Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

GC-MS metabolite profiling and antimicrobial activity of <em>Acritopappus confertus</em> essential oil from five different locations in Brazil

Thu, 08/05/2025 - 12:00
Nat Prod Res. 2025 May 8:1-7. doi: 10.1080/14786419.2025.2501677. Online ahead of print.ABSTRACTAcritopappus confertus is used in traditional communities of the municipalities of Chapada Diamantina (Bahia State, Brazil) to treat infected skin wounds. Despite its medicinal relevance, very few reports investigate its essential oil's metabolite profile and biological activity. Herein, we assessed the metabolite profile and antimicrobial activity of A. confertus collected at different locations in the Bahia State, Brazil. Twenty-nine compounds were identified by gas chromatography-mass spectrometry (GC-MS), mainly mono- and sesquiterpenes. (+)-Junenol was the main compound identified for all specimens (13-52%), and its NMR data is presented in detail. A. confertus essential oils showed promising activity against Candida albicans, Cladosporium cladosporioides, Micrococcus luteus, Microsporum canis, methicillin-resistant and methicillin-susceptible Staphylococcus aureus, Moniliophtora perniciosa, and Trichophyton rubrum. These results reinforce A. confertus as an important source of bioactive compounds, whereas (+)-junenol could be considered the chemical marker of A. confertus grown at Chapada Diamantina (Bahia State, Brazil).PMID:40337832 | DOI:10.1080/14786419.2025.2501677

Comprehensive gut microbiota and metabolomics combined with network pharmacology reveal the effects of acupuncture treatment for chemotherapy-induced nausea and vomiting

Thu, 08/05/2025 - 12:00
Transl Gastroenterol Hepatol. 2025 Apr 14;10:26. doi: 10.21037/tgh-24-35. eCollection 2025.ABSTRACTBACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) significantly impact cancer patients' quality of life. Traditional pharmacological treatments often have limited effectiveness and can cause adverse effects. Acupuncture, a key practice in traditional Chinese medicine (TCM), shows promise as a complementary therapy for CINV. The purpose of this study was to explore the effects and underlying mechanisms of acupuncture in treating CINV.METHODS: We employed a multi-faceted approach to comprehensively explore the abnormal performances of CINV model and to elucidate the regulatory effects of acupuncture in treating CINV through the integration of 16S rRNA analysis, serum metabolomics, and network pharmacology.RESULTS: Acupuncture significantly reduced kaolin consumption, mitigated anorexia, and attenuated body weight loss compared to the model group. Acupuncture was found to modulate the gut microbiota composition, enhancing beneficial taxa and reducing harmful ones. Serum metabolomic analysis revealed significant alterations in metabolic profiles, with acupuncture impacting various metabolites involved in pathways related to fatty acid biosynthesis, urea cycle, and amino acid metabolism. Spearman correlation analysis indicated a significant association between gut microbial taxa and serum metabolites. Furthermore, network pharmacology analysis identified key genes (MAPK1, STAT3, EGFR, AKT1, SRC) and pathways (PI3K/Akt, neuroactive ligand-receptor interaction) associated with the anti-CINV effects of acupuncture. In conclusion, acupuncture holds promise in ameliorating CINV through its multifaceted impact on gut microbiota, serum metabolome, and molecular pathways.CONCLUSIONS: Acupuncture was an adjunctive and important non-drug treatment for CINV, with the protective effects linked to the improvement of gut microbiota disruption and metabolic abnormalities.PMID:40337760 | PMC:PMC12056097 | DOI:10.21037/tgh-24-35

Multi-omics insights into the response of the gut microbiota and metabolites to albendazole deworming in captive <em>Rhinopithecus brelichi</em>

