PubMed

Cancer Cell Int. 2025 Mar 15;25(1):97. doi: 10.1186/s12935-025-03727-9.ABSTRACTBACKGROUND: Schisandrin B (Sch B) is an active component in Schisandra chinensis exerting anti-cancer effect, but the mechanism is obscure. This study was designed to explore the mechanism of Sch B against colorectal cancer (CRC).METHOD: Apparent experiments including cell proliferation, transwell, colony formation, etc. were carried out to assess the anti-cancer effect of Sch B to CRC cell lines, and the RNA-seq was performed prior to bioinformatics analysis to explore the key transcriptome alterations, furthermore, an untargeted metabolomics was carried out to profile the metabolic alterations after the treatment with Sch B and an integrated analysis and experiment validation were completed based on RNA-seq and metabolomics to find the critical mechanism.RESULT: The Sch B showed obviously inhibitory effect to cell proliferation, invasion and migration of CRC cell lines with a IC50 value at 75 µM. The RNA-seq and bioinformatics analysis found the ERK/MAPK pathway has been significantly suppressed by the Sch B treatment, while the chemokine, CXCL2, could activate the ERK pathway when binding to its receptor CXCR2. The metabolomics revealed the metabolic profile of CRC cell was remarkably influenced by the Sch B, focusing on the arginine and proline metabolism, ubiquinone, etc. Importantly, the integrated analysis found the DUSP11 connected the ERK pathway and the metabolisms, may mediate the anti-cancer effect of Sch B.CONCLUSION: Sch B showed obviously anti-cancer effect to the CRC through inhibiting CXCL2/ERK/DUSP11 axis, but more experiments are needed to figure out the target of Sch B and validate this mechanism in vivo.PMID:40089741 | DOI:10.1186/s12935-025-03727-9

BMC Plant Biol. 2025 Mar 15;25(1):340. doi: 10.1186/s12870-025-06333-z.ABSTRACTBACKGROUND: Common bean (Phaseolus vulgaris L.) is a thermophilic crop, and exposure to cold stress can significantly impact their yield and quality. To elucidate the impact of cold stress on cold-tolerant 'Wei Yuan' (WY) and cold-sensitive 'Bai Bu Lao' (BBL) of common bean, the mechanism of cold tolerance was studied by physiological and biochemical and multi-omics analysis.RESULTS: In this study, lower relative conductivity and higher malondialdehyde content after cold stress endowed 'WY' seedlings with cold tolerance. A total of 11,837 differentially expressed genes (DEGs) and 923 differential metabolites (DEMs) were identified by transcriptome and metabolomics analysis. Joint analysis showed that under cold stress, DEGs and DEMs in common beans are extensively engaged in sugar, amino acid and isoflavonoid biosynthesis, flavone and flavonol biosynthesis, and plant hormone signal translation, especially related to isoflavone biosynthesis. In addition, it was also found that bHLH and MYB family transcription factors may be involved in the cold signal transduction of common bean.CONCLUSIONS: The above results will provide a theoretical basis for the cold tolerance mechanism of common beans and provide help for the screening of cold-tolerant resources of common beans.CLINICAL TRIAL NUMBER: Not applicable.PMID:40089684 | DOI:10.1186/s12870-025-06333-z

