PubMed

Biodes Res. 2024 Dec 5;6:0059. doi: 10.34133/bdr.0059. eCollection 2024.ABSTRACTMultiomics research is a transformative approach in the biological sciences that integrates data from genomics, transcriptomics, proteomics, metabolomics, and other omics technologies to provide a comprehensive understanding of biological systems. This review elucidates the fundamental principles of multiomics, emphasizing the necessity of data integration to uncover the complex interactions and regulatory mechanisms underlying various biological processes. We explore the latest advances in computational methodologies, including deep learning, graph neural networks (GNNs), and generative adversarial networks (GANs), which facilitate the effective synthesis and interpretation of multiomics data. Additionally, this review addresses the critical challenges in this field, such as data heterogeneity, scalability, and the need for robust, interpretable models. We highlight the potential of large language models to enhance multiomics analysis through automated feature extraction, natural language generation, and knowledge integration. Despite the important promise of multiomics, the review acknowledges the substantial computational resources required and the complexity of model tuning, underscoring the need for ongoing innovation and collaboration in the field. This comprehensive analysis aims to guide researchers in navigating the principles and challenges of multiomics research to foster advances in integrative biological analysis.PMID:39990095 | PMC:PMC11844812 | DOI:10.34133/bdr.0059

Res Sq [Preprint]. 2025 Feb 14:rs.3.rs-5989567. doi: 10.21203/rs.3.rs-5989567/v1.ABSTRACTBackground Metabolic syndrome is a pressing public health issue and risk factor for the development of type 2 diabetes (T2D) and cardiovascular disease (CVD), yet clinical practice is lacking in biomarkers that represent pre-clinical perturbations of the heterogenous subtypes of risk. This study aimed to characterize the baseline metabolome in relation to known clinical characteristics of risk in a sample of obese adults. Methods Untargeted metabolome data from N = 126 plasma samples with baseline data from a previously completed study including obese adults with metabolic syndrome. Metabolites were acquired using validated liquid chromatography mass spectrometry methods with 15-25 internal standards quantified by peak heights. Pearson's correlations were used to determine relationships between baseline metabolites, sample characteristics (e.g., age, body mass index (BMI)), and atherosclerotic clinical characteristics (e.g., high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglycerides), adjusting for multiple comparisons using the Benjamini-Hochberg False Discovery Rate (FDR) method. Differences in metabolite levels between clinical classifications of dysglycemia (e.g., normal, prediabetes, diabetes) at baseline were assessed using ANOVA and adjusted for multiple comparisons and adjusted for covariates. Results The sample consisted primarily of female (74%) participants, predominantly white (70%), with an average age of 56 years. After FDR adjustment, two baseline metabolites were significantly associated with age (xylose, threitol), two with BMI (shikimic acid, propane-1,3-diol), one with LDL (tocopherol-alpha), and 42 with HDL cholesterol. Three metabolites were significantly associated with fasting blood glucose (FBG) levels at baseline (glucose, gluconic acid lactone, pelargonic acid). Conclusions This study identified novel metabolite associations with known markers of T2D and CVD risk. Specific metabolites, such as alpha-tocopherol, branched-chain amino acids (BCAAs), and sugar-derived metabolites like mannose and xylose, were significantly associated with age, BMI, lipid profiles, and glucose measures. Although most sample participants had normal HDL cholesterol at baseline, 42 metabolites including branched chain amino acids were significantly associated with HDL, suggesting pre-clinical perturbations in biological pathways associated with both diabetes and cardiovascular comorbidities. Metabolomic signatures specific to prediabetes and metabolic syndrome can enhance risk stratification and enable targeted prevention strategies for T2D. Longitudinal studies are needed to understand how these associations change over time in at-risk individuals compared with controls.PMID:39989952 | PMC:PMC11844646 | DOI:10.21203/rs.3.rs-5989567/v1