Thu, 08/05/2025 - 12:00
Front Microbiol. 2025 Apr 23;16:1581483. doi: 10.3389/fmicb.2025.1581483. eCollection 2025.ABSTRACTBACKGROUND: Parasite infection and deworming treatment affect the host gut microbiota. Exploring the response mechanism of the gut microbiota in Rhinopithecus brelichi (R. brelichi) to albendazole deworming treatment is of great value for protecting this critically endangered species.METHODS AND RESULTS: This study used metataxonomics and metabolomics to explore the responses of the gut microbiota and metabolites of R. brelichi to albendazole deworming treatment. The results showed that deworming significantly reduced the eggs per gram of feces (EPG). The 16S rRNA gene sequencing results showed that the richness and diversity of the gut microbiota in R. brelichi after deworming were significantly increased. Meanwhile, deworming treatment also changed the composition of the gut microbiota. At the genus level, the Christensenellaceae R7 group, UCG 002, UCG 005, uncultured rumen bacterium, and Rikenellaceae RC9 gut group were significantly enriched in the pre-deworming samples. Unclassified Muribaculaceae, Prevotella 9, and Bacteroides were significantly enriched in the post-deworming samples. Metabolomics analysis revealed that the relative abundance of 382 out of 1,865 metabolites showed significant differences between the pre- and post-deworming samples. Among them, 103 metabolites were annotated based on the HMDB and mainly classified into Prenol lipids, Carboxylic acids and derivatives, and Organooxygen compounds, etc. The KEGG enrichment analysis result indicated that these metabolites were mainly involved in energy, amino acid, lipid, and purine metabolism. Correlation analysis showed that Bacteroides and unclassified Muribaculaceae, whose relative abundances were upregulated after deworming treatment, were positively correlated with Kaempferol, 5,7-Dihydroxy-3-methoxy-4'-prenyloxyflavone, Purpurin, and Rhein, which have anti-parasitic activities. The Christensenellaceae R7 group, with a downregulated relative abundance after deworming treatment, was not only negatively correlated with the above four metabolites, but also positively correlated with Retinyl beta-glucuronide, which is a storage form of vitamin A, and positively correlated with CDP-Choline, which increases the host's susceptibility to Entamoeba histolytica and Plasmodium falciparum.CONCLUSION: This study emphasizes that deworming treatment has an impact on the gut microbiota and metabolic functions of R. brelichi. By exploiting the correlations between differential microbiota and metabolites, potential probiotics or prebiotics can be explored, thereby enhancing the efficiency of deworming and reducing its side effects.PMID:40336838 | PMC:PMC12058082 | DOI:10.3389/fmicb.2025.1581483

Improving butenyl-spinosyn production in <em>Saccharopolyspora pogona</em> through combination of metabolic engineering and medium optimization

Thu, 08/05/2025 - 12:00
Front Microbiol. 2025 Apr 23;16:1561042. doi: 10.3389/fmicb.2025.1561042. eCollection 2025.ABSTRACTButenyl-spinosyn is a high-quality biological insecticide produced by Saccharopolyspora pogona that effectively targets a broad range of insect pests. However, the large-scale production of this insecticide is hindered by its low yield. Herein, based on prior comparative genomic analysis, five mutations were individually overexpressed in aG6. Subsequently, the combinatorial overexpression of sp1322 (encoding NAD-glutamate dehydrogenase) and sp6746 (encoding dTDP-glucose 4,6-dehydratase) in aG6 resulted in strain O1322-6746. The production of butenyl-spinosyn in O1322-6746 was 77.1% higher than that in aG6. Comparative targeted metabolomic analysis uncovered that O1322-6746 exhibited increased metabolic flux toward butenyl-spinosyn precursors. Furthermore, single-factor experiments, Plackett-Burman analysis and response surface methodology were performed to optimize the fermentation medium for O1322-6746. Ultimately, butenyl-spinosyn production was enhanced to 298.5 mg/L in a 5-L bioreactor, marking the highest yield ever reported. This work demonstrated that combining metabolic engineering with medium optimization is an effective strategy to improve butenyl-spinosyn production.PMID:40336833 | PMC:PMC12055833 | DOI:10.3389/fmicb.2025.1561042

Corrigendum: Characterization of the hepatic flora and metabolome in nonalcoholic fatty liver disease

Thu, 08/05/2025 - 12:00
Front Microbiol. 2025 Apr 23;16:1591065. doi: 10.3389/fmicb.2025.1591065. eCollection 2025.ABSTRACT[This corrects the article DOI: 10.3389/fmicb.2024.1528258.].PMID:40336830 | PMC:PMC12055829 | DOI:10.3389/fmicb.2025.1591065

Paederia scandens extract alleviates obesity via modulating the gut microbiota and serum metabolome disorder

