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Results for “Pathway analysis”

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PubMed2025

Acute Changes in Rat Tissue Gene Expression Following Exposure to Flight Relevant Hypobaria.

Aeromedical evacuation (AE) is an invaluable tool for the transport of critically injured patients to care facilities. There is increasing evidence obtained from animal models and human patients that exposure to AE-relevant hypobaria within a few days of injury can worsen outcomes. The cause of this secondary injury is not well understood but it may be related to changes in gene expression induced by exposure to evacuation-relevant conditions. In order to explore the causes of secondary injury, gene expression induced by AE-relevant flight conditions was analyzed. Adult male rats were exposed to flight cabin-relevant hypobaria (8000 or 4000 ft equivalents) and/or different oxygen concentrations (21% or 100%) for 5 or 10 hr. At the end of the exposures, RNA was isolated from lung, blood, heart, and brain (hippocampus), levels of gene expression were measured via microarray analysis, and canonical pathway analysis identified the primary gene pathways enriched by the exposures. This information should be useful to not only optimize the health status of trauma patients undergoing aeromedical evacuation but also help determine which gene expression pathways could be modulated to optimize the therapeutic efficacy of the body's endogenous protection and repair mechanisms.

Animals↗

PubMed2004

Genetic analysis of pathways regulated by the von Hippel-Lindau tumor suppressor in Caenorhabditis elegans.

The von Hippel-Lindau (VHL) tumor suppressor functions as a ubiquitin ligase that mediates proteolytic inactivation of hydroxylated alpha subunits of hypoxia-inducible factor (HIF). Although studies of VHL-defective renal carcinoma cells suggest the existence of other VHL tumor suppressor pathways, dysregulation of the HIF transcriptional cascade has extensive effects that make it difficult to distinguish whether, and to what extent, observed abnormalities in these cells represent effects on pathways that are distinct from HIF. Here, we report on a genetic analysis of HIF-dependent and -independent effects of VHL inactivation by studying gene expression patterns in Caenorhabditis elegans. We show tight conservation of the HIF-1/VHL-1/EGL-9 hydroxylase pathway. However, persisting differential gene expression in hif-1 versus hif-1; vhl-1 double mutant worms clearly distinguished HIF-1-independent effects of VHL-1 inactivation. Genomic clustering, predicted functional similarities, and a common pattern of dysregulation in both vhl-1 worms and a set of mutants (dpy-18, let-268, gon-1, mig-17, and unc-6), with different defects in extracellular matrix formation, suggest that dysregulation of these genes reflects a discrete HIF-1-independent function of VHL-1 that is connected with extracellular matrix function.

Animals↗

PubMed2026

Knowledge-driven interpretable neural networks provide mechanistic insight.

Analyzing omics data in the context of pathway knowledge is critical for understanding the molecular mechanisms underlying pathological changes. However, current pathway analysis methods do not model the detailed mechanistic nature of biological interactions, limiting the understanding of pathway behavior to a relatively shallow level. To address this issue, we present a knowledge-driven machine learning framework that embeds features into pathway graphs and models reactions analytically, producing interpretable feature hierarchies and subnetworks in which functional associations are estimated to model biological interactions. The approach is agnostic to feature selection, enabling the use of full omics data sets without discarding weak signals. Applications to breast cancer microRNA-gene regulation data and COVID-19 metabolomic data highlight immune and metabolic pathways relevant to disease progression. This framework bridges predictive modeling with mechanistic interpretation and offers a foundation for integrative pathway analysis.

Humans↗

PubMed2026

Transcriptomic Changes Associated with Electroacupuncture in a DMCAO Model of Delayed Cognitive Impairment.

