PubMed

J Agric Food Chem. 2025 Feb 28. doi: 10.1021/acs.jafc.4c04734. Online ahead of print.ABSTRACTThe amount of nitrogen (N) fertilization influences the content and composition of phytochemicals in plants. However, the influence of different chemical forms of N fertilizers on the phytochemical profiles of fruits remains less known. We investigated the effect of nitrate [NO3-; supplied as CaNO3], ammoniacal [NH4+; supplied as (NH4)2SO4], and organic-N (supplied as meat and bone meal [MBM]) fertilization on the profile of volatile compounds, primary, and secondary metabolites in the fruits of Alpine strawberries (Fragaria vesca "Reine des Vallées") using global metabolomic approaches. The form of plant-available soil N varied as a function of fertilization, with (NH4)2SO4 and MBM fertilization retaining a higher proportion of N as ammoniacal-N throughout the growing period. Leaf nitrate reductase activity was 5 times higher in CaNO3 treatments, suggesting NO3- as the major N form taken up by plants in this treatment. Although ammoniacal-N fertilization resulted in lower plant biomass, the fruit yield and tissue nutrient content were similar to those of nitrate-N treatments. The plant biomass of organic-N treatment was similar to that of nitrate-N fertilization, but the fruit yield was 30% lower. Compared to nitrate-N treatment, aroma-related volatile compounds increased under organic- and ammoniacal-N fertilization, including up to a 5-fold increase in esters, a 6-fold increase in alcohols, a 3-fold increase in volatile fatty acids, and a 60% increase in organic acids. The content of primary metabolites, especially sugar, sugar alcohol, and amino acids, exhibited an opposite trend and increased in nitrate-N than under ammoniacal- and organic-N fertilization. Compared to nitrate-N, the secondary metabolites generally were higher under ammoniacal- and organic-N fertilization, with an 80% increase in the activity of phenylalanine ammonia lyase, resulting in up to 38% increase in flavones, 28% increase in flavanols, and 33% increase in anthocyanins, except for dihydroflavonols and proanthocyanidins, which decreased by 6 and 13%, respectively. The hydrolyzable tannins, including galloyl glucosides, ellagitannins, and ellagic acids, were 25% abundant under organic-N fertilization. Our results indicate that while nitrate-N generally increased the primary metabolites, organic-N and ammoniacal-N fertilization enhanced the aroma-related volatiles and secondary metabolites in strawberry fruits. Thus, precise management of the chemical form of N fertilization can be a valuable tool to improve the phytonutrient content of strawberries.PMID:40019181 | DOI:10.1021/acs.jafc.4c04734

J Glob Health. 2025 Feb 28;15:04056. doi: 10.7189/jogh.15.04056.ABSTRACTBACKGROUND: Despite advances in metabolomic research on COVID-19, existing studies have small sample sizes and few have comprehensively described the metabolic characteristics of patients with COVID-19 at each stage. In this systematic review, we aimed to summarise the similarities and differences of biomarkers in patients with COVID-19 of different severity and describe their metabolic characteristics at different stages.METHODS: We retrieved studies from PubMed, Embase, Web of Science, and the Cochrane Library published by October 2022. We performed a meta-analysis on untargeted and targeted metabolomics research data, using the ratio of means as the effect size. We compared changes in metabolite levels between patients with varying severity and controls and investigated sources of heterogeneity through subgroup analyses and meta-regression analysis.RESULTS: We included 22 cohorts from 21 studies, comprising 2421 participants, including COVID-19 patients of varying severity and healthy controls. We conducted meta-analysis and heterogeneity analysis on the 1058 metabolites included in the study. The results indicated that, compared to the healthy control group, 23 biomarkers were associated with mild cases (P < 0.05), 3 biomarkers with moderate cases (P < 0.05), and 37 biomarkers with severe cases (P < 0.05). Pathway enrichment analysis revealed significant disturbances in amino acid metabolism, aminoacyl-tRNA biosynthesis, primary bile acid biosynthesis, pantothenate and CoA biosynthesis, the tricarboxylic acid cycle, taurine and hypotaurine metabolism, and nitrogen metabolism in patients with mild, moderate, and severe disease. Additionally, we found that each severity stage exhibited unique metabolic patterns (all P < 0.05) and that the degree of metabolic dysregulation progressively worsened with increasing disease severity (P < 0.05).CONCLUSIONS: The results of our meta-analysis indicate the similarities and differences of biomarkers and metabolic characteristics of patients with different severity in COVID-19, thereby providing new pathways for the study of pathogenesis, the development precise treatment, and the formulation of comprehensive strategies.REGISTRATION: PROSPERO: CRD42022369937.PMID:40019163 | DOI:10.7189/jogh.15.04056

