Specific Biomarkers Research Articles

Extracellular vesicles characterization in patients with hypertrophic cardiomyopathy

Abstract Background Hypertrophic cardiomyopathy (HCM) is a genetic disorder, diagnosed according to the presence of phenotypical traits of the myocardium. A specific biomarker which can associate with the severity of HCM is lacking. Extracellular Vesicles (EVs), nanoparticles released by cells into biological fluids, hold promise as accessible diagnostic tools, as their abundance and molecular composition can reflect the severity of cardiac diseases (Rizzuto 2024). We aim at characterising plasma-derived EVs isolated from 28 HCM patients and 18 healthy volunteers (CTR). Methods The whole cohort underwent transthoracic echocardiography, whereas magnetic resonance and exome sequencing was performed on HCM patients. EVs were isolated via ultracentrifugation from plasma of both groups. Quantitative and qualitative assessments of EVs were performed by nanoparticle tracking analysis, transmission electron microscopy, Western blot, targeted (Olink) and untargeted (nLC-MS/MS) proteomics and FACS analysis. Plasma-derived EV subpopulations were characterised according to their cellular origin. Data are expressed as median and interquartile range (25th, 75th). Results Most patients were male (68% HCM and 66% CTR) with a median age of 58 (49-69) years (HCM) and 47 (44-52) (CTR). Among HCM patients, missense mutations in the MYH7 gene were the most identified. The median maximum wall thickness (WTMax) in HCM was 16 mm (15-19) vs 8 mm (7-9) in CTR. The isolated EVs expressed tetraspanins (CD9, CD63 and CD81), Alix and β-integrin and showed an intact phospholipid bilayer of 100 nm in size. EV concentration was reduced in HCM vs CTRL, respectively 2.8*109 EV/ml/cell count (2*109-4*109) and 4.6*10⁹ EV/ml/cell count (3*109-6*109). Among 15 plasma-derived EV subpopulations studied, those released from platelets (CD41a) and activated platelets (CD62P and CD40L) were increased in HCM patients vs CTR by 1.7 fold. Negative associations were found between E/e’, parameter of diastolic function, and cardiomyocyte-derived EVs (r= -0.2658), and between left ventricle ejection fraction and platelet-derived EVs (r=-0.2189); a positive correlation was found between WTMax and EVs derived from activated endothelial cells (r=0.2330). The proteomic analysis of EVs shows an enrichment in proteins related to platelets adhesion and inflammation in HCM patients. Conclusions HCM patients present a peculiar phenotypic pattern of EVs that may associate with diagnostic clinical features of HCM.

Improved prognosis prediction of idiopathic pulmonary arterial hypertension using targeted plasma proteomics in disease management

Abstract Background Idiopathic pulmonary arterial hypertension (IPAH), a special subgroup of PAH with unclear etiology, is characterized by rapid progression and poor prognosis underscoring the need for optimization of IPAH management and the accurate prediction of prognosis. However, it is disappointing that specific plasma biomarkers for IPAH management and prognosis are lacking in clinical practice. Up to date, the plasma biomarkers used for assessment of IPAH severity and prognosis are relied solely on indicators such as N-terminal prohormone of brain natriuretic peptide, or brain natriuretic peptide, which could reflect cardiac function but fail to promptly response to the dynamic change of disease condition due to the complexity of IPAH pathogenesis. Purpose We evaluated the prognostic value of plasma proteins in addition to current clinical predictors for prognosis prediction of IPAH. Methods Olink Immune-Response panel was used to measure 92 plasma proteins in a prospective IPAH cohort with 169 patients and a mean follow-up period of 2.4 ± 0.9 years. Six machine learning methods were used to construct predictive models, including plasma proteins-based Olink models, clinical parameters-based clinical models, and integrative models. Results A total of 18 proteins showed differential expression between patients with or without adverse clinical outcomes. Three proteins (STC1, CXADR, and IL6) were strongly correlated with clinical indicators of IPAH severity and their concentrations showed upward trends along with increased risk stratification. Elevated levels of STC1, CXADR, and IL6 are all associated with an increased risk of adverse clinical events, indicated by survival analysis, restricted cubic splines, and multivariable Cox regression analysis (STC1 HR=3.474, 95%CI: 1.129-10.692, P=0.030; CXADR: HR=1.602, 95%CI: 1.074-2.387, P=0.021; IL6: HR=1.883, 95%CI: 1.376-2.576, P<0.001). The inclusion of these three proteins into the predictive model could significantly increase the predictive power on the basis of the clinical model (AUC: 0.746 vs 0.626). Conclusions High levels of STC1, CXADR, and IL6 in plasma were associated with severe clinical phenotype and increased risk of adverse clinical events in patients with IPAH. These plasma proteins could significantly improve the prognostic performance of pre-existing clinical models, facilitating the clinical management of IPAH patients.The predictive efficient of models

