PubMed

Neuroscience. 2025 May 10:S0306-4522(25)00352-5. doi: 10.1016/j.neuroscience.2025.04.053. Online ahead of print.ABSTRACTThe research focused on exploring the differences and relationships between gut microbiota and metabolites at various stages of Alzheimer's disease (AD), specifically using APP/PS1 mice at the ages of 6 months and 10 months. To assess metabolites in serum and cortex, and to evaluate gut microbiota profiles in cecal content, UPLC-MS/MS and 16S rRNA sequencing techniques were utilized, respectively. Findings indicated that, in comparison to younger mice, serum concentrations of L-Leucine, thymine, and Glucosamine 6-phosphate were lower, whereas levels of Sorbitol and Palmitic acid were higher. Furthermore, measurements of the ACE and Chao1 indices significantly declined in the older cohort. At the phylum level, the relative abundance of Bacteroidetes showed a decline, while there was an increase in Actinobacteria and TM7 bacteria among the middle-aged subjects. The novelty of this study is we found there were notable alterations in both gut microbiota and metabolites within serum and cortex when comparing young and older APP/PS1 mice, emphasizing the important connections between metabolites and gut microbiota throughout the progression of AD. These results indicate that manipulating metabolites and gut flora may serve as a vital strategy for the prevention and management of AD.PMID:40355072 | DOI:10.1016/j.neuroscience.2025.04.053

Plant Sci. 2025 May 10:112553. doi: 10.1016/j.plantsci.2025.112553. Online ahead of print.ABSTRACTPanax ginseng C.A. Meyer was recognized as a precious traditional Chinese medicine with a long history of application. It is widely used due to its high medicinal value. Ginsenosides were identified as a group of triterpenoid secondary metabolites in ginseng and were considered the main active ingredients of ginseng. Plant endophytes were recognized as microorganisms that resided within plant tissues, coexisting with the host plant for part or all of their life cycle and interacting with the external environment together. Ginseng endophytes, as symbiotic microorganisms with ginseng, possess various functions such as enhancing yield, increasing resistance, and improving quality, making them an important microbial resource for potential utilization. In this study, we screened and identified an endophytic fungus PBF-08, which has the ability to produce ginsenosides Rg2, Rg3, and Re. By optimizing its fermentation conditions using the response surface methodology, the total ginsenoside yield was significantly increased. Additionally, ginseng adventitious roots were treated with strain PBF-08 as an elicitor, which significantly increased the ginsenoside content by regulating the expression of key enzyme genes in the ginsenoside biosynthesis pathway under optimal treatment concentration and time. Widely targeted metabolomic analysis revealed that strain PBF-08 not only possesses a complete and active terpenoid biosynthesis pathway but also synthesizes various metabolites that influence plant growth and metabolism. In summary, the strain PBF-08 was found to have potential application value in exploring new methods for obtaining ginsenosides and in developing microbial elicitors for regulating ginsenoside biosynthesis.PMID:40355047 | DOI:10.1016/j.plantsci.2025.112553

J Control Release. 2025 May 10:113835. doi: 10.1016/j.jconrel.2025.113835. Online ahead of print.ABSTRACTTumor-targeting drug delivery holds great promise for cancer treatment but faces significant challenges in penetrating solid tumors to achieve optimal therapeutic efficacy. By harnessing the natural tissue-penetration effect conferred by the CendR motif, we identified that the nucleolin (NCL)-targeted peptide F3 possesses tumor-penetrating capabilities. Co-administration of F3 with doxorubicin and the apoptosis-inducing protein TRAIL enhanced effective tumor penetration and improved antitumor activity. Taking advantage of TRAIL's natural self-trimerization, we developed a novel fusion protein, F3-TRAIL. This design enabled the trivalent assembly of F3 when fused with TRAIL, significantly enhancing its binding to NCL-positive tumor endothelial and parenchymal cells, resulting in deeper tumor penetration and superior antitumor effects compared to TRAIL alone. Mechanistic studies revealed that the multivalent F3-enhanced engagement with tumor cells potentiated TRAIL to trigger death receptor-dependent apoptosis signaling, even in TRAIL-resistant tumor cells. Building on this success, we constructed F3-HexaTR using the SpyCatcher/SpyTag superglue ligation system to generate a hexameric TRAIL, further amplifying cytotoxicity and antitumor efficacy. Combined analysis of data from TCGA and GTEx revealed significantly elevated NCL expression across 18 solid tumor types, underscoring the clinical potential of F3-directed targeted therapy. These findings highlight that F3-mediated NCL targeting is an effective strategy to overcome tumor penetration barriers, particularly for protein drug delivery. This multivalent assembly approach represents an innovative avenue for enhancing the therapeutic efficacy of various agents in the treatment of solid tumors.PMID:40355045 | DOI:10.1016/j.jconrel.2025.113835