Food Funct. 2025 Feb 28. doi: 10.1039/d4fo05757k. Online ahead of print.ABSTRACTMethionine restriction has received some attention in recent years as a novel mode of dietary intervention. Our previous study found that methionine restriction could inhibit the celiac toxic effects of wheat gluten in an in vitro model. However, the role of methionine restriction in gluten-induced celiac intestinal damage remains unclear. The aim of this study was to explore whether dietary methionine restriction could suppress the celiac toxic effects of gluten in an in vivo model, thereby mitigating intestine damage. This study systematically investigated the effects of dietary methionine restriction on celiac characteristic indicators such as symptoms, small intestine damage, and intestinal TG2 and IL-15 expression in a gluten-induced C57BL/6 mouse model. The availability of dietary methionine restriction in different ages (adolescent and adult) was also evaluated. Moreover, mouse cecum contents were assayed and co-analyzed for the metagenome of intestinal flora and target short-chain fatty acid metabolomics, with the goal of further exploring and elucidating critical pathways by which dietary methionine restriction plays a role. We discovered that dietary methionine restriction could effectively ameliorate the gluten-induced celiac-associated small intestine damage by modulating intestinal flora to inhibit butyric acid production. Specifically, dietary methionine restriction could inhibit butyric acid production with the help of s_CAG-485 sp002493045 and s_CAG-475 sp910577815, which in turn affected the mitochondrial function within the intestinal epithelial cells to assist in the repair of intestine damage. This study might provide new insights into modulating dietary patterns to mitigate intestinal damage in celiac disease and the production of novel gluten-free products.PMID:40018976 | DOI:10.1039/d4fo05757k

Mol Nutr Food Res. 2025 Feb 28:e70003. doi: 10.1002/mnfr.70003. Online ahead of print.ABSTRACTFecal volatile organic compounds (VOCs) offer insights into gut microbiota function that may drive the pathogenesis of ulcerative colitis (UC). This cross-sectional study aimed to compare dietary intake and VOC patterns in UC patients with an ileoanal pouch compared to those with an intact colon. Seven-day food records and fecal samples were collected from UC patients with an intact colon (n = 28) or an ileoanal pouch (n = 11). Fecal VOC profiles were analyzed using gas chromatography-mass spectrometry. Dietary intake in both groups was largely similar. The mean Jaccard similarity index of VOC was 0.55 (95% CI:0.53, 0.56) in the pouch compared with 0.48 (0.47, 0.49) in the colon group (p < 0.01). A lower proportion of VOC classes was detected in the pouch, including sulfide (9% vs. 57%; p < 0.01), branched-chain fatty acids (BCFAs; 45%-64% vs. 93%-96%; p < 0.01), and ketones (45%-64% vs. 93%-96%; p < 0.01), along with a higher proportion of butyric acid (91% vs. 29%; p < 0.001). Unrelated to diet, VOC profiles show less functional diversity, reduced protein and greater carbohydrate fermentation, and altered production of secondary metabolites in the UC-pouch compared with the intact colon. These differences in the metabolic environment of the gut microbiota provide insights into pathogenesis and suggest that microbial-targeted interventions should be tailored accordingly.PMID:40018833 | DOI:10.1002/mnfr.70003

