Proteomic Studies Research Articles

Protein Signature Differentiating Neutrophils and Myeloid-Derived Suppressor Cells Determined Using a Human Isogenic Cell Line Model and Protein Profiling.

Myeloid-derived suppressor cells (MDSCs) play an essential role in suppressing the antitumor activity of T lymphocytes in solid tumors, thus representing an attractive therapeutic target to enhance the efficacy of immunotherapy. However, the differences in protein expression between MDSCs and their physiological counterparts, particularly polymorphonuclear neutrophils (PMNs), remain inadequately characterized, making the specific identification and targeting of MDSCs difficult. PMNs and PMN-MDSCs share markers such as CD11b+CD14-CD15+/CD66b+, and some MDSC-enriched markers are emerging, such as LOX-1 and CD84. More proteomics studies are needed to identify the signature and markers for MDSCs. Recently, we reported the induced differentiation of isogenic PMNs or MDSCs (referred to as iPMNs and iMDSCs, respectively) from the human promyelocytic cell line HL60. Here, we profiled the global proteomics and membrane proteomics of these cells with quantitative mass spectrometry, which identified a 41-protein signature ("cluster 6") that was upregulated in iMDSCs compared with HL60 and iPMN. We further integrated our cell line-based proteomics data with a published proteomics dataset of normal human primary monocytes and monocyte-derived MDSCs induced by cancer-associated fibroblasts. The analysis identified a 38-protein signature that exhibits an upregulated expression pattern in MDSCs compared with normal monocytes or PMNs. These signatures may provide a hypothesis-generating platform to identify protein biomarkers that phenotypically distinguish MDSCs from their healthy counterparts, as well as potential therapeutic targets that impair MDSCs without harming normal myeloid cells.

Evaluating the toxicity of estetrol, 17α-ethinylestradiol, and their combination with drospirenone on zebrafish larvae: A behavioural and proteomic study

ObjectiveTo characterise and compare the toxicity of estetrol (E4) and 17α-ethinylestradiol (EE2), and their respective mixture with the progestin drospirenone (DRSP) in zebrafish (Danio rerio) embryos. MethodsZebrafish embryos were exposed to E4, EE2, DRSP, E4+DRSP, and EE2+DRSP in a fish embryo acute toxicity (FET) test. A second test examined behavioural responses and, using label-free proteomics, identified changes in protein expression in response to hormonal treatments, across a range of concentrations, including those that are considered to be environmentally relevant. ResultsIn the FET test, no effects were found from E4 at concentrations ≤100 mg/L, while EE2 induced mortality and morphological abnormalities at concentrations of 1-2 mg/L. In the behavioural test, exposure to 30 ng/L EE2 (∼200 × predicted environmental concentration – PEC) resulted in hypoactivity in fish larvae and exposure to 0.3 ng/L EE2 (∼2 × PEC) led to quantitative changes in protein abundance, revealing potential impacts on RNA processing and protein synthesis machinery. Exposure to E4 did not alter behaviour, but several groups of proteins were modulated, mainly at 710 ng/L (∼200 × PEC), including proteins involved in oxidative phosphorylation. When combined with DRSP, EE2 induced reduced effects on behaviour and proteomic responses, suggesting an antagonistic effect of DRSP. E4+DRSP induced no significant effects on behaviour or proteomic profiles at tested concentrations. ConclusionsThese findings suggest that E4-based combined oral contraceptives present a more favourable environmental profile than EE2-based contraceptives, particularly during the early developmental stages of fish.

Interleukin-13 Treatment of Living Lung Tissue Model Alters the Metabolome and Proteome-A Nano-DESI MS Metabolomics and Shotgun Proteomics Study.

Asthma is a chronic respiratory disease with one of the largest numbers of cases in the world; thus, constant investigation and technical development are needed to unravel the underlying biochemical mechanisms. In this study, we aimed to develop a nano-DESI MS method for the in vivo characterization of the cellular metabolome. Using air-liquid interface (ALI) cell layers, we studied the role of Interleukin-13 (IL-13) on differentiated lung epithelial cells acting as a lung tissue model. We demonstrate the feasibility of nano-DESI MS for the in vivo monitoring of basal-apical molecular transport, and the subsequent endogenous metabolic response, for the first time. Conserving the integrity of the ALI lung-cell layer enabled us to perform temporally resolved metabolomic characterization followed by "bottom-up" proteomics on the same population of cells. Metabolic remodeling was observed upon histamine and corticosteroid treatment of the IL-13-exposed lung cell monolayers, in correlation with alterations in the proteomic profile. This proof of principle study demonstrates the utility of in vivo nano-DESI MS for characterizing ALI tissue layers, and the new markers identified in our study provide a good starting point for future, larger-scale studies.

