PubMed

Biomedicines. 2025 Mar 18;13(3):742. doi: 10.3390/biomedicines13030742.ABSTRACTBackground/Objectives: Particulate matter (PM) is a primary health hazard associated with metabolic pathway disruption. Population characteristics, topography, sources, and PM components contribute to health impacts. Methods: In this study, NMR-based metabolomics was used to evaluate the health impacts of prolonged exposure to PM. Blood samples (n = 197) were collected from healthy volunteers in low- (control; CG) and high-exposure areas (exposure; EG) in Northern Thailand. Non-targeted metabolite analysis was performed using proton nuclear magnetic resonance spectroscopy (1H-NMR). Results: Compared to CG, EG showed significantly increased levels of dopamine, N6-methyladenosine, 3-hydroxyproline, 5-carboxylcytosine, and cytidine (p < 0.05), while biopterin, adenosine, L-Histidine, epinephrine, and norepinephrine were significantly higher in CG (p < 0.05). These metabolic disturbances suggest that chronic exposure to particulate matter (PM) impairs energy and amino acid metabolism while enhancing oxidative stress, potentially contributing to the onset of non-communicable diseases (NCDs) such as cancer and neurodegenerative conditions. Conclusions: This study highlighted the connection between sub-chronic PM2.5 exposure, metabolic disturbances, and an increased risk of non-communicable diseases (NCDs), stressing the critical need for effective PM2.5 reduction strategies in Northern Thailand.PMID:40149718 | DOI:10.3390/biomedicines13030742

Biomedicines. 2025 Mar 13;13(3):707. doi: 10.3390/biomedicines13030707.ABSTRACTBackgroung/objectives: Diffuse large B-cell lymphoma (DLBCL) is the most frequent subtype of malignant lymphoma and is a heterogeneous disease with various gene and chromosomal abnormalities. The development of novel therapeutic treatments has improved DLBCL prognosis, but patients with early relapse or refractory disease have a poor outcome (with a mortality of around 40%). Metabolic reprogramming is a hallmark of cancer cells. Fatty acid (FA) metabolism is frequently altered in cancer cells and recently emerged as a critical survival path for cancer cell survival. Methods: We first performed the metabolic characterization of an extended panel of DLBCL cell lines, including lipid droplet content. Then, we investigated the effect of drugs targeting FA metabolism on DLBCL cell survival. Further, we studied how the combination of drugs targeting FA and either mitochondrial metabolism or mTOR pathway impacts on DLBCL cell death. Results: Here, we reveal, using a large panel of DLBCL cell lines characterized by their metabolic status, that targeting of FA metabolism induces massive DLBCL cell death regardless of their OxPhos or BCR/glycolytic subtype. Further, FA drives resistance of DLBCL cell death induced by mitochondrial stress upon treatment with either metformin or L-asparaginase, two FDA-approved antimetabolic drugs. Interestingly, combining inhibition of FA metabolism with that of the mTOR oncogenic pathway strongly potentiates DLBCL cell death. Conclusion: Altogether, our data highlight the central role played by FA metabolism in DLBCL cell survival, independently of their metabolic subtype, and provide the framework for the use of drugs targeting this metabolic vulnerability to overcome resistance in DLBCL patients.PMID:40149683 | DOI:10.3390/biomedicines13030707

Biomedicines. 2025 Mar 11;13(3):685. doi: 10.3390/biomedicines13030685.ABSTRACTBackground/Objectives: First-line uterotonics include carbetocin and oxytocin, which act on the oxytocin receptor with varying potencies. Methods: In 70 pregnant Caucasian women who delivered by cesarean section, the effects of oxytocin and carbetocin on heart rate and blood pressure were compared. The pregnant women were divided into two groups: the OXY group, which received intravenous oxytocin 5 IU on an even day of the month, and the CARBE group, which received intravenous carbetocin 100 µg on an odd day of the month. Blood pressure and heart rate were measured noninvasively every 3 min from the beginning of cesarean section until the lower uterine incision, and then at 1, 2, and 3 min after the fetus and placenta were removed and the uterotonic drugs were discontinued. Subsequent measurements were taken at 3 min intervals until the end of the cesarean procedure. Results: After the administration of uterotonic drugs, a significant decrease in systolic blood pressure was observed only in the group receiving oxytocin at the first (p < 0.0001) and second minute after drug administration (p < 0.0001). Diastolic arterial pressure was significantly different in the study groups at the sixth minute after oxytocin and carbetocin administration (p = 0.004). Mean arterial pressure values were significantly different in the two study groups at the first and sixth minute after drug administration (p = 0.006; p = 0.014). With regard to heart rate, significant differences between the groups were found at 6 min after uterotonic drug administration (p = 0.019). Conclusions: Blood pressure and heart rate variability are significantly higher after oxytocin than after carbetocin administration in women delivering by cesarean section.PMID:40149661 | DOI:10.3390/biomedicines13030685

