PubMed

Chem Biol Drug Des. 2025 Feb;105(2):e70066. doi: 10.1111/cbdd.70066.ABSTRACTStachydrine (STA) has therapeutic effects on heart disorders. The current study assessed its effects on Type 2 diabetes (T2D) induced cardiac disorders by focusing on the heart-gut axis. Mice were subjected to high-fat diet (HFD) and streptozocin (STZ) to induce cardiac disorders such as inflammation and structural deteriorations, which were handled with STA. Changes regarding the composition and metabolism of gastrointestinal (GI) microbiota were then determined using a multiomics strategy, including amplicon sequencing and metabolomics. The data showed that STA improved heart function, reduced intestinal permeability, and suppressed inflammation in mice in a dose-dependent manner. However, the compound had little influence on the overall alpha diversity of gut microbiota, while it did influence the beta diversity. The analyses based on the multiomics strategy demonstrated that certain GI microbial groups, including Paramuribaculum, Allobaculum, Bifidobacterium, and Adlercreutzia, responded to the STA administration, which contributed to the alternatives of metabolites in the gut. Correlation analyses showed that Duncaniella and Ruminococcus negatively impacted health, while Muribaculum, Paramuribaculum, and Prevotella positively influenced intestinal permeability and heart health. Collectively, STA attenuated T2D-induced cardiac disorders by improving heart structure and function and suppressing inflammation, during which the GI homeostasis of the T2D mice changed to an alternative state that was different from that of healthy mice.PMID:39994907 | DOI:10.1111/cbdd.70066

Crit Care. 2025 Feb 24;29(1):88. doi: 10.1186/s13054-025-05291-0.ABSTRACTAcute respiratory distress syndrome (ARDS) is a severe complication of critical illness, characterized by bilateral lung infiltrates and hypoxemia. Its clinical and pathophysiological heterogeneity poses challenges for both diagnosis and treatment. This review outlines the evolution of ARDS definitions, discusses the underlying pathophysiology of ARDS, and examines the clinical implications of its heterogeneity. Traditional ARDS definitions required invasive mechanical ventilation and relied on arterial blood gas measurements to calculate the PaO2/FiO2 ratio. Recent updates have expanded these criteria to include patients receiving noninvasive respiratory support, such as high-flow nasal oxygen, and the adoption of the SpO2/FiO2 ratio as an alternative to the PaO2/FiO2 ratio. While these changes broaden the diagnostic criteria, they also introduce additional complexity. ARDS heterogeneity-driven by varying etiologies, clinical subphenotypes, and underlying biological mechanisms-highlights the limitations of a uniform management approach. Emerging evidence highlights the presence of distinct ARDS subphenotypes, each defined by unique molecular and clinical characteristics, offering a pathway to more precise therapeutic targeting. Advances in omics technologies-encompassing genomics, proteomics, and metabolomics-are paving the way for precision-medicine approaches with the potential to revolutionize ARDS management by tailoring interventions to individual patient profiles. This paradigm shift from broad diagnostic categories to precise, subphenotype-driven care holds promise for redefining the landscape of treatment for ARDS and, ultimately, improving outcomes in this complex, multifaceted syndrome.PMID:39994815 | DOI:10.1186/s13054-025-05291-0

