA, P value<0.05, VIP value>1.0) and Pearson correlation analysis (|ρ| > 0.7). These key differential metabolites responsible for taste differences were metabolized by 36 crucial KEGG pathways (P value<0.05, impact value>0.05). These results could expand our understandings of PBBP taste compounds and their metabolisms, and provide theoretical evidences for further quality improvement.PMID:39708645 | DOI:10.1016/j.foodchem.2024.142565
Chuanxiong Qingnao Granules (CQG) alleviates nitroglycerin-induced migraine-like pain in rats by glycerophospholipid metabolism and PI3K/Akt signaling pathway
Phytomedicine. 2024 Dec 17;136:156336. doi: 10.1016/j.phymed.2024.156336. Online ahead of print.ABSTRACTBACKGROUND AND PURPOSE: Chuanxiong Qingnao Granles (CQG), has been used to treat migraine headache (MH) for many years. However, current investigation of CQG have primarily focused on clinical studies, and the potential mechanisms underlying of its effects on MH have not been fully elucidated. In the present study, we applied an integrated approach of transcriptomics and metabolomics to elucidate the therapeutic mechanisms of CQG in nitroglycerin (NTG)-induced MH injury.METHODS AND RESULTS: Fifty rats were allocated into five random groups: control (Con), NTG, flunarizine (NTG + Flu) group, and two CQG groups (NTG + CQG-L and NTG + CQG-H). CQG notably reduced the duration of ear redness and the frequency of head scratching frequency in rats. It also lowered the levels of 5-hydroxytryptamine (5-HT), endothelin-1 (ET-1), calcitonin gene-related peptide type 1 receptor (CGPR1), and tumor necrosis factor alpha (TNF-α) and enhanced neuronal morphology following NTG-induced MH damage. Transcriptomic and metabolomic analyses pinpointed interleukin (IL)-17A, IL-13, and CC chemokine receptor type 3 (CCR3) as central CQG targets, glycerophospholipid metabolism as key metabolic pathway, and further experiments confirmed that CQG reduced the expression of IL-17A, IL-13, CCR3, and inhibited the expression of inflammatory cytokines by suppressing PI3K/Akt signaling pathway and glycerophospholipid metabolism, to attenuate neuroinflammation in MH rats.CONCLUSIONS: Taken together, CQG inhibited PI3K/Akt signaling pathway to reduced neuroinflammation, and modulated metabolic pathway of glycerophospholipid metabolism in MH. The findings of this study offer novel insights into the mechanisms underlying the therapeutic effects of CQG, highlighting its potential clinical application in treatment of MH.PMID:39708589 | DOI:10.1016/j.phymed.2024.156336
Capilliposide A alleviates DSS-induced colitis by regulating the intestinal flora and its metabolites of origin
Int Immunopharmacol. 2024 Dec 20;146:113858. doi: 10.1016/j.intimp.2024.113858. Online ahead of print.ABSTRACTUlcerative colitis is a chronic idiopathic inflammatory disease that impacts the mucous membrane of the colon. Lately, the incidence and prevalence of UC has been increasing globally. However, there are significant side effects of existing drugs for UC intervention. Accordingly, there is a pressing demand to explore novel bioactive substances for addressing UC. Natural product saponins have attracted great attention due to their obvious anti-colitis potential. Capilliposide A is a triterpenoid saponin, which is derived from Lysimachia capillipes Hemsl., exhibits good anti-inflammatory activity. Nonetheless, the impact and mechanism of CPS-A on ulcerative colitis remains obscure. This study aimed to investigate the therapeutic effects of CPS-A on the dextran sulphate sodium induced colitis mouse model and explore its mechanism. The efficacy and safety of CPS-A were evaluated in a well-established dextran sodium sulfate (DSS)-induced colitis mice model. Disease progression was monitored via clinical symptoms, histopathological examination, quantification of inflammatory cytokines, and epithelial barrier function evaluation. Plasma samples and intestinal contents were collected for non-targeted metabolomics and 16sRNA sequencing, respectively, to jointly evaluate the mechanism of action. CPS-A alleviated colitis by improving weight, Disease activity index score, histopathology, goblet cell, colon length, and expression of inflammatory factors. Moreover, CPS-A effectively preserved the integrity of the intestinal barrier by enhancing the expression of tight junction proteins and mucin in the colonic tissue of mice. Furthermore, CPS-A exerted a regulatory effect on the composition of the gut microbiota, promoting bacterial richness and diversity. It not only suppressed the abundance of detrimental bacteria while enhancing the abundance of advantageous bacteria, but also modulated the metabolites derived from the intestinal flora. Importantly, correlation analysis shows that these indicators are highly correlated. This study revealed that CPS-A exhibits a favorable therapeutic efficacy against colitis, primarily attributed to its ability to modulate the gut microbiota their associated metabolites as the key mechanisms of action.PMID:39708482 | DOI:10.1016/j.intimp.2024.113858