J Adv Res. 2025 May 10:S2090-1232(25)00309-1. doi: 10.1016/j.jare.2025.05.016. Online ahead of print.ABSTRACTINTRODUCTION: Alpha-herpesvirus poses significant health risks to humans and challenges to animal husbandry. Currently, the clinically approved antiviral drug Acyclovir exhibits limitations, including drug resistance and adverse effects. The development of broad-spectrum antiviral agents against alpha-herpesvirus is urgently needed.OBJECTIVE: This study aimed to discover a novel antiviral drug with the capacity to broadly inhibit various alpha-herpesviruses.METHODS: In this study, we conducted a high-content screening of 1,500 chemical compounds to identify potential antiviral candidates. The antiviral mechanisms were explored using phenotypic experiments, untargeted metabolomics, and molecular docking.RESULTS: We discovered that Antimycin A effectively inhibits the replication of various alpha-herpesviruses, including herpes simplex virus 1 (HSV-1), bovine herpesvirus 1 (BHV-1), and pseudorabies virus (PRV). Our study revealed that Antimycin A inhibits viral replication by disrupting the formation of pyrimidinosomes that are essential for efficient viral infection. Finally, Antimycin A effectively inhibited viral infection, prevented tissue damage, and enhanced survival in PRV-infected BALB/c mice, confirming its in vivo efficacy.CONCLUSION: Antimycin A emerges as a promising lead candidate for the development of antiviral therapies against alpha-herpesvirus infections.PMID:40354935 | DOI:10.1016/j.jare.2025.05.016

Metab Eng. 2025 May 10:S1096-7176(25)00078-3. doi: 10.1016/j.ymben.2025.05.002. Online ahead of print.ABSTRACTBacterial exopolysaccharide (EPS), as a high-value probiotic product, is known to be biosynthesized by a secondary metabolic pathway to mediate acid stress in lactic acid bacteria. However, a quantitative understanding of cellular resource coordination underlying acid stress-induced EPS production remains lacking. Systematically investigating Lactiplantibacillus plantarum HMX2, a well acknowledged EPS-producer, this study measured growth phenotypes, metabolomics, and proteomics of the target strain cultured at different pH values. Multi-omics analysis demonstrated that the EPS biosynthetic pathway was significantly up-regulated under acid stress, and pinpointed Fur as the most probable controlling transcriptional factor. Furthermore, the experimentally observed proteome re-allocation between primary metabolism and EPS biosynthesis was effectively captured by the regulatory proteome constrained flux balance analysis (RPCFBA) model via incorporating an activation function for secondary metabolism. This work, fusing the power of multi-omics analysis and genome-scale metabolic modeling, quantitatively elucidated the proteome trade-off between cellular growth and stress resistance underlying EPS production in lactic acid bacteria and shed light on the control principle of microbial secondary metabolism.PMID:40354876 | DOI:10.1016/j.ymben.2025.05.002

Food Chem Toxicol. 2025 May 10:115545. doi: 10.1016/j.fct.2025.115545. Online ahead of print.ABSTRACTUlcerative colitis (UC) is a chronic inflammatory disease primarily affecting the colon, characterized by mucosal inflammation and ulceration. Monocyte locomotion inhibitory factor (MLIF), a heat-stable pentapeptide derived from Entamoeba histolytica, has demonstrated the anti-inflammatory capacity. The aim of the current work was to test the protective effects of MLIF in a dextran sulfate sodium (DSS)-induced colitis mouse model. Our findings indicated that MLIF significantly inhibition of colitis development, including body weight, DAI score, colon length, and spleen index. MLIF slowing the progression of inflammation in the colon of mice exposed to DSS, evidenced by HE staining and mRNA expression levels of Il1b, Il6, Il18 and Il10. MLIF significantly alleviated intestinal barrier dysfunction in mice exposed to DSS, evidenced by AB-PAS staining and mRNA expression levels of Tjp1, Ocln and Muc2. Importantly, the administration of MLIF in colitis mice exerted beneficial effects on the gut microbiota, enhancing microbial diversity and abundance, and promoting the restoration of gut microbiota homeostasis. Non-targeted metabolomics results suggest that the benefits of MLIF may arise from its modulation of tryptophan metabolism pathways. In conclusion, MLIF prevention inflammation induction and preserves intestinal homeostasis against colitis induced by DSS.PMID:40354872 | DOI:10.1016/j.fct.2025.115545

