PubMed

Cells. 2025 Mar 20;14(6):463. doi: 10.3390/cells14060463.ABSTRACTOver the last few decades, the prevalence of metabolic diseases such as obesity, diabetes, non-alcoholic fatty liver disease, hypertension, and hyperuricemia has surged, primarily due to high-fat diet (HFD). The pathologies of these metabolic diseases show disease-specific alterations in the composition and function of their gut microbiome. How HFD alters the microbiome and its metabolite to mediate adipose tissue (AT) inflammation and obesity is not well known. Thus, this study aimed to identify the changes in the gut microbiome and metabolomic signatures induced by an HFD to alter obesity. To explore the changes in the gut microbiota and metabolites, 16S rRNA gene amplicon sequencing and metabolomic analyses were performed after HFD and normal diet (ND) feeding. We noticed that, at taxonomic levels, the number of operational taxonomic units (OTUs), along with the Chao and Shannon indexes, significantly shifted in HFD-fed mice compared to those fed a ND. Similarly, at the phylum level, an increase in Firmicutes and a decrease in Bacteroidetes were noticed in HFD-fed mice. At the genus level, an increase in Lactobacillus and Ruminococcus was observed, while Allobaculum, Clostridium, and Akkermansia were markedly reduced in the HFD group. Many bacteria from the Ruminococcus genus impair bile acid metabolism and restrict weight loss. Firmicutes are efficient in breaking down complex carbohydrates into short-chain fatty acids (SCFAs) and other metabolites, whereas Bacteroidetes are involved in a more balanced or efficient energy extraction. Thus, an increase in Firmicutes over Bacteroidetes enhances the absorption of more calories from food, which may contribute to obesity. Taken together, the altered gut microbiota and metabolites trigger AT inflammation, which contributes to metabolic dysregulation and disease progression. Thus, this study highlights the potential of the gut microbiome in the development of therapeutic strategies for obesity and related metabolic disorders.PMID:40136712 | DOI:10.3390/cells14060463

Cells. 2025 Mar 19;14(6):455. doi: 10.3390/cells14060455.ABSTRACTRed meat consumption is considered a risk factor for colorectal cancer (CRC) development and stimulated isolation of plasmid-like DNA molecules from bovine serum and milk, termed bovine meat and milk factors (BMMFs). BMMFs encode a conserved replication protein (Rep). Increased populations of Rep-expressing macrophages have been identified in the peritumor of CRC patients and pre-cancerous tissues when compared to the tissues of healthy individuals. This supports the concept that BMMFs increase cancer risk by indirect carcinogenesis, upon induction of chronic inflammation. However, the spread of Rep+ immune cells in tissues at greater distances from primary tumors has not yet been assessed. Here, we immunohistologically analyzed the presence of Rep+ immune cells in sets of tumor, peritumor and, additionally, distant tissues of CRC patients (n = 13). We identified consistently high numbers of BMMF-positive macrophages in mucosal tissues at distances of as much as 25 cm away from the primary tumors, at levels comparable to peritumors and associated with M2-like macrophage polarization. The broad distribution of BMMFs suggests that BMMF+ macrophages might already exist at stages of pre-cancerous dysplasia or before. Quantification of BMMF tissue expression during colonoscopy might help to preventively stratify individuals at risk of developing polyps/CRC and recommend them for enhanced surveillance and/or changes in dietary lifestyle.PMID:40136704 | DOI:10.3390/cells14060455

Cells. 2025 Mar 10;14(6):402. doi: 10.3390/cells14060402.ABSTRACTMetabolic reprogramming is a hallmark of cancer, with cancer cells acquiring many unique metabolic traits to support malignant growth, and extensive intra- and inter-tumour metabolic heterogeneity. Understanding these metabolic characteristics presents opportunities in precision medicine for both diagnosis and therapy. However, despite its potential, metabolic phenotyping has lagged behind genetic, transcriptomic, and immunohistochemical profiling in clinical applications. This is partly due to the lack of a single experimental technique capable of profiling the entire metabolome, necessitating the use of multiple technologies and approaches to capture the full range of cancer metabolic plasticity. This review examines the repertoire of tools available for profiling cancer metabolism, demonstrating their applications in preclinical and clinical settings. It also presents case studies illustrating how metabolomic profiling has been integrated with other omics technologies to gain insights into tumour biology and guide treatment strategies. This information aims to assist researchers in selecting the most effective tools for their studies and highlights the importance of combining different metabolic profiling techniques to comprehensively understand tumour metabolism.PMID:40136651 | DOI:10.3390/cells14060402