Serum proteomic profiling reveals potential inflammatory biomarkers in long-COVID patients: a comparative analysis with healthy controls

Abstract Background Long-COVID (also known as post-acute sequelae of SARS-CoV-2 infection, PASC), is defined as the persistence, or the new onset, of symptoms after recovery from the acute phase of COVID-19. It consists of a multiorgan syndrome expressing itself with a wide variety of cardiovascular and non-cardiovascular symptoms such us chest pain, fatigue, shortness of breath, autonomic dysfunction, cognitive impairment and sleep disorders even in the absence of a clear evidence of organ dysfunction. Some previous studies have suggested the potential role of an abnormal inflammatory response after SARS-CoV-2 infection, however the specific underlying mechanisms remain unclear. In this study we performed a proteomic analysis of the serum of 80 long-COVID patients to identify potential biomarkers that may act as indicators or therapeutic targets for long COVID. Methods and results We compared the levels of the proteins in both long-COVID group and a control group using multivariate and univariate analysis. Both PLS-DA and PCA analysis showed a clear distinction between the two groups; clustering analysis also clearly separated control from long-COVID patients. Proteins were then filtered based on (a) statistical analysis, considering proteins with a VIP>1 (PLSDA) and p<0.05 (t-test); (b) coefficient of variation (CV), where only proteins with CV<10 were considered; (c) and fold change (FC), for which proteins with FC<0.67 or FC>1.5 were selected for further analysis. The selected proteins were then subjected to a ROC curve analysis to identify antithrombin as a potential biomarker with an area under the curve (AUC) near 1. Other proteins, displaying an AUC > 0.98, were also identified as potential biomarkers (Sirtuin 1, NatriureticPeptide B, Hemopexin Arachidonate 5-Lipoxygenase). In addition, a multivariate ROC method, using linear SVM as classification method, identified that a combination of ten proteins would also result in an AUC near 1. Finally, a correlation analysis between the proteins of interest and the clinical manifestations was performed. A positive correlation (above 0.5) was found between dyspnea and Glucocorticoid Receptor and between memory deficit and Antithrombin. Arachidonate 5-Lipoxygenase was negatively correlated (below -0.5) with tremors and hair loss, MannoseBinding Lectin 2 was found to be positively linked to asthenia, Antithrombin with concentration deficit and Endothelin-2 with muscles aches. Conclusions The identified biomarkers are associated with inflammatory processes, corroborating literature evidence that long-COVID patients develop an inflammatory state that damages many tissues. Further studies are needed to validate this data in larger cohorts to identify specific biomarkers, and guide future preventive strategies or treatments to address long COVID and its cardiovascular and non-cardiovascular sequelae.

Insulin-like growth factor binding protein 2 predicts course of concomitant right-ventricular dilation and tricuspid regurgitation after transcatheter edge-to-edge mitral valve repair