J Ethnopharmacol. 2025 May 10:119944. doi: 10.1016/j.jep.2025.119944. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Bazi Bushen Capsule (BZBS), a traditional Chinese medicine formulation composed of multiple bioactive herbal components, has been validated in multicenter randomized double-blind controlled trials for its potent anti-aging properties. Previous studies from our group have demonstrated that BZBS effectively restores gut microbiota homeostasis and attenuates the impairment of intestinal barrier function, thereby ameliorating age-related cognitive decline. However, the specific molecular mechanisms by which BZBS modulates key microbial-metabolite networks to delay brain aging remain poorly understood and warrant further investigation.AIM OF THE STUDY: This study aims to elucidate the key microbiota-metabolite networks through which BZBS improves cognitive function and delays brain aging in senescence-accelerated mouse-prone 8 (SAMP8) mice.MATERIALS AND METHODS: Eight-week-old male SAMP8 mice were used as experimental models, randomly divided into Model, BZ-low (0.5 g/kg/d BZBS), BZ-high (1 g/kg/d BZBS), and RAPA (2 mg/kg/d rapamycin) groups. Senescence-accelerated mouse resistant 1 (SAMR1) mice served as the control group. Cognitive function was assessed using the Barnes Maze test and the three-chamber social test. The structural damage and pathological changes in the brain tissue were evaluated through transcranial Doppler, micro-computed tomography, Nissl staining, and Western blot analysis. Next, the intestinal barrier function was detected by hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and immunofluorescence (IF) staining. Characteristic bacteria were identified by 16S rRNA sequencing, and metabolomic profiling was performed using non-targeted metabolomics. Akkermansia muciniphila (Akk) was cultured, and fecal microbiota transplantation (FMT) was employed to evaluate its contribution to intestinal barrier function.RESULTS: The study revealed that BZBS therapy not only enhances cognitive capabilities but also restores the intestinal barrier function. Akk was identified as a key regulatory agent mediating the therapeutic effects of BZBS. BZBS administration significantly increased the abundance of Akk and modulated its metabolite profile, particularly components associated with spermidine, thereby reinforcing the intestinal barrier and mitigating age-related cognitive decline. Furthermore, this study demonstrated that Akk, administered via fecal microbiota transplantation, alleviated dextran sulfate sodium (DSS)-induced colitis..CONCLUSION: The results showed that BZBS capsule, a traditional Chinese medicine, may delay brain aging in SAMP8 mice by modulating Akk and its spermidine production.PMID:40354842 | DOI:10.1016/j.jep.2025.119944

Phytomedicine. 2025 Apr 26;143:156797. doi: 10.1016/j.phymed.2025.156797. Online ahead of print.ABSTRACTBACKGROUND: Bamboo has been used in traditional Asian medicine since ancient times. Silica is formed in the shoot internodes of various bamboo species. This bamboo-derived silica, referred to as bamboo biosilica or "banslochan" (in Sanskrit), possesses multiple health benefits. In Ayurveda, this has been described to have immunomodulatory properties and is a significant component of "Chywanprash", a well-known Ayurvedic formulation.OBJECTIVES: This study aims to validate the therapeutic claim of the immunomodulatory effect of bamboo biosilica by metabolite profiling-based network pharmacology approach and luciferase reporter gene assay to elucidate the probable mechanism of action.METHODS: Bamboo biosilica from internodes of Dendrocalamus longispathus Kurz. was collected from Aibawk region of Mizoram and subjected to various physicochemical tests. Hydroalcoholic extraction of bamboo biosilica and commercial food-grade silica was carried out, and different qualitative and quantitative phytochemical analyses were conducted. In-vitro, cytotoxicity of the biosilica was assessed in RAW 264.7 (murine macrophage) cells, followed by an immunomodulatory assay. The metabolite profiling-based network pharmacology of the bamboo biosilica hydroalcoholic extract was carried out to establish the probable mechanism of action, disease association and pathway analysis.RESULTS: The results showed both bamboo biosilica hydroalcoholic extract exhibited significant immunostimulatory activity compared to commercial silica. UHPLC-QTOF-MS/MS based characterization followed by network pharmacology approach confirmed the presence of flavones and acyclic monoterpenoids responsible for immunomodulatory potential via arachidonic acid metabolism, activation of NF-κβ, PI3K-Akt, and MAPK signaling pathway.CONCLUSION: This study provides the first comprehensive evidence of significant immunostimulatory effect of bamboo biosilica through multiple immune-metabolic pathways positioning it as a promising natural immunopotentiating agent.PMID:40354708 | DOI:10.1016/j.phymed.2025.156797