Proteomic Insights into Osteoporosis: Unraveling Diagnostic Markers of and Therapeutic Targets for the Metabolic Bone Disease.

Osteoporosis (OP), a prevalent skeletal disorder characterized by compromised bone strength and increased susceptibility to fractures, poses a significant public health concern. This review aims to provide a comprehensive analysis of the current state of research in the field, focusing on the application of proteomic techniques to elucidate diagnostic markers and therapeutic targets for OP. The integration of cutting-edge proteomic technologies has enabled the identification and quantification of proteins associated with bone metabolism, leading to a deeper understanding of the molecular mechanisms underlying OP. In this review, we systematically examine recent advancements in proteomic studies related to OP, emphasizing the identification of potential biomarkers for OP diagnosis and the discovery of novel therapeutic targets. Additionally, we discuss the challenges and future directions in the field, highlighting the potential impact of proteomic research in transforming the landscape of OP diagnosis and treatment.

Proteomic Characterization of Undifferentiated Small Round Cell Sarcomas With EWSR1 and CIC::DUX4 Translocations Reveals Diverging Tumor Biology and Distinct Diagnostic Markers

Undifferentiated small round cell sarcomas (USRS) of bone and soft tissue are a group of tumors with heterogenic genomic alterations sharing similar morphology. In the present study, we performed a comparative large-scale proteomic analysis of USRS (n = 42) with diverse genomic translocations including classic Ewing sarcomas with EWSR1::FLI1 fusions (n = 24) or EWSR1::ERG fusions (n = 4), sarcomas with an EWSR1 rearrangement (n = 2), CIC::DUX4 fusion (n = 8), as well as tumors classified as USRS with no genetic data available (n = 4). Proteins extracted from formalin-fixed, paraffin-embedded pretherapeutic biopsies were analyzed qualitatively and quantitatively using shotgun mass spectrometry (MS). More than 8000 protein groups could be quantified using data-independent acquisition. Unsupervised hierarchical cluster analysis based on proteomic data allowed stratification of the 42 cases into distinct groups reflecting the different molecular genotypes. Protein signatures that significantly correlated with the respective genomic translocations were identified and used to generate a heatmap of all 42 sarcomas with assignment of cases with unknown molecular genetic data to either the EWSR1- or CIC-rearranged groups. MS-based prediction of sarcoma subtypes was molecularly confirmed in 2 cases where next-generation sequencing was technically feasible. MS also detected proteins routinely used in the immunohistochemical approach for the differential diagnosis of USRS. BCL11B highly expressed in Ewing sarcomas, and BACH2 as well as ETS-1 highly expressed in CIC::DUX4-associated sarcomas, were among proteins identified by the present proteomic study, and were chosen for immunohistochemical confirmation of MS data in our study cohort. Differential expressions of these 3 markers in the 2 genetic groups were further validated in an independent cohort of n = 34 USRS. Finally, our proteomic results point toward diverging signaling pathways in the different USRS subgroups.

Characterization of effective, simple, and low-cost precipitation methods for depleting abundant plasma proteins to enhance the depth and breadth of plasma proteomics.

Plasma is an abundant source of proteins and potential biomarkers to aid in the detection, diagnosis, and prognosis of human diseases. These proteins are often present at low levels in the blood and difficult to identify and measure due to the large dynamic range of proteins. The goal of this work was to characterize and compare various protein precipitation methods related to how they affect the depth and breadth of plasma proteomic studies. Abundant protein precipitation with perchloric acid (PerCA) can increase protein identifications and depth of plasma proteomic studies. Three acid- and four solvent-based precipitation methods were evaluated. All methods tested provided excellent plasma proteomic coverage (>600 identified protein groups) and detected protein in the low pg/mL range. Functional enrichment analysis revealed subtle differences within and larger changes between the precipitant groups. Methanol-based precipitation outperformed the other methods based on identifications and reproducibility. The methods' performance was verified using eight lung cancer patient samples, where >700 protein groups were measured and proteins with an estimated plasma concentration of ∼10pg/mL were detected. Various protein precipitation agents are amenable to extending the depth and breadth of plasma proteomes. These data can guide investigators to implement inexpensive, high-throughput methods for their plasma proteomic workflows.

