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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↗

PubMed2023

NLRP12 downregulates the Wnt/β-catenin pathway via interaction with STK38 to suppress colorectal cancer.

Colorectal cancer (CRC) at advanced stages is rarely curable, underscoring the importance of exploring the mechanism of CRC progression and invasion. NOD-like receptor family member NLRP12 was shown to suppress colorectal tumorigenesis, but the precise mechanism was unknown. Here, we demonstrate that invasive adenocarcinoma development in Nlrp12-deficient mice is associated with elevated expression of genes involved in proliferation, matrix degradation, and epithelial-mesenchymal transition. Signaling pathway analysis revealed higher activation of the Wnt/β-catenin pathway, but not NF-κB and MAPK pathways, in the Nlrp12-deficient tumors. Using Nlrp12-conditional knockout mice, we revealed that NLRP12 downregulates β-catenin activation in intestinal epithelial cells, thereby suppressing colorectal tumorigenesis. Consistent with this, Nlrp12-deficient intestinal organoids and CRC cells showed increased proliferation, accompanied by higher activation of β-catenin in vitro. With proteomic studies, we identified STK38 as an interacting partner of NLRP12 involved in the inhibition of phosphorylation of GSK3β, leading to the degradation of β-catenin. Consistently, the expression of NLRP12 was significantly reduced, while p-GSK3β and β-catenin were upregulated in mouse and human colorectal tumor tissues. In summary, NLRP12 is a potent negative regulator of the Wnt/β-catenin pathway, and the NLRP12/STK38/GSK3β signaling axis could be a promising therapeutic target for CRC.

Humans↗

PubMed2026

Deficient arsenic methylation and global proteomic reprogramming in human keratinocytes during arsenic-induced skin carcinogenesis.

Chronic inorganic arsenic (iAs) exposure affects > 220 million people worldwide and skin cancer is a hallmark of long-term iAs exposure. Limited information exists regarding arsenic methylation by human keratinocytes and how methylation influences skin carcinogenesis. Inorganic arsenite (iAsIII) and its methylated metabolites disrupt diverse zinc finger proteins, leading to differential toxicity patterns. We examined arsenic methylation capacity in non-malignant human keratinocytes and interrogated proteomic remodeling across three stages of iAsIII induced malignant transformation using the well-established preclinical HaCaT model. Arsenic methylation was assessed by hydride generation cryotrapping inductively coupled-mass spectrometry and global proteomic changes were analyzed by tandem-mass tagging liquid chromatography-tandem mass spectrometry. Primary, hTERT-immortalized and HaCaT human keratinocytes exhibited negligible arsenic methylation, with iAsIII comprising at least 98.5% of total intracellular arsenic, attributable to minimal expression of arsenite methyltransferase. Proteomic profiling identified over 275 differentially expressed proteins at each stage of transformation, including multiple zinc finger proteins implicated in cell cycle control, RNA metabolism, and genome stability. Ingenuity® Pathway Analysis revealed progressive, coordinated disruption of cancer-associated pathways and regulatory networks over the transformation timeline, including zinc-coordinating upstream regulators that may explain widespread pathway dysregulation. Collectively, our findings suggest that iAsIII promotes skin carcinogenesis by disrupting C3H1- and C4-type zinc finger protein-centered regulatory networks that coordinate cancer-associated signaling and metabolic pathways in human keratinocytes, highlighting key candidates for future mechanistic studies.

Arsenic↗

PubMed2026

Prenatal BPA exposure perturbs RNA-binding protein-mediated splicing regulation and synaptogenesis in the developing cerebellum in a sex-dependent manner.