Biomedicines. 2025 Mar 10;13(3):675. doi: 10.3390/biomedicines13030675.ABSTRACTBackground/Objectives: The pathogenesis of diabetic kidney disease (DKD) is complex and multifactorial. Because of its complications and reduced number of diagnostic biomarkers, it is important to explore new biomarkers with possible roles in the early diagnosis of DKD. Our study aims to investigate the pattern of previously identified metabolites and their association with biomarkers of endothelial dysfunction, proximal tubule (PT) dysfunction, and podocyte injury. Methods: A total of 110 participants, comprising 20 healthy individuals and 90 patients divided in three groups were enrolled in the study: normoalbuminuria, microalbuminuria, and macroalbuminuria. Untargeted and targeted metabolomic methods were employed to assess urinary and serum biomarkers, as well as indicators of endothelial dysfunction, podocyte damage, and PT dysfunction through ELISA techniques. Results: Our research uncovered specific metabolites that exhibit varying levels across different sub-groups. Notably, glycine serves as a distinguishing factor between group C and the normoalbuminuric group. Furthermore, glycine is correlated with endothelial markers, especially VCAM. We observed a gradual decrease in kynurenic acid levels from group C to group P3; this biomarker also demonstrates an inverse relationship with both p-selectin and VCAM. Additionally, tryptophan levels decline progressively from group C to group P3, accompanied by a negative correlation with p-selectin and VCAM. Urinary tiglylglycine also differentiates among the patient groups, with concentrations decreasing as the condition worsens. It shows a strong positive correlation with nephrin, podocalyxin, KIM1, and NAG. Conclusions: In conclusion, glycine, tiglylglycine, kynurenic acid and tryptophan may be considered putative biomarkers for early diagnosis of DKD and T2DM progression.PMID:40149650 | DOI:10.3390/biomedicines13030675

Biomedicines. 2025 Mar 6;13(3):643. doi: 10.3390/biomedicines13030643.ABSTRACTBackground/Objectives: Cardiovascular disease (CVD) remains the leading cause of death worldwide and requires a deeper understanding of its pathogenesis for effective prevention and treatment. Familial hypercholesterolemia (FH), characterized by high levels of LDL cholesterol, is a significant risk factor for CVD. FH background remains unexplained despite advances in genetic testing. The aim was identification early changes in the plasma lipidome of individuals at high cardiovascular risk (HCVR) using liquid chromatography coupled with mass spectrometry. Methods: The lipidomic analysis examined over 400 compounds. Twenty individuals with suspected FH, very high cardiovascular risk (VHCVR), and undetectable mutations in the LDLR, APOB, or PCSK9 genes were compared to control group in a qualitative-quantitative analysis. Results: Multivariate analyses revealed statistically significant alterations in glycerophospholipids (GC), with a notable increase in phosphatidylcholines ((O-36:0/16:0), OR (95% CI): 1.246 (1.042-1.490), p = 0.0157), phosphatidylethanolamines ((O-40:7/22:6), OR (95% CI): 1.119 (1.039-1.205), p = 0.0028), and phosphatidylglycerol ((40:8/20:4), OR (95% CI): 1.053 (1.008-1.101), p = 0.0219) only in patients with HCVR. These changes, particularly in major classes of GC, underscored their potential as biomarkers for early assessment of cardiovascular risk. Lipidomic profiling revealed associations between specific lipid species and the comorbidities of arterial hypertension, atherosclerosis, and insulin resistance, implicating their role in atherosclerotic cardiovascular disease (ASCVD). Conclusions: This study points early changes in the plasma lipidome in individuals at HCVR, underline potential biomarkers, therapeutic targets for ASCVD, and offer opportunities to improve ASCVD diagnosis, therapy, and risk management strategies through detailed personalized medical approach.PMID:40149619 | DOI:10.3390/biomedicines13030643