Profiling the interactions of epigenetic regulators and their control of T cell states

Abstract Characterizing the gene regulatory mechanisms that define distinct T cell states is essential to understanding T cell biology in health and disease. Despite advances in identifying transcriptional and epigenetic differences across T cell states, the regulators of these changes remain poorly defined. We performed a systems-level proteomic and genomic study to identify transcription factor (TF) and chromatin modifying cofactor (COF) complexes that might regulate cell state in resting, activated, and exhausted T cells. We used a high-throughput, protein-binding microarray-based approach called CoRec, to profile numerous COFs and identified unique TF-COF recruitment networks for each T cell state. In our study, some COFs are recruited specifically to TFs known to drive T cell state changes, including TFs implicated in T cell exhaustion. Exhaustion-specific recruitment of COFs suggests that these TFs may drive exhaustion through targeted alteration of epigenetic marks by these COFs. This alters expression of exhaustion-related genes and can create a functional change in T cell state. Additionally, by integrating our CoRec data with other methods, we examine how these TF-COF networks relate to chromatin accessibility and genome-wide chromatin marks. The CoRec method and its integration with other methods provides an exciting new approach for profiling cell-specific TF-COF complexes and allows us to better understand and identify the epigenetic regulators of T cell states.

Oxidative stress: A driving force in CKD induced heart failure

Background: Several clinical investigations have shown that individuals with renal impairment are more likely to experience heart failure. Cardiac remodeling happens relatively early in the course of kidney injury, yet research into identification of common markers of cardiorenal signaling remains insuffcient. This may be because studies conducted in small animal models do not accurately reflect the complexity of the disease. To bridge the translational gap, we developed a swine model for chronic kidney disease (CKD) Aim: We employed proteome studies to clarify the pathophysiological impact of chronic kidney disease (CKD) on the heart and correlate to cardiac function and perfusion in order to offer mechanistic insights. Methods: We used microspheres to embolise both kidneys of swine at 10-12 weeks of age while sham operated swine served as controls. Post 6 months, we performed pressure volume loops to assess cardiac function, while coronary flow reserve (CFR) was measured by intracoronary infusion of adenosine in control and CKD. (LC-MS-MS based proteomic analyses of left ventricular tissue was performed. Paraffn embedded myocardium and kidney tissues were histologically examined for interstitial fibrosis and oxidative stress. Results: Renal embolization resulted in mild chronic kidney injury as evidenced by increased fibrosis staining and urinary NGAL (24±4 vs 48±9 pg/ml). Hemodynamic parameters showed increased wall stress (20±3 vs 40±7 ml*mmHg/g) as well as increase of end diastolic volume (1.5±0.1 vs 1.9±0.1 ml/kg) indicating dilation of the left ventricle in CKD. Quantitative proteomic analysis detected significant differences in the left ventricle of the controls when compared to those with CKD and STRING pre-ranked functional analysis showed enrichments in pathways related to reactive oxygen species. Furthermore, we detected alterations of pathways associated with remodeling of the extracellular matrix (ECM), Oxidative stress and ECM remodeling were confirmed histologically. Interestingly, in CKD we found that mitochondrial proteins like cytochrome oxidase (MT-CO2) and ATP5 synthase subunit were downregulated suggesting mitochondrial dysfunction which was associated with higher basal coronary blood flow (0.48±0.05 vs 0.87±0.11 ml/min/g). Conclusions: Our proteomic data in swine model provides strong evidence that mild CKD can induce early alterations in mitochondrial function along with oxidative stress and ECM remodeling. Thus, we aim to further our understanding by applying our proteomic findings in conjunction with functional hemodynamic data in this swine model of cardiorenal disease. German Center for Cardiovascular Research (DZHK81Z0600207 to D.M. and P.S.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Polyphosphate and tyrosine phosphorylation in the N-terminal domain of the human mitochondrial Lon protease disrupts its functions.

