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Results for “Protein expression”

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At least 19 recordsLinked to original sources

PubMed2026

Identification of a Functional CYP2C8 Variant Allele that Alters Splicing, Reduces Protein Expression, and Increases Drug Exposure.

This study investigated genetic determinants of the pharmacokinetics of the CYP2C8 index drugs repaglinide and gemfibrozil, and their interaction in healthy participants. Sequencing data from a study with montelukast revealed a novel functional CYP2C8 allele (rs2071426, CYP2C8*19), predicted to create an intronic splice donor site. In human liver samples, CYP2C8*19 associated with transcript-specific changes in CYP2C8 mRNA expression, reduced CYP2C8 protein expression, and decreased enzyme activity. Consistently, participants with the CYP2C8*19/*19 genotype had 45% greater area under the plasma repaglinide concentration-time curve from time zero to infinity (AUC0-∞) than participants with CYP2C8*1/*1 (P = 1.6 × 10-4). Participants with CYP2C8*1/*3 had 26% smaller AUC0-∞ (P = 0.0033) and those with CYP2C8*1/*4 had 51% greater AUC0-∞ (P = 8.2 × 10-4). The fold increase in repaglinide AUC0-∞ caused by gemfibrozil was 36% (P = 1.3 × 10-4) smaller in CYP2C8*19/*19 participants than in CYP2C8*1/*1 participants. In a genome-wide association study (GWAS), SLCO1B1 c.521 T>C (rs4149056) associated with increased repaglinide AUC0-∞ (P = 4.5 × 10-15; n = 172) and SLCO1A2 variants associated with decreased AUC0-∞ (P < 10-8). In a GWAS of repaglinide after gemfibrozil pretreatment, SLCO1C1 variants associated with decreased AUC0-∞ (P < 1.6 × 10-8; n = 66). Participants with the poor function SLCO1B1 genotype showed a 32% smaller fold increase in repaglinide AUC0-∞ following gemfibrozil than participants with the normal function SLCO1B1 genotype (P = 0.0045). This study characterizes CYP2C8*19 as a novel decreased function allele and shows that CYP2C8 and SLCO1B1 genotypes affect the gemfibrozil-repaglinide interaction.

Humans↗

PubMed2024

Tear fluid reflects the altered protein expressions of Alzheimer's disease patients in proteins involved in protein repair and clearance system or the regulation of cytoskeleton.

BackgroundNew biomarkers that improve diagnosis of Alzheimer's disease (AD) are warranted. Tear fluid (TF) containing variety of proteins that reflect pathophysiological changes of systemic diseases makes TF proteins potential biomarker candidates for AD.ObjectiveWe investigated the expression levels of TF proteins in persons with mild AD and cognitively healthy controls (CO) to find out if altered proteins may link to the AD pathophysiology.MethodsWe analyzed the data of the 53 study participants (34 COs, mean age 71 and Mini-Mental State Examination (MMSE) 28.9 ± 1.4 and 19 persons with AD, CDR 0.5-1, mean age 71 and MMSE 23.8 ± 2.8). All went through neurological status examination, cognitive tests, and ophthalmological examination. TF was collected using Schirmer strips. The TF protein content was evaluated via mass spectrometry-based proteomics and label-free quantification.ResultsEleven proteins having a role either in protein repair and clearance system, or regulation of cytoskeleton, showed altered expression in AD group compared to CO group. Seven of them were significantly (p ≤ 0.05) upregulated (Sti1, Twf1, Myl6, Otub1, Pls1 and Caza1) or, downregulated (HSP90) in AD group.ConclusionsAltered expression of all these up- or downregulated proteins may be linked to AD pathophysiology. Thus, our results are encouraging for searching new biomarker candidates for AD. TF is potential biomarker candidate, because TF seems to reflect altered protein levels already in mild AD dementia.

Humans↗

PubMed2025

Machine learning-based analysis of the impact of 5' untranslated region on protein expression.

The 5' untranslated region (5'UTR) plays a crucial regulatory role in messenger RNA (mRNA), with modified 5'UTRs extensively utilized in vaccine production, gene therapy, etc. Nevertheless, manually optimizing 5'UTRs may encounter difficulties in balancing the effects of various cis-elements. Consequently, multiple 5'UTR libraries have been created, and machine learning models have been employed to analyze and predict translation efficiency (TE) and protein expression, providing insights into critical regulatory features. On the one hand, these screening libraries, based on TE and mean ribosome load, struggle to accurately quantify protein expression; on the other hand, a precise method for quantifying 5'UTRs necessitates a significantly costlier library. To resolve this dilemma, we constructed a library utilizing firefly luciferase as the reporter to measure accurate protein expression. In addition, we optimized the library construction method by clustering mRNA sequences to reduce redundant data and minimize the size of the dataset. This dual strategy by increasing accuracy and reducing dataset size was found to be effective in predicting the 5'UTRs from the PC3 cell line.