Biomedicines. 2025 Mar 5;13(3):629. doi: 10.3390/biomedicines13030629.ABSTRACTBackground: Irritable Bowel Syndrome (IBS) is a complex disorder characterized by altered gut-brain interactions, with gastrointestinal microbiota and metabolic dysregulation playing key roles in its pathophysiology. Identifying specific metabolic alterations within the colonic mucosa may enhance our understanding of IBS and contribute to improved diagnostic and therapeutic approaches. Methods: This cross-sectional study analyzed the metabolomic profiles of colonic mucosal biopsies from 44 IBS patients assessed with ROME IV criteria and 69 healthy controls undergoing colonoscopy. Untargeted metabolomic profiling was conducted using liquid chromatography-mass spectrometry (LC-MS), and differential metabolite analysis was performed via fold-change calculations and machine learning-based classification. Results: IBS patients exhibited distinct mucosal metabolic profiles, with significantly elevated levels of N-acetylneuraminic acid and 1-palmitoylglycerol, suggesting compromised epithelial integrity and increased gut permeability. In contrast, cis-4-hydroxycyclohexanecarboxylic acid, a metabolite associated with protective mucosal functions, was reduced. Random Forest analysis identified these metabolites as key discriminatory features between IBS and control groups, reinforcing their potential role as biomarkers for IBS-related mucosal alterations. Conclusions: Our study highlights the unique metabolomic signatures of IBS at the mucosal level, emphasizing the role of microbial metabolites in disease pathology. These findings may facilitate the development of novel diagnostic tools and targeted therapeutic strategies, advancing personalized management for IBS patients.PMID:40149605 | DOI:10.3390/biomedicines13030629

Biomedicines. 2025 Feb 27;13(3):588. doi: 10.3390/biomedicines13030588.ABSTRACTBackground/Objectives: Temporal lobe epilepsy (TLE) often develops following an initial brain injury, where specific triggers lead to epileptogenesis-a process transforming a healthy brain into one prone to spontaneous, recurrent seizures. Although electroencephalography (EEG) remains the primary diagnostic tool for epilepsy, it cannot predict the risk of epilepsy after brain injury. This limitation highlights the need for biomarkers, particularly those measurable in peripheral samples, to assess epilepsy risk. This study investigated urinary metabolites in a rat model of TLE to identify biomarkers that track epileptogenesis progression across the acute, latent, and chronic phases and elucidate the underlying mechanisms. Methods: Status epilepticus (SE) was induced in rats using repeated intraperitoneal injections of lithium chloride-pilocarpine hydrochloride. Urine samples were collected 48 h, 1 week, and 6 weeks after SE induction. Nuclear magnetic resonance spectrometry was used for metabolomic analysis, and statistical evaluations were performed using MetaboAnalyst 6.0. Differences between epileptic and control groups were represented using the orthogonal partial least squares discriminant analysis (OPLS-DA) model. Volcano plot analysis identified key metabolic changes, applying a fold-change threshold of 1.5 and a p-value < 0.05. Results: The acute phase exhibited elevated levels of acetic acid, dihydrothymine, thymol, and trimethylamine, whereas glycolysis and tricarboxylic acid cycle metabolites, including pyruvic and citric acids, were reduced. Both the acute and latent phases showed decreased theobromine, taurine, and allantoin levels, with elevated 1-methylhistidine in the latent phase. The chronic phase exhibited reductions in pimelic acid, tiglylglycine, D-lactose, and xanthurenic acid levels. Conclusions: These findings highlight stage-specific urinary metabolic changes in TLE, suggesting distinct metabolites as biomarkers for epileptogenesis and offering insights into the mechanisms underlying SE progression.PMID:40149565 | DOI:10.3390/biomedicines13030588