Lipids Health Dis. 2025 Feb 24;24(1):69. doi: 10.1186/s12944-025-02475-z.ABSTRACTBACKGROUND: Hepatocellular carcinoma (HCC) is the third deadliest malignant tumor worldwide. Most patients are initially diagnosed as HCC at advanced stages and are too late for radical treatment by surgery, resulting in poor prognosis. Over 50% of the HCC patients are caused by hepatitis B virus (HBV) infection. Therefore, effective early identification of HCC in the high-risk population with HBV infection is crucial for early intervention of HCC.METHODS: We employed plasma lipidomics to identify critical lipid classes associated with tumorigenesis in the high-risk population with HBV infection. Potential regulatory mechanisms are validated at multi-omic levels. A machine learning algorithm is used for feature selection and diagnostic modelling, and performance of the models is evaluated by ROC curves.RESULTS: We unveiled varied profiles of plasma lipid metabolites in a cohort of 57 HBV-related HCC subjects, 57 HBV-related liver cirrhosis (LC) subjects and 61 chronic hepatitis B (CHB) subjects with matched age, sex and HBV status. We identified a correlation of the ether phosphatidylcholine (PC) synthesis with hepatocarcinogenesis in patients with HBV-related liver diseases. The diagnostic models achieved an area under ROC curve (AUC) of 0.849 for discriminating HCC from CHB and an AUC of 0.829 for discriminating HCC from LC.CONCLUSIONS: We illustrate the role of ether PC in hepatocarcinogenesis upon HBV infection and provide novel effective markers for early detection of HCC in a cohort with HBV infection.PMID:39994676 | DOI:10.1186/s12944-025-02475-z

BMC Genomics. 2025 Feb 24;26(1):192. doi: 10.1186/s12864-025-11392-5.ABSTRACTBACKGROUND: Sexual dimorphism, a widespread phenomenon across the animal kingdom, encompasses differences between sexes in size, morphology, and physiological traits. In this study, we investigated sexual dimorphism in the flexor carpi radialis (FCR) muscle, which is critical for amplexus in Asiatic toads (Bufo gargarizans), using integrated transcriptomic and metabolomic approaches.RESULTS: Male toads exhibited significantly larger FCR muscles, reflecting enhanced muscle function required for sustained amplexus. Transcriptomic analysis identified 818 differentially expressed genes (DEGs) between sexes, with 389 upregulated and 429 downregulated in males, predominantly associated with muscle contraction, sarcomere organization, and energy metabolism. Metabolomic profiling revealed 69 differentially expressed metabolites (DEMs), with male-biased enrichment in pathways involved in protein synthesis and degradation, energy metabolism, and material transport. Integrated analysis pinpointed key metabolic pathways-such as glycine, serine, and threonine metabolism; alanine, aspartate, and glutamate metabolism; fatty acid degradation; and the tricarboxylic acid (TCA) cycle-as central to the observed sexual dimorphism. Among these, the genes AGXT, ACADL, ACAT1, MDH2, and SUCLG2 emerged as pivotal regulators.CONCLUSIONS: Collectively, these findings provide novel insights into the genetic and metabolic basis of sexual dimorphism in B. gargarizans, offering a deeper understanding of the evolutionary mechanisms driving sex-specific traits in vertebrates.PMID:39994541 | DOI:10.1186/s12864-025-11392-5

BMC Plant Biol. 2025 Feb 24;25(1):244. doi: 10.1186/s12870-025-06273-8.ABSTRACTTobacco (Nicotiana tabacum L.) is a globally crop due to its distinctive flavor and economic value. In this study, we systematically analyzed the dynamic changes in volatile substances, broad-spectrum metabolites, enzymes, and biochemical compounds in tobacco leaves during flue-curing process. Combining metabolomics with enzyme activity and biochemical analysis, we identified that 43℃ is a critical period for enzyme activity and metabolite transitions, while 45 ℃ requires stringent moisture control. During the T3 stages, phenolic acids, amino acids, and derivatives were notably enriched, with increases of 19.58-fold, 18.59-fold, and 17.33-fold in lmmn001643, MWS20633g, and Lmhn004756, respectively. These compounds may serve as candidate biomarkers for non-volatile compounds. Aroma dynamics primarily contributed to the green and sweet flavor of flue-cured tobacco leaves, and the key aroma components included D114, KMW1317, and KMW0466. Differential volatile and non-volatile metabolites were enriched in four pathways, including monoterpenoid biosynthesis, tyrosine metabolism, phenylalanine metabolism, and phenylpropanoid biosynthesis. These pathways are closely related to phenylalanine ammonia-lyase and the synthesis of chlorogenic acid and rutin, which influence the aroma quality, aroma intensity, irritation, and volatility of tobacco. Additionally, the contents of caffeic acid, ferulic acid, sinapic acid, and PAL activity in phenylpropanoid biosynthesis pathway, increased with the rising temperature, accelerating reactions with alcohols and leading to increase lignin formation. This study enhances our understanding of the dynamic changes in the aroma and metabolic substances of Cuibi 1(CB-1) at the critical stages of the curing process and offers valuable insights for process improvement.PMID:39994521 | DOI:10.1186/s12870-025-06273-8