Abstract Aims Right ventricular (RV) dilation and secondary tricuspid regurgitation (TR) are highly prevalent comorbidities in patients with mitral regurgitation and are associated with a worse prognosis. TR improvement after successful transcatheter edge-to-edge mitral valve repair (M-TEER) is reported regularly, however specific factors contributing to the recovery of RV function and TR after M-TEER are poorly understood. Particularly the role of serum biomarkers in this context is unclear. We aimed to identify specific biomarkers associated with the course of concomitant RV dilation and TR after M-TEER. Methods and Results We prospectively included 242 patients undergoing M-TEER at our center and obtained pre-procedural blood samples for biomarker analysis. A commercial multiplex protein assay (Cardiovascular III, Olink, Uppsala, Sweden) was used to quantify expression levels of 92 defined biomarkers. We then analyzed differences in biomarker expression between patients with and without right ventricular reverse remodeling (RVRR) as defined by improvement of concomitant TR by at least one grade and/or downsizing of the basal RV diameter of at least 10%. 242 patients were included in this analysis, 94 had no/mild concomitant TR at baseline, 148 had moderate/severe TR. RV diameters correlated with TR severity and were significantly larger in patients with moderate/severe TR. At baseline, expression of numerous cardiometabolic biomarkers was significantly higher in patients with moderate/severe TR. These included NT-proBNP (1.9-fold, p < 0.001), matrix metalloproteinase 2 (1.4-fold, p < 0.001) as well as insulin-like growth factor binding proteins 1 (1.7-fold, p < 0.001), -2 (1.3-fold, p = 0.001) and -7 (1.4-fold, p < 0.001). Follow-up analysis was performed in patients with initial moderate/severe TR. The course of TR and RV dimensions three months after M-TEER could be assessed in 99 patients (56 with moderate TR, 43 with severe TR). RVRR had occurred in 50 patients (50.5%). Patients without RVRR had a higher prevalence of chronic pulmonary disease (24.5 vs. 2.2%, p < 0.001). No further differences in clinical characteristics were found. Specifically, RV diameter, systolic pulmonary artery pressure (sPAP) and right-ventricular systolic function did not differ substantially between both groups. Strikingly however, the expression of insulin-like growth factor binding protein 2 (IGFBP-2) was significantly higher in patients, who did not develop RVRR (fold change 1.3 compared to patients with RVRR, p = 0.022). After adjustment for covariates IGFBP-2 was independently associated with absence of RVRR (Odds Ratio 2.078, 95% Confidence interval 1.108 – 3.897, p = 0.023). Conclusions In patients undergoing M-TEER with concomitant moderate or severe TR, numerous cardiometabolic biomarkers including IGFBP-2 are upregulated. Higher levels of IGFBP-2 at baseline are independently associated with persistent TR and/or RV dilation after M-TEER.

Prognostic value of alveolar surfactant type-B in acute heart failure: a long-term comparative analysis vs NT-proBNP

Abstract Background In heart failure (HF) biomarkers are an integral component of prognostic assessment. Natriuretic peptides are the gold standard, but they do not directly reflect lung vascular injury. Surfactant type B (Surf-B) is released by type 2 alveolar cells under pressure induced trauma, with few reports just addressing its plasmatic levels in stable chronic HF (CHF). Information on acute HF (AHF) is lacking. Purpose To clarify the prognostic value of Surf-B changes vs NT-proBNP levels after decongestion therapy and to compare their prognostic ability at 1-year follow-up. Methods Patients with acute pulmonary edema (APE) underwent a combined evaluation of Surf-B and NT-proBNP serum levels with quantification of B-lines at hospital admission (time 0), discharge (time 1) and at 1 year (time 2). Results 54 patients (mean age 72.1 ± 11 years; mean LVEF 36% ± 13%; 65% men) were enrolled. At time 1, the average Surf-B, NT-proBNP and B-lines were significantly reduced compared to time 0 (p<0.0001). No correlation between Surf-B and NT-proBNP was observed either at time 0 (r=-0.21; p=0.12) or at time 1 (r=0.05; p=0.71). Despite the significant decrease in Surf-B levels from time 0 to time 1, 18.5% of patients behaved as non-responders exhibiting no changes in Surf-B; conversely, only 5.5% did not show significant reduction in NT-proBNP, despite significant decongestion. 38 patients were followed up to time 2: of these, 13 (34%) reached the composite endpoint of death or hospitalization for HF. Surf-B measured at time 1 was a strong predictor of adverse outcome. Patients with Surf-B above median at discharge displayed a worse survival-free from HF hospitalization compared to the remainders (Log rank p=0.012) (Figure). Also, patients with Surf-B above median at discharge had a more than 4-fold increased risk of the composite endpoint (HR 4.5, 95%CI 1.4-20.2, p=0.023). Conversely, NT-proBNP at discharge was not significantly associated with HF-free survival (Log rank p=0.26) (Figure) and was not a significant predictor of the composite outcome (HR 1.9, 95%CI 0.6-9.3, p=0.25). At ROC analysis, discharge Surf-B levels showed a higher area under the curve (AUC=0.763, p=0.011) than NT-proBNP values (AUC=0.69, p=0.063). Conclusions These data suggest that Surf-B, an organ specific biomarker of lung injury, is highly sensitive to the effectiveness of decongestion therapy, outperforming NT-proBNP. Given the high rate of patients who do not improve their Surf-B levels over time, the reparative processes of alveolar break damage may dissociate from mere decongestion and cardiac healing in AHF.Figure:1yr Kaplan-Meier survival curves