Genes (Basel). 2025 Mar 11;16(3):328. doi: 10.3390/genes16030328.ABSTRACTSaussurea involucrata, an endangered medicinal plant, thrives in high mountain regions at altitudes ranging from 3500 to 5000 m. Being a plant that grows at high altitudes means it possesses unique physiological mechanisms and stress-responsive genes that regulate and adapt to the high-altitude environment. While many cold-resistant genes have been cloned and their mechanisms studied, the genes and molecular mechanisms involved in adaptation to hypobaric hypoxia remain largely unexplored. This study conducted transcriptomic and metabolomic analyses on the leaves of S. involucrata under normal atmosphere (101 kPa) and low pressure (60 kPa). A total of 2383 differentially expressed genes (DEGs) and 336 differentially accumulated metabolites (DAMs) were identified utilizing RNA-seq and UPLS-MS techniques. The results indicated that S. involucrata exhibits responses to hypobaric hypoxia environments by engaging in DNA repair, membrane transport, hypoxic response, reproductive processes, and various metabolic activities associated with nutrient uptake and the effective utilization of chemical components. It is worth noting that under low-pressure treatment, flavonoids are predominantly negatively regulated, whereas terpenoids are primarily positively regulated. These findings identify key genes and metabolites in S. involucrata that respond to hypobaric hypoxia treatment, providing a theoretical basis for the development of its medicinal value and for low-altitude cultivation.PMID:40149479 | DOI:10.3390/genes16030328

Genes (Basel). 2025 Mar 3;16(3):305. doi: 10.3390/genes16030305.ABSTRACTBACKGROUND: Metabolic dysfunction is a key driver of heart failure (HF) progression. Identifying metabolic hub genes in HF may reveal novel therapeutic targets.METHODS: Transcriptomic datasets from HF patients (GEO database) and metabolism-related genes (PathCards) were analyzed. Differentially expressed genes (DEGs) were intersected with metabolism-related genes, followed by the application of the LASSO, Random Forest, and XGBoost algorithms to prioritize hub genes. Candidate genes were validated via WGCNA, an HF mouse model, and plasma metabolomics. Diagnostic performance and metabolic associations were assessed using ROC analysis and ssGSEA.RESULTS: We identified 1115 HF-associated DEGs (701 upregulated, 414 downregulated), with 119 linked to metabolism. The machine learning algorithms prioritized five genes, including SDC2, which was also validated using WGCNA and the mouse HF model. SDC2 mRNA and protein expression levels were markedly elevated in HF and demonstrated strong diagnostic accuracy. ssGSEA revealed the expression of SDC2 was correlated with dysregulated metabolic pathways, including fatty acid biosynthesis and glycerolipid metabolism, which are potentially associated with metabolic alterations in HF.CONCLUSIONS: SDC2 emerges as a central regulator bridging metabolic dysfunction and HF pathogenesis, showing potential as a diagnostic biomarker and therapeutic target.PMID:40149456 | DOI:10.3390/genes16030305

Genes (Basel). 2025 Feb 28;16(3):300. doi: 10.3390/genes16030300.ABSTRACTIn peanut cultivation, fertility and seed development are essential for fruit quality and yield, while pod number per plant, seed number per pod, kernel weight, and seed size are indicators of peanut yield. In this study, metabolomic and RNA-seq analyses were conducted on the flowers and aerial pegs (aerpegs) of two peanut cultivars JNH3 (Jinonghei) and SLH (Silihong), respectively. Compared with SLH, JNH3 had 3840 up-regulated flower-specific differentially expressed genes (DEGs) and 5890 up-regulated aerpeg-specific DEGs. Compared with the JNH3 aerpegs, there were 4079 up-regulated variety-specific DEGs and 18 up-regulated differentially accumulated metabolites (DAMs) of JNH3 flowers, while there were 3732 up-regulated variety-specific DEGs and 48 up-regulated DAMs in SLH flowers. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the DEGs of JNH3 were associated with pollen germination and phenylalanine metabolism in flower and aerpeg tissues, respectively. In contrast, the DEGs of SLH were associated with protein degradation, amino acid metabolism, and DNA repair. However, there were significant differences in the lipids and lipid-like molecules between JNH3 flowers and SLH flowers. This investigation provides candidate genes and an experimental basis for the further improvement of high-quality and high-yield peanut varieties.PMID:40149451 | DOI:10.3390/genes16030300

