Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Microplastic effects on mouse colon in normal and colitis conditions: A literature review

3 hours 25 min ago
PeerJ. 2025 Feb 10;13:e18880. doi: 10.7717/peerj.18880. eCollection 2025.ABSTRACTBACKGROUND: Taking into account the global spread of microplastic (MP) pollution, the problem of the MP impact on human health is relevant. MP enters the organism predominantly with water and food, and is mostly detected in the large intestine. Therefore, the connection between MP pollution and the increase in colitis is an important question. In order to assess the toxic and pathogenetic effects of MP, experimental studies were actively conducted during recent years, mainly on laboratory mice.OBJECTIVES: The aim of our review was to summarize and systematize the data on the MP effect on mice colon under normal conditions and during colitis in order to assess the role of MP in the development of intestinal diseases. This manuscript could be relevant for ecologists, experimental biologists, and physicians dealing with problems related to anthropogenic environmental changes and inflammatory bowel diseases.SURVEY METHODOLOGY: The search was conducted based on PubMed data about original experimental studies of the MP effects on the colon of healthy mice and mice with colitis.RESULTS: In healthy mice colon, MP can cause oxidative stress, increased permeability, immune cell infiltration, production of proinflammatory factors, and decreased mucus production. MP affects proliferation, apoptosis, and differentiation of epithelial cells, expression of tight junction components and glycocalyx, membrane transport, signaling pathways, metabolome, and intestinal microflora composition. In mice with acute and chronic experimental colitis, MP consumption leads to a more pronounced pathological process course.CONCLUSIONS: MP may be one of the factors contributing to the development of colitis in humans. However, further research is needed.PMID:39950042 | PMC:PMC11823654 | DOI:10.7717/peerj.18880

Elucidating the pharmacological foundations and mechanisms of the Sihai Shuyu formula in treating Graves' disease through integrated serum metabolomics and network pharmacology with molecular docking techniques

3 hours 25 min ago
Front Endocrinol (Lausanne). 2025 Jan 30;16:1511808. doi: 10.3389/fendo.2025.1511808. eCollection 2025.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: The Sihai Shuyu Formula (SHSY) shows promising potential for treating Graves' disease (GD), although the therapeutic mechanisms and pharmacological basis of SHSY have not been thoroughly evaluated.OBJECTIVE: This work is aim to investigate the pharmacological basis and mechanism of SHSY in the treatment of GD by integrating non-targeted serum metabolomics and network pharmacology coupled with molecular docking technology.MATERIALS AND METHODS: GD was induced in mice through injections of Ad-TSH289. Treatments included methimazole, inorganic iodine, and both low and high doses of SHSY administered via gavage. At the end of the treatment period, serum levels of thyroxine (T4) and thyrotropin receptor antibody (TRAb) were measured. Hematoxylin-Eosin (H&E) staining assessed the effects of these pharmacological interventions on thyroid gland tissues. Ultra-High Performance Liquid Chromatography with Quadrupole Time-of-Flight Mass Spectrometry (UPLC-Q-TOF-MS) was used in conjunction with network pharmacology and molecular docking to identify and predict SHSY's active chemical components and targets. A comprehensive analysis of the multi-level bioinformatic analysis, including protein-protein interactions (PPI) and functional pathways of the targets, was conducted, followed by verification through immunohistochemistry (IHC) to clarify SHSY's pharmacological basis and action mechanisms in treating GD.RESULTS: After 8 weeks of treatment, SHSY significantly reduced serum T4 and TRAb levels in GD mice and enhanced the morphology of thyroid tissues. Comparative analysis of rat blood samples and SHSY using UPLC-Q-TOF-MS identified 19 blood-entry components, the potential active components of SHSY acting on GD. Further network pharmacological analysis indicated that SHSY targets the PI3K/Akt signaling pathway through components such as PIK3CD, SRC, PIK3CA, HRAS, EGFR, PIK3R1, AKT1, PTPN11, and PIK3CB. Molecular docking confirmed the effective binding of SHSY's components to these targets. IHC confirmed that the IGF1R/PI3K/Akt signaling pathway is a significant therapeutic target of SHSY, with key substances including Guggulsterone, Betulinic aldehyde, and Forsythoside H.CONCLUSIONS: SHSY appears to effectively treat GD through the IGF1R/PI3K/Akt signaling pathway, with Guggulsterone, Betulinic aldehyde, and Forsythoside H as the critical pharmacological components. It may serve as an adjunctive treatment for GD alongside traditional therapies such as antithyroid medications, surgery, and radioiodine therapy.PMID:39950029 | PMC:PMC11821505 | DOI:10.3389/fendo.2025.1511808

Microbiota-derived 3-Methyl-L-histidine mediates the proatherogenic effect of high chicken protein diet