J Diabetes Metab Disord. 2025 Feb 20;24(1):70. doi: 10.1007/s40200-025-01582-z. eCollection 2025 Jun.ABSTRACTBACKGROUND AND OBJECTIVE: : Diabetic foot ulcer (DFU) is one of the main health challenges of diabetes complications worldwide. A wide range of factors may increase the risk of DFU. This study aimed to investigate the risk factors of DFU among diabetic patients.METHODS: This case-control study was conducted on 800 diabetic patients at the Tehran diabetes clinic of the Endocrinology and Metabolism Research Institute in Iran. The case group included 400 diabetic patients diagnosed with DFU, while the control group included 400 diabetic patients without DFU. Data were collected through medical records, validated questionnaires, and clinical examinations. The association between factors and the risk of DFU was analyzed using both crude and adjusted logistic regression models, adjusting for confounders based on a directed acyclic graphs.RESULTS: The final adjusted model demonstrated significant direct associations between the risk of DFU with a longer duration of diabetes, a history of previous DFU, peripheral neuropathy, retinopathy, high blood pressure, severe kidney function loss, and good foot self-care. However, there were significant inverse associations between DFU risk with female gender, higher education levels, being married, use of oral diabetes drugs, higher hemoglobin levels, and high physical activity.CONCLUSIONS: The risk of DFU was significantly associated with the following factors: diabetes duration, previous DFU history, peripheral neuropathy, retinopathy, blood pressure, kidney function, foot self-care, gender, education levels, marital status, diabetes drugs, hemoglobin levels, and physical activity. Further studies, especially ones in multicenter cohorts with a special focus on novel risk factors, are warranted to expand on our findings.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-025-01582-z.PMID:39989881 | PMC:PMC11842648 | DOI:10.1007/s40200-025-01582-z

J Diabetes Metab Disord. 2025 Feb 20;24(1):69. doi: 10.1007/s40200-025-01579-8. eCollection 2025 Jun.ABSTRACTOBJECTIVE: Type 2 Diabetes Mellitus (T2DM) is a global health concern, with complications such as diabetic nephropathy (DN) affecting 16.6% of patients and contributing to end-stage renal failure. Emerging research suggests that gut microbial communities may influence DN progression, potentially through mechanisms involving the renin-angiotensin system (RAS). This study aimed to evaluate changes in specific microbial genera in individuals with T2DM, both with and without DN, and to explore their associations with renal function markers and RAS activation.METHODS: A total of 120 participants were categorized into three groups: healthy controls, T2DM without DN, and T2DM with DN. Microbial abundances of genera including Escherichia, Prevotella, Bifidobacterium, Lactobacillus, Roseburia, Bacteroides, Faecalibacterium, and Akkermansia were quantified using qPCR targeting the bacterial 16 S rRNA gene. Gene expression levels of RAS-associated markers (ACE, AGT1R, AT2R, and Ang II) and inflammation-related genes (TNF-α, TLR4) were analyzed in peripheral blood mononuclear cells via qPCR.RESULTS: The study identified significant alterations in microbial composition. Genera such as Faecalibacterium, Akkermansia, Roseburia (butyrate producers), and Bifidobacterium (a potential probiotic) were markedly reduced in T2DM and DN groups compared to controls. Increased mRNA expression of RAS-related genes, including ACE, AGT1R, and Ang II, was observed in these groups. We also foun correlations between altered microbial genera, RAS gene expression, and clinical markers of renal dysfunction.CONCLUSION: The findings suggest that specific microbial genera may influence the pathogenesis of DN through RAS activation and inflammatory pathways. These insights highlight potential therapeutic targets for mitigating DN progression in T2DM patients.PMID:39989880 | PMC:PMC11842656 | DOI:10.1007/s40200-025-01579-8

Open Med (Wars). 2025 Feb 18;20(1):20241131. doi: 10.1515/med-2024-1131. eCollection 2025.ABSTRACTBACKGROUND AND PURPOSE: Gastric cancer is a kind of malignant tumor with high incidence and high mortality, which has strong tumor heterogeneity. A classic Chinese medicine, Pinellia ternata (PT), was shown to exert therapeutic effects on gastric cancer cells. However, its chemical and pharmacological profiles remain to be elucidated. In the current study, we aimed to reveal the mechanism of PT in treating gastric cancer cells through metabolomic analysis and network pharmacology.METHODS: Metabolomic analysis of two strains of gastric cancer cells treated with the Pinellia ternata extract (PTE) was used to identify differential metabolites, and the metabolic pathways were enriched by MetaboAnalyst. Then, network pharmacology was applied to dig out the potential targets against gastric cancer cells induced by PTE. The integrated network of metabolomics and network pharmacology was constructed based on Cytoscape.RESULTS: The PTE was confirmed to significantly inhibit cell proliferation, migration, and invasion of HGC-27 and BGC-823 cells. The results of cellular metabolomics showed that 61 metabolites were differently expressed in gastric cancer cells of the experimental and control groups. Through pathway enrichment analysis, 16 metabolites were found to be involved in the glycerophospholipid metabolism, purine metabolism, sphingolipid metabolism, and tryptophan metabolism. Combined with network pharmacology, seven bioactive compounds were found in PT, and the networks of bioactive compound-target gene-metabolic enzyme-metabolite interactions were constructed.CONCLUSIONS: In conclusion, this study revealed the complicated mechanisms of PT against gastric cancer. Our work provides a novel paradigm to identify the potential mechanisms of pharmacological effects derived from a natural compound.PMID:39989612 | PMC:PMC11843166 | DOI:10.1515/med-2024-1131