Sci Rep. 2025 Feb 24;15(1):6593. doi: 10.1038/s41598-025-91314-3.ABSTRACTMesenchymal stem cells (MSCs) have emerged as crucial players within the tumor microenvironment (TME), contributing through their paracrine secretome. Depending on the context, the MSC-derived secretome can either support or inhibit tumor growth. This study investigates the role of MSC-derived secretome in modulating breast cancer (BC) cell behavior, with a focus on ten-eleven translocation 1 (TET1), a DNA demethylase with known oncogenic properties in triple-negative breast cancer (TNBC). We first isolated and characterized human bone marrow-derived MSCs, and then assessed the impact of their secretome on BC cells. Treatment with the MSC-derived secretome significantly inhibited the proliferation and migration of both MDA-MB-231 and MCF-7 BC cell lines, resulting in reduced cell viability and migration rates compared to control cells. Western blot analyses revealed downregulation of Cyclin D1 and c-Myc, along with decreased expression of N-cadherin and increased expression of E-cadherin, indicating potential inhibition of the epithelial-to-mesenchymal transition. Differential gene expression analyses highlighted TET1 as significantly upregulated in TNBC tissues compared to normal samples. Further experiments confirmed that the MSC-derived secretome downregulated TET1 expression in BC cells, as evidenced by RT-qPCR and western blot analyses. To explore TET1's functional role, we silenced TET1 with siRNAs, observing cell cycle arrest and enhanced apoptosis-effects that mirrored those seen with MSC-secretome treatment. Notably, TET1 knockdown also increased MDA-MB-231 cell sensitivity to cisplatin, suggesting a role for TET1 in chemoresistance. These findings provide insight into the ability of MSCs to modulate BC cell progression through their secretome, highlighting the involvement of TET1 downregulation in inhibiting BC cell progression and enhancing cisplatin chemosensitivity. The MSC-derived secretome thus holds promise as an innovative, cell-free therapeutic approach in BC treatment.PMID:39994414 | DOI:10.1038/s41598-025-91314-3

Sci Rep. 2025 Feb 25;15(1):6686. doi: 10.1038/s41598-025-87707-z.ABSTRACTTo study the mechanism of calcitonin gene related peptide(CGRP) protecting acute pancreatitis based on metabolomics. 24 adult male rats were randomly divided into control group (Con), acute pancreatitis model group (AP), CGRP treatment group (CGRP + AP, abbreviated as CGRP) and CGRP antagonist(CGRP(8-37)) pretreatment group (preCGRP(8-37) + AP, abbreviated as CGRP37), with 6 rats in each group. After different interventions, pancreases of rats in each group were collected for pathological analysis, and serum was collected for metabolomics analysis. Pathological examination of the pancreas suggested that the inflammation of pancreatitis in AP group was significant, the inflammation of pancreatitis in CGRP group was significantly reduced, and the pancreatitis in CGRP37 group was aggravated. Metabolomics of rat serum suggested that the differences in metabolites in each group were mainly related to amino acid metabolism, coenzyme/vitamin metabolism, carbohydrate metabolism, lipid metabolism, digestive system and other metabolic pathways. According to the trend of metabolite changes, we found 6 differential metabolites that were significantly correlated with CGRP intervention, including L-Valine, 5-Aminopentanoic acid, 4-oxo-L-proline, L-glutamine, L-proline, and Ornithine, all of which were related to amino acid metabolism. CGRP can effectively protect acute pancreatitis, possibly by regulating amino acid metabolism to alleviate acute pancreatitis.PMID:39994332 | DOI:10.1038/s41598-025-87707-z

