SEARCH · Search PubMed

Results for “PROTEOMIC SIGNATURES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2026

Proteomic Signatures Related to Physical Activity Are Associated with Risks of Future Disease.

PURPOSE: Physical activity (PA) can lower the risk of developing chronic diseases. However, few studies have examined the proteomic signatures linked to PA, and the role of these signatures in the connection between PA levels and future disease risk remains unclear. This study aimed to investigate whether proteomic signatures indicative of PA are associated with the risk of developing common chronic diseases and to explore their role as statistical links in the relationship between PA levels and disease development. METHODS: We used data from a subcohort of UK Biobank participants. PA intensity data were collected from accelerometers worn by each participant. Plasma proteomics results were obtained through Olink analysis. The risks of developing each primary chronic disease were evaluated for types of PA and their associated proteomic signatures, adjusting for age, sex, ethnicity, socioeconomic status, lifestyle factors, and key measurement time-lag covariates. RESULTS: Based on the UK Biobank, we identified significant differences among the proteomic signatures of accelerometer-measured light PA, moderate-to-vigorous PA, and total PA. The main enriched pathways of these proteomic signatures included cell adhesion, cell migration, and immune response. Higher levels of accelerometer-measured PA and their associated proteomic signatures correlated with a lower risk of developing cardiometabolic disorders, cancers, psychological or neurological disorders, and respiratory diseases. CONCLUSIONS: Our findings show that PA and PA-related proteomic signatures are statistically associated with lower risks of chronic diseases. Further analyses identified proteins that were correlated with both PA and disease risk. These results need to be confirmed through longitudinal studies involving diverse populations.

Humans↗

PubMed2026

The association of cardiovascular health with new-onset pulmonary hypertension and the mediating role of proteomic signatures.

BACKGROUND: The cardiovascular health (CVH) metrics have been reported to play an important role in the development of noncommunicable chronic diseases, yet its link to pulmonary hypertension (PH) risk and the underlying biological mechanisms remain unclear. This study aimed to investigate the association of CVH with PH risk and elucidate the mediating role of plasma proteomic signatures. METHODS: A total of 279 220 participants without PH at enrollment of the UK Biobank were included. Cox regression was used to quantify the association between CVH and incident PH. Proteome-wide association analysis, mediation analysis, and functional enrichment analysis were conducted to identify protein mediators. Key hub proteins were further validated at the transcriptional level through quantitative polymerase chain reaction (qPCR) in an animal model of PH, as well as at the protein level, and by macrophage-specific knockdown of interleukin (IL)-6 and CCL4 to evaluate its impact on rat pulmonary artery smooth muscle cell (PASMC) migration and proliferation. RESULTS: Over a median 13.2-year follow-up, 1325 PH cases occurred. Compared to the lowest CVH, participants with moderate and high CVH had 59% [hazard ratio (HR): 0.41; 95% confidence interval (CI): 0.33-0.49] and 82% (HR: 0.18; 95% CI: 0.14-0.23) lower risk, respectively. Proteomic analyses revealed that this association was significantly mediated by a distinct plasma protein signature. Pathway enrichment analysis indicates that proteins are significantly enriched in inflammatory/immune pathways, and key hub proteins were identified as participating in the central mechanism pathway. In the lung tissue of PH rat models, the mRNA and protein expression levels of IL-6 and C-C motif chemokine ligand 4 (CCL4) were significantly elevated. Furthermore, functional assays demonstrated that knockdown of IL-6 or CCL4 in macrophages significantly attenuated the migration and proliferation of rat PASMCs in vitro. CONCLUSION: High CVH level, defined by Life's Essential 8 (LE8), is significantly linked to a reduced risk of developing PH. This protective effect is primarily mediated by a proteomic signature, revealing the role of signaling pathways such as cytokine-cytokine receptor interaction in the prevention of PH.

Hypertension, Pulmonary↗

PubMed2026

Machine learning-based analysis of oral rinse samples to identify candidate proteomic signatures for severe periodontitis: a pilot study.

