Osteoarthritis (OA) is a prevalent musculoskeletal disorder causing chronic pain and disability, particularly in older adults. It is a multifactorial disease characterized by joint degeneration, with varying pathophysiological mechanisms across different OA subtypes (knee, hip, spine, hand, etc.). This study aimed to explore the genetic mechanisms underlying various OA subtypes using a novel approach combining protein level ratios (rQTLs) with Mendelian Randomization (MR) analysis.

Cerebrospinal fluid (CSF) provides a unique window into brain pathology, yet challenges in unbiased mass-spectrometric (MS) discovery persist due to sample complexity and the need for optimized analytical workflows. Multiple laboratory workflows have been developed for CSF proteomics, each with distinct advantages for specific applications. To interrogate which laboratory workflow is most suitable for this biological matrix, we benchmarked five orthogonal sample-preparation strategies- MStern, Proteograph™ nanoparticle enrichment (Seer), N-glycopeptide capture (N-Gp), and two extracellular-vesicle (EV) fractions isolated by differential ultracentrifugation (P20- and P150-EV)- in CSF from 19 patients with central nervous system lymphoma. The protocols span a practical spectrum of input volume (6000-50 µL), hands-on time, and reagent cost, enabling informed method selection for translational applications. In total we performed 82 LC-MS/MS experiments and detected over 38,000 unique peptides and more than 3000 proteins across all modalities. Seer achieved the best proteomic depth (~ 17,000 unique peptides) across samples, followed by P20-EV (~ 9,000), MStern (~ 5,500), P150-EV (~ 5,000), and N-Gp (~ 1,000). None of the methods introduced systematic bias in peptide or protein isoelectric point or hydrophobicity, yet each selectively highlighted distinct biological niches: P20-EVs favoured mitochondrial signatures, N-Gp capture lysosomal and plasma membrane signatures and Seer enhanced nuclear representation. These findings demonstrate that no single protocol suffices for every research question; instead, workflow selection should align with sample-volume constraints, budget and biological question. Our comparative framework empowers investigators to match CSF proteomics strategies to specific neuro-oncological objectives, thereby accelerating the translation of CSF biomarkers into clinically actionable assays.

This study aims to investigate the impact of high altitude (HA) hypoxia on ferroptosis in lung tissue and the evaluate the preventative effect of Dimethyl fumarate (DMF) on lung inflammation.

Premature coronary artery disease (PCAD) is characterized by early onset, rapid progression, and poor prognosis, which seriously affects patients' health and quality of life. In this study, we analyzed the proteomic network and biological pathways of PCAD patients by bioinformatics methods, and mined out the key differential proteins, which provided a theoretical basis for clinical intervention.

Glycosaminoglycans (GAGs) are linear polysaccharide chains that are usually linked to proteins to create proteoglycans and play an essential role in the extracellular matrix (ECM). Mucopolysaccharidoses (MPS) are a group of rare disorders that arise due to impairment in the breakdown of glycosaminoglycans (GAGs). Key technological advances in mass spectrometry (MS) have had a significant impact on the study and diagnosis of MPS, as well as its clinical management. This review summarizes the current applications of mass spectrometry-based approaches in MPS, emphasizing its role in the understanding of pathophysiological disease mechanisms, and towards improved patient care. Mass spectrometry-based proteomics and metabolomics have identified novel biomarkers and metabolic perturbations related to the pathophysiology of MPS. In addition, mass spectrometry-based glycomics analyses have been employed for the structural characterization of GAGs to reveal their heterogeneity. The sensitivity and specificity of liquid chromatography tandem mass spectrometry (LC-MS/MS) as compared to conventional methods for the quantitation of GAGs have revolutionized diagnostics. High-resolution mass spectrometers such as Orbitrap and Fourier transform ion cyclotron resonance, permit more accurate GAG characterization. Mass spectrometry has also proven valuable in monitoring patients undergoing treatment, thereby allowing the sensitive monitoring of the therapeutic efficacy of both enzyme replacement and gene therapies. Mass spectrometry has enabled improved newborn screening and multiplex assays for screening multiple MPS types. Despite the important contributions of mass spectrometry to enhance MPS research and clinical management, there still remain challenges related to long and complex sample preparation processes, lack of standardization and lack of accessibility in routine clinical settings. We envision that future initiatives will incorporate multiple omics technologies to obtain a more holistic view of the pathophysiology of MPS. Fortunately, mass spectrometry technologies and methods continue to evolve rapidly, promising further advancements in MPS diagnosis, monitoring of patients on therapy and research that should ultimately lead to improved patient outcomes and quality of life.

