PubMed

Recent Pat Biotechnol. 2025 Jan 20. doi: 10.2174/0118722083359334250116063638. Online ahead of print.ABSTRACTPersonalized medicine is an evolving paradigm that aims to tailor therapeutic interventions to individual patient characteristics. With a growing understanding of the genetic, epigenetic, and molecular mechanisms underlying diseases, tailored therapies are becoming more feasible and effective. This review highlights the significant advancements in personalized medicine, focusing specifically on pharmacological strategies. The article explores the integration of genomics, transcriptomics, proteomics, and metabolomics in drug development and therapy optimization. Pharmacogenomics, the customization of drug therapy based on an individual's genetic makeup, receives particular emphasis. This leads to the identification of specific biomarkers that can predict therapeutic response, drug toxicity, and susceptibility to various diseases. Together with computational tools and artificial intelligence, these advancements contribute to tailored treatment plans for patients with conditions such as cancer, cardiovascular diseases, and neurological disorders. We also highlight the challenges and ethical considerations in implementing personalized medicine, such as data privacy, cost-effectiveness, and accessibility. We outline future prospects and ongoing research in this field, highlighting the importance of collaborative efforts between researchers, clinicians, pharmacists, and regulatory authorities.PMID:39838664 | DOI:10.2174/0118722083359334250116063638

Curr Pharm Biotechnol. 2025 Jan 20. doi: 10.2174/0113892010352725241226043912. Online ahead of print.ABSTRACTBreast cancer (BC) is a common malignant tumor. BC is serious and has a high mortality rate. The incidence of BC has increased in recent years. The incidence rate is higher in coastal cities than in inland areas and in urban areas than in rural areas. Affect the occurrence and development of BC, such as inflammation and immune response. One of the cutting- edge studies to gain insight into the pathogenesis of BC is through the gut microbiota (GM) influencing the health status of the human body. Advances in metabolomics analysis can provide a clearer picture of changes in the composition of GM. The composition and quantity of GM can affect the health of other parts of the body, and the disorder of GM can lead to the occurrence and aggravation of diseases in different parts of the body. This paper not only discusses the dual biological effects of GM on BC, the relationship between GM and its metabolites, and BC and its related mechanisms but also explores traditional treatments for BC as well as the treatment of BC through GM, providing theoretical support for the use of methods to regulate GM in the clinical study of BC.PMID:39838663 | DOI:10.2174/0113892010352725241226043912

J Physiol. 2025 Jan 21. doi: 10.1113/JP286772. Online ahead of print.ABSTRACTPatent foramen ovale (PFO), a cardiac anatomical anomaly inducing abnormal haemodynamics, leads to a paradoxical bypass of the pulmonary circulation. PFO closure might alleviate migraines; however, clinical evidence and basic experiments for the relationship are lacking. To explore the effect of PFO on migraine, 371 migraineurs finishing blood tests and contrast transthoracic echocardiography for the detection of PFO were prospectively included. Multivariate regression analysis revealed that PFO was independently associated with aura, and lower cystatin-C (cys-C) and calcium levels. Among them, patients with PFO who underwent percutaneous PFO closure were continuously followed up 1 year after the operation. The intensity of migraine was significantly relieved and the levels of cys-C and calcium increased after PFO closure. Untargeted and targeted metabolomics of plasma from migraineurs before and after PFO closure revealed that 5-HT and glutathione (GSH) metabolites were differentially expressed after PFO closure. The differential metabolites were then validated in the plasma and brain tissues of PFO mouse models by LC-MS/MS analysis. Desorption electrospray ionization mass imaging demonstrated that these metabolic alterations occurred mainly in the posterior cerebral cortex. Collectively, aura, cys-C and calcium could be biomarkers of migraineurs with PFO. PFO might have an impact on the posterior head associated with the regulation of 5-HT and GSH. PFO closure might relieve migraine by improving 5-HT clearance metabolism and ameliorating redox reactions. Our results may provide evidence for an indication of PFO closure in migraine and support the related potential mechanism. KEY POINTS: Aura, and levels of cystatin-C and calcium are biomarkers of migraineurs with a patent foramen ovale (PFO). The clearance of pulmonary metabolism of 5-HT and deoxygenated blood might be the reason for the improvement of migraine symptoms in patients with PFO. The posterior region of the brain is the main area responsible for PFO-induced migraine.PMID:39838589 | DOI:10.1113/JP286772