BACKGROUND: Autism spectrum disorder (ASD) is a pervasive neurodevelopmental condition characterized by social communication deficits, exhibiting a male bias in prevalence. Emerging evidence suggests that prenatal exposure to bisphenol A (BPA) may perturb neurodevelopmental trajectories relevant to ASD. While the cerebellum is increasingly recognized as a brain region implicated in ASD pathophysiology, the impact of gestational BPA exposure on its post-transcriptional alternative splicing machinery remains fundamentally undefined. METHODS: Here, we investigated sex-dependent effects of prenatal BPA exposure on the alternative splicing landscape of the neonatal rat cerebellum. We utilized RNA-seq to profile differential alternative splicing (DAS) events. Ingenuity Pathway Analysis (IPA) was used to predict biological functions and canonical pathways, and to construct the interactome network of DAS genes. To explore candidate upstream regulatory mechanisms, we performed in silico molecular docking and used high-resolution melting (HRM) qRT-PCR to validate selected splicing events. Furthermore, we assessed in vitro cellular phenotypes in primary cerebellar neurons by measuring MTS-based viability and Syn1/Psd95 puncta colocalization. RESULTS: Prenatal BPA exposure was associated with widespread DAS in genes enriched for ASD-relevant pathways in the neonatal rat cerebellum. To our knowledge, this study is the first to report molecular docking analyses predicting favorable interactions between BPA and several candidate RNA-binding proteins (RBPs), including CPEB1, RALYL, HNRNPDL, and ACO1. Our findings support a model in which BPA may perturb RBP-associated splicing regulation, including altered splicing of chromatin regulators such as Ccar1 in males. These molecular and cellular findings were accompanied by sex-stratified differences in neuronal viability and synaptic puncta measurements. BPA exposure was associated with an increased MTS viability signal in male primary cerebellar neurons, together with significant reductions in Psd95 and Syn1 puncta density, whereas female neurons showed significantly increased synaptic puncta colocalization together with reduced viability. CONCLUSIONS: In this study, we propose that prenatal BPA may be relevant to ASD-related neurodevelopmental pathways through sex-dependent changes in RBP-associated alternative splicing, including altered splicing of Ccar1 in males, together with distinct cellular outcomes. Together, these findings identify the developing cerebellum as a sensitive target of prenatal BPA exposure and highlight alternative splicing as a candidate pathway relevant to ASD biology.

Animals↗

PubMed2026

DNA Methylation and Proteomic Profiling of Postmortem Brain Tissue Reveals Epigenetic Dysregulation and Neuroinflammatory in Fragile X-associated Tremor/Ataxia Syndrome (FXTAS).

BACKGROUND: Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by FMR1 premutation CGG repeat expansions (55-200 repeats). The epigenetic landscape of the FXTAS brain remains uncharacterized. We performed genome-wide DNA methylation profiling of postmortem prefrontal cortex tissue to identify differentially methylated positions (DMPs) and candidate genes, and sought protein-level support for a neuroinflammatory signal. METHODS: DNA methylation was profiled in postmortem prefrontal cortex (Brodmann area 9) from 27 male FXTAS cases and 29 male controls using the Illumina MethylationEPIC array (EPICv1 and EPICv2 platforms), merging 721,802 common probes. Surrogate variable analysis (SVA) controlled for confounders. DMPs were defined by |Δβ| > 0.10 and FDR < 0.05; exploratory Reactome 2024 pathway analysis was performed on the DMP-associated gene list. Targeted proteomic profiling was performed in the same brain region using the Olink (proximity extension assay) Inflammation panel in 9 FXTAS cases and 12 controls, with SVA-adjusted differential abundance analysis, and concordance assessment against a prior mass spectrometry dataset. RESULTS: We identified 108 significant cg-type DMPs mapping to 80 genes (50 hypermethylated, 58 hypomethylated in FXTAS). The strongest signal was CYP2E1 (7 concordant hypomethylated DMPs, mean Δβ = -0.143), an oxidative stress gene also implicated in Parkinson's disease. FTCD, a one-carbon cycle enzyme, carried 5 hypermethylated DMPs (mean Δβ = +0.210). A cluster of DMP-associated genes with established roles in innate immune and NF-κB signaling, TRAF3 (the single most significant DMP among the inflammation genes, hypermethylated), BATF, RCOR1, and MSI2; they pointed toward neuroinflammatory dysregulation. Additional genes included LINGO1 (myelination inhibitor), SYT3 (synaptic vesicle), and SLC39A4 (zinc transporter). Exploratory Reactome enrichment using the DMP-associated gene set nominated themes including neuroinflammation resolution, axonal growth inhibition, zinc homeostasis, and CYP2E1 metabolism at nominal significance (p<0.05); however, the gene-to-pathway mapping rate was low and no pathway survived correction for multiple testing. Olink proteomic analysis independently identified 60 significantly altered inflammation proteins (59 downregulated), including CXCL8, CXCL10, IL6, IL15, IL18, TLR3, IRAK1/4, and complement C1QA, which were directionally concordant with prior mass spectrometry data. CONCLUSIONS: This integrated study reveals a genome-wide epigenetic signature in the FXTAS prefrontal cortex implicating oxidative stress, myelination failure, zinc dysregulation, one-carbon cycle disruption, and most notably a coordinated set of epigenetically altered genes governing innate immune and NF-κB signaling. Convergence of TRAF3 hypermethylation with independent downregulation of TLR3 and NF-κB-pathway proteins at the protein level supports a coherent, cross-platform model of dysregulated neuroinflammatory signaling in FXTAS, identified here through individual gene- and protein-level convergence rather than formal pathway enrichment. FTCD hypermethylation proposes a self-reinforcing epigenetic loop via SAM depletion. These multi-omic findings establish FXTAS as a disorder of pervasive epigenetic reprogramming and nominate candidate genes for future mechanistic and therapeutic investigation.