Formalin-fixed paraffin-embedded (FFPE) tissue proteomics has emerged as a promising approach for precision medicine, offering access to vast clinical archives. Despite technological advances enabling identification of thousands of proteins from FFPE samples, no proteomic diagnostic tests based on FFPE tissues have achieved regulatory approval for clinical diagnostics, raising fundamental questions about the translational viability of this approach.

Low-grade serous ovarian carcinoma (LGSOC) is a rare and largely chemoresistant subtype of epithelial ovarian cancer. Unlike treatment for high-grade serous ovarian cancer (HGSOC), management options for LGSOC patients are limited, in part, due to a lack of deep molecular characterization of this disease. To address this limitation, we aimed to define highly conserved proteome alterations in LGSOC by performing deep quantitative proteomic analysis of tumors collected from LGSOC and HGSOC patients or normal fallopian tube tissues and validating proteins within two independent proteomic datasets of LGSOC and HGSOC tumors.

Saliva-derived small extracellular vesicles (sEVs) are emerging as potential biomarkers for coronary artery disease (CAD). Early identification of these biomarkers is essential for effective management and improved patient outcomes. Our study aimed to isolate and characterize sEVs from saliva to identify non-invasive protein signatures in younger CAD patients.

The preservation of tissue architecture and morphology in formalin-fixed paraffin-embedded (FFPE) tissues enables spatial resolution at the cellular and sub-cellular levels. Laser capture microdissection (LCM) combined with liquid chromatography tandem mass spectrometry analysis permits collection of tissue areas with spatial context for proteome profiling from FFPE slides. In this study, we performed proteome profiling of non-diseased renal tubulointerstitial tissue in a cohort of young (< 40 years) and old (> 70 years) individuals with the goal of spatially correlating the histomorphology to the proteomic profile. To perform in-depth characterization of renal tubulointerstitium and to identify renal aging-associated proteins, a multiplexing strategy using tandem mass tags (TMT) was employed, resulting in the quantitation of 7,355 proteins. Our approach allowed for identification of proteins with low abundance such as fibrocystin and ninein-like protein. Notably, 162 solute carrier proteins from 47 solute carrier families were identified, which were enriched in proximal and distal tubule cells. Finally, we discovered a proteomic signature associated with renal aging, which includes metalloproteinase inhibitor 3, nicotinamide N-methyltransferase, matrix metallopeptidase 7, phenazine biosynthesis-like domain-containing protein and solute carrier family 23 member 1. Overall, our study demonstrates the power of LCM combined with proteomics to leverage archived FFPE tissue samples for investigating proteomic alterations in the renal tubulointerstitium with age at a high depth of proteome coverage.

This study, using a two-sample and two-step Mendelian randomization (MR) approach, reveals a causal relationship between specific circulating plasma proteins and osteoporosis risk, and further identifies key deCODE Genetics plasma proteins (measured in a different population and using an independent proteomic platform) mediating the effects of upstream UKB plasma proteins.Notably, proteins such as NT5C, GREM1, BOLA1, and CCL19 were found to partially mediate the effects of upstream UKB plasma proteins on bone health. These findings shed light on a multi-tiered protein regulatory network underlying osteoporosis and provide potential targets for therapeutic intervention.

Multiple myeloma (MM), the second most prevalent hematological malignancy, carries high morbidity with variability in clinical progression among patients. This necessitates accurate risk stratification for effective therapy and life planning. While extensively genomically and transcriptomically characterized, MM remains modestly studied from a proteomic perspective. As proteomics is a closer measure of phenotype than genomic and transcriptomic assessments, addressing this gap in the literature may yield new insights into disease biology and novel biomarkers.

Infantile epileptic spasm syndrome (IESS) presents significant therapeutic challenges, with the molecular mechanisms underlying variable responses to adrenocorticotropic hormone (ACTH) remaining poorly understood. This study aimed to identify ACTH-specific therapeutic biomarkers in IESS patients with effective (EF) and ineffective (IEF) responses to ACTH, providing potential clues for therapeutic interventions and insights into IESS pathogenesis.

Cytochrome P450 (CYP450) enzymes are essential for drug metabolism, xenobiotic detoxification, and procarcinogen activation, playing a pivotal role in both normal physiology and cancer biology. Their expression varies significantly across tissues and tumour types, reflecting the metabolic heterogeneity of cancers. Understanding these variations is critical for developing targeted therapies, optimizing drug efficacy, and minimizing toxicity. This study aimed to comprehensively profile CYP450 expression across colorectal cancer (CRC), head and neck squamous cell carcinoma (HNSCC), breast cancer, and hepatic cancer models using proteomic techniques.