Cancer Metab. 2025 Jan 21;13(1):2. doi: 10.1186/s40170-024-00367-x.ABSTRACTBACKGROUND: Leptomeningeal metastasis (LM) is a devastating complication of cancer that is difficult to treat. Thus, early diagnosis is essential for LM patients. However, cerebrospinal fluid (CSF) cytology has low sensitivity, and imaging approaches are ineffective. We explored targeted CSF metabolic profiling to discriminate among LM and other conditions affecting the central nervous system (CNS).METHODS: We quantitatively measured amino acids, biogenic amines, hexoses, acylcarnitines (AC), cholesteryl esters (CE), glycerides, phosphatidylcholines (PC), lysophosphatidylcholines (LPC), sphingomyelins (SM), and ceramides (Cer) in 117 CSF samples from various groups of healthy controls (HC, n = 10), patients with LM (LM, n = 47), parenchymal brain tumor (PBT, n = 45), and inflammatory disease (ID, n = 13) with internal standards using the Absolute IDQ- p400® targeted mass spectrometry kit. Metabolites detected in > 90% of samples or showing a difference in proportional level between groups ≥ 75% were used in logistic regression models when there was no single metabolite with AUC = 1 for the groups of comparison.RESULTS: PC and SM had higher levels in LM than in PBT or HC, whereas LPC had lower level in PBT than the other groups. Glycerides and Cer levels were higher in PBT and LM than in HC. Long-chain AC level in PBT was lower than in LM or HC. A regression model including Ala, PC (42:7), PC (30:3), PC (37:0), and Tyr achieved complete discrimination (AUC = 1.0) between LM and HC. In comparison of PBT and HC, twenty-six individual metabolites allowed complete discrimination between two groups, and between ID and HC fourty-six individual lipid metabolites allowed complete discrimination. Twenty-one individual metabolites (18 ACs and 3 PCs) allowed complete discrimination between LM and PBT.CONCLUSIONS: Using a commercial targeted liquid chromatography-mass spectrometry (LC-MS) metabolomics kit, we were able to differentiate LM from HC and PBT. Most of the discriminative metabolites among different diseases were lipid metabolites, for which their CNS distribution and quantification in different cell types are largely unknown, whereas amino acids, biogenic amines, and hexoses failed to show significant differences. Future validation studies with larger, controlled cohorts should be performed, and hopefully, the kit may expand its metabolite coverage for unique cancer cell glucose metabolism.PMID:39838492 | DOI:10.1186/s40170-024-00367-x

Parasit Vectors. 2025 Jan 21;18(1):19. doi: 10.1186/s13071-025-06667-5.NO ABSTRACTPMID:39838472 | DOI:10.1186/s13071-025-06667-5

Sci Rep. 2025 Jan 22;15(1):2746. doi: 10.1038/s41598-025-87130-4.ABSTRACTNumerous studies have investigated the alterations of genes, proteins, and metabolites in Behcet's disease (BD). By far, little is known about the depiction of panoramic changes underlying this disease. This study purposed to assess the consistently dysregulated genes, proteins, and metabolites in BD across publications using the vote-counting approach. This study was based on 745 studies that identified a collection of 2354 differential molecules with 3574 molecule entries in blood, peripheral blood mononuclear cells, CD4+T cells, and aqueous humor samples from patients with BD. In this study, the results of binomial analysis showed that the circulating levels of 38 molecules, including interferon-γ and interleukin 17, were consistently upregulated, whereas high density lipoprotein cholesterol, apolipoprotein A, hemoglobin, and glutathione were consistently downregulated. The levels of interferon-γ, tumor necrosis factor-α and toll like receptor 4 in peripheral blood mononuclear cells, and interferon-γ and interleukin-17 in CD4+T cells were consistently upregulated. Additionally, the levels of interferon-γ, tumor necrosis factor-α and C-X-C motif chemokine ligand 8 in aqueous humor were consistently upregulated. Collectively, this study showed that the hyperactivity of Th1 and Th17 responses played an essential role in the pathogenesis of BD, and the progression of this disease was associated with enhanced neutrophil chemotaxis, vascular endothelial injury, activation of haemostatic system, and oxidative stress.PMID:39838177 | DOI:10.1038/s41598-025-87130-4