Per Med. 2025 May 12:1-6. doi: 10.1080/17410541.2025.2499438. Online ahead of print.ABSTRACTBACKGROUND: -Omics technologies - including genomics, transcriptomics, proteomics, and metabolomics - are increasingly used in acute care settings. However, the current extent of this research has not been systematically assessed.OBJECTIVES: To characterize how -omics analyses are applied to acute medical conditions and identify trends, gaps, and implementation barriers.METHODS: Eligible studies included human subjects with acute conditions and used -omics biosample analyses for diagnostic, prognostic, or predictive purposes. Feedback from the SAEM Precision Emergency Medicine Consensus Conference informed the search and inclusion criteria. Studies of infectious diseases were excluded for separate analysis.RESULTS: Of 7,531 screened articles, 421 met inclusion criteria. Most were observational cohort studies, with single nucleotide polymorphism analysis being most common. Cardiovascular and trauma-related conditions were frequently studied. Only 12.4% of studies included children, and just 7 focused exclusively on older adults. One-third were conducted outside of emergency departments. Many studies addressed diverse, uncategorized acute conditions.CONCLUSIONS: While -omics research in acute care is growing, it remains predominantly observational with limited clinical implementation. Barriers include delayed turnaround times, insufficient EHR integration, and underrepresentation of vulnerable populations. Advancing this field requires cross-disciplinary collaboration, focused research priorities, and investment in implementation studies.PMID:40353750 | DOI:10.1080/17410541.2025.2499438

Am J Physiol Heart Circ Physiol. 2025 May 12. doi: 10.1152/ajpheart.00841.2024. Online ahead of print.ABSTRACTAims: Despite significant advancements in therapies, heart failure (HF) remains a major health challenge. Women, who are underrepresented in HF research, are particularly in need of effective treatments. B-vitamins are a promising and cost-effective option for improving cardiac function. Our study aimed to investigate the sex-specific effects of B-vitamin supplementation on HF with reduced ejection fraction in mice. Methods and results: Male and female mice underwent transverse aortic constriction (TAC) to induce pressure overload. Four weeks post-TAC, mice were randomized to receive either a standard or a vitamin B-enriched (VitB) diet. We found that in females, but not in males, VitB: i) extended survival, ii) slowed down the decrease in ejection fraction (EF), and iii) improved left ventricular morphology. The observed benefits in females were associated with evidence of improved cardiac and lung fibrosis as well as lower inflammation. In contrast, in males, VitB treatment did not reduce cardiac and lung fibrosis while inflammation remained active in the myocardium. Regarding the circulating lipidome, disturbances were normalized in females with a specific enrichment in long-chain and polyunsaturated triglycerides (TG) in response to VitB. Conversely, in males, lipidomic alterations remained under VitB treatment and were characterized by the accumulation of shorter and saturated TG in the circulation and myocardium. Conclusion: These data reveal a sex-specific response to VitB supplementation in HF in the context of pressure overload and point to a differential lipidomic remodeling that is only favorable in females.PMID:40353673 | DOI:10.1152/ajpheart.00841.2024

J Dent Res. 2025 May 12:220345251332885. doi: 10.1177/00220345251332885. Online ahead of print.ABSTRACTDue to the unclear etiology and pathogenesis of temporomandibular joint disorders (TMDs), current treatments often fail to provide long-term relief or halt disease progression. Therefore, this study aims to explore the underlying etiologic mechanisms by focusing on the causal relationship between the gut microbiome (GM) and TMD through a multi-omics approach. This includes mendelian randomization (MR) analysis of GM, metabolomics, and TMD data, as well as transcriptomic analysis. In accordance with MR guidelines, we utilized summary-level genome-wide association study data to perform bidirectional MR, identifying 28 gut microbial taxa with causal effects on TMD. The following species had the strongest associations with TMD incidence: RUG147 sp900315495 (odds ratio [OR], 2.016; 95% CI, 1.219 to 3.333; P = 0.006), CAG-194 sp002441865 (OR, 0.713; 95% CI, 0.555 to 0.916; P = 0.008), CAG-145 sp000435615 (OR, 1.166; 95% CI, 1.040 to 1.308; P = 0.009), and CAG-81 sp000435795 (OR, 1.150; 95% CI, 1.036 to 1.276; P = 0.009). To explore the mediating role of metabolites, a 2-step mediation MR approach was employed, revealing that lipid-related metabolites serve as key mediators in the GM-TMD interaction. Specifically, total cholesterol in high-density lipoprotein 3 was identified as a mediator of CAG-145 sp000435615 on TMD (-4.13%). Further analysis based on transcriptomic data identified differentially expressed and shared genes between GM and TMD, with the AGE-RAGE (advanced glycation end products-receptor for advanced glycation end products) and processes related to cell adhesion and inflammation emerging as significant pathways. These findings highlight the role of GM dysbiosis in TMD pathogenesis, potentially through disruptions in lipid metabolism and inflammatory processes, suggesting new therapeutic strategies targeting GM and its associated pathways.PMID:40353522 | DOI:10.1177/00220345251332885