Thu, 08/05/2025 - 12:00
Front Microbiol. 2025 Apr 23;16:1554537. doi: 10.3389/fmicb.2025.1554537. eCollection 2025.ABSTRACTObesity is increasingly becoming a challenge with China's economic development. There is an urgent need to identify more affordable methods to combat this condition. Paederia scandens (PS), a cost-effective herbal remedy widely used in China for treating inflammation and pain, shows potential in this regard. To investigate its anti-obesity mechanisms, we established a high-fat diet (HFD)-induced obesity model in mice. The obese mice subsequently received daily oral gavage of PS extract for 21 consecutive days. Upon the completion of the experiment, blood samples were collected to analyze lipid profiles, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C). Abdominal adipose tissue was subjected to hematoxylin-eosin (HE) staining for histological analysis, while fecal samples underwent 16S rRNA sequencing to assess gut microbiota composition. Our findings revealed that PS supplementation significantly reduced body weight, lipid metabolism biomarkers, and adipocyte size. PS treatment also restored gut microbial diversity, with 19 specific microbial taxa and 25 KEGG pathways identified as potential mediators of its anti-obesity effects. Notably, PS modulated key obesity-associated gut microbiota, including Alistipes, Lachnoclostridium, Odoribacter, Prevotellaceae UCG-001, Rikenellaceae RC9-gut group, and norank_g Bacteroidales S24-7 group. Serum metabolomics analysis implicated L-ascorbic acid, stevioside, allopurinol, and gingerol, along with amino acid and energy metabolism pathways, in the anti-obesity mechanism of PS. These results provide novel theoretical insights into the therapeutic potential of PS for obesity prevention and treatment.PMID:40336829 | PMC:PMC12055551 | DOI:10.3389/fmicb.2025.1554537

Multi-omics analysis identifies <em>Sphingomonas</em> and specific metabolites as key biomarkers in elderly Chinese patients with coronary heart disease

Thu, 08/05/2025 - 12:00
Front Microbiol. 2025 Apr 23;16:1452136. doi: 10.3389/fmicb.2025.1452136. eCollection 2025.ABSTRACTBACKGROUND: Abnormal component changes of gut microbiota are related to the pathogenesis and progression of coronary heart disease (CHD), and gut microbiota-derived metabolites are key factors in host-microbiome interactions. This study aimed to explore the key gut microbiota and metabolites, as well as their relationships in CHD.METHODS: Feces samples and blood samples were collected from CHD patients and healthy controls. Then, the obtained feces samples were sent for 16s rRNA gene sequencing, and the blood samples were submitted for metabolomics analysis. Finally, conjoint analysis of 16s rRNA gene sequencing and metabolomics data was performed.RESULTS: After sequencing, there were no significant differences in Chao 1, observed species, Simpson, Shannon, Pielou's evenness and Faith's PD between the CHD patients and controls. At phylum level, the dominant phyla were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. At genus level, the abundance of Sphingomonas, Prevotella, Streptococcus, Desulfovibrio, and Shigella was relatively higher in CHD patients; whereas Roseburia, Corprococcus, and Bifidobacterium was relatively lower. Randomforest analysis showed that Sphingomonas was more important for CHD. Through metabolomic analysis, a total of 155 differential metabolites were identified, and were enriched in many signaling pathways. Additionally, the AUC of the conjoint analysis (0.908) was higher than that of gut microbiota species (0.742).CONCLUSION: In CHD patients, the intestinal flora was disordered, as well as Sphingomonas and the identified differential metabolites may serve as was candidate biomarkers for CHD occurrence and progression.PMID:40336827 | PMC:PMC12058083 | DOI:10.3389/fmicb.2025.1452136

Biochemical impact of ALAEm supplementation in late gestation on the reproductive performance of sows