Commun Biol. 2025 Jan 21;8(1):103. doi: 10.1038/s42003-025-07548-4.ABSTRACTEnzymes play a pivotal role in orchestrating complex cellular responses to external stimuli and environmental changes through signal transduction pathways. Despite their crucial roles, measuring enzyme activities is typically indirect and performed on a smaller scale, unlike protein abundance measured by high-throughput proteomics. Moreover, it is challenging to derive the activity of enzymes from proteome-wide post-translational modification (PTM) profiling data. To address this challenge, we introduce enzyme activity inference with structural equation modeling under the JUMP umbrella (JUMPsem), a novel computational tool designed to infer enzyme activity using PTM profiling data. We demonstrate that the JUMPsem program enables estimating kinase activities using phosphoproteome data, ubiquitin E3 ligase activities from the ubiquitinome, and histone acetyltransferase (HAT) activities based on the acetylome. In addition, JUMPsem is capable of establishing novel enzyme-substrate relationships through searching motif sequences. JUMPsem outperforms widely used kinase activity tools, such as IKAP and KSEA, in terms of the number of kinases and the computational speed. The JUMPsem program is scalable and publicly available as an open-source R package and user-friendly web-based R/Shiny app. Collectively, JUMPsem provides an improved tool for inferring protein enzyme activities, potentially facilitating targeted drug development.PMID:39838083 | DOI:10.1038/s42003-025-07548-4

Acta Pharmacol Sin. 2025 Jan 21. doi: 10.1038/s41401-024-01465-8. Online ahead of print.ABSTRACTDysregulation of long non-coding RNAs (lncRNAs) is common in colorectal cancer liver metastasis (CRLM). Emerging evidence links lncRNAs to multiple stages of metastasis from initial migration to colonization of distant organs. In this study we investigated the role of lncRNAs in metabolic reprogramming during CRLM using patient-derived organoid (PDO) models. We established five pairs of PDOs from primary tumors and matched liver metastatic lesions, followed by microarray analysis. We found that USP3-AS1 was significantly upregulated in CRLM-derived PDOs compared to primary tumors. High level of USP3-AS1 was positively associated with postoperative liver metastasis and negatively correlated with the prognosis of colorectal cancer (CRC) patients. Overexpression of USP3-AS1 significantly enhanced both sphere formation efficiency and liver metastasis in PDOs. Gene set enrichment analysis revealed that USP3-AS1 upregulation significantly enriched glycolysis and MYC signaling pathways. Metabolomics analysis confirmed that USP3-AS1 promoted glycolysis in PDOs, whereas glycolysis inhibition partially attenuated the effects of USP3-AS1 overexpression on PDO growth and liver metastasis. We revealed that USP3-AS1 stabilized MYC via post-translational deubiquitination, thereby promoting glycolysis. We demonstrated that USP3-AS1 increased the stability of USP3 mRNA, resulting in higher USP3 protein expression. The elevated USP3 protein then interacted with MYC and promoted its stability by deubiquitination. The USP3-AS1-MYC-glycolysis regulatory axis modulated liver metastasis by promoting H3K18 lactylation and CDC27 expression in CRC. In conclusion, USP3-AS1 is a novel promoter of CRLM by inducing histone lactylation.PMID:39837984 | DOI:10.1038/s41401-024-01465-8