Biomed Chromatogr. 2025 Apr;39(4):e70040. doi: 10.1002/bmc.70040.ABSTRACTBile-processed Coptidis Rhizoma (BPCR) exhibits stronger efficacy in treating T2DM than Coptidis Rhizoma(CR) alone. However, the synergistic mechanism of its processing remains unknown. This study utilized HPLC to determine the content and dissolution characteristics of alkaloid components in BPCR before and after processing. The results indicated that the diffusion of the alkaloids in BPCR is stronger than that of CR, and their dissolution conforms to the Weibull equation. Additionally, BPCR significantly reduced fasting blood glucose (FBG) and serum insulin (FINS) levels in T2DM rats induced by a high-fat diet (HFD) and streptozotocin (STZ), improved glucose and lipid metabolism, and mitigated liver damage. Serum metabolomics analysis based on UPLC-Q-TOF-MS revealed that BPCR significantly regulates 27 endogenous differential biomarkers. The underlying mechanism may be related to glycerophospholipid metabolism, linoleic acid metabolism, steroid biosynthesis, and arachidonic acid metabolism pathways.PMID:40018812 | DOI:10.1002/bmc.70040

Mol Nutr Food Res. 2025 Feb 28:e70007. doi: 10.1002/mnfr.70007. Online ahead of print.ABSTRACTThis study investigates the metabolic impact of skim milk whey-derived protein concentrate (SPC) for infant formula, including its heat-treated (HT-SPC) and stored (HTS-SPC) variants, on the plasma, urine, and gut metabolites of newborn piglets, compared to conventional whey protein concentrate (WPC). Preterm piglets were fed formula containing WPC, SPC, HT-SPC, or HT-SPC, HTS-SPC for 5 days. Metabolomic analysis of plasma, urine, and colon content was performed using 1H NMR. Relative to WPC, SPC mainly affected colon content metabolites, increasing 19 metabolites in the colon and tyrosine in plasma, while decreasing pyruvate in colon content and glycine in plasma. Heat-treatment and storage of SPC led to increased metabolite concentrations in colon contents and urine. Notably, significant correlations between gut metabolites and abundant gut bacteria genes were observed only in the SPC-fed pigs. SPC induced higher branched chain amino acid concentrations in the gut, but had minimal effects on plasma and urinary metabolites, likely due to differences in dietary proteins and in microbiota metabolism. While the clinical effects of SPC-induced gut branched chain amino acids remain unclear, the results from our study suggest that SPC-based infant formula is metabolically safe for sensitive newborns, comparable to WPC-based formulas.PMID:40018800 | DOI:10.1002/mnfr.70007

Cancer Med. 2025 Mar;14(5):e70730. doi: 10.1002/cam4.70730.ABSTRACTBACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a predominant and highly lethal form of esophageal cancer, with a five-year survival rate below 20%. Despite advancements, most patients are diagnosed at advanced stages, limiting effective treatment options. Multi-omics integration, encompassing somatic genomic alterations, inherited genetic mutations, transcriptomics, proteomics, metabolomics, and single-cell sequencing, has enabled the identification of distinct molecular subtypes of ESCC.METHOD: This article systematically reviewed the current status of molecular subtyping of ESCC based on big data, summarized unique subtypes with differing treatment responses and prognostic outcomes.RESULT: Key findings included subtype-specific genetic mutations, signaling pathway alterations, and metabolomic profiles, which offer novel biomarkers and therapeutic targets. Furthermore, this review discusses the link between molecular subtypes and immunotherapy efficacy, chemotherapy response, and drug development.CONCLUSION: These insights highlight the potential of omics-based molecular typing to transform ESCC management and facilitate personalized treatment strategies.PMID:40018789 | DOI:10.1002/cam4.70730