Thu, 08/05/2025 - 12:00
Front Vet Sci. 2025 Apr 23;12:1548263. doi: 10.3389/fvets.2025.1548263. eCollection 2025.ABSTRACTAdding plant extracts to diets to enhance sow performance and health is widely regarded as a healthy and sustainable practice. In promoting antibiotic-free farming, plant extracts have emerged as a leading solution for enhancing sow fertility through nutritional strategies. The aim of this study was to investigate the biochemical impacts of supplementation of sows with ALAEm (composed of nine plant extracts) on blood and placental indices of sows in late gestation. The components of ALAEm were determined by UPLC-MS/MS. 196 normal gestation parturient sows were randomly allocated into two groups (n = 98 per group): the control group and the test group fed 20 g/d ALAEm supplementation at 74-114 d of gestation. The study examined the various clinical indexes in the blood, the expression of genes and proteins and metabolomics in the placenta. Dietary ALAEm supplementation improved sow reproductive performance (total number of piglets born alive, number of piglets weaned, wean weight), serum biochemical indices, placental structure and increased gene and protein expression of ZO-1, Claudin-1 and other placental junction-associated factors. ALAEm attenuated placental tissue oxidation, inflammation, and apoptosis, promoted placental growth (EGF and IGF-1) and angiogenesis factors (VEGFA, PIGF and other factors), and increased the nutrient transport in placental (GLUT1 and SNAT2). Dietary ALAEm supplementation decreased the number of metabolites associated with lipid metabolism through alpha-linolenic acid metabolism. Therefore, dietary supplementation of ALAEm in the late gestation may improve fertility by reducing the levels of inflammation, oxidation and apoptosis in placental tissues via the EGFR/VEGFR2-PI3K-AKT1 pathway, promoting placental growth, angiogenesis and nutrient transport, and altering the levels of placental lipid metabolites via α-linolenic acid metabolism.PMID:40336816 | PMC:PMC12055862 | DOI:10.3389/fvets.2025.1548263

Harnessing plant-microbe interactions: strategies for enhancing resilience and nutrient acquisition for sustainable agriculture

Thu, 08/05/2025 - 12:00
Front Plant Sci. 2025 Apr 15;16:1503730. doi: 10.3389/fpls.2025.1503730. eCollection 2025.ABSTRACTThe rhizosphere, a biologically active zone where plant roots interface with soil, plays a crucial role in enhancing plant health, resilience, and stress tolerance. As a key component in achieving Sustainable Development Goal 2, the rhizosphere is increasingly recognized for its potential to promote sustainable agricultural productivity. Engineering the rhizosphere microbiome is emerging as an innovative strategy to foster plant growth, improve stress adaptation, and restore soil health while mitigating the detrimental effects of conventional farming practices. This review synthesizes recent advancements in omics technologies, sequencing tools, and synthetic microbial communities (SynComs), which have provided insights into the complex interactions between plants and microbes. We examine the role of root exudates, composed of organic acids, amino acids, sugars, and secondary metabolites, as biochemical cues that shape beneficial microbial communities in the rhizosphere. The review further explores how advanced omics techniques like metagenomics and metabolomics are employed to elucidate the mechanisms by which root exudates influence microbial communities and plant health. Tailored SynComs have shown promising potential in enhancing plant resilience against both abiotic stresses (e.g., drought and salinity) and biotic challenges (e.g., pathogens and pests). Integration of these microbiomes with optimized root exudate profiles has been shown to improve nutrient cycling, suppress diseases, and alleviate environmental stresses, thus contributing to more sustainable agricultural practices. By leveraging multi-disciplinary approaches and optimizing root exudate profiles, ecological engineering of plant-microbiome interactions presents a sustainable pathway for boosting crop productivity. This approach also aids in managing soil-borne diseases, reducing chemical input dependency, and aligning with Sustainable Development Goals aimed at global food security and ecological sustainability. The ongoing research into rhizosphere microbiome engineering offers significant promise for ensuring long-term agricultural productivity while preserving soil and plant health for future generations.PMID:40336613 | PMC:PMC12056976 | DOI:10.3389/fpls.2025.1503730

Say hello to my little friend… micronutraceuticals in neuroenergetics, neuronal health, and neurodegenerative diseases

Thu, 08/05/2025 - 12:00
Front Neurosci. 2025 Apr 23;19:1498655. doi: 10.3389/fnins.2025.1498655. eCollection 2025.ABSTRACTVitamins and minerals (micronutraceuticals) maintain good health. However, the specific effects of these micronutraceuticals on brain health are often overlooked, or not even known. In this review, an overview of the direct and indirect effects of micronutraceuticals on brain energy metabolism (neuroenergetics) and neuronal health is provided. Thereafter, a holistic summary of the existing studies that have shown the impact of micronutraceuticals on neurodegenerative diseases. Lastly, this review concludes by identifying several research gaps that remain and provides suggestions for future research on these hot topics.PMID:40336537 | PMC:PMC12055844 | DOI:10.3389/fnins.2025.1498655

Co-Culture of <em>Lactobacillus bulgaricus</em> With <em>Streptococcus thermophilus</em> and <em>Bifidobacterium</em> Impact the Metabolism and Flavor of Fermented Milk