Signal Transduct Target Ther. 2025 Jan 22;10(1):27. doi: 10.1038/s41392-024-02119-1.ABSTRACTDry eye disease (DED) is a prevalent inflammatory condition significantly impacting quality of life, yet lacks effective pharmacological therapies. Herein, we proposed a novel approach to modulate the inflammation through metabolic remodeling, thus promoting dry eye recovery. Our study demonstrated that co-treatment with mesenchymal stem cells (MSCs) and thymosin beta-4 (Tβ4) yielded the best therapeutic outcome against dry eye, surpassing monotherapy outcomes. In situ metabolomics through matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) revealed increased glutamine levels in cornea following MSC + Tβ4 combined therapy. Inhibition of glutamine reversed the anti-inflammatory, anti-apoptotic, and homeostasis-preserving effects observed with combined therapy, highlighting the critical role of glutamine in dry eye therapy. Clinical cases and rodent model showed elevated expression of glutaminase (GLS1), an upstream enzyme in glutamine metabolism, following dry eye injury. Mechanistic studies indicated that overexpression and inhibition of GLS1 counteracted and enhanced, respectively, the anti-inflammatory effects of combined therapy, underscoring GLS1's pivotal role in regulating glutamine metabolism. Furthermore, single-cell sequencing revealed a distinct subset of pro-inflammatory and pro-fibrotic corneal epithelial cells in the dry eye model, while glutamine treatment downregulated those subclusters, thereby reducing their inflammatory cytokine secretion. In summary, glutamine effectively ameliorated inflammation and the occurrence of apoptosis by downregulating the pro-inflammatory and pro-fibrotic corneal epithelial cells subclusters and the related IκBα/NF-κB signaling. The present study suggests that glutamine metabolism plays a critical, previously unrecognized role in DED and proposes an attractive strategy to enhance glutamine metabolism by inhibiting the enzyme GLS1 and thus alleviating inflammation-driven DED progression.PMID:39837870 | DOI:10.1038/s41392-024-02119-1

J Biosci Bioeng. 2025 Jan 20:S1389-1723(24)00361-X. doi: 10.1016/j.jbiosc.2024.12.010. Online ahead of print.ABSTRACTIn modern Japanese soy sauce production, sealed outdoor fermentation tanks are used to ferment moromi with halotolerant starter cultures: the lactic acid bacterium Tetragenococcus halophilus and yeasts Wickerhamiella versatilis and Zygosaccharomyces rouxii. T. halophilus and W. versatilis are added in the early fermentation stage, while Z. rouxii is introduced about 1 month later to initiate alcoholic fermentation. Both W. versatilis and Z. rouxii contribute to the production of volatile organic compounds (VOC), with 4-ethylguaiacol (4-EG), uniquely produced by W. versatilis, being essential for the characteristic aroma of soy sauce. Prior metagenomic and metabolomic analyses indicated that 4-EG production occurs prior to Z. rouxii fermentation, though the increase in W. versatilis proportion follows it. Additional omics analysis of a production batch confirmed similar microbial and VOC dynamics, with no clear relationship between W. versatilis increase and 4-EG levels. To investigate this, a laboratory-scale experiment was conducted using filter-sterilized moromi supernatant as a medium, with staggered inoculations of the two yeasts. Viable cell density, 4-EG, and ethanol were measured as indicators of fermentation activity. Results showed that when W. versatilis was inoculated before Z. rouxii, 4-EG production commenced earlier, while W. versatilis cell density and ethanol production increased only after Z. rouxii fermentation began. Under these conditions, 4-EG and ethanol production were highest, suggesting that the presence rather than the increase of W. versatilis is crucial for 4-EG production. Consequently, the early addition of W. versatilis was considered an effective strategy to enhance 4-EG and VOC production in moromi.PMID:39837758 | DOI:10.1016/j.jbiosc.2024.12.010

