Circulating levels of apoptotic markers and oxidative stress parameters in women with polycystic ovary syndrome: a case-controlled descriptive study

Context: Apoptotic dysregulation plays a role in the pathogenesis of polycystic ovary syndrome (PCOS).

Objective: To evaluate circulatory apoptotic markers and oxidative stress in patients with PCOS.

Materials and methods: Forty-four women with PCOS, and 44 healthy women as controls were enrolled in the study. Oxidative stress parameters and caspases levels were measured in serum.

Results: The caspase 9 level was significantly lower and related with oxidant status in patients with PCOS, while the circulating levels of caspases 3 and 7 were statistically similar in both groups.

Discussion: This study is the first report demonstrating the circulating levels of apoptotic markers and their relationship with oxidant status in PCOS.

Conclusion: The circulating caspase 9 and oxidant status might contribute to apoptotic dysregulation in PCOS.     

Release kinetics of high-sensitivity cardiac troponins I and T and troponin T upstream open reading frame peptide (TnTuORF) in clinically induced acute myocardial infarction

Context: Troponin T upstream open reading frame peptide (TnTuORF) may be useful as a novel biomarker in acute cardiac syndromes.

Objective: The study examined the early release kinetics of TnTuORF.

Materials and methods: We analyzed the time course of the release of cardiac troponins I and T and TnTuORF in patients (n?=?31) with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy (TASH).

Results: Fifteen minutes after TASH, the levels of both troponins increased significantly (cTnT median: 18?ng/L versus 27?ng/L; cTnI median: 15?ng/L versus 25?ng/L). TnTuORF showed no variation.

Discussion: We observed a significantly greater increase in cTnI compared with cTnT.

Conclusion: Our results demonstrate that troponin assays allow early detection of myocardial injury, whereas TnTuORF levels remain unchanged in this setting.     

Platelet proteomics applied to the search for novel antiplatelet therapeutic targets

Introduction: Unwanted platelet activation is associated with numerous diseases, mainly thrombosis-related. In this context, proteomics has emerged as a novel tool with potential for drug target discovery and to scrutinize the effects of antiplatelet drugs.

Areas covered: The present review presents the main findings of platelet proteomic studies to date in the context of drug target discovery and perspectives for the future ahead. It includes data and evidences obtained from literature searches on PubMed as well as commentaries derived from the authors’ experience and opinions.

Expert commentary: Platelet proteomics applied to drug target discovery is a young field. Recent studies have shown promising data, especially in the context of coronary artery disease. However, challenges remain such as establishing definitive guidelines for blood collection and platelet isolation, essential to guarantee data reproducibility. Recent advances in quantitative platelet proteomics should lead to novel studies with higher clinical impact in the near future.     

Beta-2-glycoprotein-1 and alpha-1-antitrypsin as urinary markers of renal cancer in von Hippel–Lindau patients

Context: Von Hippel–Lindau disease (VHLD) is a rare inherited neoplastic syndrome. Among all the VHLD-associated tumors, clear cell renal cell carcinoma (ccRCC) is the major cause of death.

Objective: The aim of this paper is the discovery of new non-invasive biomarker for the monitoring of VHLD patients.

Materials and methods: We compared the urinary proteome of VHLD patients, ccRCC patients and healthy volunteers.

Results: Among all differentially expressed proteins, alpha-1-antitrypsin (A1AT) and APOH (beta-2-glycoprotein-1) are strongly over-abundant only in the urine of VHLD patients with a history of ccRCC.

Discussion and conclusion: A1AT and APOH could be promising non-invasive biomarkers.     

Biomarker discovery for drug-induced phospholipidosis: phenylacetylglycine to hippuric acid ratio in urine and plasma as potential markers

Context: Drug-induced phospholipidosis is one of the significant concerns in drug development, especially in safety assessment and noninvasive diagnostic tool is highly desirable.

Objective: The objective of this study is to explored novel biomarkers for phospholipidosis using a metabolomic approach.

Method: NMR spectrometry and LC/MS/MS analyses were applied to urine and plasma of rats administrated cationic amphiphilic drugs.

Results: The phenylacetylglycine to hippuric acid ratio in plasma was increased in time and dose-dependent manners; and it was well correlated with histopathological observation.

Conclusion: The plasma phenylacetylglycine to hippuric acid ratio is a potential marker in monitoring drug-induced phospholipidosis.     

Proteomic analysis of red blood cells and the potential for the clinic: what have we learned so far?

Introduction: Red blood cells (RBC) are the most abundant host cells in the human body. Mature erythrocytes are devoid of nuclei and organelles and have always been regarded as circulating ‘bags of hemoglobin’. The advent of proteomics has challenged this assumption, revealing unanticipated complexity and novel roles for RBCs not just in gas transport, but also in systemic metabolic homeostasis in health and disease.

Areas covered: In this review we will summarize the main advancements in the field of discovery mode and redox/quantitative proteomics with respect to RBC biology. We thus focus on translational/clinical applications, such as transfusion medicine, hematology (e.g. hemoglobinopathies) and personalized medicine. Synergy of omics technologies – especially proteomics and metabolomics – are highlighted as a hallmark of clinical metabolomics applications for the foreseeable future.