The treatment of aortic valve stenosis (AVS) remains limited to aortic valve replacement (AVR). No pharmacotherapy has yet proven efficacious, and its development is challenged by sexual dimorphism. Women display extensive valve fibrosis, and men present remarkably higher valve calcification. To accelerate the development of sex-personalised therapies, deeper molecular insights are needed. Hence, we aimed to characterise AVS sexual dimorphism using proteomics.

Systemic amyloidosis is a potentially fatal protein misfolding disorder usually underdiagnosed in low- and middle-income countries, where limited awareness and restricted access to diagnostic tools contribute to prolonged diagnostic journeys and delayed diagnoses. Accurate identification of the precursor protein is essential but remains a challenge, particularly in resource-limited settings. This study aimed to perform mass spectrometry (MS) for amyloid subtyping and to use it as the reference method to evaluate the consistency of a clinical-laboratory model (CLM) and immunohistochemistry (IHC) in determining the amyloid subtype.

Age-related macular degeneration (AMD), a degenerative disease of the photoreceptor support system of the macula, is a leading cause of vision loss in individuals over 60 years of age. In this exploratory longitudinal study, we studied VEGF-related proteins and other protein concentrations in the aqueous humor of patients with treatment naïve neovascular AMD (defined as patients with a previously untreated and recently diagnosed advanced neovascular form of AMD (NVAMD) who were eligible for an intra-vitreal administration of an anti-VEGF agent to treat choroidal neovascularization). The objectives of this small pilot study were: (1) To determine levels of VEGF-related proteins in the aqueous humor of treatment naïve NVAMD patients compared with control patients, (2) To determine whether levels of VEGF-related proteins change over time with anti-VEGF injections in NVAMD patients, (3) To put these differences into perspective relative to all protein targets and identify other off-target (non-VEGF) proteins that may be related to NVAMD or NVAMD treatment.

Colorectal cancer (CRC) has emerged as the second most prevalent cause of cancer-related mortality globally. Early identification of precancerous lesions prone to malignant transformation is pivotal in CRC prevention. Proteins, as microscopic reflections of cellular functional states, offer insights into pathological alterations within precancerous lesions through changes in their expression and function. Our review summarizes the protein research on colorectal adenomas under different sample conditions, including traditional adenomas, serrated lesions, LST, FAP and IBD. It highlights the changes in the expression patterns of key proteins and their potential mechanisms underlying the transition from precancerous to cancerous states. Additionally, it summarizes the research on post-translational modifications of characteristic protein families and associated signaling pathways, while discussing current techniques for studying protein expression and function in colorectal cancer, such as proteomics and artificial intelligence. However, current research limitations, such as small sample sizes, limited sample types, and insufficient in-depth mechanistic analysis, hinder comprehensive understanding. Future research should expand study cohorts, diversify sample types, and leverage machine learning and multi-omics approaches to develop predictive models. By doing so, a more comprehensive understanding of protein profiles during the progression from colorectal precancerous to cancerous lesions can be obtained, facilitating early CRC diagnosis and the development of targeted therapeutic interventions.

Increasing evidence highlights the crucial role of antibody-dependent cellular phagocytosis (ADCP) in colorectal cancer (CRC). However, how to use ADCP-related genes to predict prognosis in CRC and guide treatment remains unelucidated.

Plasma is the most used clinical specimen, yet diurnal variation in plasma proteins remains largely unexplored. We aimed to identify diurnally-regulated proteins in healthy individuals and assess their potential diagnostic implications, and highlight how diurnal awareness can advance future biomarker research.

Small cell lung cancer (SCLC) is an aggressive malignancy with a poor prognosis. This study aimed to analyze the urinary exosomal proteome of SCLC patients to identify and validate potential non-invasive biomarkers for improving diagnosis, treatment response monitoring, and prognosis prediction.

Sepsis is a critical condition characterized by a dysregulated immune response to infection. As sepsis develops to septic shock, its most severe form, morbidity and mortality increases. Hyaluronan is a key component of the extracellular matrix and the endothelial glycocalyx. In sepsis, plasma hyaluronan concentrations are increased and correlate with disease severity. In this study we aimed to explore and compare the proteomic profiles of hyaluronan-associated proteins in patients with the dysregulated immune response of septic shock and the sterile inflammation of acute alcohol-related pancreatitis.