BMC Plant Biol. 2025 Mar 15;25(1):335. doi: 10.1186/s12870-025-06300-8.ABSTRACTBACKGROUND: Salt stress is considered to be one of the major abiotic stresses influencing rice growth and productivity. To improve rice crop productivity in saline soils, it is essential to choose a suitable variety for mitigating salt stress and gain a deep understanding of the underlying mechanisms. The current study explored the salt tolerance mechanism of wild rice 'HD96-1 (salt resistive)' and conventional rice 'IR29 (salt sensitive)' by evaluating morph-physiological, transcriptomic, and metabolomic approaches.RESULTS: Physiological data indicated that HD96-1 had higher chlorophyll content, higher photosynthetic efficiency, more stable Na+/K+, less H₂O₂, and lower electrolyte leakage under salt stress compared with IR29. Transcriptomic and metabolomic data showed that the expression of NHXs in IR29 was significantly down-regulated under salt stress, leading to a large accumulation of Na⁺ in the cytoplasm, and that the expression of CHLH, PORA, and PORB was significantly down-regulated, inhibiting chlorophyll synthesis. HD96-1 maintained the balance of Na⁺ and K⁺ by increasing the expression of NHX4, and there was no significant change in the expression of genes related to chlorophyll synthesis, which made HD96-1 more resistant to salt stress than IR29. In addition, HD96-1 inhibited the excessive synthesis of hydrogen peroxide (H₂O₂) and alleviated oxidative damage by significantly down-regulating the expression of ACX4 under salt stress. HD96-1 promoted the accumulation of isoleucine by up-regulating genes of branched-chain amino acid aminotransferase 2 and branched-chain amino acid aminotransferase 4 and might promote the synthesis of raffinose and stachyose by up-regulating the expression of the gene for galactitol synthase 2, which, in turn, maintained a stable osmotic pressure and relieved osmotic stress. We also found that IR29 and HD96-1 alleviated the inhibition of photosynthesis by salt stress by down-regulating the expression of light-harvesting chromophore protein complex (LHCH II)-related genes and reducing the excessive accumulation of glucose metabolites, respectively. In addition, HD96-1 enhances salt tolerance by regulating C2H2 and bHLH153 transcription factors.CONCLUSION: Under salt stress, HD96-1 maintained ionic balance and photosynthetic efficiency by up-regulating the expression of NHX4 gene and reducing the overaccumulation of glucose metabolites, respectively, and mitigated osmotic stress and oxidative stress by down-regulating the expression of ACX4 and promoting the accumulation of isoleucine, respectively, thereby enhancing the adaptability to salt stress. IR29 maintained photosynthetic efficiency under salt stress by down-regulating the expression of light-harvesting chromophore protein complex (LHCH II)-related genes, thereby enhancing adaptation to salt stress.PMID:40089670 | DOI:10.1186/s12870-025-06300-8

Klin Onkol. 2025;38(1):38-44. doi: 10.48095/ccko202538.ABSTRACTBACKGROUND: The search for effective biomarkers for ovarian cancer (OC) early diagnosis is an urgent task of modern oncogynecology. Metabolic profiling by ultra-high performance liquid chromatography and mass spectrometry (UHPLC-MS) provides information on the totality of all low molecular weight metabolites of patient's biological fluids sample, reflecting the processes occurring in the body. The aim of the study was to research blood plasma and urine metabolomic profile of patients with serous ovarian adenocarcinoma by UHPLC-MS.MATERIAL AND METHODS: To perform metabolomic analysis, 60 blood plasma samples and 60 urine samples of patients diagnosed with serous ovarian carcinoma and 20 samples of apparently healthy volunteers were taken. Chromatographic separation was performed on a Vanquish Flex UHPLC System chromatograph (Thermo Scientific, Germany). Mass spectrometric analysis was performed on an Orbitrap Exploris 480 (Thermo Scientific, Germany) equipped with an electrospray ionization source. Bioinformatic analysis was performed using Compound Discoverer Software (Thermo Fisher Scientific, USA), statistical data analysis was performed in the Python programming language using the SciPy library.RESULTS: Using UHPLC-MS, 1,049 metabolites of various classes were identified in blood plasma. In patients with OC, 8 metabolites had a significantly lower concentration (P < 0.01) compared with conditionally healthy donors, while the content of 19 compounds, on the contrary, increased (P < 0.01). During the metabolomic profiling of urine samples, 417 metabolites were identified: 12 compounds had a significantly lower concentration compared to apparently healthy individuals, the content of 14 compounds increased (P < 0.01). In patients with ovary serous adenocarcinoma, a significant change in the metabolome of blood plasma and urine was found, expressed in abnormal concentrations of lipids and their derivatives, fatty acids and their derivatives, acylcarnitines, phospholipids, amino acids and their derivatives, derivatives of nitrogenous bases and steroids. At the same time, kynurenine, myristic acid, lysophosphatidylcholine and L-octanoylcarnitine are the most promising markers of this disease.CONCLUSION: The revealed changes in the metabolome can become the basis for improving approaches to the diagnosis of serous ovarian adenocarcinoma.PMID:40088435 | DOI:10.48095/ccko202538