Biology (Basel). 2025 Feb 25;14(3):231. doi: 10.3390/biology14030231.ABSTRACTNuclear receptor subfamily 1 group D member 1 (NR1D1 or REV-ERBα) is a crucial element of the circadian clock's transcriptional and translational feedback loop. Understanding its expression in humans is critical for elucidating its role in circadian rhythms and metabolic processes, and in finding potential links to various pathologies. In a longitudinal survey, we examined REV-ERBα expression at 08:00 using a real-time polymerase chain reaction (qRT-PCR) in blood mononuclear cells from Arctic native and non-native residents during equinoxes and solstices. REV-ERBα expression exhibited a pronounced seasonality, peaking at the summer solstice, and reaching a nadir at the winter solstice in both natives and non-natives, with a relatively higher summer peak in natives. After adjusting for age, sex, and body mass index, the amount and timing of light exposure, the amount of physical activity, and indigeneity emerged as significant predictors of REV-ERBα expression.PMID:40136488 | DOI:10.3390/biology14030231

Curr Issues Mol Biol. 2025 Feb 20;47(3):135. doi: 10.3390/cimb47030135.ABSTRACTFuchs' endothelial corneal dystrophy (FECD) is a progressive eye disease characterized by accelerated loss of endothelial cells and the development of focal excrescence (guttae) on Descemet's membrane, resulting in cornea opacity and vision deterioration. The development of FECD is assumed to be due to the interplay between genetic and environmental factor risks, causing abnormal extracellular-matrix organization, increased oxidative stress, apoptosis and unfolded protein response. However, the molecular knowledge of FECD is limited. The development of genome-wide platforms and bioinformatics approaches has enabled us to identify numerous genetic loci that are associated with FECD. In this review, we gathered genome-wide studies (n = 31) and sorted them according to genomics (n = 9), epigenomics (n = 3), transcriptomics (n = 15), proteomics (n = 3) and metabolomics (n = 1) levels to characterize progress in understanding FECD. We also extracted validated differentially expressed/spliced genes and proteins identified through comparisons of FECD case and control groups. In addition, highlighted loci from each omics layer were combined according to a comparison with similar study groups from original studies for downstream gene-set enrichment analysis, which provided the most significant biological pathways related to extracellular-matrix organization. In the future, multiomics study approaches are needed to increase the sample size and statistical power to identify strong candidate genes for functional studies on animal models and cell lines for better understanding FECD.PMID:40136389 | DOI:10.3390/cimb47030135

An Acad Bras Cienc. 2025 Mar 24;97(1):e20240635. doi: 10.1590/0001-3765202520240635. eCollection 2025.ABSTRACTIronwood (Libidibia ferrea) is cultivated and widely used due to its medicinal properties attributed especially to phenolic compounds. In the seedling stage, different environmental conditions influence the synthesis, composition, and accumulation of bioactive compounds in different ways, mainly under water stress. Thus, given the wide distribution, this study aimed to analyze the occurrence and distribution of phenolic compounds in L. ferrea seedling for three different states/climate typologies: Pará/Af, Amazonas/Am, and Maranhão/Aw. Gas chromatography-mass spectrometry (GC-MS) and plantlet histochemistry were applied to determine the phenolic compounds distribution present in the extracts of leaflets and roots, respectively. Three different metabolic profiles were described, of which Pará/Af and Maranhão/Aw were similar, while Amazonas/Am showed quantitative differences in the composition. Among the main phenolic compounds were found gallic acid, ferulic acid, and caffeic acid, and presented different concentrations according to origin. The only phenolic compound found for all origins was gallic acid. Therefore, it was demonstrated that the chemical profile of phenolic compounds is conserved in L. ferrea, and significant variations were not observed, which ensures the use of this species regardless of origin.PMID:40136189 | DOI:10.1590/0001-3765202520240635