Sci Rep. 2025 Feb 24;15(1):6642. doi: 10.1038/s41598-025-91251-1.ABSTRACTSeveral alkaloids found in the Zanthoxylum genus have demonstrated significant anticancer activity. However, the antitumor effects of Ethoxychelerythrine (Eth) have not been previously reported. Cell viability, colony formation, apoptosis and cell cycle analysis, intracellular and reactive oxygen species (ROS), mitochondrial membrane potential (MMP) levels of Eth against SW480 cells were evaluated. Subcutaneously transplanted SW480 cells model was used to determine the effect of Eth on tumor growth in vivo. Inflammation levels, angiogenic factors, pathological observations, quantitative reverse-transcription PCR (qRT-PCR), quantitative proteomics, metabolite profiles and western blotting were conducted. It found that Eth significantly inhibited the proliferation of SW480 and HT29 cells in vitro, with stronger inhibitory activity observed against SW480 cells. Therefore, subsequent studies focused on SW480 cells. In vitro, we observed that Eth arrested the cell cycle at the G0/G1 phase, decreased MMP levels, elevated cellular ROS levels, and induced mitochondrial apoptosis. In vitro, Eth significantly inhibited tumor proliferation and metastasis, and regulated the molecule levels of angiogenesis and inflammatory factors in serum, as well as apoptotic protein in tumor tissues. The serum proteomic revealed that the differential proteins were primarily involved in the PI3K/AKT/mTOR pathway, including laminin β1 (Lamb1), and type I collagen (Col1a1). Metabolomics showed that many abnormal levels of metabolites regulated by the PI3K/AKT/mTOR pathway were obviously reversed towards normal levels after Eth intervention. The correlation analysis between the two-omics revealed that different proteins in the PI3K/AKT pathway, particularly lactate dehydrogenase B (LDHB) and glutathione synthetase (GSS), can interact with most of different metabolites. In summary, Eth exerts anti-tumour effects by inhibiting the activation of the PI3K/AKT/mTOR pathway, which in turn activates mitochondrial apoptosis. Eth may be considered in the development of drugs for relieving colon cancer patients in the future.PMID:39994297 | DOI:10.1038/s41598-025-91251-1

Sci Rep. 2025 Feb 24;15(1):6622. doi: 10.1038/s41598-025-90426-0.ABSTRACTThe clinical manifestations of the cytokine storm (CS) associated with COVID-19 resemble the acute phase of sepsis. Metabolomics may contribute to understanding the specific pathobiology of these two syndromes. The aim of this study was to compare serum metabolomic profiles in CS associated with COVID-19 vs. septic surgery patients. In a retrospective cross-sectional study, serum samples from patients with CS associated with COVID-19, with and without comorbidity, as well as serum samples from patients with surgical sepsis were investigated. Targeted metabolomic analysis was performed on all samples using LC-MS/MS. Analysis revealed that similar alterations in the serum metabolome of patients with COVID-19 and surgical septic patients were associated with amino acid metabolism, nitrogen metabolism, inflammatory status, methionine cycle and glycolysis. The most significant difference was found for serum levels of metabolites of kynurenine synthesis, tricarboxylic acid cycle, gamma-aminobutyric acid and niacinamide. The metabolic pathway of cysteine and methionine metabolism was significantly disturbed in COVID-19 and surgical septic patients. For the first time, the similarities and differences between the serum metabolomic profiles of patients with CS associated with COVID-19 and patients with surgical sepsis were investigated for patients from the Northwest of the Russian Federation.PMID:39994234 | DOI:10.1038/s41598-025-90426-0