3 hours 25 min ago
MedComm (2020). 2025 Feb 13;6(2):e70090. doi: 10.1002/mco2.70090. eCollection 2025 Feb.ABSTRACTDiet rich in chicken protein has gained a widespread popularity for its profound effect on weight loss and glycemic control; however, its long-term effect on cardiovascular health and the underlying mechanisms remains obscure. Here, we demonstrated that higher intake of chicken protein was an independent risk factor for sub-clinical atherosclerosis. Adherence to high chicken protein diet (HCD) alleviated excessive weight gain and glycemic control regardless of the presence of gut microbiota in apolipoprotein E-deficient mice. In contrast, long-term HCD administration enhanced intestinal cholesterol absorption and accelerated atherosclerotic plaque formation in a gut microbiota-dependent manner. Integrative analysis of 16S rDNA sequencing and metabolomics profiling identified 3-Methyl-L-histidine (3-MH), resulting from an enrichment of Lachnospiraceae, as the key microbial effector to the atherogenic effect of HCD. Mechanistically, 3-MH facilitated the binding of hepatocyte nuclear factor 1A (HNF1A) to the promoter of NPC1-like intracellular cholesterol transporter 1 (NPC1L1), whereas inhibition of HNF1A-NPC1L1 axis abolished the atherogenic effect of 3-MH. Our findings uncovered a novel link between microbiota-derived 3-MH and disturbed cholesterol homeostasis, which ultimately accelerated atherosclerosis, and argued against the recommendation of HCD as weight loss regimens considering its adverse role in vascular health.PMID:39949981 | PMC:PMC11822454 | DOI:10.1002/mco2.70090

Tumor Treating Fields enhance chemotherapy efficacy by increasing cellular drug uptake and retention in mesothelioma cells

3 hours 25 min ago
Am J Cancer Res. 2025 Jan 15;15(1):271-285. doi: 10.62347/ODWL5634. eCollection 2025.ABSTRACTTumor Treating Fields (TTFields) applied with standard chemotherapy have been approved for the first-line treatment of unresectable pleural mesothelioma (PM), an aggressive malignancy with limited effective therapy options. In this study, we demonstrated that the simultaneous exposure to TTFields and doxorubicin or vinorelbine enhanced treatment efficacy in patient-derived PM cells by increasing intracellular drug concentrations. This was achieved by modulating several genes that encode transport proteins, such as the downregulation of P-glycoprotein (P-gp). Using specific, sensitive and quantitative analytical techniques, we observed a more than 70% increase in intracellular concentrations of doxorubicin and vinorelbine in samples treated with TTFields, and a greater than 50% increase in drug uptake in cells exposed to TTFields and pemetrexed. This result indicates that the increased drug concentration observed in TTFields treated cells is significant not only for drugs that are P-gp substrates but also suggests that TTFields could potentially affect other efflux pumps. However, the co-exposure to the drug and TTFields was critical to increasing intracellular drug levels, highlighting the necessity of concurrent use with drugs to enhance the antiproliferative effects of treatment. The in vitro findings were further corroborated by in vivo pharmacokinetic experiments in mice subcutaneously injected with epithelioid PM tumors. Indeed, a 30% increase in intratumor concentrations was observed when vinorelbine was administered with TTFields. Our findings suggest that TTFields could be a well-tolerated approach for enhancing intratumoral drug levels and potentially achieving a more significant therapeutic impact on PM treatment.PMID:39949944 | PMC:PMC11815374 | DOI:10.62347/ODWL5634

Identification of urinary metabolites correlated with tacrolimus levels through high-precision liquid chromatography-mass spectrometry and machine learning algorithms in kidney transplant patients

3 hours 25 min ago
Med Pharm Rep. 2025 Jan;98(1):125-134. doi: 10.15386/mpr-2805. Epub 2025 Jan 31.ABSTRACTBACKGROUND AND AIM: Tacrolimus, a widely used immunosuppressive drug in kidney transplant recipients, exhibits a narrow therapeutic window necessitating careful monitoring of its concentration to balance efficacy and minimize dose-related toxic effects. Although essential, this approach is not optimal, and tacrolinemia, even in the therapeutic interval, might be associated with toxicity and rejection within range. This study aimed to identify specific urinary metabolites associated with tacrolimus levels in kidney transplant patients using a combination of serum high-precision liquid chromatography-mass spectrometry (HPLC-MS) and machine learning algorithms.METHODS: A cohort of 42 kidney transplant patients, comprising 19 individuals with high tacrolimus levels (>8 ng/mL) and 23 individuals with low tacrolimus levels (<5 ng/mL), were included in the analysis. Urinary samples were subjected to HPLC-MS analysis, enabling comprehensive metabolite profiling across the study cohort. Additionally, tacrolimus concentrations were quantified using established clinical assays.RESULTS: Through an extensive analysis of the HPLC-MS data, a panel of five metabolites were identified that exhibited a significant correlation with tacrolimus levels (Valeryl carnitine, Glycyl-tyrosine, Adrenosterone, LPC 18:3 and 6-methylprednisolone). Machine learning algorithms were then employed to develop a predictive model utilizing the identified metabolites as features. The logistic regression model achieved an area under the curve of 0.810, indicating good discriminatory power and classification accuracy of 0.690.CONCLUSIONS: This study demonstrates the potential of integrating HPLC-MS metabolomics with machine learning algorithms to identify urinary metabolites associated with tacrolimus levels. The identified metabolites are promising biomarkers for monitoring tacrolimus therapy, aiding in dose optimization and personalized treatment approaches.PMID:39949902 | PMC:PMC11817595 | DOI:10.15386/mpr-2805