Genes (Basel). 2025 Feb 27;16(3):287. doi: 10.3390/genes16030287.ABSTRACTBackground: With global warming and climate change, the occurrence of abiotic stresses has become increasingly prevalent. Drought often occurs with high temperatures, especially in arid and semi-arid regions. However, the molecular mechanisms of plants responding to combined drought and high-temperature stress remains unclear. Results: Through integrative physiological, transcriptomic, and metabolomic analyses, we systematically investigated the adaptive mechanisms of Dendrobium huoshanense under combined drought and high-temperature stress. Our findings revealed that combined drought and high-temperature stress led to significant reductions in photosynthetic efficiency and increased oxidative damage in Dendrobium huoshanense, with high-temperature stress being the primary contributor to these adverse effects. The joint analysis shows that three core pathways-signal transduction, lipid metabolism, and secondary metabolite biosynthesis-were identified as critical for antioxidant defense and stress adaptation. Conclusions: These findings not only deepen our understanding of plant responses to combined drought and high-temperature stress but also provide new directions for future research on the cultivation and resistance improvement of Dendrobium huoshanense.PMID:40149439 | DOI:10.3390/genes16030287

Genes (Basel). 2025 Feb 24;16(3):264. doi: 10.3390/genes16030264.ABSTRACTBACKGROUND: Dendrobium devonianum is a traditional Chinese medicinal herb with notable ornamental and medicinal value.METHODS: In this study, transcriptomic and metabolomic approaches were employed to investigate gene expression and secondary metabolite changes during four developmental stages of D. devonianum flowers.RESULTS: Metabolomic analysis identified 1186 distinct metabolites, with flavonoid compounds being the most abundant category (213 types). Transcriptomic analysis revealed 31 differentially expressed genes associated with flavonoid biosynthesis and flavonoid and flavonol biosynthesis pathways. Among these, key genes regulating flavonol synthesis, including F3H (Unigene0077194) and FLS (Unigene0062137), exhibited high expression levels in the early developmental stage (S1).CONCLUSIONS: Flavonoids serve as the major active components in D. devonianum flowers, exhibiting a wide range of pharmacological properties. This study provides valuable insights into the molecular mechanisms driving flavonoid accumulation in D. devonianum, offering a foundation for further functional studies and applications in ornamental and medicinal plant research.PMID:40149416 | DOI:10.3390/genes16030264

Cancers (Basel). 2025 Mar 18;17(6):1017. doi: 10.3390/cancers17061017.ABSTRACTThyroid cancer is a very common endocrine system malignancy. Nevertheless, a dearth of precise markers makes it challenging to apply precision medicine to thyroid cancer. The limitations of standard diagnosis techniques (fine-needle aspiration biopsy), such as indeterminate cases and inaccuracies in distinguishing between different types of cancers, lead to unnecessary surgeries and thus warrant the development of more discriminatory biomarkers to improve the accuracy of existing diagnostic and prognostic techniques. Moreover, individualized therapies for thyroid cancer are necessary to avoid overtreatment of indolent lesions and undertreatment of high-risk progressive disease. As thyroid cancer metabolic signatures are associated with disease aggressiveness and responsiveness to therapy, metabolomics has been recently used for diagnostic and prognostic biomarker discovery. This strategy has enabled the detection of several metabolites from tissue samples or biofluids to facilitate the classification of disease aggressiveness and to potentially assist in individualized therapies. In this review, we summarize the utilization and potential of metabolomics in thyroid cancer.PMID:40149351 | DOI:10.3390/cancers17061017