Phytochem Anal. 2025 Jan 21. doi: 10.1002/pca.3488. Online ahead of print.ABSTRACTINTRODUCTION: The metabolome of plants is influenced by various factors, especially environmental, as the season in which they are grown. So, distinct varieties of the identical plant might show an increase or decrease in metabolites. The diversity of content of primary and secondary metabolites can also determine the variation in their biological properties. Due to the current occurrence of various fennel varieties, the crop can now be grown for the entire year.OBJECTIVE: This work used an integrated approach of LC/MS and NMR analysis to characterize the metabolome of fennel waste of different varieties by multivariate statistical analysis.METHODS: The extracts were investigated by NMR and LC/MS analysis to focus attention on the primary and secondary metabolites. Both LC-HRMS and NMR data were analyzed by principal component analysis (PCA).RESULTS: The 1H-NMR analysis led to the identification of 15 primary metabolites, such as amino acids, carbohydrates, and organic acid derivatives. The secondary metabolites identified by LC/MS analysis mainly belong to the phenolic, lipid, and fatty acid compounds classes.CONCLUSION: This integrated approach guarantees a precise and complete overview of the variations in the metabolic expression of the fennel varieties grown in different seasons.PMID:39837564 | DOI:10.1002/pca.3488

Cell Genom. 2025 Jan 15:100743. doi: 10.1016/j.xgen.2024.100743. Online ahead of print.ABSTRACTSerum metabolites are potential regulators for chronic diseases. To explore the genetic regulation of metabolites and their roles in chronic diseases, we quantified 2,759 serum metabolites and performed genome-wide association studies (GWASs) among Han Chinese individuals. We identified 184 study-wide significant (p < 1.81 × 10-11) metabolite quantitative trait loci (metaboQTLs), 88.59% (163) of which were novel. Notably, we identified Asian-ancestry-specific metaboQTLs, including the SNP rs2296651 for taurocholic acid and taurochenodesoxycholic acid. Leveraging the GWAS for 37 clinical traits from East Asians, Mendelian randomization analyses identified 906 potential causal relationships between metabolites and clinical traits, including 27 for type 2 diabetes and 38 for coronary artery disease. Integrating genetic regulation of the transcriptome and proteome revealed putative regulators of several metabolites. In summary, we depict a landscape of the genetic architecture of the serum metabolome among Han Chinese and provide insights into the role of serum metabolites in chronic diseases.PMID:39837327 | DOI:10.1016/j.xgen.2024.100743

Sci Total Environ. 2025 Jan 20;964:178409. doi: 10.1016/j.scitotenv.2025.178409. Online ahead of print.ABSTRACTAir pollution has been associated with a higher incidence of idiopathic pulmonary fibrosis (IPF), yet this metabolic mechanism remains unclear. 185,865 participants were included in the UK Biobank. We estimated air pollution exposure using the bilinear interpolation approach, including fine particle matter with diameter < 2.5 μm (PM2.5), particle matter with diameter < 10 μm (PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx). We identified metabolites and established the metabolic signature with air pollutants using an elastic net regularized regression. Cox proportional hazards models combined with generalized propensity score (GPS) were conducted to evaluate the relationships between metabolic signatures and incident IPF, and mediation analysis was performed to evaluate potential mediators. During a median follow-up of 12.3 years, 1239 IPF cases were ascertained. We identified multi-metabolite profiles comprising 87 metabolites for PM2.5, 65 metabolites for PM10, 71 metabolites for NO2, and 76 metabolites for NOx. Metabolic signatures were associated with incident IPF, with HRs of 1.20 (95 % CI: 1.13, 1.27), 1.09 (95 % CI: 1.03, 1.15), 1.23 (95 % CI: 1.16, 1.31), and 1.24 (95 % CI: 1.17, 1.31) per standard deviation (SD) increase in metabolic profiles associated with PM2.5, PM10, NO2, and NOx, respectively. Furthermore, metabolic signatures of PM2.5, PM10, NO2 and NOx significantly mediated 5.71 %, 3.98 %, 4.21 %, and 4.58 % of air pollution on IPF. Long-term air pollution was associated with a higher risk of IPF, with metabolites potentially playing a mediating role. The findings emphasize the significance of improving metabolic status for the prevention of IPF.PMID:39837121 | DOI:10.1016/j.scitotenv.2025.178409