High-quality genome of black wolfberry (<em>Lycium ruthenicum</em> Murr.) provides insights into the genetics of anthocyanin biosynthesis regulation

3 hours 25 min ago
Hortic Res. 2024 Oct 23;12(2):uhae298. doi: 10.1093/hr/uhae298. eCollection 2025 Feb.ABSTRACTBlack wolfberry (Lycium ruthenicum Murr.) is an important plant for ecological preservation. In addition, its fruits are rich in anthocyanins and have important edible and medicinal value. However, a high-quality chromosome-level genome for this species is not yet available, and the regulatory mechanisms involved in the biosynthesis of anthocyanins are unclear. In this study, haploid material was used to assemble a high-quality chromosome-level reference genome of Lycium ruthenicum, resulting in a genome size of 2272 Mb with contig N50 of 92.64 Mb, and 38 993 annotated gene models. In addition, the evolution of this genome and large-scale variations compared with the Ningxia wolfberry Lycium barbarum were determined. Importantly, homology annotation identified 86 genes involved in the regulatory pathway of anthocyanin biosynthesis, five of which [LrCHS1 (evm.TU.Chr05.295), LrCHS2 (evm.TU.Chr09.488), LrAOMT (evm.TU.Chr09.809), LrF3'5'H (evm.TU.Chr06.177), and LrAN2.1 (evm.TU.Chr05.2618)] were screened by differential expression analysis and correlation analysis using a combination of transcriptome and metabolome testing. Overexpression of these genes could significantly up- or downregulate anthocyanin-related metabolites. These results will help accelerate the functional genomic research of L. ruthenicum, and the elucidation of the genes involved in anthocyanin synthesis will be beneficial for breeding new varieties and further exploring its ecological conservation potential.PMID:39949881 | PMC:PMC11822397 | DOI:10.1093/hr/uhae298

Relevance of proteomics and metabolomics approaches to overview the tumorigenesis and better management of cancer

3 hours 25 min ago
3 Biotech. 2025 Mar;15(3):58. doi: 10.1007/s13205-025-04222-8. Epub 2025 Feb 11.ABSTRACTProteomics and metabolomics, integral combination of OMICs platform are gaining prominence in cancer research to enhance scientific knowledge of bio-molecular interactions occurs in the cellular processes during cancer progression. This approach designed to identify potential tools for addressing the complexities of this multifaceted disease. This analysis focussed on the intricate interplay between proteins and metabolites within cancer cells and their surrounding microenvironment. By reviewing current proteomics and metabolomics studies, we aim to gain invaluable insights into tumour biology, progression, and its implication in therapeutic responses. This study highlights the importance of proteomics and metabolomics in discovering therapeutic targets and diagnostic biomarkers for targeted cancer treatment. Proteomics facilitates the analysis of protein expression, modifications and interactions, exemplified by the identification of HER2 mutations leads to development of breast cancer hence targeted therapies like trastuzumab could be initiated. Metabolomics reveals metabolic alternations such as elevated 2-hydroxyglutarate levels in gliomas linked to cancer progression and treatment resistance. The integration of these approaches clarifies complex signalling network driving oncogenesis and paves the way for innovative cancer therapies, including immune cheque point inhibitors. Proteomics and metabolomics have revolutionised cancer biology by revealing intricate signalling networks, metabolic dysregulations, and unique molecular alterations. This information is crucial for early cancer identification and prognosis, and for designing personalized therapeutic strategies. Innovative technologies like artificial intelligence and high-throughput mass spectrometry further enhance the potential of these studies. Fostering multidisciplinary collaboration and data-sharing is essential for maximising the impact of these approaches to cure as well as better management of the cancer.PMID:39949840 | PMC:PMC11813842 | DOI:10.1007/s13205-025-04222-8

Metabolome and transcriptome association study reveals biosynthesis of specialized benzylisoquinoline alkaloids in Phellodendron amurense

3 hours 25 min ago
Chin Herb Med. 2024 Nov 9;17(1):178-188. doi: 10.1016/j.chmed.2024.11.003. eCollection 2025 Jan.ABSTRACTOBJECTIVE: Benzylisoquinoline alkaloids (BIAs) have pharmacological functions and clinical use. BIAs are mainly distributed in plant species across the order Ranunculales and the genus Phellodendron from Sapindales. The BIA biosynthesis has been intensively investigated in Ranunculales species. However, the accumulation mechanism of BIAs in Phellodendron is largely unknown. The aim of this study is to unravel the biosynthetic pathways of BIAs in Phellodendron amurens.METHODS: The transcriptome and metabolome data from 18 different tissues of P. amurense were meticulously sequenced and subsequently subjected to a thorough analysis. Weighted gene co-expression network analysis (WGCNA), a powerful systems biology approach that facilitates the construction and subsequent analysis of co-expression networks, was utilized to identify candidate genes involved in BIAs biosynthesis. Following this, recombinant plasmids containing candidate genes were expressed in Escherichia coli, a widely used prokaryotic expression system. The purpose of this genetic engineering endeavor was to express the candidate genes within the bacteria, thereby enabling the assessment of the resultant enzyme activity.RESULTS: The synonymous substitutions per synonymous site for paralogs indicated that at least one whole genome duplication event has occurred. The potential BIA biosynthetic pathway of P. amurense was proposed, and two PR10/Bet v1 members, 14 CYP450s, and 33 methyltransferases were selected as related to BIA biosynthesis. One PR10/Bet v1 was identified as norcoclaurine synthase, which could catalyze dopamine and 4-hydroxyphenylacetaldehyde into (S)-norcoclaurine.CONCLUSION: Our studies provide important insights into the biosynthesis and evolution of BIAs in non-Ranunculales species.PMID:39949809 | PMC:PMC11814251 | DOI:10.1016/j.chmed.2024.11.003