BMC Bioinformatics. 2025 Mar 27;26(1):93. doi: 10.1186/s12859-025-06110-7.ABSTRACTBACKGROUND: Understanding the metabolic activities of the gut microbiome is vital for deciphering its impact on human health. While direct measurement of these metabolites through metabolomics is effective, it is often expensive and time-consuming. In contrast, microbial composition data obtained through sequencing is more accessible, making it a promising resource for predicting metabolite profiles. However, current computational models frequently face challenges related to limited prediction accuracy, generalizability, and interpretability.METHOD: Here, we present the Deep Mixture of Variational Gaussian Process Experts (DMoVGPE) model, designed to overcome these issues. DMoVGPE utilizes a dynamic gating mechanism, implemented through a neural network with fully connected layers and dropout for regularization, to select the most relevant Gaussian Process experts. During training, the gating network refines expert selection, dynamically adjusting their contribution based on the input features. The model also incorporates an Automatic Relevance Determination (ARD) mechanism, which assigns relevance scores to microbial features by evaluating their predictive power. Features linked to metabolite profiles are given smaller length scales to increase their influence, while irrelevant features are down-weighted through larger length scales, improving both prediction accuracy and interpretability.CONCLUSIONS: Through extensive evaluations on various datasets, DMoVGPE consistently achieves higher prediction performance than existing models. Furthermore, our model reveals significant associations between specific microbial taxa and metabolites, aligning well with findings from existing studies. These results highlight DMoVGPE's potential to provide accurate predictions and to uncover biologically meaningful relationships, paving the way for its application in disease research and personalized healthcare strategies.PMID:40148806 | DOI:10.1186/s12859-025-06110-7

BMC Genomics. 2025 Mar 28;26(1):303. doi: 10.1186/s12864-025-11492-2.ABSTRACTBACKGROUND: The hypothalamus is a critical organ that regulates sexual development in animals. However, current research on the hypothalamic regulation of sexual maturation in female goats remains limited. In this study, we conducted metabolomic and transcriptomic analyses on the hypothalamic tissues of female Jining grey goats at different stages of sexual development (1 day old (neonatal, D1, n = 5), 2 months old (prepuberty, M2, n = 5), 4 months old (sexual maturity, M4, n = 5), and 6 months old (breeding period, M6, n = 5)).RESULTS: A total of 418 differential metabolites (DAMs) were identified in this study, among which the abundance of metabolites such as anserine, L-histidine, carnosine, taurine, and 4-aminobutyric gradually increased with the progression of sexual development. These metabolites may regulate neuronal development and hormone secretion processes by influencing the metabolism of histidine and phenylalanine. Through combined transcriptomic and metabolomic analyses, we identified that differentially expressed genes such as mitogen-activated protein kinase kinase kinase 9 (MAP3K9), prune homolog 2 with BCH domain (PRUNE2), and potassium voltage-gated channel interacting protein 4(KCNIP4) may jointly regulate the development and energy metabolism of hypothalamic Gonadotropin-releasing hormone neurons in conjunction with DAMs, including LPC22:5, 2-Arachidonyl Glycerol ether, LPE22:5, and Lysops22:5. Additionally, we elucidated the molecular mechanism through which glutathione metabolism regulates sexual maturation in goats.CONCLUSIONS: In summary, this study illustrates the dynamic changes in metabolites and mRNA within hypothalamic tissue during postnatal sexual maturation in female Jining grey goats. This research may provide significant scientific insights for future animal breeding.PMID:40148778 | DOI:10.1186/s12864-025-11492-2