Thu, 08/05/2025 - 12:00
Food Sci Nutr. 2025 May 6;13(5):e70182. doi: 10.1002/fsn3.70182. eCollection 2025 May.ABSTRACTIncorporating Bifidobacterium into fermented milk alters the balance between Lactobacillus bulgaricus and Streptococcus thermophilus. We investigated the bacterial interaction and metabolism post-fermentation and during 21-day storage. Utilizing non-targeted metabolomics and electronic nose technology, we assessed impacts on product quality and flavor. Bifidobacterium significantly increased the viability of the other two species, with AI-2 levels rising in the mixed culture. Metabonomic analysis revealed distinct metabolic profiles, with Bifidobacterium-fermented milk showing enriched key metabolites. Volatile compounds like ketones, aldehydes, esters, alcohols, and acids were identified, with 2-heptanone and 2-pentanone as initial discriminators and 2-pentanone and acetaldehyde as key flavor compounds after storage. This study advances understanding of symbiotic interactions and metabolite profiles in fermented dairy ecosystems.PMID:40336531 | PMC:PMC12055522 | DOI:10.1002/fsn3.70182

Distinct gut microbiota and metabolome features of tissue-specific insulin resistance in overweight and obesity

Thu, 08/05/2025 - 12:00
Gut Microbes. 2025 Dec;17(1):2501185. doi: 10.1080/19490976.2025.2501185. Epub 2025 May 7.ABSTRACTInsulin resistance (IR) is an early marker of cardiometabolic deterioration which may develop heterogeneously in key metabolic organs, including the liver (LIR) and skeletal muscle (MIR). This tissue-specific IR is characterized by distinct metabolic signatures, but the role of the gut microbiota in its etiology remains unclear. Here, we profiled the gut microbiota, its metabolites and the plasma metabolome in individuals with either a LIR or MIR phenotype (n = 233). We observed distinct microbial community structures LIR and MIR, and higher short-chain fatty acid (SCFA) producing bacteria, fecal SCFAs and branched-chain fatty acids and a higher postprandial plasma glucagon-like-peptide-1 response in LIR. In addition, we found variations in metabolome profiles and phenotype-specific associations between microbial taxa and functional metabolite groups. Overall, our study highlights association between gut microbiota and its metabolites composition with IR heterogeneity that can be targeted in precision-based strategies to improve cardiometabolic health. Clinicaltrials.gov registration: NCT03708419.PMID:40336254 | DOI:10.1080/19490976.2025.2501185

Gut-Liver Axis: The Role of Intestinal Microbiota and Their Metabolites in the Progression of Metabolic Dysfunction-Associated Steatotic Liver Disease

Thu, 08/05/2025 - 12:00
Gut Liver. 2025 May 8. doi: 10.5009/gnl240539. Online ahead of print.ABSTRACTMetabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as one of the most prevalent chronic liver diseases globally, and its pathogenesis is closely linked to the imbalance of intestinal microbiota and their metabolites. This article reviews the mechanisms through which intestinal microbiota influence the progression of MASLD via the gut-liver axis, elaborating on the complex roles of immune cell hyperactivation, impaired intestinal barrier function, and intestinal microbial metabolites such as short-chain fatty acids and bile acids. The imbalance of intestinal microbiota not only directly promotes the development of MASLD but also further exacerbates disease progression through abnormalities in their metabolites. Various novel therapeutic strategies are being actively developed on the basis of gut-liver axis theory, including probiotic/prebiotic/synbiotic treatment, fecal microbiota transplantation, and targeted drug therapy. These strategies aim to precisely regulate microbial homeostasis and improve glucose and lipid metabolism, thereby alleviating hepatic inflammation and fibrosis and optimizing the therapeutic outcomes of patients with MASLD. In the future, as research progresses, we will further uncover the interaction mechanisms between intestinal microbiota and MASLD and continuously explore more effective treatment methods, with the goal of improving the prognosis and quality of life for MASLD patients.PMID:40336226 | DOI:10.5009/gnl240539

Metabologenomics analysis reveals antibiotic crypticity of Kutzneria viridogrisea DSM 43850