FASEB J. 2025 Feb 28;39(4):e70415. doi: 10.1096/fj.202402780R.ABSTRACTInflammatory bowel disease (IBD) is a multifactorial disease, and patients frequently experience extraintestinal manifestations affecting multiple sites. Causes of systemic inflammation remain poorly understood, but molecules originating from the intestine likely play a role, with microbial and host small molecules polarizing host immune cells towards a pro- or anti-inflammatory phenotype. Using the dextran sodium sulfate (DSS) mouse model, which mimics the disrupted barrier function, microbial dysbiosis, and immune cell dysregulation of IBD, we investigated metabolomic and phenotypic changes at intestinal and systemic sites. Using spatial biology approaches, we mapped the distribution and relative abundance of molecules and cell types across a range of tissues, revealing significant changes in DSS-treated mice. Molecules identified as contributing to the statistical separation of treated from control mice were spatially localized within organs to determine their effects on cellular phenotypes through imaging mass cytometry. This spatial approach identified both intestinal and systemic molecular drivers of inflammation, including several not previously implicated in inflammation linked to IBD or the systemic effects of intestinal inflammation. Metabolic and inflammatory pathway interplay underpins systemic disease, and determining drivers at the molecular level may aid the development of new targeted therapies.PMID:39989432 | DOI:10.1096/fj.202402780R

J Agric Food Chem. 2025 Feb 24. doi: 10.1021/acs.jafc.4c13173. Online ahead of print.ABSTRACTThis study aimed to elucidate the antiobesity mechanisms of sweet potato extract (SPE) through biochemical, gut microbiome, liver transcriptome, and metabolome analyses. Administration of SPE to high-fat-diet-fed mice significantly reduced body weight gain, serum low-density lipoprotein cholesterol, hepatic lipid accumulation, and adipocyte hypertrophy, which were closely linked to gut microbiome composition. SPE notably increased the abundance of Eubacterium_coprostanoligenes_group_unclassified and decreased that of Kineothrix, both of which were strongly associated with short-chain fatty acid (SCFA) production. LC-QTOF-MS analysis identified resin glycoside compounds from SPE with reduced levels in mouse feces, suggesting their utilization in vivo. SPE also promoted dietary fat excretion. Liver transcriptomic and metabolomic profiling revealed that SPE may exert antiobesity effects by modulating the bile-sphingolipid metabolism, which was closely correlated with the reshaped gut microbiomes and SCFAs. These findings provide new insights into the antiobesity effects and mechanisms of SPE.PMID:39989409 | DOI:10.1021/acs.jafc.4c13173