5' Untranslated Regions↗

PubMed2026

Multiomic Integration Reveals Novel miRNA-mRNA-Protein Expression Profile in the Aged Female Retina.

PURPOSE: Aging is a leading risk factor for retinal degeneration. MicroRNAs (miRNAs) regulate posttranscriptional gene suppressors and influence inflammation and oxidative stress, two processes disrupted during retinal aging. This study aimed to identify age-related miRNA-mRNA-protein associations between young and older retinas and uncover dysregulated pathways that may contribute to retinal degeneration. METHODS: Retinal function was assessed using electroretinography (ERG), and microgliosis was quantified by microglial immunohistochemistry (IHC). A multiomics approach was used to examine molecular changes in older (30-month-old) female C57BL/6J mouse retinas and compared with young female (3-month-old) controls. Illumina sequencing profiled short miRNAs (20 bp) and bulk mRNAs (150 bp), while total proteomics via mass spectrometry assessed protein expression. Bioinformatic analyses included targetome analysis (miRNet), pathway enrichment (Gene Ontology), and clustering to identify age-associated molecular targets and pathways. RESULTS: Retinas from older mice displayed neuronal dysfunction and increased microgliosis. Sequencing revealed significant dysregulation of miRNAs linked to immune and inflammatory pathways, supported by enrichment of their predicted mRNA targets. In the older mice, mRNA expression showed broad inflammatory activation, though only 14% of dysregulated mRNAs overlapped with predicted miRNA targets. Proteomic profiling revealed a disconnect between RNA and protein expression, yet all omics layers showed enrichment in inflammatory pathways. Integrated analysis identified associations involving several gene regulatory networks in the older retina. CONCLUSIONS: This study demonstrates that at an advanced age, miRNA expression and their predicted downstream regulatory networks are dysregulated, highlighting potential molecular mechanisms underlying age-related retinal degeneration.

Animals↗

PubMed2026

A Comprehensive Analysis of Differential Protein Expression in the Plasma of Rheumatoid Arthritis Patients Utilizing Data-Independent Acquisition (DIA) Proteomics Technology.

BACKGROUND: Rheumatoid Arthritis (RA) is a Prevalent Autoimmune Disorder Affecting Millions of People Worldwide. A Thorough Understanding of Its Clinical and Pathological Features Is Essential to Improve Patient Outcomes. METHODS: This Study Combined Data-Independent Acquisition Proteomics and Enzyme-Linked Immunosorbent Assay (ELISA) to Identify and Validate Potential Plasma Protein Biomarkers for the Early Diagnosis of RA. RESULTS: Differential Proteomic Analysis Identified Differentially Expressed Proteins Between Patients With RA and Healthy Controls and Characterized Their Functions. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes Enrichment Analyses Were Performed to Explore Protein Functions and Associated Biological Pathways. The STRING Database and the Metascape Platform Were Used to Conduct an in-Depth Analysis of the Protein-Protein Interaction Network, Highlighting the Functional Attributes and Interconnections of Upregulated Proteins and Identifying Key Protein Complexes Involved in RA. ELISA Analysis of Plasma Samples Revealed Significantly Elevated SERPINA3 Levels in Patients With RA, Which Were Positively Correlated With Disease Activity Indicators-Including Erythrocyte Sedimentation Rate, C-Reactive Protein, and Disease Activity Score 28-But Were Not Correlated With Rheumatoid Factor or Its Subtypes. CONCLUSIONS: This Study Provides New Insights and Identifies Potential Biomarkers for the Early Diagnosis of RA.

Humans↗

PubMed2023

Bovine meat and milk factor protein expression in tumor-free mucosa of colorectal cancer patients coincides with macrophages and might interfere with patient survival.