This pilot study investigated whether candidate protein signatures from oral rinse samples can distinguish patients with severe periodontitis (stage III/IV) and its subtypes, generalized and localized periodontitis, from non-periodontitis controls. Participants rinsed with phosphate-buffered saline, and samples were analyzed using a Proximity Extension Assay targeting 92 inflammatory and 92 immuno-oncology proteins. A machine learning approach using repeated nested cross-validation and SHAP was implemented to identify protein signatures. The study included 38 patients (18 with localized periodontitis and 20 with generalized periodontitis) and 16 controls. After data preprocessing, 54 samples and 141 proteins were retained. Proteins Gal-1, HGF, TNFSF14, CD27, and ARG1 distinguished periodontitis from controls (ROC-AUC = 0.85, 95% CI 0.82, 0.87). For generalized periodontitis, we found a protein signature including TNFSF14, Gal-1, STAMBP, MUC-16, S100A12, HGF, CASP-8, CD27, LAP TGF-β1, TNFRSF9, and uPA (ROC-AUC = 0.92, 95% CI 0.90, 0.94). For localized periodontitis, we identified ARG1 (ROC-AUC = 0.72, 95% CI 0.68, 0.76). No proteomic signature distinguishing generalized periodontitis from localized periodontitis was identified. This pilot study indicated that oral rinses are suitable for proteomic profiling, and there was a putative protein signature that could differentiate periodontitis, generalized periodontitis, and localized periodontitis from controls. These findings warrant validation in larger independent cohorts, including a clearly defined gingivitis group, before real-world non-invasive screening applications can be considered.

Humans↗

PubMed2025

High-fat and low-fat fermented milk and cheese intake, proteomic signatures, and risk of all-cause and cause-specific mortality.

PURPOSE: This study aimed to examine the associations between the intake of high- and low-fat fermented dairy (cheese and fermented milk), their proteomic profiles, and mortality risk. METHODS: This cohort study included 25,187 participants (mean age 57.7 years, 60.9% females). Fermented dairy intake was assessed by a modified diet history method. In a random subset of this cohort (n = 4359), we constructed proteomic signatures for fermented dairy intake using 136 candidate plasma proteins. RESULTS: During 23.5 years of follow-up, 9742 participants died. High-fat cheese (> 20% fat) intake was inversely associated with risk of all-cause mortality (HR for an increment of 20 g/day, 0.97; 95% CI, 0.96-0.99, P < 0.001) and cardiovascular disease mortality (HR, 0.96; 95% CI, 0.93-0.99, P = 0.006). Low-fat cheese intake showed an inverse association with all-cause mortality (HR, 0.98; 95% CI, 0.96-1.00, P = 0.047). Low-fat fermented milk intake was inversely associated with all-cause mortality (HR for an increment of 250 g/day, 0.91; 95% CI, 0.85-0.97, P = 0.006), while high-fat fermented milk (> 2.5% fat) showed null association. A total of 42, 26, 0, and 39 proteins were identified for the signature of high-fat cheese, low-fat cheese, high-fat fermented milk, and low-fat fermented milk, respectively. Inverse associations with all-cause mortality were observed for all three signatures with identified proteins. The identified proteins were involved in biological pathways related to immune response and inflammation. CONCLUSION: Our study indicated that consuming high-fat cheese, low-fat cheese, and low-fat fermented milk was linked to survival benefits. Plasma proteins improve our understanding of the health effects of fermented dairy.

Humans↗

PubMed2024

Identification of a Proteomic Signature for Predicting Immunotherapy Response in Patients With Metastatic Non-Small Cell Lung Cancer.

Immunotherapy has improved survival rates in patients with cancer, but identifying those who will respond to treatment remains a challenge. Advances in proteomic technologies have enabled the identification and quantification of nearly all expressed proteins in a single experiment. Integrating mass spectrometry with high-throughput technologies has facilitated comprehensive analysis of the plasma proteome in cancer, facilitating early diagnosis and personalized treatment. In this context, our study aimed to investigate the predictive and prognostic value of plasma proteome analysis using the SWATH-MS (Sequential Window Acquisition of All Theoretical Mass Spectra) strategy in newly diagnosed patients with non-small cell lung cancer (NSCLC) receiving pembrolizumab therapy. We enrolled 64 newly diagnosed patients with advanced NSCLC treated with pembrolizumab. Blood samples were collected from all patients before and during therapy. A total of 171 blood samples were analyzed using the SWATH-MS strategy. Plasma protein expression in metastatic NSCLC patients prior to receiving pembrolizumab was analyzed. A first cohort (discovery cohort) was employed to identify a proteomic signature predicting immunotherapy response. Thus, 324 differentially expressed proteins between responder and non-responder patients were identified. In addition, we developed a predictive model and found a combination of seven proteins, including ATG9A, DCDC2, HPS5, FIL1L, LZTL1, PGTA, and SPTN2, with stronger predictive value than PD-L1 expression alone. Additionally, survival analyses showed an association between the levels of ATG9A, DCDC2, SPTN2 and HPS5 with progression-free survival (PFS) and/or overall survival (OS). Our findings highlight the potential of proteomic technologies to detect predictive biomarkers in blood samples from NSCLC patients, emphasizing the correlation between immunotherapy response and the idenfied protein set.