Expert commentary: The introduction of advanced proteomics technologies, especially quantitative and redox proteomics, and the integration of proteomics data with omics information gathered through orthogonal technologies (especially metabolomics) promise to revolutionize many biomedical areas, from hematology and transfusion medicine to personalized medicine and clinical biochemistry.     

Recent advances in proteomic profiling of pancreatic ductal adenocarcinoma and the road ahead

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers worldwide. However, there remain many unmet clinical needs, from diagnosis to treatment strategies. The inherent complexity of the molecular characteristics of PDAC has made it difficult to meet these challenges, rendering proteomic profiling of PDAC a critical area of research.

Area covered: In this review, we present recent advances in mass spectrometry (MS) and its current application in proteomic studies on PDAC. In addition, we discuss future directions for research that can efficiently incorporate current MS-based technologies that address key issues of PDAC proteomics.

Expert commentary: Compared with other cancer studies, little progress has been made in PDAC proteomics, perhaps attributed to the difficulty in performing in-depth and large-scale clinical studies on PDAC. However, recent advances in mass spectrometry can advance PDAC proteomics past the fundamental research stage.     

The choice of amniotic fluid in metabolomics for the monitoring of fetus health - update

Introduction: In recent years, several studies have highlighted the promising role of metabolomics in the analysis of amniotic fluid (AF), to describe and characterize the interactions occurring between the mother and the fetus during prenatal development.

Among the available biological fluids, AF represents an ideal substrate to provide dynamic information regarding fetal organogenesis and metabolism through pregnancy, since it originates from both maternal and fetal tissues and contains substances derived from placenta, fetal skin, lungs, gastric fluid, and fetal urine.

Areas covered: In this paper, we provide an update reporting the most recent results on AF metabolomics in the assessment of feto-maternal health, regarding physiological pregnancies but even fields such as prematurity, bronchopulmonary dysplasia, fetal malformations, chromosomopathies, maternal diseases, placental inflammation or infections, maternal diet or exposure to exogenous substances, according to the literature found on MEDLINE since 2015.

Expert opinion: Metabolomics shows a promising role in describing both physiology and disease; the goal would be the identification of biomarkers able to precociously and efficaciously detect pathological conditions, allowing the identification of complicated pregnancy and improving their management. However, this field is under development and its reliability still needs to be clarified, especially through more numerous and accurate studies.     

Positive effects of plantar vibration training for the treatment of diabetic peripheral neuropathy: A pilot study

Purpose: To evaluate the effectiveness of 8-week low-frequency plantar vibration training on patients with sensorimotor diabetic peripheral neuropathy (DPN).

Participants: Twelve patients took part in the investigation.

Results: An increase of the nerve conductive velocity of soral and peroneal nerves of feet, increased postural stability, and disappearance of the pain and tingling were observed.

Conclusion: The obtained results provide evidence for beneficial effects of 8-week plantar vibration training in patients with DPN.     

Proteomic analysis of synovial fluid: current and potential uses to improve clinical outcomes

Introduction: Synovial fluid (SF) is in close proximity to tissues which are primarily altered during articular disease and has significant potential to better understand the underlying disease pathogeneses of articular pathologies and biomarker discovery. Although development of mass spectrometry-based methods has allowed faster and higher sensitivity techniques, interrogation of the SF proteome has been hindered by its large protein concentration dynamic range, impeding quantification of lower abundant proteins.

Areas covered: Recent advances have developed methodologies to reduce the large protein concentration dynamic range of SF and subsequently allow deeper exploration of the SF proteome. This review concentrates on methods to overcome biofluid complexity, mass spectrometry proteomics methodologies, extracellular vesicles proteomics and the application of advances within the field in clinical disease, including osteoarthritis, rheumatoid arthritis, spondyloarthritis and juvenile arthritis. A narrative review was conducted with articles searched using PubMed, 1991–2018.

Expert opinion: The SF proteomics field faces various challenges, including the requirement for rigorous and standardised methods of sample collection/storage, the sensitivity and specificity of proteomic assays, techniques to combat the large protein concentration dynamic range and comprehensive data analysis to reduce falsely identified markers. Additionally, there are challenges in developing multi ‘omic’ integration techniques, with computational integration enhancing analysis.     

Tissue-based quantitative proteome analysis of human hepatocellular carcinoma using tandem mass tags

Context and objective: Human hepatocellular carcinoma (HCC) is a severe malignant disease, and accurate and reliable diagnostic markers are still needed. This study was aimed for the discovery of novel marker candidates by quantitative proteomics.

Methods and results: Proteomic differences between HCC and nontumorous liver tissue were studied by mass spectrometry. Among several significantly upregulated proteins, translocator protein 18 (TSPO) and Ras-related protein Rab-1A (RAB1A) were selected for verification by immunohistochemistry in an independent cohort. For RAB1A, a high accuracy for the discrimination of HCC and nontumorous liver tissue was observed.