Bovine milk and meat factors (BMMFs) are plasmid-like DNA molecules isolated from bovine milk and serum, as well as the peritumor of colorectal cancer (CRC) patients. BMMFs have been proposed as zoonotic infectious agents and drivers of indirect carcinogenesis of CRC, inducing chronic tissue inflammation, radical formation and increased levels of DNA damage. Data on expression of BMMFs in large clinical cohorts to test an association with co-markers and clinical parameters were not previously available and were therefore assessed in this study. Tissue sections with paired tumor-adjacent mucosa and tumor tissues of CRC patients [individual cohorts and tissue microarrays (TMAs) (n = 246)], low-/high-grade dysplasia (LGD/HGD) and mucosa of healthy donors were used for immunohistochemical quantification of the expression of BMMF replication protein (Rep) and CD68/CD163 (macrophages) by co-immunofluorescence microscopy and immunohistochemical scoring (TMA). Rep was expressed in the tumor-adjacent mucosa of 99% of CRC patients (TMA), was histologically associated with CD68+/CD163+ macrophages and was increased in CRC patients when compared to healthy controls. Tumor tissues showed only low stromal Rep expression. Rep was expressed in LGD and less in HGD but was strongly expressed in LGD/HGD-adjacent tissues. Albeit not reaching statistical significance, incidence curves for CRC-specific death were increased for higher Rep expression (TMA), with high tumor-adjacent Rep expression being linked to the highest incidence of death. BMMF Rep expression might represent a marker and early risk factor for CRC. The correlation between Rep and CD68 expression supports a previous hypothesis that BMMF-specific inflammatory regulations, including macrophages, are involved in the pathogenesis of CRC.

Humans↗

PubMed2026

Methyltransferase 3 promotes v-set and transmembrane domain-containing 2-like protein expression to intensify ferroptosis-mediated prostate adenocarcinoma progression through the m6A methylation modification.

BACKGROUND: Prostate adenocarcinoma (PRAD) is a common malignancy with high incidence in men. The role of v-set and transmembrane domain-containing 2-like protein (VSTM2L) in PRAD remains largely unreported. METHODS: Gene expression was analyzed using The Cancer Genome Atlas (TCGA), the Tumor Immune Estimation Resource (TIMER) 2.0, and the University of Alabama at Birmingham CANcer data analysis Portal (UALCAN) databases, and validated by quantitative real-time PCR (qRT-PCR) and western blot. Cell proliferation was assessed by 5-ethynyl-2'-deoxyuridine (EdU) staining. Apoptosis and mitochondrial membrane potential were examined by flow cytometry. Intracellular iron, Fe2+, and reactive oxygen species (ROS) levels were measured using commercial kits and flow cytometry. The role of VSTM2L in tumor growth was evaluated using xenograft mouse models, with protein expression in tumors evaluated by immunohistochemistry (IHC). The N6-methyladenosine (m6A) modification sites on VSTM2L mRNA were predicted using the sequence-based RNA adenosine methylation site predictor (SRAMP) website. The interaction between methyltransferase 3 (METTL3) and VSTM2L was confirmed by methylated RNA immunoprecipitation (MeRIP) and dual-luciferase reporter assay. Correlation analysis was performed using the TCGA database. RESULTS: VSTM2L was overexpressed in PRAD tissues and cell lines. Silencing VSTM2L inhibited PRAD cell proliferation, promoted apoptosis, and enhanced ferroptosis and oxidative stress in vitro. Consistently, VSTM2L knockdown suppressed tumor growth in vivo. Mechanically, METTL3 mediated m6A methylation to stabilize VSTM2L mRNA. Furthermore, METTL3 promoted proliferation and inhibited apoptosis, ferroptosis, and oxidative stress in PRAD cells via a VSTM2L-dependent manner. CONCLUSION: METTL3 promotes PRAD progression by stabilizing VSTM2L expression through m6A methylation, thereby inhibiting ferroptosis. This study establishes a direct link between RNA methylation and ferroptosis in PRAD, revealing the METTL3/VSTM2L axis as a novel regulatory pathway and a potential therapeutic target.

Male↗

PubMed2015

Ptpn22 and Cd2 Variations Are Associated with Altered Protein Expression and Susceptibility to Type 1 Diabetes in Nonobese Diabetic Mice.