Nat Commun. 2025 Feb 24;16(1):1910. doi: 10.1038/s41467-025-57032-0.ABSTRACTImpaired glucose uptake in the brain is an early presymptomatic manifestation of Alzheimer's disease (AD), with symptom-free periods of varying duration that likely reflect individual differences in metabolic resilience. We propose a systemic "bioenergetic capacity", the individual ability to maintain energy homeostasis under pathological conditions. Using fasting serum acylcarnitine profiles from the AD Neuroimaging Initiative as a blood-based readout for this capacity, we identified subgroups with distinct clinical and biomarker presentations of AD. Our data suggests that improving beta-oxidation efficiency can decelerate bioenergetic aging and disease progression. The estimated treatment effects of targeting the bioenergetic capacity were comparable to those of recently approved anti-amyloid therapies, particularly in individuals with specific mitochondrial genotypes linked to succinylcarnitine metabolism. Taken together, our findings provide evidence that therapeutically enhancing bioenergetic health may reduce the risk of symptomatic AD. Furthermore, monitoring the bioenergetic capacity via blood acylcarnitine measurements can be achieved using existing clinical assays.PMID:39994231 | DOI:10.1038/s41467-025-57032-0

Nat Commun. 2025 Feb 24;16(1):1911. doi: 10.1038/s41467-025-57261-3.NO ABSTRACTPMID:39994215 | DOI:10.1038/s41467-025-57261-3

Nat Commun. 2025 Feb 24;16(1):1905. doi: 10.1038/s41467-025-57005-3.ABSTRACTA promising drug target, SETDB1, is a dual methyl-lysine (Kme) reader and methyltransferase implicated in cancer and neurodegenerative disease progression. To help understand the role of the triple Tudor domain (3TD) of SETDB1, its Kme reader, we first identify a low micromolar potency small molecule ligand, UNC6535, which occupies simultaneously both the TD2 and TD3 reader binding sites. Further optimization leads to the discovery of UNC10013, a covalent 3TD ligand targeting Cys385 of SETDB1. UNC10013 is potent with a kinact/KI of 1.0 × 106 M-1s-1 and demonstrates proteome-wide selectivity. In cells, negative allosteric modulation of SETDB1-mediated Akt methylation occurs after treatment with UNC10013. Therefore, UNC10013 is a potent, selective, and cell-active covalent ligand for the 3TD of SETDB1, demonstrating negative allosteric modulator properties and making it a promising tool to study the biological role of SETDB1 in disease progression.PMID:39994194 | DOI:10.1038/s41467-025-57005-3

Physiol Plant. 2025 Jan-Feb;177(1):e70134. doi: 10.1111/ppl.70134.ABSTRACTIron (Fe) is an essential micronutrient for plant growth and development. Fe deficiency leads to growth restriction, developmental disorders, chlorosis, and yield loss of fruit trees. This study investigated the molecular and biochemical mechanisms underlying the differences in Fe absorption among various apple rootstocks under alkaline conditions. Results showed that 'Oregon Spur II' grafted onto Qingzhen No.2 (OS/Q2) exhibited foliage etiolation, while 'Oregon Spur II' grafted onto Qingzhen No.1 (OS/Q1) did not display such etiolation under alkaline conditions. Physiological experiments revealed that total Fe, ferrous Fe, and chlorophyll content in OS/Q2 were significantly lower than those in OS/Q1, whereas the Fe reductase activity in OS/Q2 was higher than that in OS/Q1. Additionally, a total of 7,025 and 9,102 differentially expressed genes (DEGs), including 488 transcription factors (TFs), were identified in OS/Q1L vs. OS/Q2L and OS/Q1R vs. OS/Q2R, respectively. Subsequently, the pathways associated with "phenylpropanoid biosynthesis", "plant hormone signal transduction", "hydrogen ion export across plasma membrane", "heme binding", and "iron binding" were identified as critical for responding to Fe deficiency under alkaline conditions. Furthermore, a total of 244 differentially accumulated metabolites (DAMs) were identified in OS/Q1R vs. OS/Q2R. A combined analysis of the transcriptome and metabolome revealed that "ABC transporters", "biosynthesis of amino acids", and "carbon fixation in photosynthetic organisms" were significantly overrepresented in the KEGG pathways of both DEGs and DAMs. These newly acquired genes and metabolites involved in Fe metabolism will enhance our capacity to employ genetic engineering technologies to maintain Fe homeostasis in plants in the future.PMID:39994109 | DOI:10.1111/ppl.70134