Physiol Plant. 2025 Jan-Feb;177(1):e70111. doi: 10.1111/ppl.70111.ABSTRACTPigeon pea is an important economic crop with medicinal and nutritional value. Unfortunately, pest infestation of leaves during postharvest storage seriously affects the quality of pigeon pea. Phytohormones play a crucial role in disease and pest defence by regulating the accumulation of specialized metabolites. Still, their impact on the postharvest storage of pigeon pea has not been reported. In this study, the physiological parameters and main phenotypes of pigeon pea leaves treated with MeJA, ABA, and GA were investigated for the first time. The activity of the antioxidant enzyme system, which eliminates reactive oxygen species, was enhanced by applying MeJA, GA, and ABA. MeJA, GA, and ABA significantly affected crown width, plant height, and relative water content in pigeon pea, respectively. Metabolomic profiling analysis identified phenolic compounds as the main differentially accumulated metabolites (DAMs). UPLC-QqQ-MS/MS identified stilbenes, flavanones, flavones, isoflavones and anthocyanins as major phenolic compounds responsive to MeJA, GA, and ABA induction. By feeding insects, it was found that the insects fed on MeJA-, ABA-, and GA-treated leaves less than on control leaves. Correlation analysis confirmed that isoflavones play an important role in this process. Moreover, the expression of key genes involved in flavonoid biosynthetic pathways and anti-insect-related genes was regulated by MeJA, GA, and ABA. Overall, this work provides a new strategy for the cultivation and storage of pigeon pea or other commercial crops and preliminarily clarifies that flavonoid metabolites under plant hormone treatment can promote plant growth and defence against insects by regulating reactive oxygen species.PMID:39989397 | DOI:10.1111/ppl.70111

Sheng Wu Gong Cheng Xue Bao. 2025 Feb 25;41(2):602-617. doi: 10.13345/j.cjb.240548.ABSTRACTFlavonoids are key bioactive components for evaluating the pharmacological activities of Chimonanthus praecox. Exploring the potential flavonoids and pharmacological mechanisms of C. praecox lays a foundation for the rational development and efficient utilization of this plant. This study employed ultra-performance liquid chromatography-tandem mass spectrometry-based widely targeted metabolomics to comprehensively identify the flavonoids in C. praecox. Network pharmacology was employed to explore the bioactive flavonoids and their mechanisms of action. Molecular docking was adopted to validate the predicted results. Finally, the content of bioactive flavonoids in different varieties of C. praecox was measured. The widely targeted metabolomics analysis identified 387 flavonoids in C. praecox, and the flavonoids varied among different varieties. Network pharmacology predicted 96 chemical components including 19 bioactive compounds, 181 corresponding targets and 2 504 disease targets, among which 99 targets were shared by the active components and the disease. Thirty-three core targets were predicted, involving 229 gene ontology terms and 99 pathways (P≤0.05), which indicated that the flavonoids components of C. praecox exhibited pharmacological activities including antioxidant, anti-inflammatory, antimicrobial, and antiviral activities. Topological analysis screened out five core components (salvigenin, laricitrin, isorhamnetin, quercetin, and 6-hydroxyluteolin) and five core targets (SRC, PIK3R1, AKT1, ESR1, and AKR1C3). The predicted bioactive flavonoids from C. praecox stably bound to key targets, which indicated that these flavonoids possessed potential bioactivities in their interactions with the targets. The flavonoids in C. praecox exerted pharmacological activities in a multi-component, multi-target, and multi-pathway manner. The combined application of metabolomics and network pharmacology provides a theoretical basis for in-depth studies on the pharmacological effects and mechanisms of C. praecox.PMID:39989059 | DOI:10.13345/j.cjb.240548

Sheng Wu Gong Cheng Xue Bao. 2025 Feb 25;41(2):588-601. doi: 10.13345/j.cjb.240655.ABSTRACTOphiopogon japonicus, a precious medicinal plant endemic to Zhejiang Province. Its tuberous roots are rich in bioactive components such as flavonoids, possessing anti-inflammatory, antioxidant, and immunomodulatory properties. To elucidate the impact of cadmium (Cd) stress on the accumulation and biosynthetic pathway of flavonoids in O. japonicus, this study exposed O. japonicus to different concentrations of Cd stress and explored the changes through integrated transcriptomics and metabolomics analysis. The results demonstrated that Cd stress (1 mg/L and 10 mg/L) significantly increased the content of flavonoids in O. japonicus in a concentration-dependent manner. The metabolomics analysis revealed a total of 110 flavonoids including flavones, flavanols, flavonols, flavone and flavonol derivatives, flavanones, isoflavonoids, chalcones and dihydrochalcones, and anthocyanins in O. japonicus, among which flavones, flavonols, flavone and flavonol derivatives, and anthocyanins increased under Cd stress. The transcriptomics analysis identified several key flavonoid biosynthesis-associated genes with up-regulated expression under Cd stress, including 14 genes encoding 4-coumarate CoA ligase (4CL), 2 genes encoding chalcone isomerase (CHI), and 14 genes encoding phenylalanine ammonia lyase (PAL). The gene-metabolite regulatory network indicated significant positive correlations of 4CL (Cluster-21637.5012, Cluster-21637.90648, and Cluster-21637.62637) and CHI (Cluster-21637.111909 and Cluster-21637.123300) with flavonoid metabolites, suggesting that these genes promoted the synthesis of specific flavonoid metabolites, which led to the accumulation of total flavonoids under Cd stress. These findings provide theoretical support for the cultivation and utilization of medicinal plants in Cd-contaminated environments and offered new perspectives for studying plant responses to heavy metal stress.PMID:39989058 | DOI:10.13345/j.cjb.240655