J Proteome Res. 2025 Mar 26. doi: 10.1021/acs.jproteome.4c00836. Online ahead of print.ABSTRACTThe Pinophyta family has long been used to protect the skin from oxidation, thanks to the action of molecules such as stilbenes, flavonoids, and lignans, which are particularly concentrated in knotwood. These molecules are of interest from a cosmetic perspective. The present study focuses on four species from larch (Larix decidua Mill.), silver fir (Abies alba Mill.), Norway spruce (Picea abies (L.) H.Karst), and Douglas fir (Pseudotsuga menziesii (Mirb.) Franco) knotwood, recovered from byproducts of the wood industry. The molecules are extracted from knotwood and used in vitro on human keratinocytes (HaCaT). Studies quantifying reactive oxygen species (ROS) have demonstrated its ability to eliminate hydroxyl radicals and superoxides. Metabolomic analyses using proton nuclear magnetic resonance (1H NMR) and multivariate statistics (PLS-DA) demonstrated that keratinocytes modulate metabolite expression after treatment with knot extracts. Indeed, our findings indicate an increase in metabolites such as glutathione, glycine, glutamate, sarcosine, taurine, and proline, which are known to reduce intracellular oxidative stress and validate the effect on ROS levels. They also indicate that knotwood extracts may affect membrane balance, collagen formation, and oxidative stress levels. This study highlights the value of metabolomic analysis in the cosmetic industry for a detailed understanding of the mechanisms implemented in a whole cell.PMID:40135641 | DOI:10.1021/acs.jproteome.4c00836

J Am Heart Assoc. 2025 Mar 26:e038061. doi: 10.1161/JAHA.124.038061. Online ahead of print.ABSTRACTBACKGROUND: There is significant interest in NO pathway modulators, specifically type 5 phosphodiesterase inhibitors (PDE5is), to treat patients with a Fontan circulation. Trials, however, have had mixed results. The relationship between the NO pathway and clinical status in patients with Fontan circulation is a significant knowledge gap.METHODS AND RESULTS: We performed targeted metabolomic analysis using liquid chromatography coupled to mass spectrometry to quantify plasma NO pathway metabolite concentrations from 2 well-characterized populations of patients with Fontan circulation: the Boston Adult Congenital Heart Disease Biobank and Fontan Udenafil Exercise Longitudinal studies. We investigated associations between NO metabolite concentrations and clinical outcomes, exercise capacity, and response to PDE5is. Increased plasma concentration of asymmetric dimethyl arginine (ADMA), an inhibitor of NO production, was associated with risk for hospitalization or death. Increased ADMA and symmetric dimethyl arginine (another inhibitor of NO production) concentrations were associated with decreased baseline exercise capacity among patients with Fontan circulation with <90% predicted peak oxygen uptake, and change in ADMA and symmetric dimethyl arginine concentrations were predictive of change in exercise capacity over time. Treatment with the PDE5i udenafil uncoupled this association. Finally, baseline ADMA and symmetric dimethyl arginine concentrations predicted response to PDE5is among patients with subnormal peak oxygen uptake.CONCLUSIONS: Plasma concentrations of metabolites that inhibit NO flux are associated with negative clinical outcomes and worse exercise capacity. Moreover, metabolite shifts over time associated with increased NO flux are associated with improved exercise capacity. In patients with a Fontan circulation, the NO pathway modulators ADMA and symmetric dimethyl arginine may be useful as biomarkers of clinical status and predictive of response to PDE5is.PMID:40135558 | DOI:10.1161/JAHA.124.038061