Research (Wash D C). 2023 Feb 27;8:0629. doi: 10.34133/research.0629. eCollection 2025.ABSTRACTFamilial hypercholesterolemia (FH) is a lipoprotein disorder characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and an increased risk of premature atherosclerotic cardiovascular disease. Recent evidences have shown that several glycerophospholipid species were markedly altered in experimental FH animals and exhibited diverse bioactivities. Nevertheless, the glycerophospholipid profiles and their associated biological implications in human FH remain largely unknown. In this study, we sought to comprehensively delineate the glycerophospholipid phenotypes in human FH and to investigate the functional roles of key FH-altered glycerophospholipid molecules on cholesterol metabolism. Targeted analysis of 328 glycerophospholipid metabolites was used to profile the differentiated alterations in patients with homozygous FH (HoFH; n = 181), heterozygous FH (HeFH; n = 452), and non-FH hypercholesterolemia (n = 382). Our findings revealed that the glycerophospholipid phenotypes of FH and non-FH hypercholesterolemia were dominated by a spectrum of metabolites involved in the lysophosphatidic acid (LPA) metabolism. Among the LPA features, palmitoyl-LPA (16:0) showed significant association with the clinical levels of LDL-C and total cholesterol in HoFH and HeFH populations. Using functional metabolomic strategy and murine FH model, we demonstrated that supplementation with LPA 16:0 elevated the plasma levels of LDL and free/esterified cholesterol and exacerbated the atherosclerotic lesions. Conversely, inhibition of autotaxin-mediated LPA 16:0 production significantly ameliorated dyslipidemia. Mechanistically, we uncovered that LPA 16:0 could disrupt hepatic cholesterol homeostasis by impairing cholesterol excretion and inhibiting primary bile acid synthesis. In summary, our study offers novel insights into lipid metabolism in human FH and posits that targeting LPA metabolism may represent a promising therapeutic strategy for reducing cholesterol levels in the FH population.PMID:40018730 | PMC:PMC11865365 | DOI:10.34133/research.0629

Front Vet Sci. 2025 Feb 13;12:1496946. doi: 10.3389/fvets.2025.1496946. eCollection 2025.ABSTRACTINTRODUCTION: Understanding the impact of housing conditions on the stress responses in farmed saltwater crocodiles (Crocodylus porosus) is crucial for optimizing welfare and management practices.METHODS: This study employed a multi-omics methodology, combining targeted and untargeted LC-MS for metabolite, lipid, and hormone profiling with 16S rRNA gene sequencing for microbiome analysis, to compare stress responses and changes in fecal samples of crocodiles housed in single versus group pens. Metabolic responses to a startle test were evaluated through multivariate analysis, and changes post-stress were examined.RESULTS: A total of 564 metabolic features were identified. Of these, 15 metabolites were linked to the cortisol biosynthesis pathway. Metabolite origin analysis showed that 128 metabolites originated from the host, 151 from the microbiota, and 400 remained unmatched. No significant differences in fecal corticosterone levels were observed between single and group pens. However, metabolic profiling revealed distinct differences in stress responses: single pen crocodiles exhibited downregulation of certain compounds and upregulation of others, affecting pyrimidine and purine metabolism pathways when compared to grouped pen crocodiles, linked to altering energy associated induced stress. Additionally, fecal microbiome analysis indicated increased Firmicutes:Bacteroides (F:B) ratio in group-housed animals, suggesting greater stress.DISCUSSION: The study highlights that while traditional stress indicators like corticosterone levels may not differ significantly between housing conditions, metabolic and microbiome analyses provide deeper insights into stress responses. Single pens are associated with less metabolic disruption and potentially better health outcomes compared to group pens. These findings underscore the value of fecal microbiome and metabolomics in assessing animal welfare in farmed crocodiles.PMID:40018705 | PMC:PMC11865912 | DOI:10.3389/fvets.2025.1496946