Mol Biotechnol. 2025 Mar 15. doi: 10.1007/s12033-025-01400-0. Online ahead of print.ABSTRACTDrought is considered one of the major limiting factors for crop production. Drought-affected areas are consistently expanding. As rice stands as a primary grain widely consumed as a staple food by people across the globe, with a particular prominence in Asian countries. Due to its short root structure, thin cuticular wax layer and quick stomatal closure, rice is considered as drought-sensitive crop. The impact of drought on rice amplifies with plant growth and its adverse effects are more pronounced during the reproductive phase, including stages such as blooming, filling and maturity. Every year rice growers are facing a considerable deterioration of yield due to abiotic stresses specially drought. To address this undesirable consequences, multi-omics approaches are successfully being utilized as a mitigation strategy. A thorough, precise and systematic comprehension of the fundamental biological and cellular mechanisms activated by crop plants during stress is achieved through a range of omics technologies, including genomics, transcriptomics, proteomics and metabolomics. The integration of multi omics approaches offers a holistic understanding of cellular dynamics during drought or other stress conditions. These omics-based tools can identify and manipulate drought-tolerant genes. Utilizing omics approaches to stack these genes in rice contributes to the development of a drought resistant plant architecture. This review article aims to compile the latest published strategies on the application of multi omics approaches to accelerate the development of drought-tolerant rice plants.PMID:40088409 | DOI:10.1007/s12033-025-01400-0

J Invest Dermatol. 2025 Feb 10:S0022-202X(25)00014-4. doi: 10.1016/j.jid.2024.11.026. Online ahead of print.ABSTRACTTopical steroid withdrawal (TSW) is a controversial diagnosis advocated by patients but often confused for atopic dermatitis. We conducted a multimodal pilot study of 16 patients fitting the TSW diagnostic profile, contrasting them against patients with atopic dermatitis (n = 10) and healthy controls (n = 11). Our clinical evaluations established objective diagnostic criteria that distinguish TSW from atopic dermatitis, metabolomics and transcriptomics of skin biopsies suggested that neuroinflammatory pathways are associated with complex I-mediated oxidation of NAD+, cellular and mouse models demonstrated that NAD+ metabolism was proinflammatory and glucocorticoid responsive, whereas functional assays demonstrated that the metabolic effects of glucocorticoids on the only cell type that aligns with the distribution and duration of TSW pathology could be mitigated by complex I blockade. These results informed a successful open-label trial using complex I-inhibiting interventions: metformin and berberine. Although this work represents a pilot study, to our knowledge, this work offers previously unreported mechanistic insights into TSW.PMID:40088241 | DOI:10.1016/j.jid.2024.11.026

J Med Virol. 2025 Mar;97(3):e70289. doi: 10.1002/jmv.70289.ABSTRACTCoronavirus disease 2019 (COVID-19) global pandemic has affected more than 600 million people up to date. The symptomatology and severity of COVID-19 are very broad, and there are still concerns about the long-term sequelae that it can have on discharged patients. The development of pulmonary fibrotic sequelae after this infection is especially worrying. Our aim was to determine if there was a metabolomic signature that could predict the development of pulmonary fibrotic sequelae. It is a multicenter prospective observation subcohort based on the COVID-FIBROTIC study. A metabolomic analysis was performed by nuclear magnetic resonance (NMR) on serum samples from patients admitted with bilateral COVID-19 pneumonia collected 2 months after hospital discharge. One year after admission, clinical, functional and radiological data were collected from these same patients. Finally, 109 patients (mean age 57.68 [DS14.03], 65.13% male) were available. Fibrotic sequelae 1 year after COVID-19 disease were found in 33% of them. Based on the NMR analysis of the serum samples, it was possible to distinguish with 80.82% of sensitivity, 72.22% of specificity and 0.83 of an area under the curve (AUC) value which patients would have radiological signs of pulmonary fibrotic pattern 1 year after sample collection. According to the metabolites participating in the discriminative model and the univariate statistics, glucose, valine, and fatty acids (═CH-CH2-CH═) were suggested as potential biomarkers of the development of pulmonary fibrotic sequelae after COVID-19. TRIAL REGISTRATION NUMBER: clinicaltrials.gov NCT04409275 (June 1, 2020).PMID:40088077 | DOI:10.1002/jmv.70289

Acta Neuropathol Commun. 2025 Mar 15;13(1):61. doi: 10.1186/s40478-025-01961-w.ABSTRACTGliomas are the most common primary brain tumors and a major source of mortality and morbidity in adults and children. Recent genomic studies have identified multiple molecular subtypes; however metabolic characterization of these tumors has thus far been limited. We performed metabolic profiling of 114 adult and pediatric primary gliomas and integrated metabolomic data with transcriptomics and DNA methylation classes. We identified that pediatric tumors have higher levels of glucose and reduced lactate compared to adult tumors regardless of underlying genetics or grade, suggesting differences in availability of glucose and/or utilization of glucose for downstream pathways. Differences in glucose utilization in pediatric gliomas may be facilitated through overexpression of SLC2A4, which encodes the insulin-stimulated glucose transporter GLUT4. Transcriptomic comparison of adult and pediatric tumors suggests that adult tumors may have limited access to glucose and experience more hypoxia, which is supported by enrichment of lactate, 2-hydroxyglutarate (2-HG), even in isocitrate dehydrogenase (IDH) wild-type tumors, and 3-hydroxybutyrate, a ketone body that is produced by oxidation of fatty acids and ketogenic amino acids during periods of glucose scarcity. Our data support adult tumors relying more on fatty acid oxidation, as they have an abundance of acyl carnitines compared to pediatric tumors and have significant enrichment of transcripts needed for oxidative phosphorylation. Our findings suggest striking differences exist in the metabolism of pediatric and adult gliomas, which can provide new insight into metabolic vulnerabilities for therapy.PMID:40087788 | DOI:10.1186/s40478-025-01961-w