J Food Sci. 2025 Mar;90(3):e70084. doi: 10.1111/1750-3841.70084.ABSTRACT2'-Fucosyllactose (2'-FL), a predominant human milk oligosaccharide, is widely employed as a commercial infant prebiotic. Nevertheless, the benefits of 2'-FL on complex gut microbiota need further exploration. The modulation of 2'-FL on adult gut microbiota composition and metabolome, particularly short-chain fatty acids (SCFAs) and tryptophan metabolism, was investigated via colonic fermentation, single bacterial strains cultivation, and prebiotic activity scoring evaluation. The 2'-FL fermentation in a complex microbial community indicated promising effects, including an increase in Bifidobacterium levels and changes in metabolic levels of tryptophan, SCFAs, and vitamins. Correlation analysis of microbiota and metabolome highlighted a positive correlation between Bifidobacterium and metabolites derived from SCFAs and indole. Scoring formulas for bacterial growth and substrate utilization were introduced to compare the overall response of 15 bacterial strains from key genera that were identified by 16S rRNA profiling to several prebiotics. In the cultivation of single bacterial strains, 2'-FL was selectively used by Bifidobacteria infantis and Enterococcus faecalis and was not degraded by potential pathogenic strains. This selective promotion of probiotics by 2'-FL was observed according to the scoring results, as 2'-FL showed higher scores for bacterial growth and substrate utilization when compared to galacto-oligosaccharides and fucose. This study demonstrated beneficial bifidogenic effect of 2'-FL in an adult complex microbial community and the potential of scoring evaluation as a quantitative tool for measuring the prebiotic effects of different oligosaccharides.PMID:40135481 | DOI:10.1111/1750-3841.70084

Small. 2025 Mar 26:e2409747. doi: 10.1002/smll.202409747. Online ahead of print.ABSTRACTBone formation is a highly metabolic process, involving extensive biosynthesis and biomineralization, both of which require substantial amounts of energy. Additionally, the regulation of the immune microenvironment and the development of a neovascularization network are equally crucial in bone formation. Inspired by the high energy demands of the bone formation process, a core-shell electrospun fiber scaffold (PFC/PCK) capable of sustainably releasing a metabolic regulator (αKG) and biomineralizing ions (CaP) is developed. In vitro experiments show that the PFC/PCK fiber scaffolds can induce hyperpolarization of mitochondrial membrane potential in bone marrow mesenchymal stem cells (BMSCs), increase energy supply, effectively regulate immune microenvironment, and remarkably promote expression of angiogenesis and osteogenesis markers. In vivo evaluation further confirms the outstanding immunoregulatory and osteo/angio-genesis capabilities of the fabricated fiber scaffolds. Importantly, transcriptome analysis identifies that the fiber scaffolds upregulate genes and signaling pathways associated with M2 macrophage activation, energy generation, angiogenesis, and osteogenesis. Additionally, metabolomics analysis confirms that the fiber scaffolds enhance bone formation by promoting the expression of osteogenic metabolites. The versatile fiber scaffolds developed in current study demonstrates a new strategy for functional bone regeneration.PMID:40135330 | DOI:10.1002/smll.202409747

Br J Hosp Med (Lond). 2025 Mar 26;86(3):1-13. doi: 10.12968/hmed.2024.0772.ABSTRACTAims/Background The incidence of coronary heart disease (CHD) has been increasing annually. Patients with severe conditions may die from myocardial infarction, heart failure or malignant arrhythmia. Intestinal flora plays an important role in various metabolic processes, such as atherosclerosis, tumour formation, and inflammation. However, its direct role in promoting plaque vulnerability must be further explored and validated. Therefore, this study aims to explore the relationship between changes in intestinal flora, its metabolites in CHD patients and the vulnerability characteristics of coronary plaques. Methods This study recruited 180 subjects, among these, 90 CHD patients diagnosed between January 2023 and January 2024 were selected as the CHD group and 90 healthy volunteers were selected as the control group following a principle of 1:1 ratio. The differences in intestinal flora composition, metabolite levels, and blood biochemical indexes were compared between the two study groups. Based on the coronary angiography (CAG) and intravascular ultrasound (IVUS) results, the CHD group was divided into two sub-groups for stratified comparative analysis: the stable plaque group (n = 49) and the vulnerable plaque group (n = 41). Results The CHD group had reduced intestinal Bifidobacteria and lactic acid bacteria counts and higher intestinal Escherichia coli and Enterococcus levels than the control group (p < 0.05). Moreover, trimethylamine-N-oxide (TMAO) and phenylacetylglutamine (PAGln) levels were significantly higher in the CHD group compared to the control group (p < 0.05). Similarly, the CHD group exhibited substantially elevated serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels compared to the control group. However, compared to the control group, the high-density lipoprotein cholesterol (HDL-C) levels were significantly lower in the CHD group (p < 0.05). Furthermore, the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum urea nitrogen (BUN), and serum creatinine (Scr) were comparable in the two experimental groups (p > 0.05). Similarly, intestinal Bifidobacteria, lactic acid bacteria, Escherichia coli, and Enterococcus compositions were comparable in CHD patients with vulnerable plaque and those with stable plaque (p > 0.05). Moreover, CHD patients with vulnerable plaque had elevated TMAO and PAGln levels than those with stable plaque (p < 0.05). However, TG, TC, HDL-C, LDL-C, ALT, AST, BUN, and Scr levels were comparable between CHD patients with a vulnerable plaque and those with stable plaque (p > 0.05). Multivariate regression analysis showed that diabetes, elevated TMAO levels, and elevated PAGln levels were potential risk factors for coronary plaque vulnerability (p < 0.05). Conclusion In summary, CHD patients exhibit significant intestinal flora imbalance, with elevated TMAO and PAGln metabolite levels, which are related to the characteristics of plaque instability.PMID:40135300 | DOI:10.12968/hmed.2024.0772