Humans↗

PubMed2026

Human Immunodeficiency Virus-Associated Proteomic Signature of Myocardial Fibrosis and Incident Heart Failure.

BACKGROUND: People with human immunodeficiency virus (HIV) (PWH) are at higher risk of myocardial fibrosis and subsequent heart failure (HF) compared to people without HIV (PWOH). Mechanisms underlying this risk and its specificity to PWH are unclear. METHODS: We measured 2594 proteins in plasma obtained concurrently with cardiovascular magnetic resonance imaging among 342 PWH and PWOH. We estimated associations with HIV serostatus and myocardial fibrosis (elevated extracellular volume fraction [ECV] ≥30% among women, ≥28% among men) using multivariable regression. Among an independent community-based cohort, we estimated associations between the identified signature and time to incident HF. RESULTS: Mean age of participants was 55 (standard deviation [SD], 6) years, 25% were female, 61% were PWH (88% on antiretroviral therapy, 74% with undetectable HIV RNA), and 52% had elevated ECV. We identified 39 proteins and 1 cluster of 42 proteins that were higher among PWH versus PWOH and positively associated with elevated ECV, independent of risk factors (false discovery rate <0.05). Among an independent cohort of 3223 PWOH (mean age, 68 [SD, 9] years; 52% female; 118 incident HF cases over a mean of 9.8 [SD, 1.4] years), we found that this protein cluster and 34 of 39 individual proteins were associated with time to incident HF. This signature was statistically enriched for T-cell activation, tumor necrosis factor signaling, ephrin signaling, and tissue maintenance and repair. CONCLUSIONS: We identified an HIV-related proteomic signature associated with myocardial fibrosis regardless of HIV serostatus and that predicted incident HF among the general population. Our results identify several novel associations related to specific immune processes that may contribute to risk of myocardial fibrosis and subsequent HF among both PWH and PWOH.

Humans↗

PubMed2026

Occupationally relevant vibrations and the brain: frequency-dependent proteomics signatures in a rat model.

INTRODUCTION: Occupational exposure to whole-body vibration (WBV), particularly in agricultural environments, has been associated with adverse cognitive and physiological effects. This study examined the neurophysiological impact of WBV in a rat model at 4 Hz and 30 Hz, frequencies representative of off-road and on-road vehicle operation. METHODOLOGY: Forty-four Sprague-Dawley rats were assigned to control (0 Hz), low-frequency (4 Hz), or high-frequency (30 Hz) vibration conditions. After three days of exposure, brain tissues were collected and analyzed using mass spectrometry-based proteomics to identify differentially expressed proteins. RESULTS: Proteomic profiling revealed distinct, frequency-dependent alterations in brain protein expression. Compared with controls, 32 cognition-related proteins were differentially regulated at 4 Hz and 29 at 30 Hz, with 13 differing between the two vibration conditions. Principal component analysis showed clear separation among groups, indicating unique proteomic signatures for each exposure frequency. Functional enrichment and protein-protein interaction analyses demonstrated involvement of synaptic plasticity, cytoskeletal organization, calcium regulation, and neurotransmitter release. Exposure to 4 Hz was associated with the upregulation of proteins involved in calcium homeostasis and synaptic integrity, suggesting potential disruption of cognitive processes. In contrast, 30 Hz increased the expression of proteins related to axonal guidance and neuroprotection, indicating a less clearly adverse response that may reflect adaptive or potentially beneficial effects. DISCUSSION: These findings provide new insight into biological mechanisms underlying WBV-induced cognitive changes and underscore the importance of vibration frequency in shaping neurophysiological outcomes. They also establish a foundation for future studies integrating proteomics with behavioural assessments in animals and humans.