J Agric Food Chem. 2025 May 12. doi: 10.1021/acs.jafc.5c03489. Online ahead of print.ABSTRACTRalstonia solanacearum, a pathogen causing bacterial wilt, threatens global crop production, necessitating sustainable biocontrol solutions. Bacillus amyloliquefaciens is a promising biocontrol agent, but the mechanisms of its interaction with R. solanacearum are not well understood. This study investigates the effects of R. solanacearum secretions on the growth, metabolite production, and antimicrobial properties of B. amyloliquefaciens BNC5. Untargeted metabolomics revealed increases in two known macrolactins (A and M), six novel macrolactins (BA1-6), and one novel polyketide (BAP1), along with decreases in 7-O-malonyl macrolactin A and a new macrolactin, BA7, following exposure to the secretions. Real-time polymerase chain reaction showed a downregulation of the tailoring enzyme gene bmmGT3. The reduced antimicrobial activity in the exposed extracts (78 vs 39-78 μg mL-1 in unexposed extracts) is likely due to diminished macrolactin efficacy in macrolactin fractions from the exposed (512-1024 μg mL-1) compared to those from the unexposed samples (4 μg mL-1). Supported by tomato pot experiments, these results suggest that applying B. amyloliquefaciens extracts prior to introducing live bacteria may enhance the management of R. solanacearum in severely affected fields, providing a sustainable alternative to chemical pesticides.PMID:40353476 | DOI:10.1021/acs.jafc.5c03489

Anal Chem. 2025 May 12. doi: 10.1021/acs.analchem.4c05410. Online ahead of print.ABSTRACTMass spectrometry imaging is a developing technique that maps the molecular composition of samples in a label-free manner. However, highly heterogeneous samples, including bones, usually cannot be easily analyzed due to challenging sample preparation, particularly in minimizing cracks and maintaining flatness. To comprehensively address these issues, we developed a sample preparation method for the fresh frozen heterogeneous samples such as knee joint and skull of murine, which includes complex structures and tissue types, such as neuronal tissue, peripheral nerve, muscle, tracks, connective tissue, cartilage, mineralized bone, and bone marrow. By controlling the sample thickness and employing an optimized drying method, we achieved minimal cracking. We found that a combination of lyophilization and 5 μm section thickness, when attached to a cryofilm, was readily achievable and significantly reduced cracking in bone tissue. Additionally, we implemented a contactless spin-flattening technique to ensure surface uniformity. Centrifuging the section at 7000g improved surface flatness, bringing the height variation within the range typically observed in soft tissues while also removing excess mounting medium and bubbles. This approach enhances the sample quality and reliability without requiring complex manual skills, making it more practical and reproducible for routine analysis. High molecular coverage was achieved, including small metabolites, metals, and lipids, by using the N-(1-naphthyl) ethylenediamine dihydrochloride (NEDC) matrix. To further explore the potential of our workflow, high-resolution MSI was performed on rat tibial growth plates at different growth stages. Numbers of N-acetyl disaccharide sulfate and PE (34:1) are found to be complementary expressed in growth plate cartilage and have different intensities at different growth stages. Our findings suggested the potential involvement of those metabolites in bone development. By addressing the challenges of sample preparation, including surface flatness, bubbles, and severe cracking, our approach significantly improves the quality of the MS imaging. Additionally, this method offers a broad detection range that encompasses both metal ions and metabolites. This advancement enables detailed and accurate molecular characterization of rigid biological samples, enhancing the potential for applications in biomedical research.PMID:40353393 | DOI:10.1021/acs.analchem.4c05410