Wed, 07/05/2025 - 12:00
J Appl Microbiol. 2025 May 7:lxaf114. doi: 10.1093/jambio/lxaf114. Online ahead of print.ABSTRACTAIMS: This study aimed to explore the secondary metabolic potential of Kutzneria viridogrisea DSM 43850 by conducting whole-genome sequencing and utilizing bioinformatics tools to analyze its biosynthetic gene clusters (BGCs). Additionally, the secondary metabolites produced by this strain were investigated under various chemical elicitors using untargeted metabolomics techniques.METHODS AND RESULTS: The complete genome of Kutzneria viridogrisea DSM 43850 was obtained by re-sequencing, followed by in-depth bioinformatics analysis to assess its secondary metabolic potential. The genome was found to encode a circular 10.2 Mb chromosome, with 4.3% of its functional genes involved in secondary metabolism. The strain harbors 52 BGCs, of which only four are associated with known products. Among these, eight gene clusters were identified as RiPPs (Ribosomally synthesized and post-translationally modified peptides), and the precursor peptide structures of four were predicted, all featuring novel scaffolds. Untargeted metabolomics analysis using LC-MS revealed that the strain could produce a series of novel secondary metabolites when induced with kanamycin and an ebselen derivative.CONCLUSIONS: This study highlights the significant secondary metabolic potential of Kutzneria viridogrisea DSM 43850, uncovering several novel BGCs and metabolic products.PMID:40336148 | DOI:10.1093/jambio/lxaf114

Invasive laser acupuncture targeting muscle: a novel approach to protect dopaminergic neurons and reduce neuroinflammation in a brain of Parkinson's disease model

Wed, 07/05/2025 - 12:00
Chin Med. 2025 May 7;20(1):59. doi: 10.1186/s13020-025-01104-2.ABSTRACTParkinson's disease (PD) affects 1-2% of the global population and presents significant therapeutic challenges. Due to the limitations of existing treatments, there is a pressing need for alternative approaches. This study investigated the effects of invasive laser acupuncture (ILA), which combines acupuncture and photobiomodulation. In this method, optical fibers are inserted into the muscle layers of the acupoint to enhance therapeutic outcomes. Mice with MPTP-induced PD were treated with ILA at 830 nm or 650 nm. Protective effects of nigrostriatal dopaminergic neurons and fibers were assessed by examining TH immunoreactivity in the brain. Neuroinflammation markers in the brain and muscle metabolomic profiles were also analyzed. Comparisons between invasive and non-invasive laser application, as well as the impact of nerve blocking with lidocaine, were also evaluated. ILA at 830 nm (ILA830) significantly improved motor performance and increased the nigrostriatal TH-positive immunoreactivities. It reduced the levels of α-synuclein, apoptotic proteins, and inflammatory cytokines, while increasing anti-inflammatory in the brain. ILA830 also decreased nigrostriatal astrocyte and microglia activation. Muscle metabolomic analysis showed distinct group clustering and significant changes in metabolites like glucose and galactose, correlating with improved motor functions. Invasive laser treatment was more effective than non-invasive, and lidocaine pre-treatment did not block its effects. ILA at 830 nm effectively ameliorates PD symptoms by protecting dopaminergic neurons, and reducing neuroinflammation in the brain. Muscle metabolomic changes by ILA830, such as increased glucose and galactose, correlate with motor improvement. This approach offers a promising strategy for PD treatment, warranting further research to optimize its use in clinical settings.PMID:40336061 | DOI:10.1186/s13020-025-01104-2

Human menstrual blood-derived stem cells secreted ECM1 directly interacts with LRP1α to ameliorate hepatic fibrosis through FoxO1 and mTOR signaling pathway