Replacing rice straw with peanut vine and <em>Broussonetia papyrifera</em> silage in beef cattle feed reduced the use of soybean meal

3 hours 25 min ago
Anim Nutr. 2024 Dec 13;20:42-53. doi: 10.1016/j.aninu.2024.11.013. eCollection 2025 Mar.ABSTRACTThe present study investigated whether replacing dietary rice straw with peanut vine (PEV) and Broussonetia papyrifera silage (BPS) reduces the use of soybean meal and explored its effects on the growth performance, blood biochemical indicators, serum metabolomics, and meat quality of fattening bulls. Forty-five Simmental crossbred bulls (initial body weight = 484.29 ± 8.49 kg) were randomly allotted into three dietary treatment groups (n = 15): (1) CON, 5% rice straw (DM basis); (2) PEV, 5% peanut vine (DM basis); and (3) BPS, 5% B. papyrifera silage (DM basis). The remaining roughage for all three treatment groups was supplemented with 25% corn silage (DM basis). The experiment lasted for 123 d, with the first 14 d serving as an adaptive period. Throughout the experiment, dietary BPS decreased the average daily dry matter intake (P < 0.001) and feed cost (P < 0.001). Serum metabolomics analysis showed that PEV affected the phenylalanine, tyrosine, and tryptophan biosynthesis pathways (P = 0.021) and lysine degradation pathway (P = 0.042), whereas BPS affected the phenylalanine, tyrosine and tryptophan biosynthesis pathways (P = 0.004), lysine degradation pathway (P = 0.012), and serotonergic synapse pathway (P < 0.001). Regarding meat quality, the redness (P = 0.025) and hue angle values (P < 0.001) of the longissimus dorsi muscle were lower in the BPS group than in the CON and PEV groups. The yellowness of the longissimus dorsi muscle was lower in the BPS group than in the PEV group (P = 0.024), and the shear force was lower in the PEV group than in the BPS group (P = 0.014). However, lysine content in beef was higher in the BPS group than in the CON group (P = 0.005). In conclusion, replacing rice straw with PEV and BPS reduced the use of soybean meal but had no adverse effects on growth performance. BPS affected the amino acid metabolism of bulls, thus decreasing feed intake and increasing the lysine content in meat. The PEV group showed better meat quality than the BPS group.PMID:39949735 | PMC:PMC11821392 | DOI:10.1016/j.aninu.2024.11.013

Dietary supplementation of <em>Lycium barbarum</em> polysaccharides alleviates soybean meal-induced enteritis in spotted sea bass <em>Lateolabrax maculatus</em>

3 hours 25 min ago
Anim Nutr. 2024 Nov 15;20:1-22. doi: 10.1016/j.aninu.2024.10.005. eCollection 2025 Mar.ABSTRACTThe aim of this experiment was to investigate the effect of Lycium barbarum polysaccharides (LBP) on alleviating soybean meal-induced enteritis (SBMIE) in spotted sea bass Lateolabrax maculatus. The diet with 44% fishmeal (FM) content was used as a blank control, and soybean meal (SM) was used to replace 50% FM as an experimental control to induce enteritis. Then, on the basis of experimental control, 0.10%, 0.15%, and 0.20% LBP were added as experimental diets. A total of 225 spotted sea bass (44.52 ± 0.24 g) were randomly divided into 5 groups and fed the corresponding diets for 52 d. The results showed that 0.15% LBP decreased serum D-lactic acid (D-LA) content and diamine oxidase (DAO) activity (P < 0.05). In addition, in all LBP supplementation groups, the intestinal tissue morphology was significantly improved (P < 0.05); the intestinal microbial structure gradually recovered to a level close to that without adding SM; and the microbial species richness and diversity were significantly increased (P < 0.05). Through transcriptomic and metabolomic analysis, it was found that the expression of proinflammatory factors such as interleukin-1β (IL-1β), interleukin-12 (IL-12), nuclear factor kappa B subunit 2 (NF-κB2), and Toll-like receptor 2 (TLR2) were significantly down-regulated in the mitogen-activated protein kinase (MAPK) and Toll-like receptor signaling pathways (P < 0.05), and the important tight junction protein gene Occludin was up-regulated (P < 0.05). In addition, LBP down-regulated saponin metabolites and up-regulated amino acid metabolites (P < 0.05). In conclusion, LBP demonstrated a significant alleviating effect on SBMIE of spotted sea bass L. maculatus.PMID:39949731 | PMC:PMC11815959 | DOI:10.1016/j.aninu.2024.10.005