Cardioprotection in coronary artery bypass graft surgery: the impact of remote ischemic preconditioning on modulating LOX-1 and SOD-1 to counteract oxidative stress

BackgroundCoronary artery bypass grafting (CABG) is frequently used to treat severe coronary artery disease (CAD), but it can lead to increased oxidative stress and inflammation, worsening patient outcomes. Remote ischemic preconditioning (RIPC) has been suggested as a potential strategy to protect against these effects by modulating oxidative stress and inflammatory responses, though its impact on specific biomarkers requires further investigation. This study aims to assess the effects of remote ischemic preconditioning on inflammation markers and oxidative stress in patients with severe CAD undergoing coronary artery bypass grafting.MethodsWe conducted a case-control study involving 80 patients with severe coronary artery disease (CAD) scheduled for coronary artery bypass grafting (CABG). Fifty percent of these patients received ischemic preconditioning prior to surgery. Plasma levels of Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and Superoxide dismutase-1 (SOD-1) levels were measured in all individuals using the ELISA method at three important time points: before surgery (visit 1 or V1), immediately post-operatively (visit 2 or V2), and one week post-operatively (visit 3 or V3).ResultsWe enrolled 80 patients, of which 40 were assigned to the studied group receiving remote ischemic preconditioning (RIPC) and 40 to the control group. There were no statistically significant differences between the groups regarding baseline, clinical, or operative characteristics. RIPC treatment significantly reduced plasma levels of Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) (p < 0.05) as well as significantly increasing total values of Superoxide dismutase-1 (SOD-1) (p < 0.05, respectively). There were notable differences between the studied and control groups at V2 and V3. The studied group had higher SOD-1 levels (p < 0.05) and significantly lower LOX-1 levels at both time points (p < 0.05).ConclusionThe significant changes in plasma levels of both LOX-1 and SOD-1 observed in this study strongly suggest that remote ischemic preconditioning (RIPC) plays an important role in reducing oxidative stress and enhancing the antioxidative status of patients. This is evidenced by the marked decrease in LOX-1 levels, alongside a corresponding increase in SOD-1 levels, indicating that RIPC may contribute to improved cardioprotection through these mechanisms.

Importance of biological markers in the assessment of endothelial dysfunction

Endothelial dysfunction (ED) is a pathogenetic link in many cardio­vas­cular diseases. One of the promising approaches to non-invasi­ve diagnostics and assessment of the ED severity may be the deter­mi­nation of specific blood biomarkers. This review is devoted to the patho­genetic role of some biochemical and molecular factors associated with ED, as potential biomarkers of noncommunicable diseases.

Unmet Needs in Spondyloarthritis: Imaging in Axial Spondyloarthritis.

Imaging biomarkers in axial spondyloarthritis (axSpA) are currently the most specific biomarkers for the diagnosis of this condition. Despite advances in imaging, from plain radiographs-which detect only damage-to magnetic resonance imaging (MRI)-which identifies disease activity and structural change-there are still many challenges that remain. Imaging in sacroiliitis is characterized by active and structural changes. Current classification criteria stress the importance of bone marrow edema (BME); however, BME can occur in various diseases, mechanical conditions, and healthy individuals. Thus, the identification of structural lesions such as erosion, subchondral fat, backfill, and ankylosis is important to distinguish from mimics on differential diagnosis. Various imaging modalities are available to examine structural lesions, but computed tomography (CT) is considered the current reference standard. Nonetheless, recent advances in MRI allow for direct bone imaging and the reconstruction of CT-like images that can provide similar information. Therefore, the ability of MRI to detect and measure structural lesions is strengthened. Here, we present an overview of the spectrum of current and cutting-edge techniques for SpA imaging in clinical practice; namely, we discuss the advantages, disadvantages, and usefulness of imaging in SpA through radiography, low-dose and dual-energy CT, and MRI. Cutting-edge MRI sequences including volumetric interpolated breath-hold examination, ultrashort echo time, zero echo time, and deep learning-based synthetic CT that creates CT-like images without ionizing radiation, are discussed. Imaging techniques allow for quantification of inflammatory and structural lesions, which is important in the assessment of treatment response and disease progression. Radiographic damage is poorly sensitive to change. Artificial intelligence has already revolutionized radiology practice, including protocolization, image quality, and image interpretation.