Cancer Med. 2025 May;14(9):e70953. doi: 10.1002/cam4.70953.ABSTRACTBACKGROUND: Neuroblastoma (NB), the common extracranial solid tumor in children, is associated with a poor prognosis, particularly in high-risk patients. MYCN amplification stands as the most prominent molecular hallmark within this high-risk subgroup. However, MYCN protein is considered "undruggable" due to its lack of a conventional enzymatic binding pocket and its predominant nuclear localization, which precludes targeting by standard small-molecule inhibitors or antibody-based therapeutics. Consequently, current therapeutic strategies have achieved limited efficacy against MYCN-driven NB. Notably, MYCN not only orchestrates diverse metabolic reprogramming pathways in tumors but also exerts a pivotal influence on cellular differentiation. To overcome this therapeutic barrier, we seek to elucidate the contribution of purine metabolism to stemness maintenance in MYCN-amplified NBs and to discover novel small-molecule inhibitors capable of inducing differentiation in high-risk NBs.METHODS: Metabolomic profiling via mass spectrometry was employed to delineate differential metabolite signatures between MYCN-amplified and non-amplified NB cells. Bioinformatics analysis of publicly available RNA sequencing datasets facilitated the systematic evaluation of purine metabolic enzyme expression. Cell differentiation, proliferation, colony formation, and cell migration assays were employed to assess the inhibitor's effects. Additionally, an in vivo xenograft model of NB was established to examine the therapeutic potential of lometrexol (LMX), a selective inhibitor of the purine biosynthesis enzyme phosphoribosylglycinamide formyltransferase (GART).RESULTS: Significant changes in nucleotide metabolism were identified in NB cell lines with high MYCN expression compared to those with low MYCN expression. The expression of purine metabolic enzyme genes was positively correlated with MYCN expression, prognosis, and differentiation status in NBs. Pharmacological inhibition of GART using LMX elicited a robust pro-differentiation response, concomitant with a significant suppression of tumorigenic potential.CONCLUSIONS: These findings establish purine metabolic enzyme inhibition as a viable therapeutic strategy to induce differentiation and attenuate tumor progression in high-risk MYCN-amplified NBs.PMID:40353332 | DOI:10.1002/cam4.70953

Front Plant Sci. 2025 Apr 25;16:1531585. doi: 10.3389/fpls.2025.1531585. eCollection 2025.ABSTRACTINTRODUCTION: Indole-3-acetic acid (IAA) is a key plant hormone involved in regulating development and responses to abiotic stress. However, excessive IAA treatment can induce oxidative stress, impair growth, and potentially lead to plant death. This study investigates the effects of excessive IAA exposure on the growth of Chrysanthemum morifolium (Boju), focusing on the underlying molecular mechanisms.METHODS: We treated C. morifolium with 10 mg/L IAA for nine consecutive days. The impact of this treatment was assessed from various perspectives, including physiological (chlorophyll, carotenoids, and MDA content), biochemical (antioxidant enzyme activities), and molecular (transcriptomic and metabolomic analyses).RESULTS: IAA treatment significantly increased chlorophyll a, chlorophyll b, and carotenoid levels by 37%, 46%, and 25%, respectively, compared to pre-treatment levels, suggesting that C. morifolium was experiencing stress. Additionally, the malondialdehyde (MDA) content was 1.79 times higher than pre-treatment levels, confirming oxidative stress. To combat this, the plant enhanced its antioxidant defense mechanisms, as shown by a 93.8% increase in peroxidase (POD) activity and a 45% increase in superoxide dismutase (SOD) activity. Exogenous IAA treatment also led to a significant reduction in endogenous hormone levels, including gibberellins (GA3 and GA4), abscisic acid (ABA), and IAA, with decreases of 93%, 45%, 99%, and 99%, respectively.Transcriptomic and metabolomic analyses identified 263 differentially expressed metabolites and 144 differentially expressed genes.DISCUSSION: These results suggest that C. morifolium is experiencing stress under prolonged IAA treatment and likely limits its growth by reducing endogenous hormone levels to mitigate oxidative stress. The transcriptomic and metabolomic results showed the upregulation of stress-related genes, including proB (Glutamate 5-kinase), proA (Glutamate-5-semialdehyde dehydrogenase), GAD (Glutamate decarboxylase), and peroxidases, alongside the downregulation of PK (Pyruvate kinase), indicateing a complex response involving the regulation of amino acid biosynthesis, coumaric acid metabolism, starch and sucrose metabolism, and pyruvate metabolism. This study highlights the nonlinear effects of IAA on plant growth and stress responses, emphasizing the intricate molecular mechanisms involved in coping with excessive IAA-induced stress.PMID:40353231 | PMC:PMC12061948 | DOI:10.3389/fpls.2025.1531585