J Cell Mol Med. 2025 Feb;29(4):e70340. doi: 10.1111/jcmm.70340.ABSTRACTCerebral ischaemia-reperfusion injury (CIRI), resulting from thrombolytic therapy for ischaemic stroke, presents a considerable challenge during postoperative recovery. Formononetin (FMN) has shown promise in the prevention and treatment of neurological diseases. However, its specific mechanism in ameliorating CIRI remains uncertain. Initially, we established a CIRI rat model to evaluate FMN's therapeutic potential by assessing neurological function, infarct area and pathological changes. Subsequently, we employed metabolomics technology to investigate FMN's impact on metabolite levels in the ischaemic brain tissue of CIRI rats. Based on the metabolomics findings, we validated FMN's effects on nicotinate and nicotinamide metabolism, as well as alanine, aspartate and glutamate metabolism, along with its influence on neuronal injury and repair. Our investigation unveiled that FMN intervention significantly diminished the Longa score and asymmetry score in CIRI rats, constricted the infarct area and ameliorated pathological alterations in the ischaemic brain tissue, including reduced DCI index and augmented Nissl body count. Metabolomics analysis indicated that FMN exerted regulatory effects on nicotinate and nicotinamide metabolism, as well as alanine, aspartate and glutamate metabolism. Following FMN intervention, there was a notable increase in the levels of related metabolites such as nicotinamide (NAM), L-aspartic acid (L-Asp), fumaric acid (FA), gamma-aminobutyric acid (GABA) and L-glutamic acid (L-Glu). RT-qPCR and Western blot outcomes demonstrated that FMN upregulated the gene and protein expression of key enzymes adenylosuccinate lyase (ADSL) and glutamic acid decarboxylase (GAD) involved in alanine, aspartate and glutamate metabolism. Moreover, FMN intervention bolstered SOD activity, diminished MDA and ROS levels and reduced TUNEL-positive expression. Furthermore, FMN intervention elevated ATP levels and markedly increased Ki67-positive expression. FMN exhibits the potential to alleviate oxidative stress injury in CIRI rats by enhancing nicotinate and nicotinamide metabolism along with alanine, aspartate and glutamate metabolism, consequently reinstating energy metabolism and conferring neuroprotective effects to ameliorate CIRI.PMID:39993962 | DOI:10.1111/jcmm.70340

Phytochem Anal. 2025 Feb 24. doi: 10.1002/pca.3517. Online ahead of print.ABSTRACTINTRODUCTION: The Zingiberaceae family is well known for its therapeutic characteristics, notably its antidiabetic and antioxidant potential, which may be linked to its diverse bioactive metabolite composition. Despite widespread usage in traditional medicine, there has been little research on the chemical composition and biological activity of Zingiberaceae plants from Manipur, India.OBJECTIVE: This study aims to comprehensively profile metabolites and evaluate the antidiabetic and antioxidant properties of seven Zingiberaceae species through in vitro assays and in silico molecular docking analysis.METHODS: Hydroalcoholic extracts of Curcuma caesia, Kaempferia parviflora, Curcuma zedoaria, Zingiber officinale, Curcuma angustifolia, Curcuma aromatica, and Curcuma longa were examined. TPC and TFC were measured using Folin-Ciocalteu and Aluminum chloride colorimetry. Antidiabetic efficacy was assessed by α-glucosidase and α-amylase inhibition tests. DPPH and ABTS tests measured antioxidant activity. GC-MS was used for metabolite profiling, and molecular docking was used to explore bioactive compound-antidiabetic protein interactions (3L4Y, 5UBA, NOX1).RESULTS: C. caesia showed the highest TPC (85.41 GAE mg/g) and TFC (126.15 QE mg/g). Z. officinale, C. angustifolia, and K. parviflora exhibited significant α-glucosidase (74%-80%) and α-amylase (62%-73%) inhibition, surpassing acarbose. Strong antioxidant activity was observed, especially in C. caesia and Z. officinale. GC-MS identified 61 bioactive compounds, with molecular docking showing strong interactions of gingerol and zederone with 3L4Y and 5UBA, and germacrone and β-sesquiphellandrene with NOX1.CONCLUSIONS: Seven Zingiberaceae species from Manipur exhibit notable antidiabetic and antioxidant potential, with C. caesia and Z. officinale showing superior efficacy. Key bioactives like gingerol, zederone, germacrone, and β-sesquiphellandrene demonstrated strong therapeutic target interactions, supporting their pharmacological potential.PMID:39993938 | DOI:10.1002/pca.3517