Conclusion: RAB1A was verified to be a potent biomarker candidate for HCC.     

Salivary protein changes in response to acute stress in medical residents performing advanced clinical simulations: a pilot proteomics study

Context: Quantitative changes of salivary proteins due to acute stress were detected.

Objective: To explore protein markers of stress in saliva of eight medical residents who performed emergency medicine simulations.

Materials and methods: Saliva was collected before the simulations, after the simulations, and following morning upon waking. Proteins were separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), identified by mass spectrometry (MS), and relatively quantified by densitometry.

Results: Salivary alpha-amylase and S–type cystatins significantly increased, while the ～26?kDa and low-molecular weight (MW) (<10?kDa) SDS-PAGE bands exhibited changes after stress.

Discussion and conclusion: Alpha-amylase and cystatins are potential salivary markers of acute stress, but further validation should be performed using larger sample populations.     

Platelet proteomics: from discovery to diagnosis

Introduction: Platelets are the smallest cells within the circulating blood with key roles in physiological hemostasis and pathological thrombosis regulated by the onset of activating/inhibiting processes via receptor responses and signaling cascades.

Areas covered: Proteomics as well as genomic approaches have been fundamental in identifying and quantifying potential targets for future diagnostic strategies in the prevention of bleeding and thrombosis, and uncovering the complexity of platelet functions in health and disease. In this article, we provide a critical overview on current functional tests used in diagnostics and the future perspectives for platelet proteomics in clinical applications.

Expert commentary: Proteomics represents a valuable tool for the identification of patients with diverse platelet associated defects. In-depth validation of identified biomarkers, e.g. receptors, signaling proteins, post-translational modifications, in large cohorts is decisive for translation into routine clinical diagnostics.     

Toxicoproteomics in human health and disease: an update

Introduction: Toxicoproteomics is an emerging area of omics, intended to explore the changes in protein expression and modifications in biological samples exposed to toxicants. The development of techniques that utilize sophisticated instruments in proteomics has facilitated the exploration of a wide-range of protein coverage and assisted the quantitative and qualitative evaluation of protein changes as a result of the toxic effects of toxic substances.

Areas covered: Studies on toxicoproteomics have an immense potential to explore the molecular mechanism of action of a variety of toxic substances through deciphering the proteomic map altered as a result of toxicant exposure. Here, we provide an overview of toxicoproteomic approaches and the current paradigm of toxicoproteomics.

Expert commentary: Research in this area continues to increase our understanding of the role of toxicants in worsening human health and toxicity driven diseases. The progress in toxicoproteomics may realize the development of novel biomarkers, drug targets and personalized medicines by incorporating the advanced proteomic applications in this field.     

MicroRNAs as possible biomarkers for screening of aortic aneurysms: a systematic review and validation study

Context: There is an urgent need to identify non-invasive biomarkers for the early detection of aortic aneurysms, preceding a fatal event. The potential role for MicroRNAs (miRNAs) as diagnostic markers for aortic aneurysms was investigated through the present systematic review.

Objective: To perform a comprehensive review on published studies examining the association of miRNAs with aortic aneurysms and further validate these results with plasma samples collected from thoracic aortic aneurysm (TAA) patients.

Methods: The literature search was performed via numerous databases and articles were only included if they fulfilled the predefined eligibility criteria. The miRNAs reported three times or more with expression consistency were validated using plasma samples from TAA patients collected before and following surgery.

Results: Twenty-four articles were selected from the literature search and 11 miRNAs were chosen for validation using our samples. The miRNAs which were further validated were found to follow the trend in the regulation pattern as with the majority of the published data. MiRNA hsa-miR-193a-5p was found to be significantly down-regulated in the plasma samples collected before the aneurysmal removal when compared with postsurgical serum samples.

Conclusions: Numerous miRNAs have been associated with aortic aneurysms, and specifically hsa-miR-193a-5p and hsa-miR-30b-5p; therefore they warrant further investigation as potential biomarkers.

Registration: The protocol of the review was registered in Prospero Databases (ID: CRD42016039953)     

An efficient survey method for estimating populations of Marsh Tits Poecile palustris,a low-density woodland passerine

Capsule: A playback survey comprising two visits to woodland in early spring can reliably detect Marsh Tits Poecile palustris and permit reasonable estimation of the number of territories.

Aims: To assess the efficacy of an efficient survey method for detecting and estimating populations of Marsh Tits.

Methods: Detection probability of colour-marked Marsh Tits, surveyed using playback, was assessed with Cormack–Jolly–Seber models. Reliability of territory estimates was compared between colour-marked and largely or wholly unmarked populations.

Results: Playback surveys over two visits in early spring were highly effective in detecting individual Marsh Tits. Territory estimates were similar for woods in years where less than 20% of the population was marked compared to years when a higher proportion of birds were colour-marked, although territories may be underestimated in larger woods with unmarked populations.

Conclusion: A playback survey comprising two visits in early spring is recommended as an efficient method of surveying Marsh Tit populations and locating individuals. A survey protocol is suggested.