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↗

PubMed2026

From prediction to mechanism: Explainable AI uncovers plasma and CSF proteomic signatures of Alzheimer's disease.

Alzheimer's disease (AD) plasma and cerebrospinal fluid (CSF) proteomics can distinguish AD from cognitively normal controls, but the generalizability of machine learning performance and the recurrence of biological signals across datasets require cautious interpretation. We developed an explainable artificial intelligence framework spanning two fluids and four ADNI proteomic datasets, covering 2082 modality specific samples, all analysed internally within ADNI. Phase 1 analysed plasma using a 119 analyte NULISA and targeted UPENN panel (n = 727; 216 CE, 511 controls). Phase 2 extended the analysis to CSF using SOMAscan7k, TMT-MS and targeted SET2, with Elecsys Aβ42, Aβ40, total tau and p-tau181 as anchor biomarkers. Only SOMAscan was subject-independent relative to Phase 1 plasma; TMT-MS and SET2 overlapped with Phase 1 for 96.0% and 97.7% of subjects and therefore are not independent replication cohorts. Under subject-level splits with fold internal preprocessing, we compared Elastic Net, Explainable Boosting Machines and gradient boosted trees with SHAP-based explanations. Among the candidate pipelines, we selected the pipeline with the highest held-out test ROC AUC for each platform; the selected values were 0.927 in plasma and 0.954-0.973 across the three CSF datasets. Because the same held out test performance was used for pipeline selection and headline reporting, these are optimistically selected single-holdout estimates, not unbiased estimates of generalizable or clinical performance. Explanations identified five recurring biological axes within ADNI: cholinergic (ACHE), tau/14-3-3 (YWHAG, YWHAZ, YWHAB, YWHAE), neuro-axonal (NEFL, NEFH), microglial/complement (CHIT1, SMOC1, CHI3L1, C7, CFH) and synaptic (NPTXR, NPTX2, DLG4, SYT5, VSNL1, ELAVL2). CSF analyses showed synaptic vesicle-cycle enrichment (q = 2 × 10-6), and CSF YWHAG correlated strongly with total tau (ρ = 0.87). Cross-fluid directional concordance was modest overall (54-57%) but increased to 73-80% among mapped analyte/protein rows reaching q < 0.05 in CSF. These findings provide hypothesis-generating, internally supported evidence within ADNI. Independent external cohorts with locked pipelines are required to evaluate generalizable performance and biological reproducibility; the overlapping TMT-MS and SET2 analyses should not be interpreted as independent replication.

Alzheimer Disease↗

PubMed2026

Transcriptomic and proteomic signatures following AS03-adjuvanted Influenza A/H7N9 vaccine.

INTRODUCTION: Vaccines targeting avian influenza virus A/H7N9 are poorly immunogenic. While the immune responses can be improved with oil-in-water emulsion adjuvants such as Adjuvant System 03 (AS03), the cellular mechanisms underpinning the adjuvant effect are incompletely characterized and poorly understood. METHODS: We enrolled 30 healthy adult participants and used RNA sequencing and quantitative proteomics to characterize the response to two doses of the influenza A/H7N9 vaccine, with and without AS03, in six immune cell types. These responses were compared to those seen after administration of an unadjuvanted seasonal in uenza A/H3N2 variant vaccine to identify signatures unique to adjuvanted influenza vaccines and correlated with later antibody responses. Transcriptomic and proteomic analyses revealed that. RESULTS: AS03-adjuvanted vaccine was associated with upregulation of immune pathways in innate immune cells within 24h following vaccination for phagocytosis, antigen presentation and processing, inflammasome activation, NK-cell mediated cytotoxicity, IgA production, and interferon-response pathways. Moreover, while major histocompatibility complex (MHC I and II) upregulation was observed across multiple immune cell types, MHCII gene transcription was also increased in the neutrophil compartment, generating the hypothesis that neutrophils may play a more important role in antigen presentation than previously understood. DISCUSSION: Taken together, these data provide a more complete mechanistic understanding of oil-in-water adjuvants and their role in enhancing the immune response for pandemic influenza preparedness. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT02921997?term=NCT02921997&viewType, idientifier NCT02921997.