INTRODUCTION: Delayed Cognitive Impairment (DCIS) occurs in approximately 31% to 77% of individuals following stroke. Clinical findings have indicated that electroacupuncture may alleviate post-stroke DCIS. However, insights derived from animal models remain limited. The present study utilized a Distal Middle Cerebral Artery Occlusion (DMCAO) mouse model to investigate the potential mechanisms of electroacupuncture through hippocampal transcriptomic analysis. MATERIALS AND METHODS: Adult male BALB/c mice were subjected to DMCAO and received electroacupuncture treatment. High-throughput RNA sequencing of hippocampal tissue was performed to identify Differentially Expressed Genes (DEGs). Enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, hierarchical clustering, and Protein-Protein Interaction (PPI) network analysis, were performed to elucidate potential biological mechanisms. RESULTS: The DMCAO model exhibited features consistent with DCIS. Electroacupuncture treatment was associated with improved cognitive performance and enhanced hippocampal neuroplasticity. A total of 116 DEGs were identified in the DMCAO group compared with the sham group, while 69 DEGs were identified in the DMCAO + electroacupuncture group compared with the untreated DMCAO group. DISCUSSION: GO enrichment analysis indicated that electroacupuncture modulated biological processes related to nerve fibers, axonal development, neuronal regulation, cellular processes, and cardiovascular protection. KEGG pathway analysis indicated involvement in pathways associated with neuronal recovery and axonal function. The PPI network comprised 28 nodes and 33 interactions, with hub genes such as Gna13, Hipk2, and Stambp playing key roles. Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) results were consistent with RNA sequencing findings. CONCLUSION: Electroacupuncture improved DCIS in the DMCAO mouse model. Transcriptomic analysis of the hippocampus provided preliminary evidence of the potential mechanisms underlying the therapeutic effects of electroacupuncture treatment following ischemic stroke.

Animals↗

PubMed2026

Proteomic and Phosphoproteomic Signatures Link Molecular Remodeling to Behavioral Outcomes Following Elderberry and DHA Supplementation in Aging Mice.

Background: Aging is a risk factor for Alzheimer's disease and related dementias, which are associated with synaptic dysfunction and cognitive decline. Elderberry (Sambucus spp.) is rich in anthocyanins with antioxidant and anti-inflammatory properties. Docosahexaenoic acid (DHA), an essential fatty acid, plays a key role in neuronal membrane integrity during brain aging. However, it remains unclear whether elderberry and DHA exert overlapping or distinct effects on brain aging and how these relate to molecular signaling. This study aimed to characterize molecular signatures induced by dietary supplementation and to determine their relationships with behavioral outcomes. Methods: 44-week-old male C57BL/6J mice were randomly assigned to control, elderberry, DHA, or combined diets for 12 weeks. Behavioral testing assessed anxiety-like behavior, spatial learning and memory. Brain tissues underwent proteomic and phosphoproteomic profiling and fatty-acid analysis. Data were analyzed using Ingenuity Pathway Analysis to identify enriched pathways, upstream regulators, and functional associations. Results: Elderberry as well as DHA supplementation induced targeted remodeling of the proteome and phosphoproteome, with pathway enrichment involving synaptogenesis, glutamatergic signaling, and long-term potentiation. Upstream-regulator analysis predicted elderberry-associated CDK5 signaling, accompanied by reduced MAPT/Tau phosphorylation at selected sites, whereas DHA supplementation was associated with CAMK-related signaling. DHA supplementation altered fatty-acid composition, increasing the n-3/n-6 ratio. Elderberry reduced anxiety-like behavior and improved target-directed search during the Barnes maze probe test. Molecular signatures were examined in relation to the measured behavioral outcomes. Conclusions: Elderberry and DHA are associated with distinct molecular networks related to synaptic function and behavioral outcomes in the aging male mouse brain. These findings support further investigation of elderberry and DHA as dietary interventions targeting molecular and behavioral features of brain aging.

Animals↗

PubMed2026

Dysregulated Sheddase Signalling as a Molecular Driver of Plaque Instability Revealed by Integrative Transcriptomics.

Atherosclerosis is a major cause of mortality due to chronic and progressive low-grade inflammation and fibroproliferative remodelling of the intima of arteries. Comprehensive understanding of the interplay between plaque biology and the mechanisms underlying plaque vulnerability and rupture is essential. Here, we aimed to investigate the transcriptomic profiles of stable and unstable atherosclerotic plaques using RNA sequencing data from human carotid atherosclerotic plaque samples based on next-generation knowledge discovery (NGKD) methods. High-throughput RNA-seq data from plaques dissected in stable and unstable regions of four patients were obtained from the Gene Expression Omnibus (GEO) database. GEO RNA-seq Experiments Interactive Navigator (GREIN) software was used to obtain raw gene-level counts and filtered metadata for this dataset. The data were further filtered and normalized using Express analyst to derive differentially expressed genes (DEGs) in unstable plaques compared to stable plaques. The DEGs were further analysed using WebGestalt, STRING DB, preranked gene set enrichment analysis (GSEA), and Ingenuity Pathway Analysis (IPA) software. We identified 4792 DEGs in unstable plaques based on a p-value cutoff of < 0.05. NGKD analysis revealed that the sheddase pathway, collagen degradation, activation of matrix metalloproteinases (MMPs), and extracellular matrix (ECM) degradation ranked among the top five upregulated pathways, whereas the inhibition of MMPs and smooth muscle contraction pathways were identified as the most prominent downregulated pathways in unstable plaques. We found that the sheddase pathway was one of the most significantly upregulated canonical pathways in unstable plaques and this finding opens new avenues for potential therapeutic interventions in patients with atherosclerosis.