Integrated analysis of biochemical, transcriptomic, and metabolomic response mechanisms in Ussuri catfish (Pseudobagrus ussuriensis) under acute heat stress
Ecotoxicol Environ Saf. 2024 Dec 20;290:117563. doi: 10.1016/j.ecoenv.2024.117563. Online ahead of print.ABSTRACTFish metabolism, growth, development, and physiological conditions are highly sensitive to fluctuations in water temperature. The Ussuri catfish (Pseudobagrus ussuriensis) is an important native economic species in China. However, research on heat stress in P. ussuriensis, particularly concerning gene expression and metabolites, remains limited. In this study, we conducted histological observations, biochemical measurements, transcriptomic analysis, and metabolomic analysis on liver tissue from a control group (22 ℃), an acute heat stress group (34 ℃, with samples taken at 0, 3, 6, 12, and 24 h), and a recovery group (sampled 24 h after recovery to 22 ℃). Histopathological analysis showed that liver damage worsened with the duration of heat stress. Biochemical results indicated that acute heat stress significantly impacted the activities of superoxide dismutase, catalase, and alanine aminotransferase, as well as the levels of glutathione, malondialdehyde, and total antioxidant capacity, with alterations remaining even after temperature recovery. Transcriptomic and metabolomic analyses revealed that compared to the control group, 3482, 800, 980, and 1479 differentially expressed genes (DEGs) were detected at 0, 6, and 24 h of acute heat stress and at 24 h post-recovery, respectively. Similarly, 114, 151, 365, and 326 differentially expressed metabolites (DEMs), respectively, were detected at the same time points. Furthermore, when comparing 24 h of heat stress with 24 h of recovery, 1279 DEGs and 157 DEMs were identified. Functional enrichment analysis revealed that these DEGs and DEMs were significantly enriched in key pathways, such as endoplasmic reticulum protein processing and glutathione metabolism, with significant changes continuing into the recovery phase. Additionally, substantial alterations in the expression levels of amino acids, sugars, and lipids were observed during heat stress. These findings provide valuable insights into the defense mechanisms of fish under high-temperature stress and lay a theoretical foundation for breeding heat-resistant P. ussuriensis strains, as well as improving sustainable aquaculture management.PMID:39708448 | DOI:10.1016/j.ecoenv.2024.117563
Associations of gestational anxiety and depression with neonatal hair steroid levels
Psychoneuroendocrinology. 2024 Dec 19;172:107260. doi: 10.1016/j.psyneuen.2024.107260. Online ahead of print.ABSTRACTOBJECTIVE: To investigate the association prenatal maternal depression and anxiety may have on the levels of neonatal hair steroids (i.e. cortisol, cortisone, and the cortisol/cortisone ratio) at birth.METHODS: Altogether, 271 mother-infant pairs derived from the Finnish Kuopio Birth Cohort Study were assessed for maternal depression and anxiety using the Edinburgh Postnatal Depression Scale (EPDS: EPDS-10 for depression, EPDS-3A for anxiety) during the first (T1) and third (T3) trimesters. The levels of cortisol and cortisone were determined from neonatal hair samples obtained at birth. Linear mixed models adjusted for sex, preterm birth, smoking during pregnancy, and gestational diabetes were used.RESULTS: Neither T1 nor T3 EPDS-10 predicted the levels of neonatal hair steroids. T3 EPDS-3A (p = 0.012), but not T1 EPDS-3A, was linked to reduced neonatal hair cortisol levels. Neither T1 nor T3 EPDS-3A were significant predictors of neonate cortisone levels or cortisol/cortisone ratios.CONCLUSION: Prenatal maternal anxiety, but not depression, may lead to pronounced alterations in some markers of fetal stress systems. Future research should further determine whether prenatal maternal symptoms of anxiety would form an optimal intervention target in order to attenuate fetal stress responses.PMID:39708437 | DOI:10.1016/j.psyneuen.2024.107260