BMC Plant Biol. 2025 Mar 27;25(1):391. doi: 10.1186/s12870-025-06414-z.ABSTRACTBACKGROUND: The 'Yinhongli' cultivar of Chinese plum (Prunus salicina Lindl.) is characterized by a distinctive bicolored peel phenotype, in which anthocyanins serve as crucial determinants of both its visual characteristics and nutritional quality. However, the molecular mechanism of underlying light-dependent anthocyanin biosynthesis of plum, especially its regulatory network and pathway, need to be further studied and explored.RESULTS: Comprehensive physiological analyses demonstrated distinct pigmentation patterns, revealing that dark-treated (YD) plum peels retained green coloration, whereas light-exposed (YL) and bag-removed samples (YDL) exhibited red pigmentation. Utilizing an integrated approach combining metabolomic and transcriptomic analyses, we identified 266 differentially accumulated flavonoids (DAFs), among which seven anthocyanin metabolites were established as principal determinants of peel coloration. Transcriptomic profiling revealed 6,900 differentially expressed genes (DEGs) between YD and YL, demonstrating significant correlations between the phenylpropanoid and flavonoid biosynthetic pathways. Through Weighted Gene Co-expression Network Analysis (WGCNA) and correlation heatmap analysis, we identified crucial regulatory networks encompassing five structural genes (PAL, 4CL, F3'H, CHI, and UFGT) and 15 candidate regulatory genes, including six light signal transduction factor genes (UVR8, COP1, PHYBs, PIF3, and HY5) and nine transcription factor genes (MYB1, MYB20, MYB73, MYB111, LHY, DRE2B, ERF5, bHLH35, and NAC87). Subsequent RT-qPCR validation demonstrated significant light-mediated up-regulation of key structural genes (PAL, F3H, CHI, 4CL, and UFGT) involved in anthocyanin biosynthesis along with positive regulatory factors (DRE2B and NAC87). Conversely, a cohort of negative regulators, including HY5, MYB1, MYB20, MYB73, MYB111, LHY, ERF5, and bHLH35, showed marked down-regulation in response to light exposure, suggesting their potential repressive roles in the light-dependent anthocyanin biosynthesis pathway.CONCLUSIONS: This investigation provides comprehensive insights into the molecular mechanisms of anthocyanin biosynthesis in light-dependent anthocyanin biosynthesis in 'Yinhongli' plum, identifying critical structural genes and potential regulatory TFs. The findings offer substantial contributions to the understanding of anthocyanin regulation in fruit crops and provide a valuable foundation for molecular breeding initiatives aimed at enhancing quality traits in plum cultivars.PMID:40148754 | DOI:10.1186/s12870-025-06414-z

Mol Biotechnol. 2025 Mar 27. doi: 10.1007/s12033-025-01426-4. Online ahead of print.ABSTRACTTransgenesis, the introduction of foreign genetic material into the genome of an organism, has become a crucial and transformative technique in the realm of drug discovery. This review article provides a comprehensive overview of the integral role that transgenesis plays in the drug discovery process, with a specific focus on target identification and target validation. By examining the recent advancements and innovative approaches, this article aims to shed light on the importance of transgenesis in accelerating drug development. In the context of target identification, transgenesis has allowed for the creation of relevant disease models, enabling researchers to study the genetic and molecular basis of various disorders. The use of transgenic animals, such as mice and zebrafish, has facilitated the identification of potential drug targets by mimicking specific human disease conditions. This review also discusses emerging technologies, such as CRISPR-Cas9 and other genome editing tools, which have revolutionized the field of transgenesis. These technologies have enhanced the precision and efficiency of genetic manipulations in transgenic animals, making the creation of disease-relevant models more accessible and cost-effective. Moreover, integration of omics technologies, such as genomics, transcriptomics, proteomics, and metabolomics, has provided a holistic view of the molecular changes in transgenic models, further aiding in target identification and validation. This review emphasizes the importance of transgenesis in target identification and validation and underscores its vital role in shaping the future of drug discovery.PMID:40148722 | DOI:10.1007/s12033-025-01426-4

EMBO Rep. 2025 Mar 27. doi: 10.1038/s44319-025-00425-5. Online ahead of print.ABSTRACTGlioblastoma multiforme (GBM) is the most lethal form of malignant brain tumor in adults. Dysregulation of protein synthesis contributes to cancer cell plasticity, driving GBM cell heterogeneity, metastatic behavior, and drug resistance. Understanding the complex network and signaling pathways governing protein translation, is therefore an important goal for GBM treatment. Here we identify a novel signaling network centered on the E3 ubiquitin ligase praja2 that controls protein translation in GBM. Praja2 forms a multimeric complex with the RNA helicase DDX6, which inhibits translation of target RNAs within processing bodies (P-bodies). Stimulation of cAMP signaling through activation of G-protein-coupled receptors induces P-body assembly through praja2-mediated non-proteolytic polyubiquitylation of DDX6. Genetic inactivation of praja2 reshapes DDX6/mRNA complexes and translating polysomes and promotes cellular senescence and GBM growth arrest. Expression of an ubiquitylation-defective DDX6 mutant suppresses the assembly of P-bodies and sustains GBM growth. Taken together, our findings identify a cAMP-driven network that controls translation in P-bodies and GBM growth.PMID:40148504 | DOI:10.1038/s44319-025-00425-5