Adult↗

PubMed2026

Proteomic signatures of mitochondrial dysfunction associated with atrial fibrillation in goats.

Atrial fibrillation (AF) increases energy demand in atrial myocytes, yet the mitochondrial mechanisms underlying this stress remain poorly defined. Using previously published proteomic data from left atrial tissue of AF and sham-operated goats, we performed organelle-specific bioinformatic analyses of the mitochondrial fraction. Over-representation and consensus pathway analyses consistently highlighted enrichment of oxidative phosphorylation (OXPHOS) subunits. Gene set enrichment and network analyses implicated Heat Shock Protein Family A Member 9 (HSPA9) as a potentially central regulatory hub coordinating the dysregulation of Complex I and III subunits, with 69% of regulatory relationships showing pathway concordance. These results indicate a coordinated, system-wide mitochondrial adaptation in AF, integrating energy production, proteostasis, and respiratory chain regulation.

Animals↗

PubMed2026

Proteomic signatures for sudden cardiac death and related intermediate phenotypes.

BACKGROUND: Novel markers for sudden cardiac death (SCD) are needed. OBJECTIVE: This study aimed to explore whether a protein risk score derived from a large-scale proteomics dataset improves risk prediction of SCD in the general population. METHODS: A total of 52,705 individuals with 1459 unique plasma protein measurements were included from the UK Biobank Pharma Proteomics Project. A protein risk score was developed using lasso-penalized Cox regression on 40,722 participants enrolled at the English centers and validated on 11,983 participants enrolled at the remaining centers. RESULTS: The protein risk score formula developed from the derivation set comprised 64 unique plasma proteins including latent-transforming growth factor beta-binding protein 2, protein tyrosine phosphatase receptor sigma, and spondin-1. In the test set, a per standard deviation increase in protein risk score was associated with a hazard ratio of 2.60 (95% confidence interval [CI] 2.12-3.18) for SCD. Adding a protein risk score to SCD clinical risk factors resulted in a concordance index increase of 0.063 (95% CI 0.037-0.105) for SCD. For ventricular arrhythmia-mediated SCDs, an increase in concordance index when a protein risk score was added to SCD clinical risk factors was 0.070 (95% CI 0.010-0.188). A protein risk score added to SCD clinical risk factors resulted in a risk reclassification of 16.9% (95% CI 9.0-24.7) at a 10-year risk threshold of 5%. A protein risk score was significantly associated with intermediate phenotypes of SCD including corrected QT prolongation, an increase in left ventricular mean myocardial thickness, and a decrease in left ventricular global longitudinal strain. CONCLUSION: A protein risk score derived from a single plasma sample significantly improved risk prediction of SCD and related intermediate phenotypes.

Humans↗

PubMed2026

Proteomic signatures of adipocyte recruitment in breast cancer.

The tumor microenvironment (TME) is increasingly recognized as a dynamic regulator of breast cancer progression, with adipocytes functioning as active contributors rather than passive bystanders. Here, we investigated the proteomic and morphologic reprogramming of breast cancer-associated adipocytes (BrCAAs) in response to triple-negative breast cancer (TNBC). Using conditioned medium from HCC1143 cells, we established an in vitro BrCAA model and performed mass spectrometry-based proteomics. Comparative profiling revealed 256 differentially expressed proteins, enriched for pathways including fatty acid degradation, carbon metabolism, and glycogen turnover, consistent with a metabolic shift from energy storage to energy supply. Gene ontology and protein-protein interaction analyses further identified cytoskeletal remodeling, adhesion dynamics, and secretory pathway activation, supporting BrCAA-driven microenvironmental remodeling. In the MMTV-PyMT mouse model, morphometric analysis demonstrated progressive size reduction and increased contour irregularity of adipocytes adjacent to tumors, correlating with proteomic evidence of metabolic stress. Importantly, BrCAAs localized at tumor interfaces were associated with increased microvessel density and CD105+ endothelial activation compared to desmoplastic zones. Proteomic enrichment highlighted pro-angiogenic remodeling, with validation of basigin (BSG), integrin αV (ITGAV), and 2,4-dienoyl-CoA reductase 1 (DECR1). Collectively, our findings establish BrCAAs as metabolically and structurally reprogrammed stromal components that promote tumor metabolism and localized angiogenesis, representing potential therapeutic targets in aggressive breast cancer.