Front Pharmacol. 2025 Mar 11;16:1491935. doi: 10.3389/fphar.2025.1491935. eCollection 2025.ABSTRACTINTRODUCTION: Older adults are a high-risk group for hypertension, with specific characteristics regarding symptoms and treatment. Yishenjiangya granules (YJG), a traditional Chinese medicinal decoction, are widely used to reduce blood pressure and improve clinical symptoms. This study aimed to use metabolomics to explore the clinical effects and underlying mechanisms of YJG in hypertension in older adults.METHODS: The study enrolled patients aged ≥65 years, with systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg in sitting positions on different days; the control group comprised 30 healthy participants with normal blood pressure and biochemistry indicators. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to analyze plasma metabolites in patients with hypertension before and after YJG intervention.RESULTS: After YJG treatment, blood pressure decreased significantly; some metabolites showed a trend approaching the control group. UPLC-Q-TOF-MS analysis identified 30 YJG-targeted plasma metabolites in older adult patients with hypertension, including three major metabolic pathways: linoleic acid, arachidonic acid, and glycerophospholipid metabolism.CONCLUSION: This study identified that metabolite changes may underlie the clinical mechanism of YJG in treating older adult patients with hypertension, providing a basis for further treatment of hypertension.PMID:40135238 | PMC:PMC11933063 | DOI:10.3389/fphar.2025.1491935

Front Nutr. 2025 Mar 11;12:1518014. doi: 10.3389/fnut.2025.1518014. eCollection 2025.ABSTRACTBACKGROUND: Hyperuricemia (HUA) is the presence of excessive uric acid (UA) in blood, which leads to an increased risk of chronic kidney disease and gout. There are about 120 million hyperuricemia patients in China, which has surpassed diabetes as the second largest chronic disease.OBJECTIVE: The aim of the present study was to investigate the hypouricemic effects of Dendrobium huoshanense C. Z. Tang and S. J. Cheng (DH), and provide a basis for its development into anti HUA products.METHODS: This study established a mouse HUA model by gavage of potassium oxonate (PIO) and hypoxanthine (HX), and treated with DH to investigate the therapeutic effect of DH on hyperuricemia. Use a biochemical assay kit to detect changes in the levels of UA, creatinine (Cr), and urea nitrogen (BUN) in mouse serum; Use ELISA kit to detect the activity of xanthine oxidase (XOD) in serum; Untargeted Metabolomics analysis was performed on the serum of each group of mice using liquid chromatography-mass spectrometry. This study recruited 23 HUA volunteers, volunteers drank 0.5 g DH daily for four consecutive weeks, with serum UA levels measured once a week.RESULTS: Animal experiments have shown that DH has therapeutic effects on HUA, mainly manifested as: DH effectively reduces the levels of UA, Cr, and BUN in the serum of HUA mice, lowers XOD activity in the serum, and alleviates kidney tissue and glomerular damage. Metabolomics analysis showed that there were 306 significant differences in metabolites between the Sham group, HUA model group, and DH group. Pathway analysis of these differential metabolites revealed that they were mainly involved in pyrimidine metabolism, histidine metabolism, and riboflavin metabolism. Clinical research results show that after drinking DH, UA levels in HUA volunteers significantly decreased, and most HUA volunteers' UA levels decreased to normal levels.CONCLUSION: DH has the effect of preventing and treating hyperuricemia, and it belongs to the same class of traditional Chinese medicine as medicine and food, with extremely low toxicity and high safety. Therefore, DH is suitable for preparation as a product for preventing and treating HUA in functional food and other products.PMID:40135225 | PMC:PMC11933096 | DOI:10.3389/fnut.2025.1518014