Mol Nutr Food Res. 2025 Feb 23:e202400539. doi: 10.1002/mnfr.202400539. Online ahead of print.ABSTRACTHoney is known to promote alcohol metabolism effectively. However, the effects of its individual chemical components system on alcohol metabolism and their mechanisms of action have not yet been fully elucidated. We constructed polyphenols and ascorbic acid systems (PAAS) of six different floral kinds of honey by exogenous substances, to investigate their effects on alcohol metabolism in the liver. PAAS consists of 22 kinds of polyphenols (including arbutin and caffeic acid) and ascorbic acid. The results demonstrated that PAAS improved the activity of alcohol dehydrogenase (ADH) and the expression of adh1, but had no significant effect on acetaldehyde dehydrogenase (ALDH) and expression of adh2, which caused a decrease in blood ethanol concentration but no difference in acetaldehyde concentration. Correlation analysis illustrated that arbutin and trans-4-hydroxycinnamic acid in PAAS were important potential substances for promoting alcohol metabolism. In addition, PAAS could also reduce the deleterious effects of alcohol by modulating unsaturated fatty acid biosynthesis, purine metabolism, and other metabolic pathways in the liver. These findings revealed the mechanisms by which PAAS promoted hepatic alcohol metabolism as well as protected the liver and provided a theoretical basis for exploring the mechanisms in honey synergistically promote alcohol metabolism.PMID:39988877 | DOI:10.1002/mnfr.202400539

Environ Sci Technol. 2025 Feb 23. doi: 10.1021/acs.est.4c11413. Online ahead of print.ABSTRACTNanoenabled agriculture technology exhibits potential in reducing arsenic uptake in rice; however, a systematic understanding of the rice-soil-microorganism process of nanomaterials (NMs) is lacking. Soil amendment of metalloid NMs, including SiO2, hydroxyapatite, S0, and Se0 at 10-100 (0.1-5.0 for Se NMs) mg/kg, increased rice biomass by 76.1-135.8% in arsenic-contaminated soil (17.0 mg/kg) and decreased arsenic accumulation in plant tissues by 9.3-78.2%. The beneficial effects were nanoscale-specific and NMs type- and concentration-dependent; 5 mg/kg Se NMs showed the greatest growth promotion and decrease in As accumulation. Mechanistically, (1) Se NMs optimized the soil bacterial community structure, enhancing the abundance of arsM by 104.2% and subsequently increasing arsenic methylation by 276.1% in rhizosphere compared to arsenic-alone treatments; (2) metabolomic analyses showed that Se NMs upregulated the biosynthesis pathway of abscisic acid, jasmonic acid, and glutathione, with subsequent downregulation of the arsenic transporter-related gene expression in roots by 42.2-73.4%, decreasing the formation of iron plaque by 87.6%, and enhancing the arsenic detoxification by 50.0%. Additionally, amendment of metalloid NMs significantly enhanced arsenic-treated rice yield by 66.9-91.4% and grain nutritional quality. This study demonstrates the excellent potential of metalloid NMs for an effective and sustainable strategy to increase food quality and safety.PMID:39988829 | DOI:10.1021/acs.est.4c11413