Humans↗

PubMed2026

Proteomic analysis identifies pathways related to immune dysregulation in patients with hematologic malignancies after COVID-19 infection.

Patients with hematologic malignancies (HMs) are particularly vulnerable to coronavirus disease 2019 (COVID-19) because of underlying immune dysfunction and treatment-related immunosuppression. However, proteomic features associated with different clinical trajectories in this population remain insufficiently characterized. We performed serum proteomic analysis in 40 HM patients with COVID-19 and 15 healthy controls. Compared with controls, HM patients showed impaired immune-related responses during the acute phase of COVID-19. Acute-phase proteomic patterns differed across outcome groups; however, because outcome groups were closely intertwined with initial COVID-19 severity, ICU admission, and systemic illness, and because multivariable adjustment was not performed due to the limited sample size, these patterns should be interpreted as severity- and outcome-associated profiles rather than independent trajectory-specific markers. Fatal cases showed evidence of dysregulated immune activation, whereas patients later classified as having long COVID exhibited broader suppression of immune-related pathways. In addition to immune alterations, pathways related to platelet activation and cardiac-related dysfunction were associated with adverse clinical trajectories. Enzyme-linked immunosorbent assay validation supported the association of selected proteins with outcome groups during acute infection. These findings provide a proteomic overview of COVID-19 in HM patients and offer a basis for future mechanistic studies and larger external validation cohorts.IMPORTANCEPatients with hematologic malignancies are highly vulnerable to severe coronavirus disease 2019 (COVID-19), acute death, and long COVID due to preexisting immune dysfunction. However, the proteomic signatures linked to adverse clinical trajectories remain poorly understood. Our serum proteomic study identifies distinct acute-phase immune profiles associated with different outcomes: broad immune suppression characterizes long COVID, while dysregulated immune activation is associated with fatal cases. Platelet activation and cardiac-related pathways are also linked to poor outcomes. These findings provide key molecular insights for this high-risk population, supporting future biomarker development, risk stratification, and targeted clinical management.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT05683353.

Humans↗

PubMed2026

Beyond ion channel dysfunction: Integration of the transcriptome and proteome from patient-specific re-engineered cardiac cells, and population-level QT genome-wide association study reveals broad cellular dysfunction.

BACKGROUND: Congenital long QT syndrome (LQTS) is a cardiac channelopathy with increased risk of cardiac-triggered syncope/seizures, sudden cardiac arrest, and sudden cardiac death. OBJECTIVE: This study aimed to describe the transcriptomic and proteomic profiles in patient-derived inducible pluripotent stem cell-derived cardiomyocyte (iPSC-CM) models of the 3 canonical genotypes of congenital LQTS: LQT1, LQT2, and LQT3 and integrate these omics-level findings with each other and with population/clinical level QT-genome-wide association study (GWAS) data. METHODS: LQT1, LQT2, LQT3 and respective isogenic control iPSC-CMs were cultured, and RNA and protein samples were collected. RNA sequencing and mass spectrometry-enabled proteomic analysis was performed. PrediXcan analysis was performed using QT GWAS summary statistics and transcriptome expression data. Differential gene and protein expression and ingenuity pathway analysis (IPA) was performed comparing each LQT genotype with its respective isogenic control. RESULTS: 1645 differentially expressed genes (DEGs) were identified; 13 were altered in all 3 LQTS genotypes. IPA analysis of DEGs revealed 301 altered pathways; 47 were altered in all LQTS genotypes. Proteomic analysis identified 2561 differentially expressed proteins (DEPs); 30 were altered in all 3 genotypes. IPA analysis of DEPs identified 646 altered pathways. 306 genes/proteins were identified as significantly altered in both the transcriptome and proteome; pathway analysis of these 301 genes identified 201 altered pathways. 7 pathways were altered in all 3 LQTS genotypes in both the transcriptome and proteome. Integration of the population-level PrediXcan results and the cardiomyocyte-derived omics results identified multiple shared pathways. CONCLUSION: Multi-omics analysis of LQTS and integration of omics results with QT GWAS data reveals that primary LQTS-causative ion channel defects precipitate secondary alterations in a wide range of cellular pathways. Our findings suggest more broad molecular level changes throughout the cell. This study lays the foundation for further exploration of broad cellular changes resulting from ion channel disturbances and how they contribute to disease mechanism.