Anim Nutr. 2024 Nov 22;21:11-24. doi: 10.1016/j.aninu.2024.11.002. eCollection 2025 Jun.ABSTRACTThis study investigated the effects of Lycium barbarum residues (LBR) and fermented L. barbarum residues (FLBR) on the growth performance and meat quality of lambs. Eighteen lambs were randomly assigned into three groups and fed either a basal diet (CON) or the same diet supplemented with 5.0% LBR or FLBR for a period of 90 days. The underlying mechanisms responsible for the beneficial effect of LBR and FLBR on the longissimus thoracis (LT) and intramuscular fat (IMF) tissues of lambs were examined using multiomics techniques. Our findings showed that FLBR supplementation significantly enhanced the average daily gain, feed efficiency, and nutrient digestibility (P < 0.05 or P < 0.01). Serum total protein (P = 0.007) and glucose (P = 0.002) levels were higher in the FLBR-fed lambs, while urea nitrogen level was lower (P = 0.001). Additionally, the levels of rumen acetate (P = 0.002) and propionate (P = 0.011) were significantly elevated, while ammonia-nitrogen (NH3-N), isobutyrate and isovalerate decreased (P < 0.05 or P < 0.01) following FLBR supplementation. Post-mortem meat quality was also improved by FLBR, as evidenced by enhanced total antioxidant capacity, superoxide dismutase activity, pH, redness (a∗), tenderness and water holding capacity (P < 0.05 or P < 0.01), alongside a reduction in the malonaldehyde content (P < 0.001). Transcriptomic analysis identified 962 differentially expressed genes (DEGs, FLBR vs CON) and 782 DEGs (FLBR vs LBR) in LT, and 1313 DEGs (FLBR vs CON) and 1221 DEGs (FLBR vs LBR) in IMF. The ribosome signaling pathway related genes in LT tissue were activated by the FLBR diet (P < 0.05), showing a higher anabolism of protein. The genes involved in fatty acid biosynthesis in IMF tissue were upregulated by the FLBR diet (P < 0.05), showing a higher anabolism of lipids. Metabolomics analysis identified the 1732 differential metabolites in LT tissue following FLBR supplementation, with significant alterations in metabolites such as carnosine, L-arginine and L-proline, which may serve as potential biomarkers for meat quality betterment. In conclusion, FLBR supplementation might have modified anabolism of proteins and fatty acid, as well as muscle metabolomic profiles, leading to improvements in both growth performance and meat quality in fattening lambs.PMID:40135170 | PMC:PMC11931312 | DOI:10.1016/j.aninu.2024.11.002

JIMD Rep. 2025 Mar 24;66(2):e70010. doi: 10.1002/jmd2.70010. eCollection 2025 Mar.ABSTRACTPhenylketonuria (PKU) is an inborn error of metabolism responsible for an accumulation of phenylalanine, which leads to cognitive and developmental disorders if left untreated. Most studies of adult PKU focus on neuropsychiatric complications, but new questions have been raised about systemic manifestations of PKU in adulthood. Fifteen adults with classic PKU with poor metabolic control and 15 matched healthy controls were recruited to compare their blood metabolomes by an untargeted multimodal approach (polar, apolar, and lipids) by LC/MS and a targeted approach to the tryptophan pathway. Targeted analysis revealed systemic serotonin hypometabolism and aberrant kynurenine metabolism, as well as potential implication of microbiota by differences in some indole compounds compared to controls. Untargeted analysis confirms previous findings regarding the TCA cycle, alanine aspartate glutamate metabolism, arginine and proline metabolism, and revealed some new metabolic perturbations such as arginine biosynthesis or glyoxylate and dicarboxylate metabolism. Future studies involving larger numbers of patients with varying degrees of metabolic control are needed to confirm these findings.PMID:40135139 | PMC:PMC11932803 | DOI:10.1002/jmd2.70010