Wed, 07/05/2025 - 12:00
Stem Cell Res Ther. 2025 May 7;16(1):230. doi: 10.1186/s13287-025-04351-0.ABSTRACTBACKGROUND: Human menstrual blood-derived stem cells (MenSCs), a major class of mesenchymal stem cells (MSCs), modulate intercellular signals via paracrine factors. Previous studies found that MenSC-derived secretomes exert protective effects against liver fibrosis. However, the underlying mechanisms of these observations remain unclear.METHODS: Extracellular Matrix Protein 1 (ECM1), identified in MenSCs culture medium using mass spectrometry, was employed to stably overexpress ECM1-HA or silence in MenSCs using lentiviral vectors. These genetically engineered cells were either intravenously injected into the carbon tetrachloride (CCl4)-induced liver fibrosis mice or co-cultured with hepatic stellate cells (HSCs)-LX-2. The interaction between ECM1 and low-density lipoprotein receptor-related protein 1α (LRP1α) was confirmed using Co-Immunoprecipitation (Co-ip), Duolink Proximity Ligation Assays (PLA) and pull-down. LRP1 deficient mice were generated via intravenous administration of adeno-associated-virus-8. The downstream molecular mechanisms were characterized by non-target metabolomics and multiplex immunohistochemical staining. RNA sequencing was performed to evaluate the genetic alterations in various genes within the MenSCs.RESULTS: MenSC-secreted ECM1 exhibits potential to ameliorate liver fibrosis by inactivating HSCs, improving liver functions, and reducing collagen deposition in both cellular and mouse model of the CCl4-induced liver fibrosis. Mechanistically, a novel interaction was identified that ECM1 directly bound to cell surface receptor LRP1α. Notably, the antifibrotic efficacy of MenSC was negated in LRP1-deficient cells and mice. Moreover, the ECM1-LRP1 axis contributed to the alleviation of liver fibrosis by suppressing AKT/mTOR while activating the FoxO1 signaling pathway, thereby facilitating pyrimidine and purine metabolism. Additionally, ECM1-modified MenSCs regulate the transcription of intrinsic cytokine genes, further mitigating liver fibrosis.CONCLUSIONS: These findings highlight an extensive network of ECM1-LRP1 interaction, which serve as a link for providing promising insights into the mechanism of MenSC-based drug development for liver fibrosis. Our study also potentially presents novel avenues for clinical antifibrotic therapy.PMID:40336034 | DOI:10.1186/s13287-025-04351-0

Compound probiotics alleviate hyperuricemia-induced renal injury via restoring gut microbiota and metabolism

Wed, 07/05/2025 - 12:00
BMC Microbiol. 2025 May 8;25(1):280. doi: 10.1186/s12866-025-04012-5.ABSTRACTTo investigate the role and mechanisms of gut microbiota in hyperuricemia-induced renal injury, we established renal failure models using unilateral nephrectomized mice. After four weeks of adenine and potassium oxalate-supplemented diet, probiotic intervention was administered. Renal pathological and functional changes were assessed through H&E staining and plasma biochemical analysis. Gut microbiota composition and metabolite profiles were evaluated using 16 S rRNA gene sequencing and non-targeted metabolomics of fecal samples.Our findings demonstrate that the compound probioticS effectively attenuated hyperuricemia-associated renal dysfunction and interstitial fibrosis. The intervention reduced oxidative stress, mitophagy, and apoptosis in renal tubules. Probiotic treatment enhanced gut microbiota diversity, notably increasing the abundance of Prevotella_9, Dorea, and unclassified Bacteroidota, while decreasing unclassified Desulfovibrio. KEGG enrichment analysis revealed that probiotic intervention upregulated arginine and proline metabolism, as well as tyrosine metabolism in feces. Furthermore, it enhanced the metabolism of arginine, proline, valine, leucine, and isoleucine in plasma.Notably, sulfocholic acid and urocanic acid showed negative correlations with oxidative stress markers, autophagy, and apoptosis indicators. Similarly, plasma L-proline levels were inversely correlated with these pathological parameters.These results suggest that the compound probiotics may mitigate hyperuricemia-induced kidney damage through restoration of gut microbiota homeostasis and preservation of plasma and fecal metabolites. The protective mechanisms likely involve attenuation of hyperuricemia-associated oxidative stress, mitochondrial dysregulation, and phagocytosis-induced apoptosis.Our study provides compelling evidence that probiotic supplementation represents a promising therapeutic strategy for hyperuricemia-induced renal injury, potentially through modulation of gut microbiota and associated metabolic pathways.PMID:40335932 | DOI:10.1186/s12866-025-04012-5

Transcriptomic and metabolic changes during tassel branching development in maize