Phosphorylation plays a crucial role in the regulation of many fundamental cellular processes. Phosphorylation levels are increased in many cancer cells where they may promote changes in mitochondrial homeostasis. Proteomic studies on various types of cancer identified 17 phosphorylation sites within the human ATP-dependent protease Lon, which degrades misfolded, unassembled and oxidatively damaged proteins in mitochondria. Most of these sites were found in Lon's N-terminal (NTD) and ATPase domains, though little is known about the effects on their function. By combining the biochemical and cryo-electron microscopy studies, we show the effect of Tyr186 and Tyr394 phosphorylations in Lon's NTD, which greatly reduce all Lon activities without affecting its ability to bind substrates or perturbing its tertiary structure. A substantial reduction in Lon's activities is also observed in the presence of polyphosphate, whose amount significantly increases in cancer cells. Our study thus provides an insight into the possible fine-tuning of Lon activities in human diseases, which highlights Lon's importance in maintaining proteostasis in mitochondria.

Search for cerebrospinal fluid biomarkers in patients with major psychiatric disorders: Multiplex immunoassay findings and proximity extension assay prospects.

Multiplex immunoassays have been developed to detect multiple proteins simultaneously and are used to search for biomarkers, including those present in major psychiatric disorders. This study aimed to review multiplex immunoassay studies on cerebrospinal fluid (CSF) biomarkers in patients with schizophrenia, bipolar disorder (BD), and major depressive disorder (MDD) and examine future research directions using improved proteomic techniques. According to the results of previous multiplex immunoassay studies, increased CSF IFN-β, IL-8, MCP-2, MMP-2, PAI-1, sICAM-1, and sVCAM-1 and decreased CSF ACE, APP, fibrinogen, and GDNF were observed in patients with schizophrenia, while CSF HGF and S100B were positively correlated with psychotic symptom and CSF IL-11, IL-29/IFN-λ1, and TSLP were negatively correlated. Increased CSF IFN-β and IL-1β and decreased CSF Aβ42, APP, IL-6, and NCAM-1 were observed, while CSF S100B was positively correlated with manic symptom in patients with BD. Increased CSF IL-4, MCP-1, MIP-1β, and MMP-2 were observed in patients with MDD, while CSF HGF and MMP-2 were positively correlated with depressive symptom and CSF IL-15 and MCP-1 were negatively correlated. However, signal cross-talk and cross-reactivity problems have been observed in previous studies using multiplex immunoassay. The proximity extension assay can be used to overcome cross-reactivity and enable ultrasensitive multiplexed detection and quantification of more than 1000 target proteins. However, proteomic studies using proximity extension assay technology in patients with schizophrenia, BD, or MDD are still scarce. Therefore, future high-quality proteomic studies are required to identify CSF biomarkers for larger sets of target proteins in patients with major psychiatric disorders.

Small peptide CSF fingerprint of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by abnormal protein aggregation in the motor neurons. Present and earlier proteomic studies to characterize peptides in cerebrospinal fluid (CSF) associated with motoneuron pathology did not target low molecular weight proteins and peptides. We hypothesized that specific changes in CSF peptides or low molecular weight proteins are significantly altered in ALS, and that these changes may support deciphering molecular pathophysiology and even guide approaches towards therapeutic interventions. Cerebrospinal fluid (CSF) from 50 ALS patients and 50 non-ALS controls was collected, centrifuged immediately after collection, aliquoted into polypropylene test tubes, frozen within 30-40 min after the puncture, and stored at -80°C until use. Peptides were sequenced using capillary electrophoresis or liquid chromatography/mass spectrometry (CE-MS/MS or LC-MS/MS). In the CSF of 50 patients and 50 non-ALS controls 33 peptides were found, of which 14 could be sequenced using a non-lytic single-pot proteomic detection method, CE/MS. ALS deregulated peptides vs. controls included Integral membrane protein 2B, Neurosecretory protein VGF, Osteopontin, Neuroendocrine protein 7B2 (Secretogranin-V), EGF-containing fibulin-like extracellular matrix protein 1, Xylosyltransferase 1 XT-1, Chromogranin-A, Superoxide dismutase SOD-1, Secretogranin-1 (Chromogranin B), NR2F2 Nuclear Receptor Subfamily 2 Group F Member 2 and Collagen alpha-1(VII) chain. Most striking deregulations in CSF from ALS patients were found in VGF, Osteopontin, SOD-1 and EFEMP1 peptides. No associations of disease severity, duration and region of onset with sequenced peptides were found.