Humans↗

PubMed2026

Temporal Transcriptomic Profiling of NMBA-Induced Rat Esophageal Squamous Carcinogenesis Identifies Early Inflammatory Activation and Late NRF2-Associated Oxidative-Stress Remodeling.

Temporal molecular events during early esophageal squamous carcinogenesis remain incompletely defined, in part because human precursor tissues are difficult to obtain sequentially. We used the N-nitrosomethylbenzylamine (NMBA)-induced rat model to characterize stage-associated transcriptional programs during esophageal squamous carcinogenesis. Vehicle-control reference esophageal tissues and NMBA-treated esophageal tissues, collected at weeks 6 and 29, were profiled using Affymetrix Rat Genome 230 2.0 arrays, followed by pathway analysis and qRT-PCR validation of selected genes. Relative to vehicle-control reference tissues, 173 genes were differentially expressed at week 6, whereas 1628 genes were differentially expressed at week 29, indicating marked expansion of transcriptional dysregulation during carcinogenic progression. Sixteen genes were differentially expressed only at week 6, while 157 genes were altered at both time points. Pathway analysis suggested that inflammatory and immunologic processes were prominent during the early response to NMBA exposure, whereas late-stage carcinogenesis was characterized by NRF2-associated oxidative-stress response and dysregulation of multiple glutathione S-transferase family members. A subset of progression-associated genes, including Defb4, Gsta2, Sbsn, Spink5, Plcd4, Hbb, and Hba-a2, showed increasing dysregulation from week 6 to week 29. These findings define temporally distinct molecular programs in NMBA-induced esophageal squamous carcinogenesis and provide a framework for prioritizing candidate pathways and genes relevant to esophageal cancer prevention, early detection, and progression biology.

Animals↗

PubMed2025

Proteomic signature of dementia risk in type 2 diabetes.

INTRODUCTION: Type 2 diabetes (T2D) significantly increases dementia risk, yet the molecular mechanisms underlying this association remain unclear. OBJECTIVES: This study aimed to identify protein signatures that distinguish dementia risk in T2D patients, develop a proteomic prediction model, and elucidate biological pathways connecting T2D and dementia. METHODS: We analyzed 2,920 plasma proteins from 52,958 participants (including 3,292 with T2D) in the UK Biobank Pharma Proteomics Project with a median follow-up of 14.6 years. Cox regression models with interaction terms identified T2D-specific protein associations with dementia risk. Machine learning models were developed to predict dementia in T2D patients. Pathway analysis and weighted gene co-expression network analysis identified biological mechanisms linking T2D and dementia. RESULTS: We identified 471 proteins with significant interaction effects between T2D and dementia risk. In non-T2D individuals, elevated levels of neuronal pentraxin receptor (NPTXR, HR = 0.74, 95 %CI:0.66-0.83) and carbonic anhydrase 14 (CA14, HR = 0.67, 95 %CI:0.60-0.75) were exclusively associated with decreased dementia risk. Conversely, in T2D patients, elevated rho guanine nucleotide exchange factor 12 (ARHGEF12, HR = 1.45, 95 %CI:1.10-1.91) was specifically associated with increased dementia risk. A 51-protein model accurately predicted 15-year dementia risk in T2D patients (AUC = 0.835, C-index = 0.829), outperforming conventional clinical risk scores and maintaining high accuracy for Alzheimer's disease and vascular dementia. Pathway analysis revealed enrichment of IL6-JAK-STAT3 signaling in T2D-related dementia, while dysregulation of fatty acid metabolism was specific to T2D-associated Alzheimer's disease. CONCLUSIONS: This large-scale proteomic analysis identifies specific molecular signatures that differentiate dementia risk in diabetic and non-diabetic populations, with potential applications for early risk stratification and targeted interventions. The identified pathways provide novel insights into the pathophysiological processes connecting T2D and dementia and suggest potential therapeutic targets.