The Enigma That Is ROHHAD Syndrome: Challenges and Future Strategies

Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is a rare syndrome presenting in early childhood associated with a high risk of mortality between 50 and 60%. It is characterised by rapid, early onset of obesity between 1.5–7 years, along with central hypoventilation and hypothalamic dysfunction, such as central hypothyroidism, hyperprolactinemia, disorders of sodium and water balance, growth hormone deficiency, adrenocortical insufficiency, or disorders of puberty and features of autonomic dysregulation. Up to half of cases have neural crest tumours, most commonly ganglioneuromas or ganglioneuroblastomas. The incidence of ROHHAD syndrome in any population is unknown. Currently, there is no specific diagnostic or genetic biomarker for ROHHAD, and diagnosis is based on clinical signs and symptoms, which is often challenging, and consequently may be delayed or unrecognised. Early diagnosis is important, as without intervention, ROHHAD is associated with high morbidity and mortality. Aetiology remains unclear; an autoimmune origin has been postulated, with immunosuppressive agents being used with variable benefit. With no cure, multidisciplinary management is largely supportive. Therefore, there are many unanswered questions in ROHHAD syndrome. In this review article, we outline the challenges posed by ROHHAD syndrome, including aetiology, genetics, diagnosis, screening, management, and prognosis. We present research priorities to tackle these issues to improve outcomes.

Serum proteomic analysis identified ITIH4 as a potential novel biomarker for feline infectious peritonitis

Feline infectious peritonitis (FIP) is a fatal feline disease. At present, the reference standard for FIP diagnosis is immunohistochemistry (IHC) of organs, but this method involves high time-related costs, invasive sampling procedures and professional requirements. Serological detection is a common auxiliary method for diagnosing diseases. As a result, we assessed the changes in the serum proteome of FIP patients with the aim of identifying novel specific serum biomarkers that could aid in the clinical diagnosis of FIP. Pre- and postinfection groups were compared and 92 differentially expressed proteins (DEPs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEPs revealed that the enriched GO terms and KEGG pathways among the DEPs were immune activation, peptidase regulator activity and the complement and coagulation cascade pathways. The level of peptidase regulator interalpha-trypsin inhibitor heavy chain 4 (ITIH4) in cat serum was significantly correlated with FIP. The areas under the ROC curve (AUCs) of full-length ITIH4 (f-ITIH4) and cleaved ITIH4 (c-ITIH4) expression were 0.922 and 1.000, respectively, which allowed the discrimination of FIP cats from healthy cats. These results suggest that ITIH4 may be a potential serum biomarker for detecting early FIP. SignificanceFIP causes fatal disease in cats of almost all ages, and there is currently no effective vaccine or treatment for FIP. Therefore, early diagnosis is extremely important for disease prevention and control. The results of the model and clinical samples revealed that ITIH4 was significantly increased in the serum of FIP cats. This study is the first to propose ITIH4 as a diagnostic biomarker in cats with FIP and our results suggest that serum ITIH4 levels might identify cats with FIP during the early stage.