Folic acid alleviates the negative effects of dexamethasone induced stress on production performance in Hyline Brown laying hens

3 hours 25 min ago
Anim Nutr. 2024 Dec 14;20:54-65. doi: 10.1016/j.aninu.2024.11.011. eCollection 2025 Mar.ABSTRACTMultiple stressors are believed to deteriorate production performance and cause substantial economic losses in commercial poultry farming. Folic acid (FA) is an antioxidant compound that can improve oocyte function and regulate gut microbiota composition. The current study was conducted to investigate the role of FA in alleviating stress and improving production performance. Sixty Hyline Brown laying hens at 21 weeks of age were randomly divided into three groups, with 10 replicates in each group and each replicate containing two chickens. Each group received basic diet and saline injection (Con group), basic diet with dexamethasone (DXM) injection (DXM group), or basic diet supplemented with FA (13 mg/kg in the premix) with DXM injection (FA group). The feeding trial lasted five weeks. Birds in the DXM and FA groups receiving subcutaneous DXM injections at a dosage of 4.50 mg/kg per day during the first seven days of the trial. Results showed that the levels of corticosterone, triglyceride, total cholesterol, and malondialdehyde in serum were significantly increased in the DXM group (P < 0.05), while the concentrations of FA and 5-methyltetrahydrofolate were decreased in the DXM group (P < 0.05). Laying hens in the DXM group had lower laying rates and egg quality, including egg weight, eggshell thickness, eggshell strength, albumen height, and Haugh units (P < 0.05). Conversely, FA alleviated these negative impacts. Through transcriptome analysis, a total of 247 and 151 differentially expressed genes were identified among the three groups, and 32 overlapped genes were further identified. Moreover, 44 and 59 differential metabolites were influenced by DXM and FA, respectively. Kyoto Encyclopedia of Genes and Genomes enrichment from the transcriptome and metabolomics showed that the reduced production performance may be due to the disturbance of oocyte production, calcium metabolism, and oxidative stress. Analysis of 16S rRNA gene amplicon sequences revealed the differential microbial composition and potential functional changes among the different groups. LEfSe analysis showed that Mucispirillum and Nautella were the predominant bacteria in the DXM group, while Clostridium was the predominant bacteria in the FA group. Functional prediction demonstrated that stressors enhanced fatty acid biosynthesis, while betaine biosynthesis and retinol metabolism were elevated in the FA group. Dietary FA reversed the elevated levels of bile acids (BA), including cholic acid, taurodeoxycholic acid, and taurochenodeoxycholic acid (P < 0.05). The DXM group showed an overall decrease in short-chain fatty acids (SCFA), but FA restored the concentrations of acetic acid, propionic acid, and isobutyric acid (P < 0.05). In conclusion, this study reveals that dietary FA can alleviate the degradation of production performance caused by stress through improving circulating antioxidant capacity, maintaining intestinal microbiota homeostasis, and regulating SCFA and BA biosynthesis. Thus, highlighting the prominent role of gut microbe-host interactions in alleviating multi-stresses.PMID:39949729 | PMC:PMC11821403 | DOI:10.1016/j.aninu.2024.11.011

Primary metabolomics and transcriptomic techniques were used to explore the regulatory mechanisms that may influence the flavor characteristics of fresh Corylus heterophylla Corylus avellana

3 hours 25 min ago
Front Plant Sci. 2025 Jan 30;15:1475242. doi: 10.3389/fpls.2024.1475242. eCollection 2024.ABSTRACTTo explore the flavor related regulatory mechanisms of fresh Corylus heterophylla × Corylus avellana, a joint analysis of metabolome and transcriptome were utilized to compare the two typical C. heterophylla × C. avellana varieties with different flavors ('yuzhui' and 'pingou21') in this paper. The results showed that the genes including E2.4.1.67-1, E2.4.1.67-2, SUS-1, SUS-2, SUS-4, SUS-5, SUS-7, SUS-8, SUS-9, UGP2-2 were identified as responsible for regulating the levels of stachyose, manninotriose and raffinose in hazelnuts. CS and OGDH were deemed as the genes involved in the citric acid cycle, which was a central metabolic pathway that generated energy through the oxidation of carbohydrates, fats and proteins in hazelnuts. The genes trpD, ALDO, PK-1, PK-2, ilvH, argE-1, argE-4, argE-5, argD, PDAH, GLTI were regarded as involved in the biosynthesis of various amino acids like tryptophan, valine, alanine, and arginine. These amino acids determined the taste of C. heterophylla × C. avellana and were important precursors of other flavor-related compounds. The genes LOX2S-2, LOX2S-3, LOX2S-4 and LCAT3 were viewed as involved in the regulation of lipid biosynthesis, specifically involving 13(S)-HPODE, 9,10,13-trihome and 13(S)-HOTrE in C. heterophylla × C. avellana. These findings highlight the significance of genes and metabolites and internal regulatory mechanisms in shaping the flavor of fresh C. heterophylla × C. avellana cultivated in temperate continents. This study provides the theoretical basis for breeding excellent food functional hazelnut varieties.PMID:39949634 | PMC:PMC11821611 | DOI:10.3389/fpls.2024.1475242