CYP2E1↗

PubMed2025

Interaction and regulation of the mitochondrial proteome - in health and disease.

INTRODUCTION: Mitochondria contain multiple pathways including energy metabolism and several signaling and synthetic pathways. Mitochondrial proteomics is highly valuable for studying diseases including inherited metabolic disorders, complex and common disorders like neurodegeneration, diabetes, and cancer, since they all to some degree have mitochondrial underpinnings. AREAS COVERED: The main mitochondrial functions and pathways are outlined, and systematic protein lists are presented. The main energy metabolic pathways are as follows: iron-sulfur cluster synthesis, one carbon metabolism, catabolism of hydrogen sulfide, kynurenines and reactive oxygen species (ROS), and others, described with the aim of laying a foundation for systematic mitochondrial pathway analysis based on proteomics data. The links of the proteins and pathways to functional effects and diseases are discussed. The disease examples are focussed on inherited metabolic disorders, cancer, neurological, and cardiovascular disorders. EXPERT OPINION: To elucidate the role of mitochondria in health and disease, there is a need for comprehensive proteomics analyses with stringent, systematic data treatment for proper interpretation of mitochondrial pathway data. In that way, comprehensive hypothesis-based research can be performed based on proteomics data.

Humans↗

PubMed2026

Loss of ovarian function and estrogen therapy remodel the brain's synaptic and metabolic proteome.

Menopause is linked to cognitive decline and reduced brain metabolism, whereas estrogen (E2) therapy has been shown to mitigate these effects. Understanding the molecular mechanisms by which ovarian hormones and E2 influence neuroprotection is essential for developing strategies to maintain brain health in women. In this study, we examined how the loss of ovarian hormones, with or without E2 treatment, affects the brain proteome and mitochondrial energy production in aged female C57BL/6J mice (36-40 wk). The mice underwent sham or ovariectomy (OVX) surgery and were fed a high-fat diet for 10 wk; 6 wk after surgery, OVX mice received either sesame oil or E2 treatment for 4 wk. Proteomic analysis of brain homogenates revealed 4,992 proteins regulated by E2, with pathway analysis showing increased signaling proteins related to synaptogenesis. OVX reduced proteins involved in synaptic function, branched-chain amino acid and ketone metabolism, the tricarboxylic acid cycle, and oxidative phosphorylation (Complexes I, IV, and V), whereas E2 restored protein expression within these pathways. Despite alterations in OxPhos proteins, basal and state 3 mitochondrial respiration remained unchanged, although notable impairments in Complex IV enzymatic activity were apparent in OVX, which were partially reversed by E2 treatment. Overall, these results indicate that E2 supports brain health by maintaining proteins crucial for synaptic integrity and metabolism, while partially offsetting the functional decline in mitochondrial bioenergetics associated with menopause.NEW & NOTEWORTHY The menopausal transition, marked by declining estrogen levels, alters cognition, neuroplasticity, and brain metabolism. Although hormone therapy benefits cognition, its molecular effects on the brain remain unclear. Using whole-brain proteomics in aged ovariectomized (OVX) mice with or without estrogen treatment, we found that OVX reduced proteins linked to synaptogenesis and mitochondrial metabolism. Estrogen reversed these declines, restoring pathways supporting neuronal signaling and energy balance, identifying estrogen-regulated proteins critical for maintaining brain health during menopause.