Comparison of urinary 3-hydroxybenzo(a)Pyrene (3-OHBaP) and trans-anti-7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo(a)Pyrene (TetraolBaP) as biomarkers of exposure to carcinogenic BaP

IntroductionBiomonitoring of exposure to carcinogenic Benzo(a)Pyrene is generally based on measurement of urinary 3-hydroxybenzo(a)pyrene (3-OHBaP), but its analysis is complex and only reflects the BaP detoxification pathway. TetraolBaP, another BaP metabolite resulting from the metabolic activation pathway, is now available but has not yet been studied in occupational settings or compared with 3-OHBaP. MethodsBiomonitoring was carried out on 118 subjects working in the aluminium smelting industry. 3 urine samples were collected from each subject at the beginning and end of the working week. Pyrene metabolite (1-hydroxypyrene) and the two BaP biomarkers (3-OHBaP and TetraolBaP) were analysed using LC-Fluorescence and GC-NCI-MS-MS. ResultsThe workers studied were found to be highly exposed, with 1-OHP and 3-OHBaP frequently exceeding maximum recommended values in occupational settings. Maximum concentrations were measured at end of shift+16h for all biomarkers, highlighting dermal exposure and/or temporary storage. Correlations were strong between 1-OHP and 3-OHBaP (r = 0.68–0.75) as well as between 3-OHBaP and TetraolBaP (r = 0.67–0.78), and moderate between 1-OHP and TetraolBaP (r = 0.59–0.76). While TetraolBaP levels were higher at low PAH exposures, TetraolBaP increased much more slowly at high exposures, indicating progressive saturation of the bioactivation pathway. The [3-OHBaP]/[TetraolBaP] ratio was found to be significantly lower in chronically exposed workers. Urinary TetraolBaP levels corresponding to 1-OHP (2.5 μg/L or 1 μmol/mol creatinine) or 3-OHBaP (0.4 nmol/mol creatinine) guidance values were found to range between 0.84 and 0.95 nmol/mol creatinine. ConclusionsTetraolBaP, resulting from carcinogenic BaP's metabolic activation pathway, was shown to be a diagnostically specific and sensitive biomarker for determining subjects' toxic internal exposure to PAHs in different contexts (occupational settings, environment) and assessing health risks.

Optical Biosensors for Detection of Cancer Biomarkers: Current and Future Perspectives.

Optical biosensors are emerging as a promising technique for the sensitive and accurate detection of cancer biomarkers, enabling significant advancements in the field of early diagnosis. This study elaborates on the latest developments in optical biosensors designed for detecting cancer biomarkers, highlighting their vital significance in early cancer diagnosis. When combined with targeted nanoparticles, the bio-fluids can help in the molecular stage diagnosis of cancer. This enhances the discrimination of disease from the normal subjects drastically. The optical sensor methods that are involved in the disease diagnosis and imaging of cancer taken for the present review are surface plasmon resonance, localized surface plasmon resonance, fluorescence resonance energy transfer, surface-enhanced Raman spectroscopy and colorimetric sensing. The article meticulously describes the specific biomarkers and analytes that optical biosensors target. Beyond elucidating the underlying principles and applications, this article furnishes an overview of recent breakthroughs and emerging trends in the field. This encompasses the evolution of innovative nanomaterials and nanostructures designed to augment sensitivity and the incorporation of microfluidics for facilitating point-of-care testing, thereby charting a course towards prospective advancements.

The environmental impact on aging: Insights from buccal mucosa and molecular biomarkers

Buccal epithelial cells serve as a primary barrier against the inhalation and ingestion of harmful substances, working alongside immune system cells such as natural killer cells to protect the body from health-damaging factors. These epithelial cells can also be used as an alternative tissue source for monitoring the genotoxic effects of external factors such as chemical exposure. This assessment can be performed using molecular biomarkers of aging, which reflect biological age and indicate cellular aging acceleration due to internal and external damage factors, such as environmental hazards. In contrast to chronological age, which merely reflects the passage of time, biological age accounts for individual variation in aging processes. Molecular biomarkers are crucial for distinguishing between normal and pathological processes in the body and for identifying the effects of external factors such as chemical exposures. The identification of specific biomarkers enhances the ability to detect and monitor adverse biological responses and accelerated aging. This review aims to highlight the routes through which environmental hazards enter the body, the application of buccal epithelial cells in assessing genetic modifications, and the introduction of potential molecular biomarkers. However, further research is necessary to elucidate the roles of these biomarkers in determining aging rates and individual variability. Understanding their implications may also help identify new therapeutic targets for preventing premature aging, treating age-related diseases, and developing potential treatments.