Proteomic Analysis of Prehypertensive and Hypertensive Patients: Exploring the Role of the Actin Cytoskeleton.

Hypertension is a pervasive and widespread health condition that poses a significant risk factor for cardiovascular disease, which includes conditions such as heart attack, stroke, and heart failure. Despite its widespread occurrence, the exact cause of hypertension remains unknown, and the mechanisms underlying the progression from prehypertension to hypertension require further investigation. Recent proteomic studies have shown promising results in uncovering potential biomarkers related to disease development. In this study, serum proteomic data collected from Qatar Biobank were analyzed to identify altered protein expression between individuals with normal blood pressure, prehypertension, and hypertension and to elucidate the biological pathways contributing to this disease. The results revealed a cluster of proteins, including the SRC family, CAMK2B, CAMK2D, TEC, GSK3, VAV, and RAC, which were markedly upregulated in patients with hypertension compared to those with prehypertension (fold change ≥ 1.6 or ≤-1.6, area under the curve ≥ 0.8, and q-value < 0.05). Pathway analysis showed that the majority of these proteins play a role in actin cytoskeleton remodeling. Actin cytoskeleton reorganization affects various biological processes that contribute to the maintenance of blood pressure, including vascular tone, endothelial function, cellular signaling, inflammation, fibrosis, and mechanosensing. Therefore, the findings of this study suggest a potential novel role of actin cytoskeleton-related proteins in the progression from prehypertension to hypertension. The present study sheds light on the underlying pathological mechanisms involved in hypertension and could pave the way for new diagnostic and therapeutic approaches for the treatment of this disease.

Resequencing of Brazilian locally adapted cattle breeds revealed variants in candidate genes and transcription factors for meat fatty acid profile.

The beef cattle industry has experienced a shift driven by a market demand for healthier meat, cost efficiency and environmental sustainability in recent years. Consequently, there has been a growing focus on the fatty acids content and functions of meat in cattle breeding programmes. Besides, a deeper understanding of the biological mechanisms influencing the expression of different phenotypes related to fatty acid profiles is crucial. In this study, we aimed to identify Single-Nucleotide Variants (SNV) and Insertion/Deletion (InDels) DNA variants in candidate genes related to fatty acid profiles described in genomic, transcriptomic and proteomic studies conducted in beef cattle breeds. Utilizing whole-genome re-sequencing data from Brazilian locally adapted bovine breeds, namely Caracu and Pantaneiro, we identified SNVs and InDels associated with 23,947 genes. From these, we identified 318 candidate genes related to fatty acid profiles that contain variants. Subsequently, we select only genes with SNVs and InDels in their promoter, 5' UTR and coding region. Through the gene-biological process network, approximately 19 genes were highlighted. Furthermore, considering the studied trait and a literature review, we selected the main transcription factors (TF). Functional analysis via gene-TF network allowed us to identify the 30 most likely candidate genes for meat fatty acid profile in cattle. LIPE, MFSD2A and SREBF1 genes were highlighted in networks due to their biological importance. Further dissection of these genes revealed 15 new variants found in promoter regions of Caracu and Pantaneiro sequences. The gene networks facilitated a better functional understanding of genes and TF, enabling the identification of variants potentially related to the expression of candidate genes for meat fatty acid profiles in cattle.