By congenic strain mapping using autoimmune NOD.C57BL/6J congenic mice, we demonstrated previously that the type 1 diabetes (T1D) protection associated with the insulin-dependent diabetes (Idd)10 locus on chromosome 3, originally identified by linkage analysis, was in fact due to three closely linked Idd loci: Idd10, Idd18.1, and Idd18.3. In this study, we define two additional Idd loci--Idd18.2 and Idd18.4--within the boundaries of this cluster of disease-associated genes. Idd18.2 is 1.31 Mb and contains 18 genes, including Ptpn22, which encodes a phosphatase that negatively regulates T and B cell signaling. The human ortholog of Ptpn22, PTPN22, is associated with numerous autoimmune diseases, including T1D. We, therefore, assessed Ptpn22 as a candidate for Idd18.2; resequencing of the NOD Ptpn22 allele revealed 183 single nucleotide polymorphisms with the C57BL/6J (B6) allele--6 exonic and 177 intronic. Functional studies showed higher expression of full-length Ptpn22 RNA and protein, and decreased TCR signaling in congenic strains with B6-derived Idd18.2 susceptibility alleles. The 953-kb Idd18.4 locus contains eight genes, including the candidate Cd2. The CD2 pathway is associated with the human autoimmune disease, multiple sclerosis, and mice with NOD-derived susceptibility alleles at Idd18.4 have lower CD2 expression on B cells. Furthermore, we observed that susceptibility alleles at Idd18.2 can mask the protection provided by Idd10/Cd101 or Idd18.1/Vav3 and Idd18.3. In summary, we describe two new T1D loci, Idd18.2 and Idd18.4, candidate genes within each region, and demonstrate the complex nature of genetic interactions underlying the development of T1D in the NOD mouse model.

Alleles↗

PubMed1977

Viral proteins expressed on the surface of murine leukemia cells.

Leukemic cells of AKR mice contain as constituents of their membranes the murine leukemia virus envelope protein gp70 and the precursor polyprotein of the viral internal (core) structural proteins. Both gp70 and the core polyprotein are represented on the cell surface as glycoproteins, as evidenced by incorporation of [3H]glucosamine into their structure and the binding of these proteins to lectins. The glycosylated core polyprotein exists in at least two serologically distinguishable forms: the 95,000-dalton polyprotein reacts with antisera prepared against the viral proteins p30, p12, and p10, whereas the 85,000-dalton polyprotein reacts with antisera prepared against the viral proteins p30 and p12, but not p10. Additional heterogeneity in these cell surface polyproteins has been observed wtih leukemias induced by exogenous leukemia viruses. Spontaneous leukemia cells of AKR mice invariably express gp70 and the core polyprotein on their cell surface; normal thymocytes of young AKR mice express gp70, but not the core polyprotein on their surface.

AKR murine leukemia virus↗

PubMed2026

Activation of mTOR pathway by human cytomegalovirus promoting host ribosomal protein expression by coordinated transcriptional and translational controls.

Human cytomegalovirus (HCMV) profoundly reprograms host transcription and RNA metabolism, yet its impact on transcription start site (TSS) regulation of host genes remains poorly understood. Here, we employed NanoCap Analysis of Gene Expression sequencing (NanoCAGE-seq) to investigate HCMV-driven changes in alternative TSS usage across the host transcriptome. We identified widespread TSS switching, with ribosomal protein genes (RPGs) emerging as a highly enriched category. Alternative TSS usage produced isoforms with distinct 5'untranslated regions (UTRs), thereby altering cis-regulatory elements that shape translational efficiency. Integrative transcriptomic and proteomic analyses revealed a paradoxical accumulation of RPG proteins despite transcriptional downregulation during infection. Using 5' Rapid Amplification of cDNA Ends (5'RACE), we characterized four RPGs of RPL4, RPS11, RPS23, and RPS24 that generated 5'UTR variants through alternative TSS usage. Notably, isoforms containing a 5'terminal oligopyrimidine (5'TOP) motif were significantly enriched, correlating with mTOR activation induced by HCMV. Functional assays with bicistronic reporter constructs in HEK293 cells and infection models in human embryonic lung fibroblasts demonstrated that the RPL4 5'TOP isoform exhibited enhanced mTORC1-driven translation compared with non-5'TOP counterparts. Importantly, RPL4 upregulation facilitated viral protein synthesis and boosted production of infectious virions. Together, our findings reveal that dynamic TSS switching of RPGs provides a simple, yet effective, mechanism for fine-tuning mTORC1-responsive translation. By co-opting host transcriptional and translational programs, HCMV enhances ribosome function to optimize the cellular environment for productive viral replication.

Humans↗

PubMed2026

Impact of BCL-2 rs2279115 and rs3943258 variants on protein expression and clinical outcome of urothelial bladder carcinoma.