Chemosphere. 2025 Jan 20;372:144111. doi: 10.1016/j.chemosphere.2025.144111. Online ahead of print.ABSTRACTAnaerobic digestion (AD) offers great potential for pollutant removal and bioenergy recovery. However, it faces challenges when using livestock manure (LSM) as a feedstock given its high content of refractory materials (e.g., lignocellulose, long-chain carbohydrates, lipids, and crude protein). This would significantly inhibit AD-microbial activities, reduce organic transformation efficiency and limit gas production. To overcome this, multifunctional metal-doped hydrochars (HCs) were introduced here as AD supplements/accelerators, given that LSM degradation under AD results in complex dissolved organic matter (DOM). To assess this, the current study investigates the molecular interactions/transformations within DOM during LSM-AD coupled with metal-doped HCs, via batch-mode experiments. Expansive data mining techniques were employed to analyze DOM using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). Substantial increments in peptide-like along with decrements in highly unsaturated-like molecules were observed in HC@MnCl2 containing-system. This indicates an increased capability for substrate hydrolysis and potential utilization of soluble microbial products (SMPs) (i.e., highly unsaturated-like molecules), leading to enhanced methane recovery (223.23 mL/g-VSadded, 1.77 times more than the control). However, accumulation of DOM-highly unsaturated molecules (i.e., a lack of SMPs' degradation) accompanied with low methane production (39.68 mL/g-VSadded) was noticed for HC@NiFe2O4. DOM reactivity during LSM-AD was validated via paired mass difference molecular network, indicating predominance of CHO and N-containing groups' transformations for HC@MnCl2 and HC@NiFe2O4, respectively. Potential metabolites and abundant pathways were verified via KEGG database. This study improves our understanding of LSM-AD-DOM complex transformation matrix, the fate of bioavailable/recalcitrant compounds, and identification of potential DOM regulators from thousands of molecules.PMID:39837067 | DOI:10.1016/j.chemosphere.2025.144111

Ecotoxicol Environ Saf. 2025 Jan 20;290:117738. doi: 10.1016/j.ecoenv.2025.117738. Online ahead of print.ABSTRACTMonogalactosyldiacylglycerol (MGDG), as the primary lipid component of thylakoid membranes, has a significant part in plant growth and stress response. The current study employed two transgenic wheat lines (MG1516 and MG1314) overexpressing the MGDG synthase gene (TaMGD) and wild-type cv "JW1" to explore the function of TaMGD in response to high temperature stress during the anthesis stage of wheat. Under high-temperature stress, the overexpressed wheat lines exhibited higher grain weight, increased antioxidant enzyme activity, and lower H2O2 and malondialdehyde contents in leaves. Transcriptomic analysis suggests that overexpression of TaMGD influenced multiple metabolic pathways in response to high-temperature stress, including carbon metabolism, amino acid metabolism, photosynthesis, and lipid-related metabolism. Overall, 146 differentially expressed metabolites (DEMs) were identified in MG1516 and wild-type (WT) under heat stress, with MG1516 exhibiting a higher number of upregulated metabolites, particularly glycolipids, organic acids, and organic oxygen compounds. Furthermore, lipid content and unsaturation analysis revealed that the overexpressing wheat line had a higher lipid content and greater saturation than WT under heat stress. Our findings demonstrate that overexpression of TaMGD in wheat affects multiple metabolic pathways, including photosynthesis, carbon, and amino acid metabolism, in reply to high-temperature stress through the modification of cell membrane lipid content, fatty acid unsaturation and other factors.PMID:39837009 | DOI:10.1016/j.ecoenv.2025.117738