Steps to understanding diabetes kidney disease: a focus on metabolomics.

Diabetic nephropathy (DN), a leading cause of chronic kidney disease and end-stage kidney disease (ESKD), poses global health challenges given its increasing prevalence. DN increases the risk of mortality and cardiovascular events. Early identification and appropriate DN management are crucial. However, current diagnostic methods rely on general traditional markers, highlighting the need for DN-specific diagnostics. Metabolomics, the study of small molecules produced by metabolic activity, promises to identify specific biomarkers that distinguish DN from other kidney diseases, decode the underlying disease mechanisms, and predict the disease course. Profound changes in metabolic pathways are apparent in individuals with DN, alterations in the tricarboxylic acid cycle and amino acid and lipid metabolism, suggestive of mitochondrial dysfunction. Metabolomics aids prediction of chronic kidney disease progression; several metabolites serve as indicators of renal functional decline and the risk of ESKD. Integration of such information with other omics data will further enhance our understanding of DN, paving the way to personalized treatment. In summary, metabolomics and multi-omics offer valuable insights into DN and are promising diagnostic and prognostic tools.

Ionising radiation exposure-induced regulation of selected biomarkers and their impact in cancer and treatment

Ionising radiation (IR) is a form of energy that travels as electromagnetic waves or particles. While it is vital in medical and occupational health settings, IR can also damage DNA, leading to mutations, chromosomal aberrations, and transcriptional changes that disrupt the functions of certain cell regulators, genes, and transcription factors. These disruptions can alter functions critical for cancer development, progression, and treatment response. Additionally, IR can affect various cellular proteins and their regulators within different cell signalling pathways, resulting in physiological changes that may promote cancer development, progression, and resistance to treatment. Understanding these impacts is crucial for developing strategies to mitigate the harmful effects of IR exposure and improve cancer treatment outcomes. This review focuses on specific genes and protein biomarkers regulated in response to chronic IR exposure, and how their regulation impacts disease onset, progression, and treatment response.

Metabolic biomarkers of neonatal sepsis: identification using metabolomics combined with machine learning

BackgroundSepsis is a common disease associated with neonatal and infant mortality, and for diagnosis, blood culture is currently the gold standard method, but it has a low positivity rate and requires more than 2 days to develop. Meanwhile, unfortunately, the specific biomarkers for the early and timely diagnosis of sepsis in infants and for the determination of the severity of this disease are lacking in clinical practice.MethodsSamples from 18 sepsis infants with comorbidities, 25 sepsis infants without comorbidities, and 25 infants with noninfectious diseases were evaluated using a serum metabolomics approach based on liquid chromatography‒mass spectrometry (LC‒MS) technology. Differentially abundant metabolites were screened via multivariate statistical analysis. In addition, least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) analyses were conducted to identify the key metabolites in infants with sepsis and without infections. The random forest algorithm was applied to determine key differentially abundant metabolites between sepsis infants with and without comorbidities. Receiver operating characteristic (ROC) curves were generated for biomarker value testing. Finally, a metabolic pathway analysis was conducted to explore the metabolic and signaling pathways associated with the identified differentially abundant metabolites.ResultsA total of 189 metabolites exhibited significant differences between infectious infants and noninfectious infants, while 137 distinct metabolites exhibited differences between septic infants with and without comorbidities. After screening for the key differentially abundant metabolites using LASSO and SVM-RFE analyses, hexylamine, psychosine sulfate, LysoPC (18:1 (9Z)/0:0), 2,4,6-tribromophenol, and 25-cinnamoyl-vulgaroside were retained for the diagnosis of infant sepsis. ROC curve analysis revealed that the area under the curve (AUC) was 0.9200 for hexylamine, 0.9749 for psychosine sulfate, 0.9684 for LysoPC (18:1 (9Z)/0:0), 0.7405 for 2,4,6-tribromophenol, 0.8893 for 25-cinnamoyl-vulgaroside, and 1.000 for the combination of all metabolites. When the septic infants with comorbidities were compared to those without comorbidities, four endogenous metabolites with the greatest importance were identified using the random forest algorithm, namely, 12-oxo-20-trihydroxy-leukotriene B4, dihydrovaltrate, PA (8:0/12:0), and 2-heptanethiol. The ROC curve analysis of these four key differentially abundant metabolites revealed that the AUC was 1 for all four metabolites. Pathway analysis indicated that phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and porphyrin metabolism play important roles in infant sepsis.ConclusionSerum metabolite profiles were identified, and machine learning was applied to identify the key differentially abundant metabolites in septic infants with comorbidities, septic infants without comorbidities, and infants without infectious diseases. The findings obtained are expected to facilitate the early diagnosis of sepsis in infants and determine the severity of the disease.