Untargeted Spatial Metabolomics and Spatial Proteomics on the Same Tissue Section
Anal Chem. 2024 Dec 21. doi: 10.1021/acs.analchem.4c04462. Online ahead of print.ABSTRACTAn increasing number of spatial multiomic workflows have recently been developed. Some of these approaches have leveraged initial mass spectrometry imaging (MSI)-based spatial metabolomics to inform the region of interest (ROI) selection for downstream spatial proteomics. However, these workflows have been limited by varied substrate requirements between modalities or have required analyzing serial sections (i.e., one section per modality). To mitigate these issues, we present a new multiomic workflow that uses desorption electrospray ionization (DESI)-MSI to identify representative spatial metabolite patterns on-tissue prior to spatial proteomic analyses on the same tissue section. This workflow is demonstrated here with a model mammalian tissue (coronal rat brain section) mounted on a poly(ethylene naphthalate)-membrane slide. Initial DESI-MSI resulted in 160 annotations (SwissLipids) within the METASPACE platform (≤20% false discovery rate). A segmentation map from the annotated ion images informed the downstream ROI selection for spatial proteomics characterization from the same sample. The unspecific substrate requirements and minimal sample disruption inherent to DESI-MSI allowed for an optimized, downstream spatial proteomics assay, resulting in 3888 ± 240 to 4717 ± 48 proteins being confidently directed per ROI (200 μm × 200 μm). Finally, we demonstrate the integration of multiomic information, where we found ceramide localization to be correlated with SMPD3 abundance (ceramide synthesis protein), and we also utilized protein abundance to resolve metabolite isomeric ambiguity. Overall, the integration of DESI-MSI into the multiomic workflow allows for complementary spatial- and molecular-level information to be achieved from optimized implementations of each MS assay inherent to the workflow itself.PMID:39708340 | DOI:10.1021/acs.analchem.4c04462
MAPK14/p38α shapes the molecular landscape of endometrial cancer and promotes tumorigenic characteristics
Cell Rep. 2024 Dec 20;44(1):115104. doi: 10.1016/j.celrep.2024.115104. Online ahead of print.ABSTRACTThe molecular underpinnings of high-grade endometrial carcinoma (HGEC) metastatic growth and survival are poorly understood. Here, we show that ascites-derived and primary tumor HGEC cell lines in 3D spheroid culture faithfully recapitulate key features of malignant peritoneal effusion and exhibit fundamentally distinct transcriptomic, proteomic, and metabolomic landscapes compared with conventional 2D monolayers. Using a genetic screening platform, we identify MAPK14 (which encodes the protein kinase p38α) as a specific requirement for HGEC in spheroid culture. MAPK14/p38α has broad roles in programming the phosphoproteome, transcriptome, and metabolome of HGEC spheroids, yet has negligible impact on monolayer cultures. MAPK14 promotes tumorigenicity in vivo and is specifically required to sustain a sub-population of spheroid cells that is enriched in cancer stemness markers. Therefore, spheroid growth of HGEC activates unique biological programs, including p38α signaling, that cannot be captured using 2D culture models and are highly relevant to malignant disease pathology.PMID:39708320 | DOI:10.1016/j.celrep.2024.115104
Metabolomic Changes Associated With the Change in HVPG After DAAs Therapy in HCV Cirrhotic Patients
Liver Int. 2025 Jan;45(1):e16204. doi: 10.1111/liv.16204.ABSTRACTBACKGROUND AND AIMS: In response to direct-acting antivirals (DAAs) therapy, patients who experience a decrease in hepatic venous pressure gradient (HVPG) considerably reduce liver complications and have increased survival. This study aimed to assess the metabolomic changes associated with the changes in HVPG from the start of DAA therapy until 48 weeks after effective DAA therapy in patients with advanced HCV-related cirrhosis.METHODS: We carried out a multicenter longitudinal study in 31 patients with advanced hepatitis C virus (HCV)-related cirrhosis. We performed a non-targeted metabolomic analysis using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry, as well as analysis of inflammation-related biomarkers using Luminex technology. The statistical analysis was performed by Generalised Linear Mixed-effects Models (GLMM), correcting for multiple testing.RESULTS: We found that increases of 2,3-butanediol (AMR = 1.15; q-value = 0.023) and taurocholic acid (AMR = 1.06; q-value < 0.001) were significantly associated with increases in HVPG and inflammatory biomarker levels from before DAA therapy to one year after completion of successful HCV treatment.CONCLUSIONS: These metabolites have a potential role as indicators of portal hypertension evolution.PMID:39708286 | DOI:10.1111/liv.16204