Sci Signal. 2025 Jan 21;18(870):eadn9868. doi: 10.1126/scisignal.adn9868. Epub 2025 Jan 21.ABSTRACTChronic exposure to manganese (Mn) induces manganism and has been widely implicated as a contributing environmental factor to Parkinson's disease (PD), featuring notable overlaps between the two in motor symptoms and clinical hallmarks. Here, we developed an adult Drosophila model of Mn toxicity that recapitulated key parkinsonian features, spanning behavioral deficits, neuronal loss, and dysfunctions in lysosomes and mitochondria. Metabolomics analysis of the brain and body tissues of these flies at an early stage of toxicity identified systemic changes in the metabolism of biotin (also known as vitamin B7) in Mn-treated groups. Biotinidase-deficient flies showed exacerbated Mn-induced neurotoxicity, parkinsonism, and mitochondrial dysfunction. Supplementing the diet of wild-type flies with biotin ameliorated the pathological phenotypes of concurrent exposure to Mn. Biotin supplementation also ameliorated the pathological phenotypes of three standard fly models of PD. Furthermore, supplementing the culture media of human induced stem cells (iPSCs) differentiated midbrain dopaminergic neurons with biotin protected against Mn-induced mitochondrial dysregulation, cytotoxicity, and neuronal loss. Last, analysis of the expression of genes encoding biotin-related proteins in patients with PD revealed increased amounts of biotin transporters in the substantia nigra compared with healthy controls, suggesting a potential role of altered biotin metabolism in PD. Together, our findings identified changes in biotin metabolism as underlying Mn neurotoxicity and parkinsonian pathology in flies, for which dietary biotin supplementation was preventative.PMID:39836750 | DOI:10.1126/scisignal.adn9868

PLoS One. 2025 Jan 21;20(1):e0311567. doi: 10.1371/journal.pone.0311567. eCollection 2025.ABSTRACTThis study aimed to evaluate the potential of phytochemicals from two native UAE plant species, Arthrocnemum macrostachyum and Tamarix nilotica, as anti-cancer agents. The plant extracts were obtained using two methods, maceration, and microwave-assisted extraction (MAE), and were subsequently evaluated for their in vitro cytotoxicity against three cancer cell lines: breast (MDA-MB-231), colon (HCT-116), and lung (A-549). Results suggest that: 1) MAE is more efficient than maceration in recovering metabolites from plant biomass based on measurements of total phenolic content, radical scavenging activity, and bioactivity of extracts based on in vitro cytotoxicity. 2) Only T. nilotica extracts were found to be bioactive based on cytotoxicity measurements. 3) Cancer cell lines displayed differential sensitivity to T. nilotica crude extracts, with breast cancer cells being the most sensitive and lung cancer cells being the least sensitive. 4) Solid-phase fractionation of T. nilotica crude extract using different percentages of methanol resulted in several fractions that were 100-fold more cytotoxic compared to the crude unfractionated extract. The 30% and 70% methanol fractions exhibited the highest cytotoxicity towards breast and colon cancer cell lines, respectively. 5) Untargeted metabolomics using UHPLC-Q-ToF-MS of T. nilotica crude extracts revealed 909 molecular features, of which only 327 were annotated using MS/MS fragmentation. The results suggest that T. nilotica extracts have potential as anti-cancer agents and that MAE is an efficient method for extracting phytochemicals from plant biomass. The study also revealed that cancer cell lines exhibited differential sensitivity to the extracts and that solid-phase fractionation of crude extract using different percentages of methanol can yield fractions that are more cytotoxic than the crude extract.PMID:39836644 | DOI:10.1371/journal.pone.0311567

Adv Sci (Weinh). 2025 Jan 21:e2408753. doi: 10.1002/advs.202408753. Online ahead of print.ABSTRACTRenal fibrosis is a common pathway involved in the progression of various chronic kidney diseases to end-stage renal disease. Recent studies show that mitochondrial injury of renal tubular epithelial cells (RTECs) is a crucial pathological foundation for renal fibrosis. However, the underlying regulatory mechanisms remain unclear. Pyruvate carboxylase (PC) is a catalytic enzyme located within the mitochondria that is intricately linked with mitochondrial damage and metabolism. In the present study, the downregulation of PC in various fibrotic animal and human kidney samples is demonstrated. Renal proximal tubule-specific Pcx gene knockout mice (PcxcKO) has significant interstitial fibrosis compared to control mice, with heightened expression of extracellular matrix molecules. This is further demonstrated in a stable PC knock-out RTEC line. Mechanistically, PC deficiency reduces its interaction with sulfide:quinone oxidoreductase (SQOR), increasing the ubiquitination and degradation of SQOR. This leads to mitochondrial morphological and functional disruption, increased mtDNA release, activation of the cGAS-STING pathway, and elevated glycolysis levels, and ultimately, promotes renal fibrosis. This study investigates the molecular mechanisms through which PC deficiency induces mitochondrial injury and metabolic reprogramming in RTECs. This study provides a novel theoretical foundation and potential therapeutic targets for the pathogenesis and treatment of renal fibrosis.PMID:39836535 | DOI:10.1002/advs.202408753