Female↗

PubMed2024

Cross-platform proteomics signatures of extreme old age.

In previous work, we used a SomaLogic platform targeting approximately 5000 proteins to generate a serum protein signature of centenarians that we validated in independent studies that used the same technology. We set here to validate and possibly expand the results by profiling the serum proteome of a subset of individuals included in the original study using liquid chromatography tandem mass spectrometry (LC-MS/MS). Following pre-processing, the LC-MS/MS data provided quantification of 398 proteins, with only 266 proteins shared by both platforms. At 1% FDR statistical significance threshold, the analysis of LC-MS/MS data detected 44 proteins associated with extreme old age, including 23 of the original analysis. To identify proteins for which associations between expression and extreme-old age were conserved across platforms, we performed inter-study conservation testing of the 266 proteins quantified by both platforms using a method that accounts for the correlation between the results. From these tests, a total of 80 proteins reached 5% FDR statistical significance, and 26 of these proteins had concordant pattern of gene expression in whole blood generated in an independent set. This signature of 80 proteins points to blood coagulation, IGF signaling, extracellular matrix (ECM) organization, and complement cascade as important pathways whose protein level changes provide evidence for age-related adjustments that distinguish centenarians from younger individuals. The comparison with blood transcriptomics also highlights a possible role for neutrophil degranulation in aging.

Humans↗

PubMed2026

Plasma Proteome Signatures in Sickle Cell Anemia and the Effect of Hydroxyurea Treatment.

Sickle Cell Anaemia (SCA) is a monogenic blood disorder caused by a mutation in the β-globin gene, yet it presents with marked clinical variability. Although hydroxyurea (HU) is an established therapy, its precise mechanism of action remains incompletely understood. Plasma proteins represent valuable biomarkers for elucidating disease mechanisms and treatment responses. In this study, plasma proteome profiling of 31 healthy controls and 76 SCA patients identified 43 differentially abundant proteins (DAPs) that form a highly interconnected interaction network. Proteins with increased abundance in SCA were largely associated with immune and inflammatory responses, whereas those with reduced levels were linked to coagulation and proteolytic pathways. HU therapy was associated with elevated levels of haptoglobin (HP) and hemopexin (HPX), key mediators of free hemoglobin scavenging. We also identified several previously unreported plasma proteins altered in SCA, broadening the landscape of potential biomarkers and HU-responsive targets. Many DAPs significantly correlated with clinical indices, such as transfusion frequency, vaso-occlusive crises, white blood cell counts, and platelet counts, offering insights into disease mechanisms and potential utility in disease management. Notably, overlap with β-thalassemia-associated signatures suggests shared pathophysiological pathways between these hemoglobinopathies. Collectively, these findings provide a strong foundation for translational validation in larger, independent cohorts.

Humans↗

PubMed2025

Proteomic signatures and predictive modeling of cadmium-associated anxiety in middle-aged and elderly populations: an environmental exposure association study.

BACKGROUND: Emerging evidence implicates environmental contaminants such as cadmium (Cd) as modifiable risk factors for anxiety. Despite growing recognition of heavy metal toxicity in neuropsychiatric disorders, the molecular mechanisms linking environmental exposure to anxiety pathogenesis remain poorly understood. METHODS: Based on the established cohort of individuals with cognitive impairment in cadmium-contaminated areas, this cross-sectional association study enrolled 50 middle-aged and elderly hospitalized patients from these regions, adhering to the STROBE guidelines. Blood concentrations of cadmium (Cd), lead (Pb), and mercury (Hg) were analyzed in relation to anxiety severity assessed via the Hamilton Anxiety Rating Scale (HAMA). Plasma proteomic profiling was performed using data-independent acquisition (DIA) quantitative technology with an LC-MS/MS platform (timsTOF Pro, Bruker Daltonics), systematically characterizing 2,531 proteins across all samples. Machine learning techniques, specifically XGBoost and LASSO, were employed to identify biomarkers that were subsequently validated through mediation analysis and animal experiments, allowing for the screening of key protein signatures. Finally, clinical variables were integrated to construct a comprehensive model, which was then thoroughly evaluated. RESULTS: Anxious individuals exhibited significantly higher blood Cd levels than controls (β = 0.50, 95% CI: 0.07-0.93, p < 0.01), with anxiety positively correlating with depression (r = 0.62, p = 0.003) and inversely with ApoE3 genotype prevalence. Proteomics identified 120 differentially expressed proteins in anxious patients, enriched in oxidative phosphorylation and neurodegenerative pathways. CCDC126 emerged as a cadmium-associated biomarker, validated in rat models exposed to Cd. Combining CCDC126, blood Cd, Pb, and hypertension, a clinical prediction model achieved robust discrimination (AUC = 0.80, validation cohort). CONCLUSIONS: This first integrative environmental-proteomic study highlights cadmium's synergistic role in anxiety pathophysiology and psychiatric comorbidity. The predictive model offers translatable potential for early risk stratification, while CCDC126 provides mechanistic insights for targeted interventions in populations exposed to environmental pollutants.