Biomarkers of mature neuronal differentiation and related diseases.

The nervous system regulates perception, cognition and behavioral responses by serving as the body's primary communication system for receiving, regulating and transmitting information. Neurons are the fundamental structures and units of the nervous system. Their differentiation and maturation processes rely on the expression of specific biomarkers. Neuron-specific intracellular markers can be used to determine the degree of neuronal maturation. Neuronal cytoskeletal proteins dictate the shape and structure of neurons, while synaptic plasticity and signaling processes are intricately associated with neuronal synaptic markers. Furthermore, abnormal expression levels of biomarkers can serve as diagnostic indicators for nervous system diseases. This article reviews the markers of mature neuronal differentiation and their relationship with nervous system diseases.

How Are We Addressing Axial Psoriatic Arthritis in Clinical Practice?

Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting the musculoskeletal system, skin and nails. In addition to peripheral joints, inflammation of the spine and sacroiliac joints may occur. Yet, research into this axial phenotype has lagged behind partly because of the challenge in its clinical identification with a lack of specific clinical, molecular or imaging biomarkers. In the absence of a validated definition of what constitutes axial PsA (axPsA), guidelines for the management of axial involvement in PsA in clinical practice are scarce. On the basis of a literature review and their clinical expertise, a group of rheumatology experts provide their opinion to aid the diagnosis and management of axial PsA in clinical practice.

Obstáculos para o diagnóstico e tratamento do transtorno do espectro autista

Objective: To understand the obstacles that reduce accessibility to the diagnosis and treatment of autism spectrum disorder (ASD). Literature review: ASD is a disorder characterized by difficulties in social interaction, impairments in communication and restricted patterns of behavior. Its diagnosis is clinical, based on behavioral observations and the patient's history and on criteria defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM – 5). Treatment includes pharmacological and behavioral approaches. However, the difficulties and challenges found in the literature include the symptomatological heterogeneity of ASD, the need for training health professionals and a more accurate assessment through a multidisciplinary team. Late diagnosis or its absence can lead to unfavorable outcomes in adult life, such as: anxiety, depression, and difficulty in interpersonal relationships. Recent studies include the use of specific biomarkers and innovative therapies that are not yet accessible. Final considerations: Early diagnosis and appropriate treatment are ideal for improving the quality of life of individuals with ASD. The importance of the doctor and new studies to improve therapeutic choice in ASD is also highlighted.

Evaluation of a Risk Model for Sepsis Early Prediction in Infants with Epidermolysis Bullosa

Abstract Objective Epidermolysis bullosa (EB) is a severe hereditary condition characterized by fragile skin that can lead to complications, including severe infections such as sepsis. Current research on sepsis in children with EB is limited, and there is a need for specific biomarkers that can aid in early detection and management. Methods This study analyzed blood samples from 92 children diagnosed with EB, 42 of whom developed sepsis. We investigated various inflammatory proteins and clinical parameters as potential biomarkers. Multivariate analysis was used to determine predictors of sepsis occurrence. Results Elevated levels of C-reactive protein (CRP), interleukin-6 (IL-6), lactate, and decreased oxygen saturation were significantly associated with sepsis in children with EB. The predictive model displayed an area under the receiver operating characteristic curve of 0.80 in the training set and 0.77 in the validation set, indicating good predictive accuracy. Conclusion Our findings suggest that CRP, IL-6, lactate, and oxygen saturation are reliable predictors of sepsis in children with EB. These biomarkers should be monitored closely to facilitate early diagnosis and improve outcomes in this vulnerable population. The study underscores the need for tailored research and diagnostic strategies for children with EB at risk of sepsis.