Toxicol Res (Camb). 2025 Mar 24;14(2):tfaf035. doi: 10.1093/toxres/tfaf035. eCollection 2025 Apr.ABSTRACTChronic kidney disease (CKD) is acknowledged as one of the largest public health problems in the world, characterized by a complex and diverse pathogenesis. Adenine-induced CKD, a classical model with multiple injury mechanisms, has been extensively employed in CKD research. However, the complete elucidation of the mechanisms underlying adenine-induced CKD remains elusive. In this study, the impacts of adenine (200 mg/kg/day) intake on the urine metabolome of rats were initially investigated using non-targeted metabolomics, and then targeted metabolomics was used to quantitatively verify key metabolites on crucial metabolic pathways. Interestingly, the interconnectedness of two significant pathways was discovered and validated through molecular biology techniques. The results found that adenine can cause significant perturbations in purine metabolism and the biosynthetic pathways of phenylalanine, tyrosine, and tryptophan. Subsequent targeted metabolomic analysis revealed a significant reduction in amino acid and hypoxanthine and creatinine levels in the kidneys of CKD rats, accompanied by an increase in xanthine level. Further analysis found that purine pathway can increase ROS production and affect the level of aromatic amino acid transporter SLC7A5, thus influencing the biosynthesis pathway of phenylalanine, tyrosine and tryptophan, ultimately contributing to kidney injury. This discovery provides offers novel insights into the underlying pathological mechanism of adenine-induced CKD. The development of chronic kidney disease is induced by multiple pathways of aromatic amino acid metabolism and purine metabolism.PMID:40135063 | PMC:PMC11932014 | DOI:10.1093/toxres/tfaf035

Drug Des Devel Ther. 2025 Mar 21;19:2133-2155. doi: 10.2147/DDDT.S499852. eCollection 2025.ABSTRACTBACKGROUND: Alzheimer's disease (AD) is associated with various pathological states for which there is no effective treatment. First documented in the Eastern Han Dynasty's medical classic, "Treatise on Febrile and Miscellaneous Diseases" (200-210 Anno Domini), Banxia Xiexin Decoction (BXD) stands as a quintessential approach to treating spleen ailments. Recent studies have shown BXD's effectiveness in mitigating memory impairment associated with AD. Yet, the precise mechanisms underlying BXD's action against AD require further exploration.AIM OF THE STUDY: To explore the important components of BXD in exerting anti-AD effects and the underlying molecular mechanisms using network pharmacology, metabolomics analysis, and in vitro and in vivo validation strategies. Initially, candidates for BXD's application in AD therapy were identified through extensive database searches, followed by an analysis of protein-protein interactions (PPI). To elucidate BXD's therapeutic pathways in AD, we engaged in Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) assessments. Further, we delved into BXD's primary constituents through ultra-high-pressure liquid chromatography coupled with Q Exactive mass spectrometry and molecular docking techniques. Finally, AD-associated Aβ42-SY5Y cells and APPswe/PS1dE9 (APP/PS1) transgenic mice models were utilized to further determine the activity and mechanisms of BXD through various molecular or phenotypic assays and metabolomics analysis.RESULTS: Our findings identified the PI3K/Akt signaling pathways as central to BXD's effects. Using in vitro and in vivo models, we found the activity of BXD against AD to be mediated by the suppression of neuroinflammation and apoptosis, accompanied by activation of the PI3K/Akt pathway. Finally, we observed robust changes in metabolite levels in the plasma of BXD-treated APP/PS1 mice.CONCLUSION: Through systematic data analysis and experimental validation, the therapeutic advantages and fundamental molecular mechanisms of BXD in treating AD were revealed. These findings underscore the promising prospects and compelling potential of BXD, which targets the PI3K/Akt signaling pathway and inflammation, apoptosis, as a therapeutic strategy for improving AD.PMID:40134954 | PMC:PMC11934878 | DOI:10.2147/DDDT.S499852