Front Microbiol. 2025 Feb 13;16:1535451. doi: 10.3389/fmicb.2025.1535451. eCollection 2025.ABSTRACTBACKGROUND: Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder, usually accompanied by gut microbiota dysregulation. Gut microbiota homeostasis is considered effective for ASD. Reportedly, Dachaihu decoction (DCHD) can efficiently regulate gut microbiota and inflammation. However, the mechanisms underlying the effects of DCHD in the treatment of ASD remain unclear.OBJECTIVE: This study investigated the potential effects and mechanisms of DCHD in treating ASD.METHODS: In the animal experiment, propionic acid was administered to construct an ASD rat model. The ASD rats were treated with DCHD, and the efficacy was assessed using the behavioral detections, such as open field test, elevated plus maze test, novel object recognition test. Additionally, the levels of IL-6, TNF-α, IL-10, T-SOD, MDA, GSH and CAT were determined using kits, and histological staining was used to evaluate brain morphology. Moreover, tight junction proteins (ZO-1 and occludin) expression levels were evaluated using RT-qPCR, whereas Iba1 expression level was assessed by immunofluorescence staining. The 16S rRNA sequencing and metabolomic analysis of feces revealed the potential targets of DCHD against ASD. In a small human trail, the clinical scales ADOS-2 and Autism Behavior Checklist (ABC) assessed autism severity. Gastrointestinal problems and brain function were evaluated based on food intolerance and event-related potential, respectively.RESULTS: DCHD significantly improved autism-like behaviors and increased antioxidant enzyme activity, decreased inflammation and enhanced the intestinal barrier by the animal experiment. Furthermore, the DCHD treatment altered the gut microbiota profile, with increased probiotics Adlercreutzia, Parvibacter, Turicibacter, and Christensenellaceae. Further, DCHD increased the beneficial metabolite indole-3-acetate and decreased the cognitive impairment-related metabolites asymmetric dimethylarginine and homogentisic acid. Meanwhile, the small clinical trial revealed that DCHD significantly alleviated the core symptoms of ASD, with decreased ADOS-2 and ABC scale scores. DCHD also decreased the levels of specific egg white/yolk and milk IgG antibodies and shortened the MMN and P3b latencies.CONCLUSION: This study demonstrated that DCHD may alleviate ASD via inhibiting oxidative stress, reducing inflammation, and modulating the gut microbiota in rats. Combined with human trial, DCHD may be a promising drug for treating ASD. This study provides a scientific rationale for treating mental disorders related to gut microbiota dysbiosis.PMID:40018671 | PMC:PMC11867326 | DOI:10.3389/fmicb.2025.1535451

Front Endocrinol (Lausanne). 2025 Feb 13;15:1418932. doi: 10.3389/fendo.2024.1418932. eCollection 2024.ABSTRACTOBJECTIVE: CLCN7 mutation caused abnormal osteoclasts, resulting in osteopetrosis. Depending on the type of mutation, CLCN7 mutations can lead to severe or relatively benign forms of osteopetrosis. However, the serum metabolic alterations in osteopetrosis caused by CLCN7 mutation are still unknown. We aimed to investigate the differences in the metabolome of osteopetrosis patients caused by CLCN7 mutation versus healthy controls (HC), uncovering potential subtype diagnosis biomarkers.METHODS: 19 osteopetrosis patients caused by CLCN7 mutation and 19 HC were recruited for liquid chromatography-tandem mass spectrometry analysis. The screened pathway was validated in the myeloid cell specific Clcn7G763R mutant mouse model by quantitative real-time PCR analysis.RESULTS: Three metabolic pathways were significantly enriched, including glycerophospholipid metabolism (P=0.036948), arachidonic acid metabolism (P=0.0058585) and linoleic acid metabolism (P=0.032035). Ten differential expressed metabolites were located in these three pathways and classified ability with areas under the curve over 0.7 in receiver operating characteristic analysis, suggesting a certain accuracy for being the potential biological markers. Especially, we found that the proteins in glycerophospholipid metabolism were predicted to interact with ClC-7 and further verified that the expression of coding genes were significantly up-regulated in myeloid cell specific Clcn7G763R mutant mouse.CONCLUSION: This study provides data on serum metabolomics in osteopetrosis caused by CLCN7 mutation and provides new potential metabolic markers and pathways for diagnosis and pathogenesis of osteopetrosis.PMID:40018371 | PMC:PMC11865745 | DOI:10.3389/fendo.2024.1418932

Front Mol Biosci. 2025 Feb 13;12:1567250. doi: 10.3389/fmolb.2025.1567250. eCollection 2025.NO ABSTRACTPMID:40017631 | PMC:PMC11865747 | DOI:10.3389/fmolb.2025.1567250