BACKGROUND: Urothelial bladder carcinoma (UBC) is the ninth most common malignancy worldwide and ranks thirteenth in cancer-related mortality. A significant challenge in managing non-muscle-invasive UBC (NMIBC) is the high recurrence rate, compounded by a paucity of robust prognostic biomarkers. Given that evasion of apoptosis is a hallmark of carcinogenesis, the apoptosis regulator BCL-2 oncogene plays a critical role by negatively regulating the intrinsic apoptotic pathway, often leading to protein overexpression and malignant cell immortalization. METHODS AND RESULTS: This study evaluated the BCL-2 allelic variants rs2279115 (G > T) and rs3943258 (T > C), including their haplotype structures, in association with BCL-2 immunohistochemical expression in UBC patients. Genetic and immunostaining data were analyzed alongside prognostic factors, environmental exposure, and clinical history. Furthermore, we sought to exhibit BCL-2 immunohistochemical staining patterns via immunofluorescence in selected samples. Our findings revealed that the rs2279115 variant is significantly associated with BCL-2 positive expression. Specifically, the TT genotype in the genotypic model (p = 0.035) and the GT genotype in the overdominant model (p = 0.045) were linked to protein status. Additionally, the CT haplotype was independently associated with high-grade tumors. CONCLUSIONS: The presence of the CT haplotype - in either homozygosity or heterozygosity - exerted a risk effect of high-grade (p = 0.020). In conclusion, these findings suggest that BCL-2 variants, haplotype structures, and immunohistochemical expression may offer relevant insights into the molecular characteristics of urothelial bladder cancer. Further prospective validation is needed to determine whether BCL-2 profiling can serve as a useful complementary tool for risk assessment in clinical practice.

Humans↗

PubMed1976

Oncornavirus-like protein expression in human prostatic tissue.

A sensitive competition radioimmunoassay using 125 I-labelled p 30 interspecies antigen, antiserum specific to the interspecies antigen of the feline leukaemia virus, and aqueous tissue extracts from prostate was used to examine benign hyperplastic prostates for the presence of protein components able to complete with the interspecies viral antigens. Six of 20 prostatic nodular hyperplastic tissues were competitive in radioimmunoassay with the 125 I-labelled viral antigen for binding sites on the antiviral antibodies. These findings suggest the presence of oncornavirus-like proteins in prostatic nodular hyperplasia. No correlation could be made between the presence of competing protein and histological features of acute or chronic prostatitis and squamous metaplasia.

Antibodies, Viral↗

PubMed2026

Influence of nicotine on protein expression around hydrophilic osseointegrated implants: A proteomic study in male rats.

OBJECTIVE: To ensure the success of dental implant treatment, various factors must be considered, including osseointegration and systemic conditions. There is evidence in the literature that smokers may exhibit alterations in tissue healing, which can compromise the success of implant rehabilitation. Therefore, this study aimed to investigate the influence of nicotine on the protein profile of bone tissue around hydrophilic implants during the osseointegration process in rats. DESIGN: Bone tissue samples from the control and nicotine groups (n = 3 per group) were subjected to protein extraction, mass spectrometry, and bioinformatic analyses. Protein identification was performed using Proteome Discoverer 2.1 software and the SEQUEST algorithm, and the protein data were compared with those of a protein database of Rattus norvegicus obtained from UniProt. RESULTS: A total of 740 proteins were detected in both the control group and the nicotine-exposed group. Among them, the proteins biglycan, periostin and histone H4 were highlighted because of their higher abundance in the healthy implant group, while they were reduced in the nicotine-exposed group. CONCLUSIONS: Nicotine has the potential to alter the protein profile of bone tissue around hydrophilic implants during osseointegration, which may impair tissue remodeling and healing.

Animals↗

PubMed2026

Identification of a Novel Thermal Promoter and Its Application in Glutamate Decarboxylase Protein Expression in Bacillus licheniformis.

As a thermotolerant bacterium, Bacillus licheniformis is an attractive chassis for high-temperature biomanufacturing. Here, we identified a novel temperature-responsive promoter, PycgM, which maintained strong transcriptional activity at 37-52 °C. In a promoter-mCherry reporter system, PycgM exhibited 2287.3-fold higher activity than P2 at 52 °C, demonstrating excellent compatibility with a thermotolerant host. Truncation analysis identified a 150-bp core functional region responsible for optimal activity under induction and heat stress. When applied to drive glutamate decarboxylase expression at 50 °C, PycgM enabled γ-aminobutyric acid production of 391.67 g/L with a 98.69% conversion rate, representing a 275% increase over 37 °C fermentation. The whole-cell biocatalyst retained 86% activity after five reuse cycles, and SEM analysis indicated acceptable structural stability despite moderate morphological changes. These results demonstrate that PycgM is a robust, high-temperature genetic element for efficient enzyme and metabolite production in thermotolerant hosts.