ACS Appl Mater Interfaces. 2025 Feb 23. doi: 10.1021/acsami.4c21532. Online ahead of print.ABSTRACTSkin trauma often results from pain, swelling, and scarring and can significantly interfere with daily activities. Extracts from the American cockroach, a rapidly reproducing insect, have been recognized for therapeutic properties in wound management. Traditional extraction methods use solvents such as ethanol to obtain the active compounds, but these methods may compromise the intrinsic biological properties of American cockroach extracts. In this study, we investigated the use of nanovesicles isolated from fresh American cockroaches in skin wound treatment and focused on their biological characteristics and therapeutic efficacy. Fresh and dried American cockroach nanovesicles (F-ACNVs and D-ACNVs, respectively) were procured via ultrahigh-speed centrifugation. We found that F-ACNVs exhibited superior cell proliferation-promoting activity. By employing metabolomics, proteomics, and long noncoding RNA (lncRNA) omics, we identified a rich repertoire of metabolites, proteins, and lncRNAs within F-ACNVs. In vitro and in vivo experiments demonstrated that F-ACNVs significantly enhanced the proliferation and migration of human umbilical vein endothelial cells (HUVECs) and human skin keratinocytes (HACATs) as well as the repair of skin mechanical trauma. These effects may be mediated through the activation of angiogenic signaling pathways. Our research introduces a novel therapeutic strategy for treating skin trauma and offers insight into the medicinal potential of insects such as the American cockroach while emphasizing the importance of preserving the intrinsic biological properties of insects for optimal therapeutic outcomes.PMID:39988799 | DOI:10.1021/acsami.4c21532

Clin Exp Dent Res. 2025 Feb;11(1):e70103. doi: 10.1002/cre2.70103.ABSTRACTOBJECTIVE: Cell secretomes represent a promising strategy for periodontal and bone regeneration. The objective of this study was to characterize the secretome of human gingival fibroblasts (GF) from periodontally diseased tissues (GF-perio) using proteomics.MATERIALS AND METHODS: Conditioned media of GF-perio from periodontitis patients (n = 6, 48-h serum-free culture) were subjected to liquid chromatography with tandem mass spectrometry. Global profiles, differentially expressed proteins (DEPs), and functional/gene-set enrichment (FEA) were analyzed using bioinformatics. Selected bone regeneration-related proteins were additionally measured using a multiplex immunoassay. Conditioned media of GF from periodontally healthy subjects were used as a reference.RESULTS: Overall, 1833 proteins were detected in GF-perio secretomes, including several growth factors, cytokines, chemokines, and extracellular matrix proteins important for wound healing and regeneration. Key bone-related cytokines (FGF2, MCP1, GPNMB, MMP2, IL6, IL8) were confirmed by an immunoassay. Compared to the reference group, 127 exclusive proteins and 73 DEPs (p < 0.05) were identified in the GF-perio group. FEA revealed significant enrichment of "exosome" and "cytoplasm" related cellular components in GF-perio secretomes.CONCLUSION: The secretome of GF from periodontally diseased tissues may hold therapeutic potential, with several proteins important for wound healing and regeneration, especially those related to exosome functions.PMID:39988729 | DOI:10.1002/cre2.70103

Eur J Hum Genet. 2025 Feb 23. doi: 10.1038/s41431-025-01815-y. Online ahead of print.ABSTRACTChromatin remodeling is an important system controlling gene expression. CHD3, which is a causative gene of Snijders Blok-Campeau syndrome (SNIBCPS), is a member of the chromodomain helicase DNA-binding (CHD) family related to chromatin remodeling. SNIBCPS is characterized by developmental delay (DD), intellectual disability (ID), macrocephaly, and facial features including a prominent forehead and hypertelorism. Hypersociability/overfriendliness is a notable behavioral feature in patients. Here, we describe five SNIBCPS patients with CHD3 variants from four families, including a sibling pair caused by parental gonosomal mosaicism. We observed two distinct phenotypes in our patients in accordance with previous observations. Phenotype 1: macrocephaly, hypertelorism, overgrowth, DD, and ID; and Phenotype 2: microcephaly, growth retardation, DD, and ID. Phenotype 1 was consistent with the typical SNIBCPS phenotype, while Phenotype 2 was distinct. To understand further the features of the patients with SNIBCPS, we generated chd3-knockout (KO) zebrafish using CRISPR-Cas9 genome editing. No morphological changes were observed in chd3-KO zebrafish. However, behavioral tests showed that chd3-KO zebrafish had strong and sustained interest in others, and were less aggressive toward others, suggesting a recapitulation of the hypersociability/overfriendliness phenotype in patients with SNIBCPS. Metabolomic analysis using whole brains showed changes in metabolites processed by specific mitochondrial enzymes in chd3-KO zebrafish. The administration of metformin, which reportedly ameliorates mitochondrial dysfunction and behavioral abnormalities, attenuated the abnormal behavior of chd3-KO zebrafish. Our study helps delineate the phenotypes of patients with SNIBCPS, provides insights into a characteristic behavior of the disease, and suggests a potential treatment to improve the behavioral symptoms of patients.PMID:39988727 | DOI:10.1038/s41431-025-01815-y