Front Mol Biosci. 2025 Feb 13;12:1524121. doi: 10.3389/fmolb.2025.1524121. eCollection 2025.ABSTRACTINTRODUCTION: Non-functioning adrenal adenomas (NFAs) are typically regarded as benign tumors that lack hormonal secretion. However, emerging evidence has shown that some patients with NFAs and hypertension experience improvements in blood pressure after adrenalectomy, indicating a potential correlation between NFAs and hypertension. Nevertheless, the precise mechanisms that underpin this phenomenon remain elusive.METHODS: We collected data from all patients with adrenal adenomas who underwent unilateral laparoscopic partial or total adrenalectomy at the First Affiliated Hospital of Xi'an Jiaotong University in 2023. A statistical analysis was conducted on factors such as tumor diameter, duration of hypertension, BMI, and age. Additionally, we gathered serum samples from six patients who experienced postoperative blood pressure improvement and six patients who did not. These samples were subjected to targeted and untargeted metabolomic analyses to identify significant serum metabolites.RESULTS: Our findings revealed that 50.9% of patients with NFAs and hypertension experienced blood pressure improvement after surgery. Additionally, patients in the improvement group (IG) exhibited larger tumor diameters alongside shorter durations of hypertension compared to their counterparts in the nonimprovement group (NIG). Untargeted metabolomic analysis identified 89 differentially abundant metabolites in the serum between the IG and NIG. In particular, we found that guanidinoacetic acid (GAA), a precursor of creatine synthesis that possibly participates in the occurrence of hypertension, was enriched in patients in the IG and reduced after surgery.DISCUSSION: The findings of our study indicated that duration of hypertension and tumor diameter may exert an influence on the extent of postoperative blood pressure improvement, and NFAs might promote hypertension through GAA-related creatine metabolism.PMID:40017629 | PMC:PMC11864923 | DOI:10.3389/fmolb.2025.1524121

Front Pharmacol. 2025 Feb 13;16:1547131. doi: 10.3389/fphar.2025.1547131. eCollection 2025.ABSTRACTThe process of drug discovery and development is both lengthy and intricate, demanding a substantial investment of time and financial resources. Bioinformatics techniques and tools can not only accelerate the identification of drug targets and the screening and refinement of drug candidates, but also facilitate the characterization of side effects and the prediction of drug resistance. High-throughput data from genomics, transcriptomics, proteomics, and metabolomics make significant contributions to mechanics-based drug discovery and drug reuse. This paper summarizes bioinformatics technologies and tools in drug research and development and their roles and applications in drug research and development, aiming to provide references for the development of new drugs and the realization of precision medicine.PMID:40017606 | PMC:PMC11865229 | DOI:10.3389/fphar.2025.1547131

J Agric Food Chem. 2025 Feb 28. doi: 10.1021/acs.jafc.4c09602. Online ahead of print.ABSTRACTIrinotecan (CPT-11) is a chemotherapy agent commonly used for the treatment of gastrointestinal tumors, with diarrhea being a frequent adverse effect. Hesperidin is a flavonoid abundant in citrus fruits and has shown potential in managing CPT-11-induced diarrhea (CID). However, the mechanisms underlying its effects remain unclear. This study established a mouse model of CID using CPT-11 administration to evaluate the effects of hesperidin on diarrhea severity, intestinal pathology, gut microbiota composition, and metabolite profiles by conducting biochemical analysis, histopathology, immunohistochemistry, 16S rRNA sequencing, and untargeted metabolomics. In addition, transcriptomic analysis, molecular docking, and molecular dynamics simulations were conducted to investigate potential mechanisms of action. Hesperidin supplementation was found to significantly alleviate CID in mice. Analysis of gut microbiota using 16S rRNA sequencing revealed that hesperidin improved microbial composition, with key taxa such as Alistipes, Limosilactobacillus, Rikenella, and Mucispirillum playing a central role in ameliorating CID. Furthermore, hesperidin enhanced intestinal barrier function by upregulating tight junction proteins, mitigating epithelial damage, and reducing the expression of IL-17A, TARF6, p38, phosphorylated-p38 (P-p38), and AP-1 proteins in the colon. These findings suggest that hesperidin supplementation mitigates CID by modulating gut microbiota and inhibiting the IL-17 signaling pathway, thereby improving intestinal barrier integrity.PMID:40017447 | DOI:10.1021/acs.jafc.4c09602