Prediction and analysis of the tumor invasiveness of pulmonary ground-glass nodules based on metabolomics
Clin Exp Med. 2024 Dec 21;25(1):22. doi: 10.1007/s10238-024-01529-3.ABSTRACTIn recent years, the incidence of ground-glass nodular lung adenocarcinoma has gradually increased. Preoperative evaluation of the tumor invasiveness is very important, but there is a lack of effective methods. Plasma samples of ground-glass nodular lung adenocarcinoma and healthy volunteers were collected. Pulmonary nodules with different densities were compared by metabolomics. Different invasive degrees of lung adenocarcinoma were contrasted as well. Multivariate statistical methods were applied to search for significant metabolites from comparisons between two groups. The common metabolites among the different comparisons were selected and then assessed by various indices. Five metabolites were discovered for lung adenocarcinoma with different invasive degrees. Significant metabolites were selected for pulmonary nodules with different densities as well. When these metabolites were cross-compared, only the level of lysoPC(18:3) was significantly lower in ground-glass nodular lung adenocarcinoma than healthy population, as opposed to other metabolites. After identifying the invasive degree of pulmonary ground-glass nodules, lysoPC(18:3) showed a satisfactory sensitivity and specificity, both greater than 0.85. Metabolomics analysis has favorable advantages in the study of ground-glass nodular lung adenocarcinoma. LysoPC(18:3) may have the potential to differentiate precancerous lesions from invasive lung cancer, which could help clinicians to make proper judgment before surgery.PMID:39708148 | DOI:10.1007/s10238-024-01529-3
Focusing on the Dark Side of the Moon: Involvement of the Nonlesional Skin in Vitiligo
J Invest Dermatol. 2024 Dec 20:S0022-202X(24)02886-0. doi: 10.1016/j.jid.2024.10.598. Online ahead of print.ABSTRACTResearch over the last decade has revealed that the normally pigmented skin of patients with vitiligo is not normal at all, as evidenced by alterations in cutaneous morphology and modifications in cellular and metabolic functions that ultimately drive immune activation against melanocytes. Furthermore, nonlesional skin is in a state of subclinical inflammation until triggered by internal and/or external exposomal events. Therefore, targeting early processes that drive immune dysregulation in normally pigmented skin may avoid or reduce melanocyte loss. Thus, shifting the focus to nonlesional skin may prevent the appearance of clinical manifestations of the disease rather than treating the lesions.PMID:39708041 | DOI:10.1016/j.jid.2024.10.598
Salivary Metabolomic Signatures in Pediatric Eosinophilic Esophagitis
Allergy. 2024 Dec 21. doi: 10.1111/all.16450. Online ahead of print.NO ABSTRACTPMID:39707873 | DOI:10.1111/all.16450
Bixa orellana (Bixaceae) seeds as a potential source of bioactive compounds for modulating postprandial hyperglycemia
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
New insights into the combined effects of aflatoxin B1 and Eimeria ovinoidalis on uterine function by disrupting the gut-blood-reproductive axis in sheep
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
The metabolome of male and female individuals with knee osteoarthritis is influenced by 18-months of weight loss intervention: the IDEA trial
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
Multiomics joint analysis reveals the potential mechanism of differences in the taproot thickening between cultivated ginseng and mountain-cultivated ginseng
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
Integrated metabolomic and transcriptomic analyses of flavonoid accumulation in different cultivars of Platostoma palustre
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
Elucidating the role of gut microbiota metabolites in diabetes by employing network pharmacology
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
Based on metabolomics analysis: metabolic mechanism of intestinal tract of Scylla paramamosain under low-salt saline-alkali water aquaculture environment
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