Humans↗

PubMed1991

[An electrophysiological analysis of pathways from lateral septum to hippocampal CA1 area in rat].

Upon stimulating the lateral septal region, a population spike could be recorded in the stratum pyramidale of hippocampal CA1 together with a recordable EPSP in the apical dendrites (stratum radiatum). After destruction of hippocampal CA3, CA4 pyramidal cells by intraventricular microinjection of kainic acid, electrical stimulation of the lateral septum could no longer evoke EPSP in the apical dendrites. This experiment suggests that the neural connection of the lateral septo-CA1 apical dendrites is mediated by the collaterals of the ipsilateral CA3 pyramidal cells. But after the destruction of CA3, CA4, electric stimulation of lateral septum could still evoke EPSP in the basal dendrites (stratum oriends). The neural connection mediating the response of the lateral septo-CA1 basal dendrites was not reported before, but the neural pathway remains to be investigated.

Animals↗

PubMed2025

Chromosome-level genome assembly with telomeric repeats at scaffold ends for Rhabdosargus sarba.

Rhabdosargus sarba, the goldlined seabream, is a euryhaline marine fish of great aquaculture potential. Genome sequencing and assembly of R. sarba was carried utilizing a multi-platform sequencing strategy that included long-read sequencing (PacBio HiFi), short-read sequencing (Illumina), and chromatin interaction mapping (Hi-C). The final genome assembly size after scaffolding was 764.59 Mb in 31 scaffolds with an N50 length of 33.98 Mb. Repeat profiling of primary assembly showed that 28.71% of the genome comprises of repeat elements. Gene prediction utilising the evidence from ab initio prediction and transcriptome data revealed 26,913 protein encoding genes and functional annotation and pathway analysis showed their participation in 332 pathways. This genome is an excellent resource for future research on genetic improvement and molecular breeding programmes for R. sarba.

Animals↗

PubMed1992

Amino acid substitutions in the Dictyostelium G alpha subunit G alpha 2 produce dominant negative phenotypes and inhibit the activation of adenylyl cyclase, guanylyl cyclase, and phospholipase C.

Previous studies have demonstrated that the Dictyostelium G alpha subunit G alpha 2 is essential for the cAMP-activation of adenylyl cyclase and guanylyl cyclase and that g alpha 2 null mutants do not aggregate. In this manuscript, we extend the analysis of the function of G alpha 2 in regulating downstream effectors by examining the in vivo developmental and physiological phenotypes of both wild-type and g alpha 2 null cells carrying a series of mutant G alpha 2 subunits expressed from the cloned G alpha 2 promoter. Our results show that wild-type cells expressing G alpha 2 subunits carrying mutations G40V and Q208L in the highly conserved GAGESG (residues 38-43) and GGQRS (residues 206-210) domains, which are expected to reduce the intrinsic GTPase activity, are blocked in multicellular development. Analysis of down-stream effector pathways essential for mediating aggregation indicates that cAMP-mediated activation of guanylyl cyclase and phosphatidylinositol-phospholipase C (PI-PLC) is almost completely inhibited and that there is a substantial reduction of cAMP-mediated activation of adenylyl cyclase. Moreover, neither mutant G alpha 2 subunit can complement g alpha 2 null mutants. Expression of G alpha 2(G43V) and G alpha 2(G207V) have little or no effect on the effector pathways and can partially complement g alpha 2 null cells. Our results suggest a model in which the dominant negative phenotypes resulting from the expression of G alpha 2(G40V) and G alpha 2(Q208L) are due to a constitutive adaptation of the effectors through a G alpha 2-mediated pathway. Analysis of PI-PLC in g alpha 2 null mutants and in cell lines expressing mutant G alpha 2 proteins also strongly suggests that G alpha 2 is the G alpha subunit that directly activates PI-PLC during aggregation. Moreover, overexpression of wild-type G alpha 2 results in the ability to precociously activate guanylyl cyclase by cAMP in vegetative cells, suggesting that G alpha 2 may be rate limiting in the developmental regulation of guanylyl cyclase activation. In agreement with previous results, the activation of adenylyl cyclase, while requiring G alpha 2 function in vivo, does not appear to be directly carried out by the G alpha 2 subunit. Our data are consistent with adenylyl cyclase being directly activated by either another G alpha subunit or by beta gamma subunits released on activation of the G protein containing G alpha 2.