J Phycol. 2025 Mar 25. doi: 10.1111/jpy.70008. Online ahead of print.ABSTRACTCyanobacteria, particularly Raphidiopsis raciborskii, are known for their harmful blooms, posing significant ecological and economic challenges in aquatic ecosystems. This study investigates the strain-specific adaptive mechanisms of five R. raciborskii strains (CS-505, CS-506, UAM/DH-KmRr, UAM/DH-BiRr, and UAM/DH-MRr) under chill/light stress (low temperature and high light intensity), focusing on growth, pigment composition, photosynthetic activity, gene expression, and toxin production. Results revealed that growth rates were significantly reduced under stress for all strains, with the Polish strain UAM/DH-MRr showing the highest resilience. Stress conditions caused a reduced chlorophyll a level and increased carotenoid/Chl a ratio, suggesting photoprotective adaptations. Photosynthetic quantum efficiency (Fv/Fm) declined during chill/light but was recovered post-stress, while electron transport rates (rETR) were not significantly altered. Enhanced respiration and increased photosynthetic oxygen evolution were observed, particularly in CS-506 and UAM/DH-MRr. Principal component analysis (PCA) highlighted pigment content and parameters related to photosynthetic electron transport as key factors influencing response; no variable-specific groupings were observed among strains regarding the broad range of parameters. Gene expression analyses revealed divergent transcriptional regulation of genes involved in photosynthesis and cylindrospermopsin (CYN) biosynthesis, with toxic CS-505 upregulating cyr genes under stress, while CS-506 down-regulated them. Intracellular CYN levels decreased under stress, yet cell quotas increased in CS-505, which warrants further investigation. Our results indicate the complexity of strain-specific responses to chill/light stress and highlight the importance of understanding physiological mechanisms for predicting and managing cyanobacterial blooms in diverse climates.PMID:40132033 | DOI:10.1111/jpy.70008

J Proteome Res. 2025 Mar 25. doi: 10.1021/acs.jproteome.4c01116. Online ahead of print.ABSTRACTThe accurate and rapid identification of bacterial pathogens poses a significant challenge in clinical diagnostics, environmental monitoring, and microbial research. Lipidomics and proteomics serve as powerful methodologies for bacterial characterization; however, the complexity of biological matrices and the low abundance of bacterial lipids often limit effective detection. This study introduces graphene-polyglycerol amine (G-PGA) as a novel nanomaterial that enhances the selective trapping and detection of Escherichia coli (E. coli) using desorption electrospray ionization mass spectrometry and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The antimicrobial properties of G-PGA reveal a minimum inhibitory concentration (MIC) of 250 μg/μL and a minimum bactericidal concentration (MBC) of 500 μg/μL. Optimal sonication conditions (10 min) maximize G-PGA's surface activity, facilitating effective bacterial trapping while maintaining cellular integrity, as confirmed by scanning electron microscopy and atomic force microscopy. Molecular docking simulations show a strong affinity between G-PGA and the β-barrel assembly machinery (BAM) proteins of E. coli, suggesting potential disruption of critical bacterial processes. Preconcentration with G-PGA significantly improves detection sensitivity and signal-to-noise ratio in mass spectrometry analyses, highlighting its potential as a transformative tool for rapid, sensitive, and highly specific bacterial identification in lipidomics and proteomics.PMID:40131341 | DOI:10.1021/acs.jproteome.4c01116

Minerva Pediatr (Torino). 2025 Mar 25. doi: 10.23736/S2724-5276.25.07751-1. Online ahead of print.ABSTRACTNowadays, pediatric cardiology is still a very complex topic. Children are not small adults and very little is known about how heart diseases can affect their metabolic profile both in the acute phase and in the long term. In this context, metabolomics analysis could provide multiple information in the field of pediatric cardiology. For instance, it could be used to predict the occurrence of fetal cardiac abnormalities or predict the outcomes of complex open-heart surgeries for each patient to improve the survival rate and provide better treatment. In this review, the authors describe all the metabolomics applied to pediatric cardiology studies from 2013 to 2024. We noted that the most discussed topics are congenital heart diseases, probably due to the complexity of these patients. Nevertheless, even if the number of studies is limited, they highlight the multiple possibilities provided by metabolomics for the management of neonates and children with heart diseases.PMID:40131235 | DOI:10.23736/S2724-5276.25.07751-1