BMC Sports Sci Med Rehabil. 2025 Mar 14;17(1):50. doi: 10.1186/s13102-025-01094-6.ABSTRACTBACKGROUND: There is a gap in knowledge regarding the utility of preoperative exercise (PEx) among gastrointestinal (GI) cancer patients undergoing surgery and how PEx impacts surgical outcomes. This study seeks to evaluate the mechanism behind PEx among patients undergoing major abdominal surgery for GI cancer through a randomized controlled trial (RCT).METHODS: This was a single center RCT conducted at The Ohio State University Wexner Medical Center. Eligible patients diagnosed with GI cancers with planned abdominal surgery were randomized to receive PEx or a Sedentary (Non-PEx) arm between October 2020 and May 2022. To investigate if PEx could lead to systemic change in circulation, we employed secretomics and metabolomics analyses of patient serum samples before and after exercise to detect inflammatory and tumorigenic responses, with the primary endpoint of investigating the mechanisms through which PEx modulates the inflammatory response in patients undergoing GI cancer surgery.RESULTS: Between October 2020 and May 2022, 64 patients were enrolled in the study, with 28 randomized to the PEx group and 36 to the non-PEx group. The two cohorts were comparable in terms of age, gender, and comorbidity burden. The median length of stay was 6 days across the entire cohort, with no significant differences between the groups. Similarly, the overall 30-day readmission rate was 15.7%, and the median comprehensive complication index score was 20.9, both of which showed no differences between the PEx and non-PEx groups. Secretomics and metabolomics analyses of patient serum samples revealed a shift towards an anti-inflammatory and anti-tumorigenic phenotype, with significant changes in secretion and metabolic profiles observed in post-PEx serum compared to pre-PEx serum from the same patients.CONCLUSIONS: PEx has the potential to mitigate the pro-inflammatory and pro-tumorigenic state of GI cancer by modulating specific cellular pathways. This study provides evidence into the mechanisms underlying these effects, but additional research is required to explore their applicability in therapeutic development. These findings build upon existing research to support the advancement of exercise-inspired therapeutic strategies in the future.TRIAL REGISTRATION: The trial was registered at Clinicaltrials.gov (NCT04602026) on 20/10/2020.PMID:40087747 | DOI:10.1186/s13102-025-01094-6

Sci Rep. 2025 Mar 15;15(1):8932. doi: 10.1038/s41598-025-93336-3.ABSTRACTAs basis for evidence-based analgesia refinement, species-specific pharmacokinetic and tolerability profiles of carprofen were determined in rats for least aversive administration routes and prolonged treatment. Further, potential influence on behavioral pain indicators was evaluated. LC-MS/MS determined plasma concentrations in Sprague-Dawley rats (n = 21/sex) after subcutaneous (s.c.) injection (5 mg/kg) and during a 5-day treatment via the drinking water (d.w., 10 mg/kg/24 h). Irwin test parameters, clinical scoring, body weight, body temperature, fluid and food intake, grimace scale, burrowing, nesting, hematology, and histopathology were investigated. Plasma concentrations early after injection were higher in females, reached a maximum (Cmax) of 39.16 ± 7.38 µg/ml at 3 h after injection and remained above an estimated in-vitro-derived therapeutic threshold (24.3 µg/ml) for at least 6 h with a T1/2 of 7.06 h. Carprofen-medicated d.w. was readily consumed, with constant target dose intake over the 5-day treatment period reaching a Cmax of 38.68 ± 8.67 µg/ml at 24 h. Tolerability and behavioral parameters revealed only minor changes, such as transient sedation (s.c.) and decreased body temperature (females). Gastrointestinal adverse effects were not detected. Carprofen's pharmacokinetic profile allows for a practicable s.c. injection interval. Acceptance and tolerability during prolonged oral treatment with the assessed dose of 10 mg/kg/24 h makes its non-invasive administration promising for analgesia refinement in rats.PMID:40087482 | DOI:10.1038/s41598-025-93336-3