Adenylyl Cyclases↗

PubMed2026

Multi-omics identifies lipid accumulation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome cell lines: a case-control study.

BACKGROUND: In recent years, evidence has indicated a metabolic shift towards increased demand for lipids in various lymphoid cell populations from people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). We previously screened the mitochondrial function and gene expression of B cell-derived lymphoblastoid cell lines (LCLs) generated from the blood of people with ME/CFS to characterise a model for hypothesis discovery and testing, observing elevated expression of gene products facilitating amino acid and fatty acid degradation for energy. METHOD: In this follow-up study we have expanded this characterisation by profiling the polar metabolomes and non-polar lipidomes of an all-female cohort of 17 healthy control and 15 ME/CFS LCLs, and we integrated this new data with the previously generated proteomic and transcriptomic data. RESULTS: In the polar metabolome we detected no significantly altered individual features, while integrated multi-omic analysis by MetaboAnalyst indicated 15 dysregulated pathways. Next, in the non-polar lipidome, we identified that PC(O-38:4) had significantly reduced levels in ME/CFS LCLs and was almost entirely discriminative of ME/CFS status. Among all detected classes of lipids we found that triradylglycerolipids ("triglycerides"), diradylglycerolipids and fatty acids were the most significantly affected and were elevated, and that most lipids exhibited average levels higher than in healthy controls. BioPAN pathway analysis of the lipidomic data predicted a more-active gene product that we confirmed to be significantly elevated in both our proteomic and transcriptomic data, this being phosphatidylserine synthase 1 (PTDSS1), plus 7 other gene products that were concordantly altered in expression in the transcriptomic data. We also found that ME/CFS LCLs exhibited a significant tendency towards more saturated lipid content. CONCLUSIONS: LCLs generated from circulating B cells from people with ME/CFS show accumulation of lipids, skewed lipid profiles and altered activity of related metabolic enzymes such as PTDSS1. These findings will inform future hypothesis-driven studies of primary lymphoid cell populations from people with ME/CFS to dissect specific immunometabolic mechanisms that may be involved in the syndrome, particularly relating to intersections between lipid abnormalities and potential effects on immune cell effector functions.

Fatigue Syndrome, Chronic↗

PubMed2026

Uncovering ShuangZi Powder's Anti-Ovarian Cancer Mechanism: A Systems Biology and Experimental Approach.

INTRODUCTION: This study investigated the anti-ovarian cancer (OC) effects of Shuangzi Powder (SZP) and its regulatory impact on the tumor microenvironment. METHOD: This study employed systems biology approaches, integrating molecular docking and experimental validation, to explore the pharmacological mechanisms of SZP in OC treatment. To identify potential bioactive compounds and target genes of SZP, network pharmacology, protein- protein interaction network analysis,.Gene Ontology (GO) analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were conducted. RESULTS: Among the 11 bioactive ingredients identified in SZP, 1,767 potential therapeutic targets were predicted, while 2,637 differentially expressed genes were found to be associated with OC. KEGG pathway analysis revealed significant enrichment in pathways related to cancer, apoptosis, the PI3K-Akt signaling pathway, and the PD-L1/PD-1 checkpoint pathway. Treatment of A2780 cells with β,β-Dimethylacrylshikonin (DMAS) inhibited cell viability, migration, and invasion. Moreover, DMAS downregulated the expression of cell cycle- and apoptosis-related genes (CCNB1, CHEK1, CCNE1, and PARP1) and upregulated the immune checkpoint gene PD-L1. DISCUSSION: These findings indicate that multiple components, targets, and pathways are involved in OC treatment by SZP. CONCLUSION: DMAS, one of the bioactive ingredients of SZP, was predicted and preliminarily validated to exert inhibitory effects on OC cells, mainly through the regulation of the cell cycle, apoptosis, and immune response, as demonstrated by molecular docking and experimental analyses.

Ovarian Neoplasms↗

PubMed2026

Integrated GC-HRAM-MS and UHPLC-QTOF-MS metabolomics reveal mineral-induced metabolic adaptation of Lactiplantibacillus pentosus 9D3 during milk fermentation.