Bacillus licheniformis↗

PubMed2026

Biogenic Silver Nanoparticles from the Cell-Free Supernatant of Mychonastes sp. B1: Antibacterial and Antibiofilm Effects, and Wound Healing Activity Supported by Gene and Protein Expression Analysis.

The biogenic synthesis of silver nanoparticles (AgNPs) using microalgae provides a sustainable alternative to conventional physicochemical methods. In this study, AgNPs were synthesized from the cell-free supernatant of the freshwater microalga Mychonastes sp. B1 and characterized by ultraviolet-visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), and field-emission scanning electron microscopy with energy-dispersive X-ray spectroscopy (FE-SEM/EDS). The nanoparticles were predominantly spherical (15-55 nm), highly stable (ζ =  - 42.8 mV), and appeared to be capped by extracellular polymeric substances. The biogenic AgNPs (GS-AgNPs) exhibited potent antibacterial activity, with minimum inhibitory concentrations (MICs) of 2.0 µg/mL against Staphylococcus aureus and 2.5 µg/mL against Pseudomonas aeruginosa, and significantly (p < 0.05) inhibited biofilm formation. Fibroblast viability remained at or above 80% at AgNP concentrations up to 1.5 µg/mL, which promoted cell migration and increased wound closure by 8.1% at 24 h (p < 0.05). Exposure to 1.5 µg/mL AgNPs significantly upregulated extracellular matrix markers (Col1a1 2.3-fold, Fn1 3.3-fold at mRNA level; COL1A1 2.1-fold, FN1 2.7-fold at the protein level). These findings indicate that GS-AgNPs possess antimicrobial and wound healing properties, highlighting their potential as biocompatible nanomaterials for biomedical applications.

Silver↗

PubMed2026

[Study on mechanism of Wendan Decoction in intervening in nonalcoholic fatty liver disease based on proteomics and network pharmacology].

This study systematically explored the molecular mechanism of Wendan Decoction(WDD) in treating nonalcoholic fatty liver disease(NAFLD) by integrating network pharmacology, proteomics, and experimental validation. A mouse NAFLD model was established using a high-fat diet, and the mice were randomly divided into a blank control group, a model group, a positive drug group(simvastatin, 3.03 mg·kg~(-1)), and low-(3.035 g·kg~(-1)), medium-(6.07 g·kg~(-1)), and high-dose(12.14 g·kg~(-1)) WDD groups, with intervention lasting for 6 weeks. After the intervention, the serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), triglycerides(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), and high-density lipoprotein cholesterol(HDL-C) were measured using an automatic biochemical analyzer. The serum levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) were detected by ELISA. Liver histopathology was observed via hematoxylin-eosin(HE) staining and oil red O staining. Network pharmacology was used to predict potential targets and pathways, and proteomics was applied to identify differentially expressed proteins and related pathways. RT-qPCR and Western blot were performed to detect mRNA and protein expression of relevant genes. Animal experiments demonstrated that WDD dose-dependently ameliorated hepatic steatosis, inflammation, and lipid deposition, significantly reducing serum levels of ALT, AST, TG, TC, LDL-C, and pro-inflammatory cytokines(IL-1β, IL-6, and TNF-α), while significantly increasing serum HDL-C levels. Network pharmacology screening identified naringenin, baicalein, and other key active components, which were involved in pathways such as the peroxisome proliferator-activated receptor(PPAR), lipid, and atherosclerosis pathways. Proteomics further revealed differentially expressed pathways including the PPAR and advanced glycation end product-receptor(AGE-RAGE) signaling pathways. Integrated analysis highlighted the PPAR signaling pathway as the core mechanism. Molecular biology validation showed that WDD significantly regulated the mRNA expression of sterol regulatory element-binding protein-1c(SREBP-1c), fatty acid synthase(FASN), carnitine palmitoyl transferase 1A(CPT1A), acyl-CoA oxidase 1(ACOX1), and PPARα, as well as protein expression of PPARα, CPT1A, and PPARγ in mouse liver tissue. These results suggested that WDD might exert a multi-component, multi-target, and multi-pathway synergistic effect to improve lipid metabolism disorders and inflammatory responses with the PPAR signaling pathway as the central hub, thereby alleviating NAFLD progression.

Animals↗

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

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↗