Tomato rot by <em>Rhizopus microsporus</em> alters native fungal community composition and secondary metabolite production

3 hours 25 min ago
Front Microbiol. 2025 Jan 30;16:1508519. doi: 10.3389/fmicb.2025.1508519. eCollection 2025.ABSTRACTRhizopus rot is considered one of the most common diseases influencing global production and yield of horticulture commodities. However, the factors contributing to this pattern of prevalence are uncertain. Here, we focused on R. microsporus, which is known to rely on its endosymbiotic bacterium, Mycetohabitans, to produce toxins that interfere with plant development and inhibit the growth of other fungi. We assessed the impact of the symbiotic R. microsporus harboring its endosymbiont as well as the fungus cured of it on: (1) the magnitude of spoilage in tomato fruits, as evaluated by Koch's postulate for pathogenicity, (2) the shifts in native communities of endophytic fungi inhabiting these fruits, as examined by ITS rRNA gene metabarcoding and (3) secondary metabolites generated by these communities, as analyzed using multi-analyte LC-MS/MS. The pathogenicity test showed that the symbiotic endobacterium-containing R. microsporus W2-50 was able to cause tomato fruit spoilage. This was accompanied by decreased relative abundance of Alternaria spp. and an increase in the relative abundance of Penicillium spp. that may have facilitated the observed spoilage. In conclusion, symbiotic W2-50 appeared to facilitate fruit spoilage, possibly through successful colonization or toxin production by its endosymbiont.PMID:39949627 | PMC:PMC11823476 | DOI:10.3389/fmicb.2025.1508519

The gut microbiota regulates diabetic retinopathy in adult rats

3 hours 25 min ago
Front Microbiol. 2025 Jan 29;16:1479792. doi: 10.3389/fmicb.2025.1479792. eCollection 2025.ABSTRACTINTRODUCTION: Diabetic retinopathy (DR) is the most common complication of diabetes. Neuronal apoptosis, activated microglia, and microvascular changes are early features of DR. The gut microbiota is critical for the maturation and activation of microglia in the brain, and DR patients exhibit gut dysbiosis. However, the effect of the gut microbiota on retinal microglia under normal or diabetic conditions is still unclear.METHODS: Type 2 diabetes (T2D) was established in male adult Brown Norway (BN) rats, and they were treated with gavage of broad-spectrum antibiotic (ABX) suspension. Retinal fundus fluorescein angiography was performed to observe the dynamic growth process and leakage of blood vessels. Retro-orbital injection of FITC-Dextran was performed to observe the changes in blood-retinal barriers. After treatment with ABX and diabetes lasting for more than 6 months, 16S RNA sequencing of stool samples was performed to determine changes in the gut microbiome and mass spectrometry was used to analyze metabolome changes. IBA1, IB4, and Brn3 staining were performed on adult rats' retinal wholemount or sections to observe the changes in microglia, blood vessels and the number of ganglion cells.RESULTS: Long-term (6 months) T2D caused gut dysbiosis with increased average taxa numbers. We showed that broad-spectrum antibiotics (ABXs) gavage can reduce the average number of gut microbiota taxa and retinal microglia in adult male BN rats with or without T2D. Interestingly, adult male BN rats with T2D for more than 6 months showed a loss of retinal ganglion cells (RGCs) without significant changes in retinal microglia or retinal vascular vessels. However, ABX gavage reduced retinal microglia and alleviated RGC damage in these T2D rats.CONCLUSION: Our data suggests that ABX gavage-induced gut dysbiosis can reduce retinal microglia in adult rats and alleviate RGC loss in long-term T2D rats. Targeting the gut microbiota may be a future therapeutic strategy for DR management.PMID:39949626 | PMC:PMC11822567 | DOI:10.3389/fmicb.2025.1479792

Characterization of serum metabolome and respiratory microbiota in children with influenza A virus infection