Animals↗

PubMed2026

Exploring the Potential Molecular Targets of Cyanidin-3-O-glucoside for Type 2 Diabetes Mellitus Treatment.

INTRODUCTION: This study aims to elucidate the multi-target molecular mechanism of cyanidin-3-O-glucoside (C3G) in treating Type 2 Diabetes (T2DM) through network pharmacology methods. METHODS: The study was designed to predict the targets of C3G through public databases and to screen for T2DM-related targets. Protein-protein interaction (PPI) network analysis, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the common targets. Core targets were further validated through molecular docking and molecular dynamics (MD) simulations. RESULTS: This research identified a total of 57 potential targets of C3G in the treatment of T2DM. Subsequent PPI analysis identified ALB (Degree=43), AKT1 (Degree=41), and TNF (Degree=41) as the top three hub proteins. Pathway analysis indicated significant involvement in the insulin signaling pathway (P = 4.205×10-9), AMPK signaling pathway (P = 9.582×10-7), and FoxO signaling pathway (P = 1.315×10-6). Molecular docking revealed strong binding affinities between C3G and NOS3 (-9.5 kcal/mol), PPARG (-9.0 kcal/mol), TNF (-8.5 kcal/mol), and INSR (-8.4 kcal/mol). MD simulations further confirmed that the C3G-target complex has excellent binding stability. DISCUSSION: C3G may intervene in the pathological progression of T2DM by regulating key pathways such as insulin sensitivity, inflammatory responses, and oxidative stress. Further studies suggest that INSR and NOS3 may be new targets through which C3G exerts its effects, but their specific mechanisms and in vivo biological functions still need to be elucidated by subsequent experiments. CONCLUSION: C3G may intervene in the progression of T2DM in a multi-pathway synergistic manner by targeting key molecules such as INSR and NOS3.

Anthocyanins↗

PubMed1985

Role of passive potassium fluxes in cell volume regulation in cultured HeLa cells.

Cultured HeLa cells behave as ideal osmometers when subjected to hyperosmolar media, and show no volume regulatory behavior. In hypoosmolar solutions, cell swelling is not as great as predicted, and this is due largely to a loss of intracellular KCl. In hyperosmolar solutions there is a stimulation of the ouabain-insensitive but loop diuretic-sensitive 86Rb+ (K+) pathway. Analysis of the K+, Na+ and Cl- dependency of this K+ flux pathway demonstrates that the increase is principally due to an increase in its maximal velocity (Vmax). The sensitivity of this pathway to diuretic inhibition is unchanged in hyperosmolar media. Diuretic-sensitive 86Rb+ (K+) efflux stimulated by hypertonicity shows no marked dependence on external K+. The K+ loss observed in hypoosmolar media is distinct from the K+ transport pathway stimulated by hyperosmolar media on the basis of its sensitivity to furosemide and anion dependence.

Cell Membrane Permeability↗

PubMed2025

Decreased intestinal abundance of Akkermansia muciniphila is associated with metabolic disorders among people living with HIV.