Transl Psychiatry. 2025 Feb 23;15(1):65. doi: 10.1038/s41398-025-03274-x.ABSTRACTAcylcarnitines (ACs) are involved in bioenergetics processes that may play a role in the pathophysiology of depression. Previous genomic evidence identified four ACs potentially linked to depression risk. We carried forward these ACs and tested the association of their circulating levels with Major Depressive Disorder (MDD) diagnosis, overall depression severity and specific symptom profiles. The sample from the Netherlands Study of Depression and Anxiety included participants with current (n = 1035) or remitted (n = 739) MDD and healthy controls (n = 800). Plasma levels of four ACs (short-chain: acetylcarnitine C2 and propionylcarnitine C3; medium-chain: octanoylcarnitine C8 and decanoylcarnitine C10) were measured. Overall depression severity as well as atypical/energy-related (AES), anhedonic and melancholic symptom profiles were derived from the Inventory of Depressive Symptomatology. As compared to healthy controls, subjects with current or remitted MDD presented similarly lower mean C2 levels (Cohen's d = 0.2, p ≤ 1e-4). Higher overall depression severity was significantly associated with higher C3 levels (ß = 0.06, SE = 0.02, p = 1.21e-3). No associations were found for C8 and C10. Focusing on symptom profiles, only higher AES scores were linked to lower C2 (ß = -0.05, SE = 0.02, p = 1.85e-2) and higher C3 (ß = 0.08, SE = 0.02, p = 3.41e-5) levels. Results were confirmed in analyses pooling data with an additional internal replication sample from the same subjects measured at 6-year follow-up (totaling 4141 observations). Small alterations in levels of short-chain acylcarnitine levels were related to the presence and severity of depression, especially for symptoms reflecting altered energy homeostasis. Cellular metabolic dysfunctions may represent a key pathway in depression pathophysiology potentially accessible through AC metabolism.PMID:39988721 | DOI:10.1038/s41398-025-03274-x

Phytochem Anal. 2025 Feb 23. doi: 10.1002/pca.3518. Online ahead of print.ABSTRACTINTRODUCTION: Blood stasis syndrome (BSS) is one of the common syndromes in traditional Chinese medicine. The Chinese medicine compound composed of "Danggui-Guizhi (DG-GZ)"as the core has the effect of reducing blood stasis and promoting blood circulation. However, the difference of efficacy of DG-GZ traditional decoction and dispensing granules in reducing blood stasis are still unclear.OBJECTIVE: Investigation of the difference of decoction and dispensing granules of Danggui (DG) and Guizhi (GZ) in blood stasis syndrome (BSS) in an animal study (Six groups, n = 6).METHODOLOGY: All rats were randomly divided into six groups: control, model, Danggui-Guizhi dispensed granules ( DGK-GZK), Danggui-Guizhi decoction (DG-GZ), Danggui granules-Guizhi decoction (DGK-GZ), and Danggui decoction -Guizhi granules (DG-GZK) groups (n = 6). The blood stasis model was constructed by exposing rats to ice-cold water. Whole blood viscosity (WBV) was used to compare the effects of DG-GZ (4:3 w/w) decoction and dispensing granules in improving BSS. Metabolomics analysis of urine and 16S rRNA gene sequencing were used to investigate metabolic analysis and gut microbiota changes in rats with BSS.RESULTS: The results of WBV showed that DG-GZ and its granules exhibited efficacy against blood stasis, and the effect of DGK-GZK in relieving blood stasis was greater than that of other administration groups. Urine metabolomics demonstrated that DGK-GZK could reverse the abnormal levels of butyrate, citrate, taurine, creatinine, glucose, and other metabolites in BSS rats. DGK-GZK could promote the enrichment of the g__Prevotellaceae_NK3B31_group, g__Ligilactobacillus, and g__Roseburia.CONCLUSIONS: The effect of DGK-GZK intervention in BSS was stronger than that of other compound groups. This study also provides basic experimental data for exploring the difference in efficacy between traditional decoction and dispensing granules.PMID:39988642 | DOI:10.1002/pca.3518