3 hours 25 min ago
Front Cell Infect Microbiol. 2025 Jan 30;14:1478876. doi: 10.3389/fcimb.2024.1478876. eCollection 2024.ABSTRACTThe risk of children being infected with Influenza A virus (IAV) is high, and if not treated promptly, it can lead to serious illness. Compared with control group, IAV infection decreased the contents of platelet, white blood cell, lymphocyte, eosinophil, basophil, CD3+ T cells, CD4+ T cells, CD8+ T cells, and B cells, while increasing the number of red blood cell. Additionally, IAV infection increased serum concentrations of total protein, albumin and lipase, while decreasing the contents of calcium, triglyceride, total bilirubin, direct bilirubin, indirect bilirubin and gamma-glutamyltransferase. However, the interactions between the respiratory microbiome and metabolites and their impact on IAV in children remains unclear. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF/MS) and 16S rRNA gene sequencing were employed to analysis the respiratory microbiome and serum metabolic characteristics of 85 patients with IAV infection and age-matched 55 controls with respiratory disease who tested negative for 13 types of respiratory pathogens. The serum metabolic profile of IAV patients was significantly changed, and the purine metabolism was destroyed. Purine metabolism was also enriched in H3N2 patients compared to H1N1, with increased xanthine, deoxyguanosine, and inosine. The respiratory microbiome structure in children with IAV, including H1N1 and H3N2, was significantly different from that of the control, with significantly increased Chao index. The Mantel test revealed the correlation and consistency in the trends of Haemophilus, Ureaplasma and Inosine. This study revealed the characteristics of the respiratory microbiome and serum metabolites in pediatric patients with IAV, providing a new direction for exploring the pathogenesis of IAV in children.PMID:39949573 | PMC:PMC11821643 | DOI:10.3389/fcimb.2024.1478876

Comparative metabolomic in-depth exploration of red raspberry: new insights into changes in phytochemicals between different breeds

3 hours 25 min ago
Anal Methods. 2025 Feb 14. doi: 10.1039/d4ay01988a. Online ahead of print.ABSTRACTBased on a non-targeted metabolomic approach, a comprehensive analysis of the metabolic profiles of two raspberry cultivars, Selina (TSM) and Tulameen (CSM), was conducted to explore the potential for further processing of these two varieties. A total of 752 metabolites were identified in both raspberry varieties, with 375 metabolites detected in negative ion mode and additional metabolites identified in positive ion mode. The total number of differential metabolites between TSM and CSM was 62, with orthogonal partial least squares discriminant analysis (OPLS-DA) revealing that the main differential metabolites between the two varieties were phenolic compounds, organic acids, and alkaloids. KEGG pathway analysis identified the top three significantly different metabolic pathways as biosynthesis of amino acids; valine, leucine, and isoleucine biosynthesis; and alanine, aspartate, and glutamate metabolism. In conclusion, this study comprehensively analyzed the metabolic characteristics of TSM and CSM raspberry varieties, providing valuable insights and revealing their potential application prospects. Compared to previous studies, this research provides new insights into the metabolic differences between TSM and CSM cultivars, specifically highlighting newly identified metabolites that were not reported before. These findings include novel differences in phenolic compounds and alkaloids, which play important roles in plant stress response and have potential health benefits. This enhances our understanding of the unique properties of each cultivar and underscores the biological functions of the newly identified metabolites, contributing to the broader field of functional food development.PMID:39949318 | DOI:10.1039/d4ay01988a

Analysis of the bioactive parts and components of Aralia elata (Miq.) Seem based on non-targeted metabolomics and its hepatoprotective effects induced by cyclophosphamide

3 hours 25 min ago
J Food Sci. 2025 Feb;90(2):e70057. doi: 10.1111/1750-3841.70057.ABSTRACTIn the present study, non-targeted metabolomics was utilized to identify the bioactive components in the root, seed, and leaf of Aralia elata (Miq.) Seem (A. elata), a traditional Chinese specialty vegetable. The relative content indicated that saponins, flavonoids, and phenolic acids were the main bioactive components, whereas principal component analysis showed significant differences among the three parts. ABTS, DPPH, ferric reducing antioxidant power, and hydroxyl radical scavenging capacity assays were conducted to evaluate the antioxidant activities of extracts from the three parts, and the root extract demonstrated the highest antioxidant potential. Correlation analyses revealed that saponins possessed the best antioxidant capacity. Twelve saponins in the root were identified from the total saponins (tSAs) by liquid chromatography-high-resolution mass spectrometry. The protective effect of tSAs on cyclophosphamide-induced liver damage was evaluated using BRL-3A cells. The tSAs significantly enhanced the cellular antioxidant levels, reduced the levels of aspartate aminotransferase and alanine aminotransferase by 38.81% and 37.43%, respectively, and demonstrated evident hepatoprotective effects. PRACTICAL APPLICATION: This research could help develop dietary supplements rich in antioxidants from the roots of Aralia elata (Miq.) Seem and also pave the way for novel therapies for liver diseases.PMID:39949249 | DOI:10.1111/1750-3841.70057

The effects of post-harvest pretreatments and drying methods on in vitro bioaccessibility of phenolics and carotenoids in tomato (Solanum lycopersicum) cultivars