Tumori testisa u pasa

The aim of this research paper was to review the literature on testicular tumors in dogs, as the future of diagnostics and choice of therapy for oncological patients lies in tumor markers and proteomics research. Older dogs are prone to developing testicular tumors, which are usually benign, but in some cases can be malignant. The suspicion of a testicular tumor often arises incidentally during the clinical examination of a patient for another problem or during a systematic examination. It occurs most frequently in non-castrated individuals over the age of 10 years, and only very rarely do patients with testicular tumors show any symptoms. Histopathological examination is considered an objective diagnostic method for differentiating the types of testicular tumors in dogs. A testicular biopsy is also possible but does not guarantee a therapeutic effect. Histologically, testicular tumors in dogs are divided into germ cell tumors, testicular stromal tumors and mixed testicular tumors. Previous research determined serum and immunohistochemical markers for testicular tumors in dogs, and it has been found that there is a significant difference in the expression of anti-Müllerian hormone, testosterone and 17-beta-estradiol in the serum and tissue of testicular tumors in dogs, which is useful for diagnosis and treatment decisions. Recent research has focused on proteomics, which analyzes the entire protein component, and biomedical research has already begun to use it for diagnostic and prognostic markers of testicular tumors. To date, no proteomic studies have been performed on testicular tumors in dogs, but the expression of various proteins associated with oncogenic effects has been determined in dogs with different tumors compared to healthy dogs.

Establishing Quality Control Metrics for Large-Scale Plasma Proteomic Sample Preparation.

Large-scale plasma proteomics studies have been transformed due to the multiplexing and automation of sample preparation workflows. However, these workflows can suffer from reproducibility issues, a lack of standardized quality control (QC) metrics, and the assessment of variation before liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The incorporation of robust QC metrics in sample preparation workflows ensures better reproducibility, lower assay variation, and better-informed decisions for troubleshooting. Our laboratory conducted a plasma proteomics study of a cohort of patient samples (N = 808) using tandem mass tag (TMT) 16-plex batches (N = 58). The proteomic workflow consisted of protein depletion, protein digestion, TMT labeling, and fractionation. Five QC sample types (QCstd, QCdig, QCpool, QCTMT, and QCBSA) were created to measure the performance of sample preparation prior to the final LC-MS/MS analysis. We measured <10% CV for individual sample preparation steps in the proteomic workflow based on data from various QC sample steps. The establishment of robust measures for QC of sample preparation steps allowed for greater confidence in prepared samples for subsequent LC-MS/MS analysis. This study also provides recommendations for standardized QC metrics that can assist with future large-scale cohort sample preparation workflows.

Yanang water extract exhibits a protective effect against methomyl-induced cytotoxicity in RAW 264.7 cells via suppression of apoptosis and cell cycle arrest

Methomyl, an extremely hazardous substance, is widely used for controlling insects and pests in agricultural production. This compound can cause several illnesses in humans. In this research, we determined the alleviation potential of Yanang water extract (YWE) against methomyl-induced cytotoxicity in RAW 264.7 macrophage cells and examined the underlying mechanisms of action. The YWE (2.5 – 10 μg/mL) exhibited no toxicity against RAW 264.7 cells, whereas methomyl significantly reduced RAW 264.7 cell growth, resulting in the progression of apoptosis and cell cycle arrest. Supplementation of YWE on methomyl treated RAW 264.7 cells revealed a pronounced protective effect via the suppression of caspase-9 and caspase-3 mRNA expression levels. Proteomics studies were used to assess the effect of methomyl on RAW 264.7 cells, revealing an increase of proteins associated with apoptosis and cell cycle arrest, whereas in the YWE co-treatment condition these proteins were suppressed. Moreover, an increase in proteins involved with cell cycle progression and anti-apoptosis was found in YWE co-treatment. Our findings suggest that YWE is potentially involved in mitigating methomyl-induced cytotoxicity, via the suppression of apoptosis and cell cycle arrest.

Analysis of proteomics and in silico allergenicity prediction of soluble proteins in selenium-enriched peanut leaves

Selenium (Se) is one of the nutrients contained in plants and an essential trace element for human growth. Peanut (Arachis hypogaea L.) is a good material for dietary Se enrichment. To investigate the effects of Se on the soluble proteins from peanut leaves, a comparative proteomics study was performed on soluble peanut leaf proteins (SPLPs), which were extracted from Se-enriched peanut leaves with different Se contents. Then, the allergenicity of the SPLPs was analyzed using in silico approaches. Bioinformatics analysis revealed that low Se treatment activated the antioxidative system and enhanced photosynthesis, glutathione metabolism and primary metabolism. Furthermore, the Bet v 1 domain-containing protein was affected the most by Se enrichment and can be classified as an allergen by docking simulation. ELISA confirmed that the allergenicity of SPLPs was significantly lower than that of the peanut protein, and this lower allergenicity could give the SPLPs a wider range of applications.