J Fish Biol. 2025 Feb 28. doi: 10.1111/jfb.70009. Online ahead of print.ABSTRACTCo-infection with infectious haematopoietic necrosis virus (IHNV) and Flavobacterium psychrophilum is increasing in prevalence in salmonid aquaculture, and this is accompanied by increased economic losses. The aim of this study was to investigate the synergistic effects of IHNV and F. psychrophilum co-infection on mortality and pathophysiology in masu salmon Oncorhynchus masou. We performed challenge experiments involving co-infection with these pathogens and analysed the proteomic profiles in the kidneys of deceased fish using liquid chromatography tandem mass spectrometry (LC-MS/MS). The onset of co-infectious disease started earlier, and the mortality rate was significantly higher (90%-100%) compared with single infection. Moreover, co-infected fish exhibited severe clinical signs, which were a combination of the clinical signs associated with each single pathogen. Proteomic analysis found that the innate immune response and metabolomic pathways involving pentose-phosphate, fructose and nucleotides were altered in deceased co-infected fish compared with mono-infected fish, and fructose metabolism and the pentose-phosphate cycle were activated in co-infected deceased fish. These findings highlight the need for more comprehensive preventive measures to reduce the risk of multiple pathogen infections and improve the management of co-infectious diseases.PMID:40017429 | DOI:10.1111/jfb.70009

Plant Commun. 2025 Feb 26:101293. doi: 10.1016/j.xplc.2025.101293. Online ahead of print.ABSTRACTThe rapid growth of population-scale whole genome resequencing, RNA sequencing, bisulfate sequencing, metabolomics and proteomic profiling has led quantitative genetics into a big omics data era. Performing omics data association analysis, such as genome, transcriptome, proteome and methylome wide association analysis, and integrative analysis on multiple omics datasets requires various bioinformatics tools that rely on advanced programming skills and command-line tools, which are challenging for wet-lab biologists. Here, we present EasyOmics a stand-alone R Shiny application with a user-friendly interface for wet-lab biologists to perform population-scale omics data association, integration and visualization. The toolkit incorporates multiple functions designed to meet the increasing demand for population-scale omics data analyses, ranging from data quality control, heritability estimation, genome-wide association analysis, conditional association analysis, omics quantitative trait locus mapping, omics-wide association analysis, omics data integration and visualization etc. A wide range of publication quality graphs can be prepared in EasyOmics with point-and-click. EasyOmics is a platform-independent software that can be run under all operating systems with a docker container for quick installation. It is freely available to non-commercial users at docker hub https://hub.docker.com/r/yuhan2000/easyomics.PMID:40017036 | DOI:10.1016/j.xplc.2025.101293

Hereditas. 2025 Feb 27;162(1):29. doi: 10.1186/s41065-025-00384-w.ABSTRACTBACKGROUND: Bladder cancer (BLCA) represents one of the most prevalent urological malignancies worldwide. Bridging integrator 1 (BIN1), a well-characterized tumor suppressor that interacts with and inhibits oncogenic Myc transcription factors, has demonstrated crucial roles in various cancer types. However, its specific functions and underlying molecular mechanisms in BLCA development and progression remain poorly understood. This study aims to elucidate the role of BIN1 in regulating BLCA cell proliferation, metastasis, and cancer stem cell properties.METHODS: Using urinary proteomics analysis, we identified BIN1 as a significantly dysregulated protein in BLCA. The clinical significance of BIN1 was further validated through comprehensive analyses of public databases. BIN1 expression levels defined distinct molecular and immunological subtypes of BLCA. Through proteomic profiling of BIN1-overexpressing UMUC3 cells and corresponding controls, we identified ALDH1 as a key downstream effector in the BIN1-regulated ALDH1/NOTCH signaling axis. We employed multiple experimental approaches, including Western blot analysis, quantitative RT-PCR, immunofluorescence staining, wound healing assays, transwell migration assays, colony formation assays, tumor sphere formation assays, flow cytometry, CCK8 proliferation assays, and cell transfection experiments.RESULTS: We observed significant downregulation of BIN1 in both BLCA tissues and cell lines compared to normal adjacent tissues and SV-HUC-1 cells, respectively. BIN1 overexpression inhibited cancer cell proliferation by promoting apoptosis and suppressed epithelial-mesenchymal transition (EMT), thereby reducing local invasion and distant metastasis. Additionally, BIN1 regulated cancer stem cell properties through modulation of ALDH1 expression, with NOTCH2 acting as a crucial downstream mediator of ALDH1 signaling.CONCLUSION: Our findings demonstrate that BIN1 functions as a tumor suppressor in BLCA and suggest its potential utility as both a diagnostic biomarker and therapeutic target for BLCA treatment.PMID:40016843 | DOI:10.1186/s41065-025-00384-w