BACKGROUND: Previous studies have shown changes in gut microbiota after human immunodeficiency virus (HIV) infection, but there is limited research linking the gut microbiota of people living with HIV (PLWHIV) to metabolic diseases. METHODS: A total of 103 PLWHIV were followed for 48 weeks of anti-retroviral therapy (ART), with demographic and clinical data collected. Gut microbiome analysis was conducted using metagenomic sequencing of fecal samples from 12 individuals. Nonalcoholic fatty liver disease (NAFLD) was diagnosed based on controlled attenuation parameter (CAP) values of 238 dB/m from liver fibro-scans. Participants were divided based on the presence of metabolic disorders, including NAFLD, overweight, and hyperlipidemia. Akkermansia abundance in stool samples was measured using RT-qPCR, and Pearson correlation and logistic regression were applied for analysis. RESULTS: Metagenomic sequencing revealed a significant decline in gut Akkermansia abundance in PLWHIV with NAFLD. STAMP analysis of public datasets confirmed this decline after HIV infection, while KEGG pathway analysis identified enrichment of metabolism-related genes. A prospective cohort study with 103 PLWHIV followed for 48 weeks validated these findings. Akkermansia abundance was significantly lower in participants with NAFLD, overweight, and hyperlipidemia at baseline, and it emerged as an independent predictor of NAFLD and overweight. Negative correlations were observed between Akkermansia abundance and both CAP values and body mass index (BMI) at baseline and at week 48. At the 48-week follow-up, Akkermansia remained a predictive marker for NAFLD. CONCLUSIONS: Akkermansia abundance was reduced in PLWHIV with metabolic disorders and served as a predictive biomarker for NAFLD progression over 48 weeks of ART.

Humans↗

PubMed2026

Meta-QTL Analysis Reveals Consensus Genomic Regions and Candidate Genes for Resistance to Sudden Death Syndrome in Soybean.

Sudden death syndrome (SDS), caused by Fusarium virguliforme, is one of the most economically important diseases limiting soybean production worldwide. Although numerous quantitative trait loci (QTL) associated with SDS resistance have been reported, inconsistencies among mapping populations, marker systems, and experimental conditions have hindered the identification of robust resistance loci for soybean improvement. In this study, a comprehensive meta-analysis was conducted to integrate published QTL and identify stable consensus genomic regions associated with SDS resistance. After a systematic literature survey and data curation, 153 QTL derived from 14 linkage-mapping studies were analyzed using a custom R-based workflow, resulting in the identification of 23 consensus meta-QTL (MQTL) distributed across 17 chromosomes. Several MQTL, particularly those located on chromosomes 6, 8, 18, and 20, were supported by multiple independent studies and represented major genomic hotspots for SDS resistance. Physical localization and functional annotation of these MQTL identified 217 candidate genes, including genes predicted to be involved in plant defense, signal transduction, transcriptional regulation, and secondary metabolism. Gene Ontology enrichment analysis identified response to salicylic acid as the only biological process that remained significant after FDR correction, whereas Kyoto Encyclopedia of Genes and Genomes pathway analysis did not identify significantly enriched pathways. Independent support using five published genome-wide association studies further supported several MQTL, especially those on chromosomes 6, 18, and 20, thereby increasing confidence in these genomic regions. The identified MQTL and prioritized candidate genes provide potential genomic resources for future marker development, improvement applications, and functional validation aimed at improving soybean resistance to SDS.

Fusarium virguliforme↗

PubMed2024

Prenatal cannabis exposure is associated with alterations in offspring DNA methylation at genes involved in neurodevelopment, across the life course.

Prenatal cannabis exposure (PCE) is of increasing concern globally, due to the potential impact on offspring neurodevelopment, and its association with childhood and adolescent brain development and cognitive function. However, there is currently a lack of research addressing the molecular impact of PCE, that may help to clarify the association between PCE and neurodevelopment. To address this knowledge gap, here we present epigenome-wide association study data across multiple time points, examining the effect of PCE and co-exposure with tobacco using two longitudinal studies, the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Christchurch Health and Development Study (CHDS) at birth (0 y), 7 y and 15-17 y (ALSPAC), and ~27 y (CHDS). Our findings reveal genome-wide significant DNA methylation differences in offspring at 0 y, 7 y, 15-17 y, and 27 y associated with PCE alone, and co-exposure with tobacco. Importantly, we identified significantly differentially methylated CpG sites within the genes LZTS2, NPSR1, NT5E, CRIP2, DOCK8, COQ5, and LRP5 that are shared between different time points throughout development in offspring. Notably, functional pathway analysis showed enrichment for differential DNA methylation in neurodevelopment, neurotransmission, and neuronal structure pathways, and this was consistent across all timepoints in both cohorts. Given the increasing volume of epidemiological evidence that suggests a link between PCE and adverse neurodevelopmental outcomes in exposed offspring, this work highlights the need for further investigation into PCE, particularly in larger cohorts.

DNA Methylation↗