Front Plant Sci. 2025 Apr 25;16:1543380. doi: 10.3389/fpls.2025.1543380. eCollection 2025.ABSTRACTINTRODUCTION: Potato (Solanum tuberosum L.), as an important food crop on the Qinghai-Tibet Plateau, is prone to low temperature and frost damage during the seedling stage, causing economic losses for farmers.METHODS: In this study, metabolome and transcriptome analyses were conducted on the leaves of Atlantic (cold-resistant) and KY140 (cold-sensitive) potato varieties following exposure to cold stress (CS).RESULTS: After CS, 298 and 195 differentially accumulated metabolites (DAMs) were identified in Atlantic and KY140, respectively, with 124 common DAMs, including lipids, flavonoids, alkaloids, organic acids, amino acids and their derivatives, nucleotides and their derivatives, lignans and coumarins, phenolic acids, and terpenoids. A total of 6928 and 2428 differentially expressed genes(DEGs) were identified in Atlantic and KY140, respectively, with 1131 common DEGs. Joint analysis of DAMs and DEGs, "flavonoid-related metabolism," "lipid metabolism," and "amino acid metabolism" were plotted. Cinnamic acid, caffeic acid, naringenin, and γ-aminobutyric acid (GABA) might participate in the regulation of potato resistance to CS. The genes StPAL(Soltu.Atl.09_2G005110) and StGAD(Soltu.Atl.11_3G000340) encode enzymes responsible for the biosynthesis of cinnamic acid and GABA, respectively, suggesting their involvement in the regulation of cold resistance in potato.DISCUSSION: Our results provided novel insights into the molecular mechanisms underlying cold resistance in potato.PMID:40353224 | PMC:PMC12062144 | DOI:10.3389/fpls.2025.1543380

3 Biotech. 2025 Jun;15(6):160. doi: 10.1007/s13205-025-04320-7. Epub 2025 May 9.ABSTRACTIndigofera longiracemosa, a member of the Fabaceae family documented in traditional medicine for its therapeutic potential, holds promise as a viable natural indigo source. The dearth of reliable and coherent research on the safety and medicinal advantages of phytochemicals obtained from this specific plant species prompted us to examine therapeutic potential of extracts prepared from the leaf and stem of this dye yielding plant. The aerial parts (leaf and stem) of I. longiracemosa were extracted separately using solvents of increasing polarity. In vitro anti-inflammatory studies such as lipoxygenase inhibition, albumin denaturation, and protease inhibitory activity revealed leaf methanolic extract (LME) to show the best anti-inflammatory property. Furthermore, short term toxicity studies (acute and sub-acute) were done in Balb/c mice to evaluate LME's toxicity. In acute toxicity study, LME administered at 2000 mg/kg body weight was found to be non-toxic. Consequently, sub-acute toxicity study was done in both male and female Balb/c mice at three doses (100, 200 and 400 mg/kg body weight, respectively). Following sub-acute toxicity study for 28 days, serum analysis and histological evaluation of tissues did not reveal any signs of toxicity at the administered doses, thereby indicating non-toxic nature of LME. Furthermore, to identify phytochemicals associated with LME, HRLCMS-QTOF untargeted metabolomics was done, and the predominant phytochemicals identified were phenols. The enhanced anti-inflammatory property observed in LME may be attributed to the predominance of phenols. Our studies have, therefore, illustrated the non-toxic nature and therapeutic potential of LME, an extract prepared from I. longiracemosa.PMID:40352767 | PMC:PMC12064542 | DOI:10.1007/s13205-025-04320-7