BMC Genomics. 2025 Feb 27;26(1):200. doi: 10.1186/s12864-025-11389-0.ABSTRACTBACKGROUND: Melatonin improves the production performance of animal furs, particularly in promoting wool and cashmere growth. Although most studies of melatonin enhancing cashmere growth have focused primarily on gene and phenotype levels, its impact on metabolites has not received attention. To investigate the influence of melatonin on metabolites, genes, gene‒metabolite interactions, and associated signaling pathways in secondary hair follicles (SHFs), we performed multiomics analyses of skin and blood samples collected 30 days after sustained melatonin release.RESULTS: The results demonstrated that two melatonin interventions during SHF anagen in cashmere goats induce the early growth of SHFs, increase the active secondary follicle density (ASFD), and improve cashmere yield and quality. Transcriptomic analysis revealed 509 differentially expressed genes (DEGs), including key genes such as KRTs and KRTAPs, and genes associated with the WNT signaling pathway (LEF1, WNT3/4, and FZD3/5), suggesting their critical roles in melatonin-mediated SHF development. Metabolomic analysis revealed 842 metabolites in the skin samples and 1,162 in the blood samples. Among these, 177 differentially regulated metabolites (DRMs) in the skin were significantly enriched in pathways such as alpha-linolenic acid metabolism, glyoxylate and dicarboxylate metabolism, the citrate cycle (TCA cycle), and several amino acid metabolic pathways. Similarly, 122 DRMs in the blood were enriched in pathways related to protein digestion and absorption, central carbon metabolism in cancer, and aminoacyl-tRNA biosynthesis. Finally, the integrative analysis revealed partially coenriched metabolic pathways and relationships between DEGs and DRMs.CONCLUSIONS: In summary, by integrating transcriptomics and metabolomics, this study provides novel insights into the role of melatonin in promoting SHF development. Furthermore, these findings establish a theoretical foundation for the broader application of melatonin-based technologies to promote cashmere growth.PMID:40016679 | DOI:10.1186/s12864-025-11389-0

BMC Nephrol. 2025 Feb 27;26(1):104. doi: 10.1186/s12882-025-04026-1.ABSTRACTBACKGROUND: Perform proteomic and metabolomic analysis on bilateral renal pelvis urine of patients with unilateral calcium oxalate kidney stones to identify the specific urinary microenvironment associated with stone formation.METHODS: Using cystoscopy-guided insertion of ureteral catheters, bilateral renal pelvis urine samples are collected. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is employed to identify differential proteins and metabolites in the urine microenvironment. Differentially expressed proteins and differential metabolites are further analyzed for their biological functions and potential metabolic pathways through Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, Reactome pathway analysis and Biomolecular Interaction Network Database protein-protein interaction (PPI) network analysis.RESULTS: In the urine from the stone-affected side, 36 differential proteins were significantly upregulated, 4 differential proteins were downregulated, and 10 differential metabolites were significantly upregulated. Functional and pathway analyses indicate that the differentially expressed proteins are primarily involved in inflammatory pathways and complement and coagulation cascades, while the differential metabolites are mainly associated with oxidative stress.CONCLUSION: The proteomic and metabolomic profiles of the urinary microenvironment in stone-affected kidneys provide a more precise reflection of the pathophysiological mechanisms involved in stone formation and development.PMID:40016672 | DOI:10.1186/s12882-025-04026-1