Cadmium↗

PubMed2026

Transcriptomic and proteomic signatures underlying nymphal adaptation and foam production in the forage pest Mahanarva spectabilis.

The spittlebug Mahanarva spectabilis (Distant, 1909) (Hemiptera: Cercopidae) is an important pest of forage grasses in South America, where its nymphs cause pasture damage by feeding on xylem sap and producing a characteristic foam that protects them against environmental stressors. To investigate the molecular basis of this adaptation, we integrated RNA-seq analysis of nymphs with LC-MS/MS proteomics of the Batelli gland, the primary source of foam secretion. De novo assembly of 100,666 unigenes revealed broad functional diversity, with strong representation of detoxification enzymes (CYP450s, GSTs, UGTs, carboxylesterases), transporters and ion pumps, cuticle proteins, and stress- and immunity-related genes. Nearly 16% of loci exhibited alternative splicing, particularly within detoxification, chemosensory and osmoregulatory gene families, highlighting evidence of transcriptomic variability. Signal peptide and secreted protein predictions identified 168 high-confidence candidate secreted proteins, including detoxification enzymes, proteases, structural proteins and immune-related factors, several of which are consistent with antimicrobial and surfactant-related functions. Proteomic profiling of the Batelli gland confirmed 500 proteins, enriched in chaperones, metabolic enzymes, detoxification pathways and osmoregulatory components, with the most abundant proteins corresponding to Hsp70 chaperones, ATP synthases, cuticle proteins and carbonic anhydrases. Together, these results provide an integrative transcriptomic and proteomic overview for M. spectabilis nymphs, highlighting genes and proteins associated with xylem feeding, foam production and responses potentially related to environmental stress tolerance. This comprehensive dataset not only advances the understanding of spittlebug biology but also identifies candidate molecular targets that may inform innovative strategies for controlling nymphal stages and mitigating spittlebug damage in forage systems.

Animals↗

PubMed2026

Identification of intranasal oxytocin plasma proteome signatures.

BACKGROUND: The hypothalamic peptide oxytocin regulates a range of central and peripheral activities, ranging from uterine contractions to energy homeostasis. Oxytocin-based therapeutics are under investigation for neuropsychiatric and metabolic disease, including obesity. The mechanisms underlying oxytocin effects are poorly understood. This study profiles 4725 serum proteins in 19 healthy men across the adiposity spectrum (9 normal-weight, BMI < 25 kg/m2; 10 overweight/obese, BMI ≥ kg/m2) following exogenous, intranasal oxytocin administration to identify markers of pharmacodynamic effect. METHODS: In a double-blind, randomized controlled crossover design, 25 men were exposed to a single dose of 24 IU intranasal oxytocin vs. placebo. Fasting blood was drawn immediately prior and at 15, 30, and 55 min after oxytocin/placebo administration for proteomic analysis (SOMA Scan, Soma Logic, Inc.). RESULTS: As previously reported in the parent study, intranasal oxytocin reduced caloric intake at the test meal; here, we examined proteomic predictors of this behavioral effect. Proteomic data was available for 19 men. We identified 198 differentially expressed proteins in response to intranasal oxytocin in fasting men across the adiposity spectrum. The pathways identified are involved in intracellular signaling pathways, as well as immune regulation and inflammation. Oxytocin modulated a cluster of proteins that was associated with subsequent caloric intake at the test meal. CONCLUSIONS: These data provide insights into mechanisms underlying pharmacologic oxytocin effects on human physiology and a framework for future investigations.

Humans↗