Sci Rep. 2025 Mar 14;15(1):8861. doi: 10.1038/s41598-025-93235-7.NO ABSTRACTPMID:40087341 | DOI:10.1038/s41598-025-93235-7

Sci Rep. 2025 Mar 15;15(1):8923. doi: 10.1038/s41598-025-91710-9.ABSTRACTUnderstanding the metabolic profile within the follicular microenvironment is crucial for optimizing reproductive efficiency in camels. In this study, we examined the metabolomic profile of camel follicular fluid (FF) during the breeding (n = 10) and non-breeding seasons (n = 10). Gas chromatography-mass spectrometry (GC-MS) was utilized to describe the metabolites present in follicular fluid samples. The results found considerable differences in the metabolomics profiles between the breeding and non-breeding seasons. Hexadecenoic acid, galactose and glucose levels were significantly (P < 0.05) higher in camel FF during the breeding season, while 9-octadecenamide, oleonitrile, glycine, octadecanamide, cholesterol, and propanoic acid were higher (P < 0.05) in FF during the non-breeding season. Multivariante analyses pointed to those 9 metabolites, and univariate analysis showed hexadecenoic acid, galactose, glucose, and oleanitril were the most significant ones in camel follicular fluid collected during both breeding and non-breeding seasons. The univariate and multivariate analyses showed an increase in the levels of hexadecanoic acid, galactose, glucose, and a depletion in the level of oleanitrile in the breeding season compared to the non-breeding season. The ROC curve and statistical analysis showed that hexadecanoic acid, galactose, and oleanitril with AUC = 1 were promising to be seasonal biomarkers of fertility in female camels. In conclusion, the metabolomic analysis of camel FF reveals distinct changes in metabolite levels between breeding and non-breeding seasons, reflecting adaptive metabolic responses to support reproductive processes. These results offer valuable insights into the reproductive physiology of camels and offer practical implications for potential biomarkers and assessing the reproductive status in camels, which can be utilized in reproductive management and conservation efforts in these valuable animal species.PMID:40087336 | DOI:10.1038/s41598-025-91710-9

Anal Bioanal Chem. 2025 Mar 15. doi: 10.1007/s00216-025-05820-4. Online ahead of print.ABSTRACTMass spectrometry (MS) is a versatile technique for elucidating the chemical composition of biological samples. Beyond analysis of crude extracts, MS can be further applied to spatially resolve compounds across the area of a sample with a technique called mass spectrometry imaging (MSI). The infrared matrix-assisted laser desorption ionization (IR-MALDESI) platform combines elements of matrix-assisted laser desorption ionization (MALDI) and electrospray ionization (ESI) to enable MSI of mammalian tissue using endogenous water in the sample as a matrix. For laser-based techniques such as IR-MALDESI, changes in topography across the sample surface cause inconsistent ablation as the sample surface moves above and below the focal plane of the laser. The localization of chemical species in plants reveals crucial information about metabolic processes as reported by Nemes and Vertes (Anal. Chem. 79 (21), 8098-8106, 2007) and biosynthetic pathways by Zou et al. (Trends in Plant Science, 2024) and can even inform selective breeding of crops as discussed by Sakurai (Breed Sci 72 (1), 56-65, 2022); however, leaf topography raises a unique challenge. Features such as veins and trichomes exhibit unique topography, but flattening risks delocalization of analytes and activation of unwanted signaling pathways, and transferring metabolites to a membrane for indirect analysis may incur delocalization and limit metabolomic coverage. To overcome these challenges, a chromatic confocal sensor probe (CA probe) was incorporated for IR-MALDESI-MSI of sections of a collard (Brassica oleracea var. viridis) leaf. The CA probe measures the height at all points of the sample, and automatic z-axis corrections (AzC) are generated from height differences to continuously raise and lower the stage. These stage height corrections keep the sample surface in focus of the laser for the duration of analysis. This method has been applied to relatively homogenous samples, but has not yet been characterized on heterogeneous leaf tissue with considerable topography. Herein, data quality is compared between MSI analyses with and without AzC applied, focusing on the localization of analytes known to be concentrated in different layers of collard leaves.PMID:40087179 | DOI:10.1007/s00216-025-05820-4