Occupational second-hand smoke exposure: A comparative shotgun proteomics study on nasal epithelia from healthy restaurant workers

Non-smokers exposed to second-hand smoke (SHS) present risk of developing tobacco smoke-associated pathologies. To investigate the airway molecular response to SHS exposure that could be used in health risk assessment, comparative shotgun proteomics was performed on nasal epithelium from a group of healthy restaurant workers, non-smokers (never and former) exposed and not exposed to SHS in the workplace. HIF1α-glycolytic targets (GAPDH, TPI) and proteins related to xenobiotic metabolism, cell proliferation and differentiation leading to cancer (ADH1C, TUBB4B, EEF2) showed significant modulation in non-smokers exposed. In never smokers exposed, enrichment of glutathione metabolism pathway and EEF2-regulating protein synthesis in genotoxic response were increased, while in former smokers exposed, proteins (LYZ, ATP1A1, SERPINB3) associated with tissue damage/regeneration, apoptosis inhibition and inflammation that may lead to asthma, COPD or cancer, were upregulated. The identified proteins are potential response and susceptibility/risk biomarkers for SHS exposure.

Unravelling the Role of Candida albicans Prn1 in the Oxidative Stress Response through a Proteomics Approach.

Candida albicans Prn1 is a protein with an unknown function similar to mammalian Pirin. It also has orthologues in other pathogenic fungi, but not in Saccharomyces cerevisiae. Prn1 highly increases its abundance in response to H2O2 treatment; thus, to study its involvement in the oxidative stress response, a C. albicans prn1∆ mutant and the corresponding wild-type strain SN250 have been studied. Under H2O2 treatment, Prn1 absence led to a higher level of reactive oxygen species (ROS) and a lower survival rate, with a higher percentage of death by apoptosis, confirming its relevant role in oxidative detoxication. The quantitative differential proteomics studies of both strains in the presence and absence of H2O2 indicated a lower increase in proteins with oxidoreductase activity after the treatment in the prn1∆ strain, as well as an increase in proteasome-activating proteins, corroborated by in vivo measurements of proteasome activity, with respect to the wild type. In addition, remarkable differences in the abundance of some transcription factors were observed between mutant and wild-type strains, e.g., Mnl1 or Nrg1, an Mnl1 antagonist. orf19.4850, a protein orthologue to S. cerevisiae Cub1, has shown its involvement in the response to H2O2 and in proteasome function when Prn1 is highly expressed in the wild type.

Cholesterol transport and beyond: Illuminating the versatile functions of HDL apolipoproteins through structural insights and functional implications.

High-density lipoproteins (HDLs) play a vital role in lipid metabolism and cardiovascular health, as they are intricately involved in cholesterol transport and inflammation modulation. The proteome of HDL particles is indeed complex and distinct from other components in the bloodstream. Proteomics studies have identified nearly 285 different proteins associated with HDL; however, this review focuses more on the 15 or so traditionally named "apo" lipoproteins. Important lipid metabolizing enzymes closely working with the apolipoproteins are also discussed. Apolipoproteins stand out for their integral role in HDL stability, structure, function, and metabolism. The unique structure and functions of each apolipoprotein influence important processes such as inflammation regulation and lipid metabolism. These interactions also shape the stability and performance of HDL particles. HDLs apolipoproteins have multifaceted roles beyond cardiovascular diseases (CVDs) and are involved in various physiological processes and disease states. Therefore, a detailed exploration of these apolipoproteins can offer valuable insights into potential diagnostic markers and therapeutic targets. This comprehensive review article aims to provide an in-depth understanding of HDL apolipoproteins, highlighting their distinct structures, functions, and contributions to various physiological processes. Exploiting this knowledge holds great potential for improving HDL function, enhancing cholesterol efflux, and modulating inflammatory processes, ultimately benefiting individuals by limiting the risks associated with CVDs and other inflammation-based pathologies. Understanding the nature of all 15 apolipoproteins expands our knowledge of HDL metabolism, sheds light on their pathological implications, and paves the way for advancements in the diagnosis, prevention, and treatment of lipid and inflammatory-related disorders.