Diabetes. 2025 Jan 21:db240385. doi: 10.2337/db24-0385. Online ahead of print.ABSTRACTDiabetes mellitus (DM) leads to a more rapid development of DM cardiomyopathy (dbCM) and progression to heart failure in women than men. Combination of high-fat diet (HFD) and freshly-injected streptozotocin (STZ) has been widely used for DM induction, however emerging data shows that anomer-equilibrated STZ produces an early onset and robust DM model. We designed a novel protocol utilising a combination of multiple doses of anomer-equilibrated STZ injections and HFD to develop a stable murine DM model featuring dbCM analogous to humans. Furthermore, we examined the impact of biological sex on the evolution of cardiometabolic dysfunction in DM. Our study included six experimental protocols (8 weeks) in male and female C57BL/6J mice (n=109): Fresh STZ+HFD, Anomer-equilibrated STZ+HFD, HFD, Fresh STZ, Anomer-equilibrated STZ, Control diet+vehicle. Animals were characterised by extensive phenotyping in vivo and ex vivo. Anomer-equilibrated STZ+HFD led to induction of stable experimental murine DM characterised by impaired glucose homeostasis, cardiometabolic dysfunction and altered metabolome of liver, skeletal muscle, kidney and plasma. dbCM was more severe in female mice including systolic dysfunction and reduced cardiac energy reserve. This study established a novel, robust model of inducible murine DM and emphasised the impact of biological sex on DM progression and severity.PMID:39836371 | DOI:10.2337/db24-0385

Funct Integr Genomics. 2025 Jan 21;25(1):20. doi: 10.1007/s10142-025-01536-x.ABSTRACTRice (Oryza sativa L.), Poaceae family, forms staple diet of half of world's population, and brinjal (Solanum melongena L.), an important solanaceous crop, are consumed worldwide. Rhizosphere research is gaining importance towards application of knowledge for improving productivity, sustainable agricultural practice, and rhizoremediation for nature restoration. While there are reports on rhizobacteriome of rice, studies comparing structural, functional and metabolomic traits of microbial communities in rhizospheres of rice and brinjal are not yet available. We demonstrated, in Oryza sativa (1144-Hybrid, Dhiren, Local Saran cultivars) and Solanum melongena (Jhiloria, Chandtara, Jotshna cultivars) rhizospheres from Malda, India, using integrated approach of 16 S ribosomal sequencing, shotgun metagenomics, and microbial metabolomics to decipher microbial diversity, association with soil physicochemical characteristics, key genes and pathways. Ectoine biosynthesis was significantly expressed in brinjal (Jhiloria), but not in rice rhizosphere. The dominant brinjal rhizobacteriome-specific bacteria comprised Thermus sp., Petrobacter succinatimandens, Thermoanaerobacter sp., and Diaphorobacter sp., that were involved in house-keeping functions including pentose phosphate pathway, biosynthesis of amino acids, lipopolysaccharide, and photosynthesis. The dominant bacteria unique to rice rhizobacteriome (Local Saran) consisted of Aeromonas sp., associated with catechol meta-cleavage, while Clostridium sp., Faecalibacterium prausnitzii, and Roseburia sp. were involved with lysine biosysnthesis in rice (1144-Hybrid). Our results imply novel information for improved breeding of brinjal specific cultivar with enhanced ectoine production associated with osmotic stress tolerance, rice specific cultivars with enhanced lysine production significant to human nutrition and catechol removal for the maintenance of environmental quality.PMID:39836258 | DOI:10.1007/s10142-025-01536-x