Psychol Res Behav Manag. 2025 May 5;18:1085-1097. doi: 10.2147/PRBM.S508610. eCollection 2025.ABSTRACTBACKGROUND: Major depressive disorder (MDD) leads to significant distress and disruption across social, occupational, and other functional domains. Although cerebrospinal fluid (CSF) biomarkers have been identified as potential indicators and therapeutic targets for depression, their causal relationship with MDD remains unclear.METHODS: We analyzed publicly available CSF metabolomics and genotype data, quantifying 338 distinct metabolites. Among these, 296 were chemically validated and classified into eight major metabolic groups, while 38 remained undefined. To assess the genetic association with depression, we used summary statistics from a GWAS (F5_DEPRESSIO dataset, including 53,313 diagnosed cases and 394,756 controls from Finland). An integrated approach combining Mendelian randomization (MR), inverse variance weighting (IVW), and linkage disequilibrium score regression (LDSC) was applied to explore the causal impact of CSF metabolites on depression risk.RESULTS: Our analysis identified 62 metabolites significantly associated with depression (p < 0.05). Sensitivity tests revealed heterogeneity in five metabolites: 5-hydroxyindoleacetic acid, X-19438, ethylmalonic acid, γ-glutamylglutamine, and β-alanine. A focused analysis on 14 metabolites further supported a potential causal link with depression. LDSC confirmed significant genetic heritability for metabolites such as creatinine, arginine succinate, N-acetylisourea, 3-amino-2-piperidone, and carboxyethyl-GABA. Systematic leave-one-out analyses demonstrated that these associations are driven by multiple interacting SNPs rather than a single variant.CONCLUSION: This study provides novel insights into the potential causal relationship between CSF metabolites and depression, highlighting 14 key metabolites with significant associations. The robustness of these findings is supported by MR and sensitivity analyses. Further longitudinal studies are warranted to confirm the clinical relevance of these CSF biomarkers in MDD.PMID:40352659 | PMC:PMC12063630 | DOI:10.2147/PRBM.S508610

RSC Adv. 2025 May 9;15(19):15240-15251. doi: 10.1039/d4ra08652j. eCollection 2025 May 6.ABSTRACTNatural products (NP) have proven to be a rich source of potentially bioactive compounds, and metabolomics is the current method of choice for characterizing natural extracts. To integrate the vast amount of data and information produced by modern metabolomics workflows, we recently developed a sample-centric approach for the semantic enrichment and alignment of metabolomics datasets. The resulting Experimental Natural Products Knowledge Graph (ENPKG) is queryable and integrates both newly acquired digitalized experimental data and information, and previously reported knowledge. It allows the highlighting of putative bioactive compounds at the extract level by comparing, for example, the occurrence of compounds of a given chemical class with bioactivity results. Using this approach, we recently described potent anti-Trypanosoma cruzi activity of two rotenoids, deguelin and rotenone. These compounds were identified in six active extracts from four plant species: Cnestis palala (Connaraceae), Chadsia grevei, Pachyrhizus erosus, and Desmodium heterophylum (Fabaceae). In this work, we present the results of the phytochemical investigation of four of these extracts and the establishment of a library of structural analogs for in vitro bioactivity testing. This work led to the isolation, characterization, and biological evaluation of the anti-T. cruzi potential of 41 compounds, including 11 rotenoids and seven compounds reported for the first time. Thanks to modern metabolite annotation and single-step isolation procedures, this work also demonstrates the possibility of considering natural extract libraries as a reservoir of rapidly accessible pure NPs. This perspective could increase the options for NP research and help accelerate NP drug discovery efforts.PMID:40352392 | PMC:PMC12062876 | DOI:10.1039/d4ra08652j

Hortic Res. 2025 Mar 18;12(7):uhaf091. doi: 10.1093/hr/uhaf091. eCollection 2025 Jul.ABSTRACTFood legume crops, including common bean, faba bean, mungbean, cowpea, chickpea, and pea, have long served as vital sources of energy, protein, and minerals worldwide, both as grains and vegetables. Advancements in high-throughput phenotyping, next-generation sequencing, transcriptomics, proteomics, and metabolomics have significantly expanded genomic resources for food legumes, ushering research into the panomics era. Despite their nutritional and agronomic importance, food legumes still face constraints in yield potential and genetic improvement due to limited genomic resources, complex inheritance patterns, and insufficient exploration of key traits, such as quality and stress resistance. This highlights the need for continued efforts to comprehensively dissect the phenome, genome, and regulome of these crops. This review summarizes recent advances in technological innovations and multi-omics applications in food legumes research and improvement. Given the critical role of germplasm resources and the challenges in applying phenomics to food legumes-such as complex trait architecture and limited standardized methodologies-we first address these foundational areas. We then discuss recent gene discoveries associated with yield stability, seed composition, and stress tolerance and their potential as breeding targets. Considering the growing role of genetic engineering, we provide an update on gene-editing applications in legumes, particularly CRISPR-based approaches for trait enhancement. We advocate for integrating chemical and biochemical signatures of cells ('molecular phenomics') with genetic mapping to accelerate gene discovery. We anticipate that combining panomics approaches with advanced breeding technologies will accelerate genetic gains in food legumes, enhancing their productivity, resilience, and contribution to sustainable global food security.PMID:40352287 | PMC:PMC12064956 | DOI:10.1093/hr/uhaf091