Milk fermentation by plant-associated probiotic strains is constrained by poor adaptation to dairy matrices. This study evaluated genome-guided micronutrient supplementation to improve the performance and metabolomic profile of Lactiplantibacillus pentosus 9D3 in milk. Individual supplementation with Mn2+ or Mg2+ significantly enhanced bacterial growth and acidification, whereas Fe2+, Zn2+, and B-group vitamins showed limited effects. Optimal supplementation with 50 mg/L Mn2+ and 100 mg/L Mg2+ increased viable counts from 7.54 to 8.89 log CFU/mL. A cell population increase of ∼1.9 log CFU/mL was achieved despite reducing the inoculum level from 10% to 6%. Integrated metabolomic profiling using GC-HRAM-MS and UHPLC-QTOF-MS identified 299 metabolites across supplemented fermented milk, non-supplemented fermented milk, and unfermented milk, with group separation. Pathway analysis revealed significant enrichment of seven metabolic pathways, including purine, pyrimidine, galactose, propanoate, butanoate, amino sugar and nucleotide sugar, and α-linolenic acid metabolism. These findings support cost-efficient precision fermentation of functional dairy products.

Dairy products↗

PubMed1992

Coregulation of purine and histidine biosynthesis by the transcriptional activators BAS1 and BAS2.

We have found cross-pathway regulation between purine and histidine biosynthesis in yeast. The transcription factors BAS1 and BAS2/PHO2, which are also regulators of the histidine pathway, participate in the regulation of the purine biosynthetic pathway. Analysis of four genes of the purine pathway (ADE1, ADE2, ADE5,7, and ADE8) shows that their expression is repressed by adenine. The maximal basal and induced expression of these purine genes requires the presence of both BAS1 and BAS2. The factor BAS1 has been shown to bind at a site containing the TGACTC hexanucleotide motif in the ADE2 and ADE5,7 promoters. This motif is required for both basal and induced activation of the ADE2 gene by BAS1 and BAS2.

Base Sequence↗

PubMed2025

Exploring the Relationship Between Serological Metabolites and Oral Cancer: A Mendelian Randomization Study.

BACKGROUND: Oral cancer is a prevalent malignant tumor, comprising ∼5% to 6% of all tumors. The 5-year survival rate for this condition is ∼50%. However, the early symptoms of oral cancer are often inconspicuous and easily overlooked, leading to frequent misdiagnosis or missed diagnosis. Although some previous studies have investigated the correlation between oral cancer and serum metabolites, the exact relationship remains unclear. Consequently, it is of utmost importance to develop effective early diagnosis methods and explore the pathogenesis of oral cancer to enhance patients' survival rates and quality of life. METHODS: This Mendelian randomization (MR) study utilized the Genome-Wide Association Study (GWAS) catalog to obtain instrumental variables (IVs) that link 486 serum metabolites with oral cancer. The study then conducted a causal analysis, using serological metabolites as exposure factors and oral cancer as the outcome. The samples used in the study were exclusively from the European population. The main method used for the univariate MR analysis was the inverse variance weighting method. After excluding confounding factors, MR analysis was performed again. Sensitivity analyses were subsequently conducted to enhance the robustness of the MR results. Furthermore, metabolic pathway analysis was carried out on serum metabolites associated with oral cancer, aiming to identify and explore potential metabolic pathways. RESULTS: After MR analysis, 8 serum metabolites were screened out that are highly correlated with the causal relationship with oral cancer, including androsterone sulfate (OR=2.11, 95% CI: 1.37-3.27, P =0.0007), X-12100--hydroxytryptophan (OR=0.12, 95% CI: 0.02-0.73, P =0.022), gamma-glutamylphenylalanine (OR=7.57, 95% CI: 1.17-48.85, P =0.033), 7-methylxanthine (OR=0.22, 95% CI: 0.05-0.90, P =0.035), urate (OR=12.03, 95% CI: 1.16-124.32, P =0.037), palmate (16:0) (OR=11.01, 95% CI: 1.11-109.13, P =0.040), creatinine (OR=0.03, 95% CI: 0.00-0.90, P =0.047), guanosine (OR=2.66, 95% CI: 1.00-7.04, P =0.049), and the absence of heterogeneity and horizontal pleiotropy in this study indicates that the MR results obtained are quite reliable. CONCLUSION: Androsterone sulfate, gamma-glutamylphenylalanine, urate, palmitate (16:0), creatinine, and guanosine have been identified as risk factors for oral cancer. In contrast, X-12100--hydroxytryptophan and 7-methylxanthine may have a protective effect against oral cancer. The findings of this study have significant implications for early oral cancer diagnosis and offer valuable insights into the disease's pathogenesis.

Mendelian Randomization Analysis↗