Wed, 07/05/2025 - 12:00
BMC Plant Biol. 2025 May 7;25(1):596. doi: 10.1186/s12870-025-06607-6.ABSTRACTBACKGROUND: Tassel branch number shapes plant architecture, which is crucial for maize adaptation to high-density planting. Therefore, unrevealing the molecular mechanisms of tassel branching is essential for crop breeding. To gain better insights into this mechanism, we integrated metabolomic and transcriptomic analysis to explore differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs) between two types of materials with distinct tassel branching numbers.RESULTS: We identified a pair of maize sibling lines, unbranched tassel line (UBT) and multibranched tassel line (MBT). UBT has only one spike without branches due to the inhibition of branch meristems, while MBT has multiple branches. Gene Ontology (GO) enrichment analysis of DEGs revealed significant enrichment in organ growth regulation, hormone response and auxin signaling pathway. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DAMs revealed enrichment in plant hormone signal transduction. Integrated transcriptomic and metabolomic analysis revealed enrichment of the tryptophan metabolism, a crucial auxin biosynthetic pathway, suggesting its potential involvement in tassel branching development.CONCLUSIONS: The elevated levels of indole-3-acetamide in the tryptophan metabolism pathway suggest an increase in auxin accumulation, which may subsequently suppressed branch meristem formation in UBT through downregulation of BARREN STALK 1 expression and modulation of auxin signaling pathways.PMID:40335919 | DOI:10.1186/s12870-025-06607-6

Alterations in hepatic amino acid metabolism related to MASLD in individuals with obesity

Wed, 07/05/2025 - 12:00
J Physiol Biochem. 2025 May 8. doi: 10.1007/s13105-025-01086-7. Online ahead of print.ABSTRACTDeregulation of amino acid (AA) metabolism has been reported in several pathological conditions, including metabolic diseases (e.g., obesity and diabetes), cardiovascular diseases, and cancer. However, the role of alterations in AA levels in chronic liver disorders such as metabolic dysfunction-associated steatotic liver disease (MASLD) remains largely unexplored. In this study we aimed to evaluate the hepatic AA composition in patients with different stages of MASLD, and their relationship with MASLD-related risk factors. A case-control study was conducted in 40 patients with obesity undergoing bariatric surgery at Virgen de la Arrixaca University Hospital (Murcia, Spain), where MASLD diagnosis was confirmed by histological analysis of liver biopsies, and hepatic AA levels were measured using ultra-performance liquid chromatography high-resolution time-of-flight mass spectrometry. Our results revealed that the hepatic AA profile was significantly altered in patients with MASLD. More specifically, comparison between MASLD patients revealed a significant increase in hepatic levels of arginine, glycine and cystine in MASH samples compared to steatotic livers. In addition, hepatic concentrations of arginine, lysine and cystine positively correlated with histopathological diagnosis and other MASLD-related parameters, including transaminases and CK-18 levels. These findings suggest that alterations in certain hepatic AA levels such as arginine, lysine, glycine and cystine in MASLD patients could have translational relevance in understanding the onset of this disease.PMID:40335876 | DOI:10.1007/s13105-025-01086-7

Volatile organic compound exposure is associated with hyperuricemia in the general population: an analysis of 6878 adults from the NHANES

Wed, 07/05/2025 - 12:00
Metabolomics. 2025 May 7;21(3):60. doi: 10.1007/s11306-025-02261-z.ABSTRACTBACKGROUND: Hyperuricemia is clinically significant as the primary risk factor for gout and is strongly associated with cardiovascular diseases, hypertension, and chronic kidney disease. However, its relationship with exposure to volatile organic compounds (VOCs) remains unclear. This study explores the association between urinary VOC metabolite concentrations and the prevalence of hyperuricemia.RESEARCH DESIGN AND METHODS: Data from adults aged ≥ 18 years with at least one urinary VOC measurement were obtained from the 2011-2018 National Health and Nutrition Examination Survey (NHANES). Associations between sixteen urinary VOC metabolite levels and hyperuricemia were analyzed using univariate and multivariable logistic regression, adjusted for demographic and clinical covariates.RESULTS: Data of a total of 6,878 participants were analyzed. Multivariable analysis revealed that, after adjusting for relevant confounders, there were significant associations between higher levels of certain urinary VOC metabolites and hyperuricemia. Specifically, as compared to the lowest level (tertile 1), higher levels (tertile 3) of BMA (aOR = 1.38), CEMA (aOR = 1.59), CYMA (aOR = 1.41), 3HPMA (aOR = 1.34), PGA (aOR = 1.41), HPMMA (aOR = 1.48), MA (aOR = 1.33), 2HPMA (aOR = 1.34), and DHBMA (aOR = 1.35) were significantly associated with increased odds of hyperuricemia.CONCLUSIONS: The findings indicate that specific urinary VOC metabolites are independently associated with an increased likelihood of hyperuricemia. These findings provide a direction for future experimental studies to investigate the underlying mechanisms and confirm causal relationships.PMID:40335851 | DOI:10.1007/s11306-025-02261-z

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