Commun Biol. 2025 Feb 23;8(1):294. doi: 10.1038/s42003-025-07638-3.NO ABSTRACTPMID:39988621 | DOI:10.1038/s42003-025-07638-3

Vascul Pharmacol. 2025 Feb 21:107474. doi: 10.1016/j.vph.2025.107474. Online ahead of print.ABSTRACTGlycosylation is a post-translational modification in which complex, branched carbohydrates (glycans) are covalently attached to proteins or lipids. Asparagine-link protein (N-) glycosylation is among the most common types of glycosylation. This process is essential for many biological and cellular functions, and impaired N-glycosylation has been widely implicated in inflammation and cardiovascular diseases. Different technical approaches have been used to increase the coverage of the N-glycome, revealing a high level of complexity of glycans, regarding their structure and attachment site on a protein. In this context, new insights from genomic studies have revealed a genetic regulation of glycosylation, linking genetic variants to total plasma N-glycosylation and N-glycosylation of immunoglobulin G (IgG). In addition, RNAseq approaches have revealed a degree of transcriptional regulation for the glycoenzymes involved in glycan structure. However, our understanding of the association between cardiovascular risk and glycosylation, determined by a complex overlay of genetic and environmental factors, remains limited. Mostly, plasma N-glycosylation profiling in different human cohorts or experimental investigations of specific enzyme functions in models of atherosclerosis have been reported. Most of the uncovered glycosylation associations with pathological mechanisms revolve around the recruitment of inflammatory cells to the vessel wall and lipoprotein metabolism. This review aims to summarise insights from omics studies into the immune and metabolic regulation of N-glycosylation and its association with cardiovascular and metabolic disease risk and to provide mechanistic insights from experimental models. The combination of emerging techniques for glycomics and glycoproteomics with already achieved omics approaches to map the transcriptomic, epigenomic, and metabolomic profile at single-cell resolution will deepen our understanding of the molecular regulation of glycosylation as well as identify novel biomarkers and targets for cardiovascular disease prevention and treatment.PMID:39988310 | DOI:10.1016/j.vph.2025.107474

Fish Shellfish Immunol. 2025 Feb 21:110224. doi: 10.1016/j.fsi.2025.110224. Online ahead of print.ABSTRACTExcess adiposity impairs immune function and host defense in obese individuals, but studies on this concept in fish remain limited. In aquaculture, rapid growth is often encouraged through intensive farming practices, leading to overfeeding and negatively impacting production. This study aimed to induce obesity in rainbow trout through overfeeding, exploring metabolic abnormalities, immune response alterations, and infection susceptibility via transcriptomic and metabolomic analyses. In the overfed group, fish were fed until they refused to eat, while the control group was fed according to recommended feeding rates for four weeks. Sampling was conducted at weeks 1, 2, and 4 for serological, histopathological, metabolomic, and transcriptomic analyses. After four weeks, mortality rates were compared following Aeromonas salmonicida challenge, and immunological changes assessed one day post-infection. Overfed fish exhibited significant increases in weight gain (WG), body mass index (BMI), elevated AST/ALT levels, hepatocyte hypertrophy, lipid droplet formation, and triglyceride accumulation. At 1, 2, and 4 wpf, the overfed group exhibited distinct metabolic changes, with key alterations in glycolysis/gluconeogenesis, lipid metabolism and amino acid metabolism. KEGG analysis of transcriptomic data revealed a significant decrease in complement and coagulation cascades, including C3, FB, FH, an FI, accompanied by heightened TNF and IL-17 signaling pathways, involving the upregulation of genes such as TNF-α, IL-1β, and IL-6, indicating an enhanced inflammatory response. The overfed group experienced higher mortality post-infection. Excess energy from overfeeding led to hepatic fat accumulation, liver damage, and reduced innate immune responses, particularly in complement activation. These physiological disruptions compromised immune function, highlighting the detrimental effects of overfeeding-induced obesity on fish health. This study offers critical insights into the immunological mechanisms linking obesity to increased disease susceptibility.PMID:39988219 | DOI:10.1016/j.fsi.2025.110224