Cancer Genomics Proteomics. 2025 Mar-Apr;22(2):285-305. doi: 10.21873/cgp.20502.ABSTRACTBACKGROUND/AIM: Oncogenic processes are delineated by metabolic dysregulation. Drug likeness is pharmacokinetically tested through the CYP450 enzymatic system, whose genetic aberrations under epigenetic stress could shift male organisms into prostate cancer pathways. Our objective was to predict the susceptibility to prostate neoplasia, focused on benign prostatic hyperplasia (BPH) and prostate cancer (PCa), based on the pharmacoepigenetic and the metabolic profile of Caucasians.MATERIALS AND METHODS: Two independent cohorts of 47,389 individuals in total were assessed to find risk associations of CYP450 genes with prostatic neoplasia. The metabolic profile of the first cohort was statistically evaluated and frequencies of absorption-distribution-metabolism-excretion-toxicity (ADMET) properties were calculated. Prediction of miRNA pharmacoepigenetic targeting was performed.RESULTS: We found that prostate cancer and benign prostatic hyperplasia patients of the first cohort shared common cardiometabolic trends. Drug classes C08CA, C09AA, C09CA, C10AA, C10AX of the cardiovascular, and G04CA, G04CB of the genitourinary systems, were associated with increased prostate cancer risk, while C03CA and N06AB of the cardiovascular and nervous systems were associated with low-risk for PCa. CYP3A4*1B was the most related pharmacogenetic polymorphism associated with prostate cancer susceptibility. miRNA-200c-3p and miRNA-27b-3p seem to be associated with CYP3A4 targeting and prostate cancer predisposition. Metabolomic analysis indicated that 11β-OHT, 2β-OHT, 15β-OHT, 2α-OHT and 6β-OHT had a high risk, and 16α-OHT, and 16β-OHT had an intermediate disease-risk.CONCLUSION: These findings constitute a novel integrated signature for prostate cancer susceptibility. Further studies are required to assess their predictive value more fully.PMID:39993800 | DOI:10.21873/cgp.20502

Int J Biol Macromol. 2025 Feb 22:141366. doi: 10.1016/j.ijbiomac.2025.141366. Online ahead of print.ABSTRACTAlthough natural polysaccharides often have growth-promoting effects on animals, little is known about how polysaccharides act when they are administered as feed additives. This work shows that Amomum longiligulare polysaccharide 1 (ALP1) improves the growth performance of piglets by promoting the proliferation of jejunal epithelial cells. ALP1 improves the growth performance of piglets, increasing the average daily gain by 32.71 % and reducing the feed-to-gain (F/G) ratio by 21.93 %. The gut microbiota is an important regulatory target of polysaccharides. The results of jejunal microbiota transplantation trials indicate that the jejunal microbiota from ALP1-fed piglets exhibits better growth performance and that the F/G ratio is reduced by 12.72 %. Furthermore, 16S rDNA sequencing and nontargeted metabolomic analyses reveal that ALP1 supplementation can increase the abundance of Lactobacillus in the jejuna of piglets, resulting in a high abundance of 11Z-eicosenoic acid (EA). In addition, EA increases the villus height-to-crypt depth (VH/CD) ratio in the jejunum by 27.41 %, potentially increasing epithelial cell proliferation. These results suggest that oral ALP1 supplementation promotes growth by modulating the composition of the jejunal microbiota and its associated metabolites.PMID:39993675 | DOI:10.1016/j.ijbiomac.2025.141366