3 hours 25 min ago
J Food Sci. 2025 Feb;90(2):e70001. doi: 10.1111/1750-3841.70001.ABSTRACTTwo pretreatments (ultrasound sonication [US] and microwave [MW]) and drying techniques (hot air [HA] and freeze-drying [FD]) were used to assess the in vitro bioaccessibility of phenols, carotenoids, and antioxidant activity in three tomato cultivars (Zzx171, Zzx162, and Zzx65). The metabolome-chemometric analysis showed that tomato cultivars dried by FD and HA differed in metabolites. HA samples contained methoxytyrosine and aconitane-type diterpenoids. US-HA enhanced total phenol content bioaccessibility by 64.72%-74.25% in three tomato cultivars after digestion (intestinal phase). US-HA increased the protocatechuic acid levels in all three tomato cultivars in the intestinal phase, but by 55.23% in Zzx65 compared to the undigested samples. Despite all adopted postharvest pretreatments and drying, US-HA retained chlorogenic acid, 4-O-caffeinyliquinic acid, and rutin better, due to microstructure changes in the intestinal phase, and Zzx65 treated with US-HA retained the most. In undigested samples, US-FD improved total carotenoids, lycopene, and β-carotene retention, but the inaccessibility was reduced significantly during in vitro digestion. Cultivar × postharvest treatment affected all phenolic compounds, carotenoids, and antioxidant activities in the intestinal phase. US-HA had improved antioxidant power (FRAP) and 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) scavenging activity in the intestinal phase. PRACTICAL APPLICATION: Tomatoes are an important part of the human diet. Their high perishability reduces their nutritional and microbiological quality. The lack of cold storage infrastructure in developing countries contributes to food waste. Convective hot air drying is suitable for recycling fresh market waste products as supplement powders. The ultrasound pretreatment protects bioactive compounds in tomato fruit and is non-thermal. There are several limitations, including equipment cost, energy efficiency, and integration with commercial systems, which limit ultrasound-assisted drying's scalability. The integration of US-HA treatment (ultrasound-assisted hot air drying) could reduce food waste and contribute to the sustainable development goals in agricultural industries.PMID:39949245 | DOI:10.1111/1750-3841.70001

Mefloquine Suppresses Metastasis in Renal Cell Carcinoma Through Targeting SPC25

3 hours 25 min ago
Cancer Sci. 2025 Feb 13. doi: 10.1111/cas.70001. Online ahead of print.ABSTRACTRenal cell carcinoma (RCC) is the third most common malignant tumor in the urinary system, often presenting with distant metastases at diagnosis. Approximately one-quarter of patients undergoing nephrectomy experience distant recurrence. Despite the recent advancements in combination-targeted and immune checkpoint inhibitor therapies, the development of new therapeutic strategies and the identification of biomarkers for metastatic risk remain crucial. The study found that high SPC25 expression is closely associated with poor clinical outcomes, and knocking down SPC25 significantly inhibits tumor cell proliferation and migration. Non-targeted metabolomics analysis also revealed that SPC25 knockdown reduces tumor cell activity, resulting in a low-invasive state. Additionally, this study utilized high-throughput molecular docking to screen small molecule drugs targeting SPC25, aiming to find drugs that inhibit RCC metastasis. The research discovered that mefloquine, at concentrations that do not significantly kill tumor cells, can markedly inhibit RCC metastasis. It was the first to report that mefloquine achieves its anti-metastatic effects by binding to SPC25 and inhibiting epithelial-mesenchymal transition. These results suggest that SPC25 has the potential to serve as an early biomarker for metastatic risk in RCC and highlight a novel strategy where mefloquine inhibits RCC metastasis through SPC25 binding, offering new avenues to improve the prognosis of RCC patients.PMID:39948743 | DOI:10.1111/cas.70001

Nanoparticle-Elicited Eustress Intensifies Cucumber Plant Adaptation to Water Deficit

3 hours 25 min ago
Environ Sci Technol. 2025 Feb 13. doi: 10.1021/acs.est.4c13531. Online ahead of print.ABSTRACTUnder changing climates, engineering drought-resistant crops is critical for reducing food insecurity. Here, we leverage plant "stress memory" and ROS-generating silica nanoparticles (NPs) to enhance the drought tolerance of cucumber plants. Under PEG-mimicking drought conditions, cucumber seeds primed with fumed silica NPs (40 mg/L, 4 h) exhibited an increased seed germination rate (from 66.7 to 80.0%), enhanced seedling vigor (59.3%), and improved root and shoot length (24.4 and 74.1%, respectively) compared to seeds primed with water. In contrast, silicic acid and traditional silicon fertilizers at the same dose did not show priming effects, indicating that the released Si did not contribute to the observed outcomes. Metabolomics reveals that silica seed priming accelerated the mobilization of seed-stored reserves. Vegetative tissues also exhibit enhanced drought resistance, and metabolomics analysis reveals that the drought resistance strategy involves the upregulation of sugars (glucose, sucrose, trehalose, maltose; 34.7-74.8%), amino acids (methionine, 6-fold), signaling molecules (salicylic acid, 2.5-fold), and antioxidants (ascorbic acid, 2-hydroxycinnamic acid, ferulic acid, P-coumaric acid; 16.0-83.8%). Transcriptomics analysis reveals that several drought- and even desiccation-tolerant associated genes exert more pronounced transcript changes in silica-primed leaves. The life cycle study shows that silica seed priming does not generate any yield penalty or compromise the nutritional quality of the fruits. Importantly, offspring seeds exhibit enhanced vigor and drought tolerance, indicating the transgenerational transmission of the acquired drought resilience. The findings of this study provide a promising approach for engineering crops that are resilient to climate change.PMID:39948725 | DOI:10.1021/acs.est.4c13531

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