J Ethnopharmacol. 2025 Mar 13:119632. doi: 10.1016/j.jep.2025.119632. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Quality control is a powerful method for ensuring the effectiveness and safety of herbal medicines. Phyllanthus emblica L. fruit (PE) has been extensively used in both Ayurvedic and traditional Chinese medicine. However, the current Indian and Chinese pharmacopeias set a minimum concentration threshold of gallic acid to identify qualified PE samples, without providing a clear framework to distinguish superior-quality PE samples.AIM OF THE STUDY: To establish an efficacy-oriented quality grading framework for herbal medicines, using PE, a medicinal plant known for its hepatoprotective activity, as an example.METHODS: First, a mouse model of alcohol-induced liver injury was developed to evaluate the hepatoprotective effects of PE. Second, a combined strategy of serum pharmacochemistry, network pharmacology, metabolomics and experimental validation was employed to identify key quality markers (Q-markers) linked to the hepatoprotective effects of PE. Finally, PE samples from different sources were collected to assess their hepatoprotective activities and Q-marker concentrations. A discriminant analysis model was then developed to classify PE samples into different quality grades by using Q-marker concentration as the predictive factor and hepatoprotective activity as the evaluation criterion.RESULTS: PE significantly alleviated liver damage, as evidenced by a reduction in pathological abnormalities and serum aminotransferase levels. Six hepatoprotective Q-markers in PE were identified and verified, including gallic acid, methyl gallate, corilagin, chebulagic acid, ellagic acid and quercitrin. Significant variability in Q-marker concentrations and hepatoprotective effects was observed among different sources of PF samples, and a discriminant analysis model accurately classified PE samples into distinct quality grades.CONCLUSIONS: This study successfully established an efficacy-oriented quality grading framework for PE, providing a methodological approach for the quality classification of herbal medicines.PMID:40089198 | DOI:10.1016/j.jep.2025.119632

J Allergy Clin Immunol. 2025 Mar 13:S0091-6749(25)00274-X. doi: 10.1016/j.jaci.2025.02.037. Online ahead of print.ABSTRACTBACKGROUND: Inhaled corticosteroids (ICS) are frequently prescribed medications for asthma symptoms, but higher doses can increase risks of adrenal insufficiency through suppression of endogenous cortisol production. Understanding which patients may be at increased risk for developing adrenal suppression related to ICS use may help providers improve treatment regimens for asthma patients; however, the mechanisms underlying ICS-related adrenal insufficiency have not been clarified.OBJECTIVE: This study identifies metabolite signatures and biochemical pathways associated with ICS-related adrenal insufficiency in asthma patients.METHODS: Global metabolite profiling (metabolomics) was integrated with electronic medical records data including the development of adrenal suppression, in two independent asthma cohorts. The discovery cohort, Pharmacogenomics of Adrenal Suppression with Inhaled Corticosteroids (PhASIC), included 711 adult asthma patients on ICS. Untargeted metabolomic profiling identified 1,397 metabolites, of which 810 were selected for further analysis. Using plasma cortisol as a biomarker for adrenal status (outcome), linear regression models were implemented to identify associations between metabolites and plasma cortisol, adjusted for potential confounders. Metabolite associations were validated in an additional 575 patients on ICS. Pathway and network analyses were performed using bioinformatic approaches to identify altered metabolic pathways related to the outcome.RESULTS: Of 810 endogenous metabolites, 12 demonstrated significant associations with adrenal insufficiency after correction for multiple comparisons. In the validation cohort, three of these 12 replicated, including two steroid metabolites (tetrahydrocortisol glucuronide and tetrahydrocortisol glucuronide (5)) and homocitrulline. Pathway and network analyses revealed alterations in biochemical pathways related to the metabolism of steroids, bile acids, urea cycle and long-chain polyunsaturated fatty acids.CONCLUSIONS: We have identified specific metabolites within steroid and non-steroid metabolic pathways that are associated with adrenal insufficiency with ICS use.PMID:40089116 | DOI:10.1016/j.jaci.2025.02.037