Environ Res. 2025 Feb 22:121213. doi: 10.1016/j.envres.2025.121213. Online ahead of print.ABSTRACTDue to their large specific surface area and strong hydrophobicity, microplastics (MPs) are highly susceptible to adsorb environmental pollutants, of which heavy metals (HMs) are the most representative inorganic pollutants. However, there is controversy in different studies as to whether the toxic effects of the combined action of MPs and HMs on zebrafish larvae are antagonistic or synergistic. Herein, we firstly evaluated the combined effects of 10 μm polystyrene MPs (PS-MPs) on zebrafish larvae after exposure for 96 h at two different concentrations (5 mg/L, 0.5 mg/L) and Cu2+ (0.05 mg/L). Our study primarily showed that the combined exposure of PS-MPs and Cu2+ could induce developmental toxicity, oxidative stress, immunotoxicity and neurotoxicity. Furthermore, LC/MS-based nontargeted metabolomics analysis demonstrated that the combined exposure of PS-MPs with Cu2+ induced metabolic disturbances. Furthermore, our results showed that the combined exposure of 10 μm PS-MPs with Cu2+ exhibited a synergistic effect on the toxicity of zebrafish larvae. In conclusion, this study provides a reference for future research related to combined exposure of PS-MPs and Cu2+ on fish.PMID:39993620 | DOI:10.1016/j.envres.2025.121213

Environ Res. 2025 Feb 22:121134. doi: 10.1016/j.envres.2025.121134. Online ahead of print.ABSTRACTThe pesticide imidacloprid and the heavy metal copper provide some degree of protection to plants, while at the same time causing varying degrees of damage to bees. However, few studies have investigated the negative effects of imidacloprid and copper exposure on newly emerged bees (young bees), especially when both are present in a mix. In this study, young bees were exposed to sterile sucrose solutions containing imidacloprid (10 μg/L, 100 μg/L), copper (10 mg/L, 50 mg/L), or a mix of both (10 μg/L + 10 mg/L) for 5 days to assess their gut system and behavior, with survival and dietary consumption recorded over 21 days. We found that imidacloprid and copper reduced honeybee survival, dietary intake, and learning ability, decreased gut microbiota diversity, and caused metabolic disruptions. Notably, the mix of imidacloprid and copper had a synergistic negative effect. Correlation analyses revealed that the honeybee gut microbiota influences bee immunity and behavior by regulating metabolic pathways related to ascorbate, tryptophan, and carbohydrates. Our results demonstrate that imidacloprid and copper, either alone or in a mix, alter young bee health through a complex mechanism of toxicity. These findings highlight imidacloprid and copper's negative effects on young honeybees, offering insights for future pesticide and heavy metal impact research.PMID:39993618 | DOI:10.1016/j.envres.2025.121134

NanoImpact. 2025 Feb 22:100552. doi: 10.1016/j.impact.2025.100552. Online ahead of print.ABSTRACTAlthough the ecotoxicity of polystyrene nanoplastics (PS-NP) to fish has been widely reported, their impact on the metabolic processes in fish gills and the underlying mechanisms remains unclear. Here, we investigated the effects of PS-NP on the morphology, oxidative stress, and metabolism of Acrossocheilus yunnanensis gills using conventional physicochemical indicators and metabolomics analysis. The results showed that PS-NP caused oxidative stress, and resulted in gill tissue lesions (e.g., proliferation and sloughing of gill epithelial cells). Metabolomics results showed that PS-NP exposure induced 75-164 differentially expressed metabolites (DEMs) in fish gills, and they were mainly related to lipid metabolism. DEMs induced by high concentration of PS-NP compared with low concentration of PS-NP were not only significantly enriched in glycerophospholipid metabolism, but also in sphingolipid metabolism, nucleic acid metabolism, and a variety of signaling pathways. In conclusion, the results of this work suggest that PS-NP cause disruption of phospholipid metabolism mainly by disrupting the integrity of gill tissue, which provides a new perspective for understanding the impact mechanism of PS-NP on fish gills. Given that fish play essential roles in maintaining ecological balance, the adverse effects of PS-NP on fish gills could ultimately disrupt the stability and health of the aquatic ecosystem.PMID:39993567 | DOI:10.1016/j.impact.2025.100552