Sci Rep. 2025 Mar 28;15(1):10666. doi: 10.1038/s41598-025-92322-z.ABSTRACTThe B115 strain, isolated from the inter-root soil of healthy plants in a continuous cropping site of Panax notoginseng, was identified as Bacillus velezensis B115 by 16S rDNA sequence comparison and comparative genomic analysis. B115 is a strain of beneficial microorganisms present in the inter-root zone of plants, with favorable plant growth-promoting properties and antagonistic effects against the plant pathogen Fusarium oxysporum. However, the whole genome of B115 remains unclear, thus restricting its potential applications. To address this gap, the whole genome of B115 has been sequenced and annotated to elucidate the molecular mechanisms underlying its plant growth-promoting and antimicrobial activities. The genome analysis revealed that B115 comprises a single circular chromosome of 4,200,774 bp and a plasmid region 16,878 bp long, possessing a GC content of 45.95%. Moreover, 4349 protein-coding genes were predicted. Notably, the B115 genome contains a substantial number of genes (103) involved in the biosynthesis, transport, and catabolism of secondary metabolites. Through genome mining, 13 BGCs and 540 genes encoding secondary metabolites with predicted roles were identified, including members of the surfactin and fengycin families. Utilizing LC-MS/MS technologies, 2318 metabolites were detected in the fermentation broth of B. velezensis B115, encompassing compounds such as Corynebactin, Gamabufotalin, Pracinostat, Indoleacetic acid, (8)-Gingerol, Luteolin, Liquiritigenin, and other metabolites with antimicrobial, growth-promoting, antioxidant, and antitumor properties. By exploring secondary metabolite-related genes and predicting potential secondary metabolites from the B115 genome based on the whole-genome sequence results, we further elucidate the genomic basis for its ability to promote plant growth and inhibit pathogen activity.PMID:40148367 | DOI:10.1038/s41598-025-92322-z

Physiol Plant. 2025 Mar-Apr;177(2):e70175. doi: 10.1111/ppl.70175.ABSTRACTNorway spruce and Scots pine show enhanced lignin synthesis under shade, along with differential expression of defense-related genes that render disease resilience. In general, phenylalanine (Phe) is the precursor for lignin synthesis in plants, and tyrosine (Tyr) forms an additional lignin precursor specifically in grasses. Phenylalanine ammonia-lyase (PAL) and tyrosine ammonia-lyase (TAL) from the lignin biosynthesis pathway use either Phe or Tyr as precursors for lignin production, respectively. Grasses possess a bifunctional phenylalanine/tyrosine ammonia-lyase (PTAL) that potentially can use both Phe and Tyr for lignin biosynthesis. Metabolomic profiles of seedlings revealed higher levels of Phe and Tyr under shade in Scots pine, while Norway spruce showed differential regulation of only Tyr under shade. Sequence analysis and phylogeny of PAL homologs in the two conifers, coupled with correlation of up-regulation of precursors for lignin synthesis (Phe/Tyr) and enhanced lignin synthesis along with differential expression of PAL homologs under shade, suggest the potential presence of a bifunctional ammonia-lyases (BAL) in conifers. This finding is novel and comparable to PTALs in grasses. Exome sequence analysis revealed a latitudinal variation in allele frequencies of SNPs from coding regions of putative PAL and BAL in Norway spruce, which may impact enzyme activity affecting lignin synthesis. Metabolomic analysis additionally identified metabolites involved in plant immunity, defense and stress response.PMID:40148258 | DOI:10.1111/ppl.70175