J Lipid Res. 2025 Mar 13:100778. doi: 10.1016/j.jlr.2025.100778. Online ahead of print.ABSTRACTBACKGROUND: Plasma 1-H nuclear magnetic resonance (1H-NMR) metabolomic measures have yielded significant insight into the pathophysiology of cardiometabolic disease, but their interrelated nature complicates causal inference and clinical interpretation. This study aimed to investigate the associations of unrelated 1H-NMR metabolomic profiles with coronary artery disease (CAD) and ischemic stroke (ISTR).METHODS: Principal component analysis was performed on 168 1H-NMR metabolomic measures in 56,712 unrelated European participants from UK Biobank to retrieve uncorrelated principal components (PCs), which were used in Cox-proportional hazard models. For each outcome, two-sample Mendelian randomization (MR) analyses were then conducted based on three non-overlapping databases, followed by a meta-analysis.RESULTS: The first six PCs collectively explaining 88% of the total variance were identified. For CAD, results from Cox and MR analyses were generally directionally consistent. The pooled odds ratios (ORs) [95% CI] for CAD per one-SD increase in genetically-influenced PC1 and PC3 (both characterized by distinct ApoB-associated lipoprotein profiles) were 1.04 [1.03, 1.05] and 0.94 [0.93, 0.96], respectively. Besides, the pooled OR [95% CI] for CAD per one-SD increase in genetically-influenced PC4, characterized by simultaneously decreased small HDL and increased large HDL, and independent of ApoB, was 1.05 [1.03, 1.07]. For ISTR, increases of PC3 and PC5 (characterized by increased amino acids) were associated with a lower risk and a higher risk, respectively.CONCLUSIONS: This study confirms associations of ApoB-associated lipoprotein profiles with CAD and ISTR, and highlights the possible existence of an ApoB-independent lipoprotein profile, characterized by a distinctive HDL sub-particle distribution, driving CAD.PMID:40089107 | DOI:10.1016/j.jlr.2025.100778

Int Immunopharmacol. 2025 Mar 14;152:114444. doi: 10.1016/j.intimp.2025.114444. Online ahead of print.ABSTRACTBACKGROUND: Traditional Chinese medicines, as a burgeoning field of medication, significantly alleviate ulcerative colitis (UC) by improving intestinal microbiota-metabolism. Our previous studies demonstrated the significant efficacy of Hudi Enteric-coated capsules (HDEC), Qingchang Wenzhong decoction (QCWZ), and Modified Wumei pill (MWMP) using a mouse model of colitis. However, the mechanism of these therapies through the modulation of microbiota-metabolism remains uncertain.OBJECTIVE: Three multicenter randomized controlled trials were designed to explore the effects of three therapies on the microbiota-metabolism of UC patients with different severity.METHODS: A total of 143 patients with different severities of UC were recruited from 10 hospitals. The clinical efficacy of HDEC for mild UC, QCWZ for moderate UC, and MWMP for severe UC (SUCs) was evaluated by colorectal Mayo scores and systemic inflammatory indicators. The 16S rRNA sequencing and metabolomics were used to analyze intestinal microbiota and metabolite profiles.RESULTS: Three therapies used alone or combined with mesalazine (MS) were comparable to MS alone in improving Mayo scores and hematic inflammatory parameters. Microbial diversities and architectures of SUCs showed the greatest response to MWMP+MS than other medications, as reflected by the enriched Ruminococcus and Anaerostipes together with the reduced Enterococcus, Streptococcus, and Streptococcus anginosus. Furthermore, MWMP+MS boosted the production of the microbiota-derived short-chain fatty acids (SCFAs) of SUCs. These differential microbes and metabolites further displayed significant statistical relationships with clinical parameters.CONCLUSION: Herbal therapies, especially MWMP+MS, effectively improve microbiota composition and SCFA metabolism, which correlates with the improvements of serum inflammatory markers and endoscopic findings in patients.PMID:40088871 | DOI:10.1016/j.intimp.2025.114444

J Pharm Biomed Anal. 2025 Mar 11;260:116813. doi: 10.1016/j.jpba.2025.116813. Online ahead of print.ABSTRACTAtractylodis Macrocephalae Rhizoma (AMR) is one of the commonly used medicinal and edible herbs in China. To prevent infestation of moths and mildew, chemical-fumigation is applied during post-harvest processing, which would produce harmful substances. Ultralow oxygen (ULO) storage, as a potential controlled atmosphere preservation method for Traditional Chinese Medicines (TCMs), has no residue of chemical hazards, but its impact on chemical composition of TCMs is unclear. Here, to evaluate the impact of ULO preservation on the quality of AMR, a UPLC-QTOF-MS/MS-based non-targeted metabolomics approach was employed to screen out the differential components after AMR had been stored under ULO conditions for 18 months. The differential components were identified, and further semi-quantified with peak areas. Additionally, the differential components with known activity were quantified using HPLC-DAD and GC-TQ-MS/MS analysis. The molecular weight distribution and monosaccharide composition of polysaccharides were analyzed using HPGPC-ELSD and HPLC-DAD to assess the impact of ULO on the carbohydrates. As it showed, 20 differential components of AMR under ULO were screened and identified when compared to normal atmosphere (NA) with 21 % oxygen concentration. As storage duration increased, the levels of atractylenolides I, II, and III in both ULO and NA storage conditions increased, with significant differences in their total content (16.06 mg/g in ULO vs. 47.57 mg/g in NA). Confirmatory experiments revealed that atractylone is the precursor compound of atractylenolides and the total content of atractylenolides I, II, and III produced from atractylone in ULO storage was only 62.12 % of that in NA at 18th month. The total sugar content of AMR polysaccharides in ULO storage was 107.28 % of that in NA and the molar ratios of monosaccharides were also relatively constant. All the results indicated that ULO preservation slowed down the chemical transformation of AMR, including small molecules and polysaccharides. Therefore, the quality of AMR stored in ULO is more stable and it is proposed to be an efficient preservation method for AMR.PMID:40088835 | DOI:10.1016/j.jpba.2025.116813

Phytomedicine. 2025 Mar 7;140:156631. doi: 10.1016/j.phymed.2025.156631. Online ahead of print.ABSTRACTBACKGROUND: Sjögren's syndrome (SS) is a complicated autoimmune disorder, encompassing multifaceted pathogenesis of inflammatory response, immune dysregulation and metabolic abnormalities. Shaoteng Decoction (STD) is a type of traditional Chinese medicine preparation that has been shown to effectively improve inflammatory damage and immune dysfunction in patients with SS. Nevertheless, the exact mechanism has not been unspecified.PURPOSE: This work aims to determine the mechanism of STD treatment on SS, identifying potential therapeutic targets and their relationships.METHODS: Non-obese diabetic mice served as a disease model. This study analyzes potential signaling pathways of STD treatment for SS through network pharmacology, and assesses the role of STD in reducing inflammatory damage using pathological staining, ELISA, and immunohistochemistry. Additionally, the study apply gut microbiota, metabolomics, and proteomics analyses to identify the key microbiota, metabolites and proteins, aiming to find potential action targets of STD. We use Western blotting and immunohistochemistry to verify the authenticity of the relevant targets and study the interactions among gut microbiota, metabolites, and proteins.RESULTS: Proteobacteria is the important intestinal bacteria, Bile Acid Biosynthesis is the main metabolic pathway, IfI30, Ndufv3, and Ndufs6 are the crucial differential expressed proteins. Moreover, there is a strong correlation among the three. STD treats SS by reducing the abundance of Proteobacteria, increasing Bile Acid Biosynthesis, decreasing IfI30 expression, and increasing the expression of Ndufv3 and Ndufs6.CONCLUSION: STD inhibits inflammatory responses, improves immune dysregulation and energy metabolism abnormalities, and prevents the progression of SS through regulating the gut microbiota, enhancing Bile Acid Biosynthesis, and modulating proteins expression levels.PMID:40088738 | DOI:10.1016/j.phymed.2025.156631

J Hazard Mater. 2025 Mar 11;491:137919. doi: 10.1016/j.jhazmat.2025.137919. Online ahead of print.ABSTRACTThe extensive application of molybdenum disulfide (MoS2) nanosheets in various fields involving in water treatment inevitably results in their release into wastewater treatment plants, and eventually into aquatic environments following disinfection. However, little is known about the transformations and toxicity evolution of MoS2 during chlorination. This study discovered that MoS2 is unstable to NaClO exposure, and more soluble ions are released under UV/NaClO co-treatment due to the generation of •OH and chlorine radicals. Compared to NaClO alone, UV/NaClO treatment caused significant structural disorder and compositional alterations in MoS2 (oxidation and chlorine incorporation), reducing its colloidal stability and hydrophilicity. Relative to pristine MoS2, chlorinated MoS2 showed stronger toxic effects against algae, including strengthened envelopment, morphological shrinkage and inner membrane collapse. Chlorination clearly intensified the abiotic and biotic ROS-dependent oxidative stress of MoS2, leading to exacerbated cell growth (34.6 % at 10 μg/mL) and photosynthesis inhibition, and membrane damage. Metabolomics confirmed the aggravated toxicity of chlorinated MoS2 in terms of the down-regulation of carbohydrates, amino acids, unsaturated fatty acids, and TCA cycle. This study underlines the significant role of chlorination processes in modifying MoS2 ecotoxicity and proposes the necessity to systematically assess the risks of MoS2-based nanomaterials while developing water treatment processes accordingly.PMID:40088668 | DOI:10.1016/j.jhazmat.2025.137919