Search Results (225)

Schizophrenia (SCZ) is a complex psychiatric disorder with heterogeneous molecular underpinnings that remain poorly resolved by conventional single-omics approaches, limiting biomarker discovery and mechanistic insights. To address this gap, we applied an artificial intelligence (AI)-driven multi-omics framework to an open access dataset comprising plasma proteomics, post-translational modifications (PTMs), and metabolomics to systematically dissect SCZ pathophysiology. In a cohort of 104 individuals, comparative analysis of 17 machine learning models revealed that multi-omics integration significantly enhanced classification performance, reaching a maximum AUC of 0.9727 (95% CI: 0.8889–1.000) using LightGBMXT, compared to 0.9636 (95% CI: 0.8636–1.0000) with CNNBiLSTM for proteomics alone. Interpretable feature prioritization identified carbamylation at immunoglobulin-constant region sites IGKC_K20 and IGHG1_K8, alongside oxidation of coagulation factor F10 at residue M8, as key discriminative molecular events. Functional analyses identified significantly enriched pathways including complement activation, platelet signaling, and gut microbiota-associated metabolism. Protein interaction networks further implicated coagulation factors F2, F10, and PLG, as well as complement regulators CFI and C9, as central molecular hubs. The clustering of these molecules highlights a potential axis linking immune activation, blood coagulation, and tissue homeostasis, biological domains increasingly recognized in psychiatric disorders. These results implicate immune–thrombotic dysregulation as a critical component of SCZ pathology, with PTMs of immune proteins serving as quantifiable disease indicators. Our work delineates a robust computational strategy for multi-omics integration into psychiatric research, offering biomarker candidates that warrant further validation for diagnostic and therapeutic applications. Full article

Background: Diabetes and cancer are two of the most life-threatening disorders affecting individuals of all ages worldwide. This study aimed to develop a novel Acrocomia aculeata (bocaiuva) fruit pulp oil-loaded nanoemulsion and evaluate its inhibitory effects on α-glucosidase and pancreatic lipase, as well as its antiglycant activity and cytotoxicity against cancer cells. Additionally, this study assessed the impact of both the oil and the nanoemulsion on blood cells. Methods: The pulp oil was extracted by cold pressing. The oil’s physicochemical properties were determined according to the AOAC and the Brazilian Pharmacopeia. The lipid profile was performed by GC-MS. The nanoemulsion was prepared by the phase inversion method using ultrasonic stirring for particle size reduction and for homogenization. Response Surface Methodology was used for optimizing nanoemulsion preparation. Enzyme inhibition tests were conducted using assay kits. Cytotoxicity in cancer cells was evaluated using the Sulforhodamine B assay. Results: Comprehensive physicochemical and chemical characterization of bocaiuva oil was performed, identifying oleic acid (71.25%) as the main component. The oil contains 23.04% saturated fatty acids, 73.79% monounsaturated acids, and 3.0% polyunsaturated fatty acids. The nanoemulsion (particle size 173.6 nm; zeta potential −14.10 mV) inhibited α-glucosidase (IC₅₀: 43.21 µg/mL) and pancreatic lipase (IC₅₀: 41.99 µg/mL), and revealed a potent antiglycation effect (oxidative IC₅0: 18.36 µg/mL; non-oxidative pathway IC₅₀: 16.33 µg/mL). The nanoemulsion demonstrated good cytotoxicity and selectivity against prostate cancer cells (IC₅₀: 19.13 µg/mL) and breast cancer cells (IC₅₀: 27.22 µg/mL), without inducing hemolysis, platelet aggregation, or anticoagulant effects. Conclusions: In this study, a comprehensive physical and chemical characterization of bocaiuva fruit pulp oil was conducted for the first time as a preliminary step toward its future standardization as an active ingredient in cosmetic and pharmaceutical formulations. The resulting nanoemulsion represents a novel alternative for managing diabetes and cancer. Although the nanoemulsion exhibited lower cytotoxicity compared to doxorubicin, it remains promising due to its composition of essential fatty acids, phenols, and carotenoids, which offer multiple health benefits. Further studies are needed to validate its efficacy and safety in clinical applications. Full article

Despite the prevalence of fucosylated IgG in plasma, specific IgGs with low core fucosylation sporadically emerge in response to virus infections and blood cell alloantigens. This low fucosylation of IgG is implicated in the pathogenesis of SARS-CoV-2 and dengue infections. In COVID-19, the presence of IgGs with low core fucosylation (afucosylated IgGs) targeting spike protein predicts disease progression to a severe form and actively mediates this progression. This study reveals that SARS-CoV-2 infection of megakaryocytes promotes the generation of pathogenic afucosylated anti-spike IgGs, leading to outcomes, such as pulmonary vascular thrombosis, acute lung injury, and mortality in FcγRIIa-transgenic mice. Platelets from mice injected with virus-infected human megakaryocytes express significant activation biomarkers, indicating a direct link between the immune response and platelet activation. Mice injected with virus-infected human megakaryocytes demonstrate an elevated rate of thrombus formation induced by FeCl₃ (4%) and a reduction in bleeding time, emphasizing the intricate interplay of viral infection, immune response, and hemostatic complications. Treatment with inhibitors targeting FcγRIIa, serotonin, or complement anaphylatoxins of mice injected with spike-expressing MKs successfully prevents observed platelet activation, thrombus formation, and bleeding abnormalities, offering potential therapeutic strategies for managing severe outcomes associated with afucosylated IgGs in COVID-19 and related disorders. Full article

Background: Coagulation disorders, including both bleeding and thrombotic complications, are common in patients undergoing hemodialysis (HD). Here, we aimed to characterize platelet function in patients undergoing hemodialysis three times per week, compared to healthy controls. Methods: Platelet function was assessed using the Multiplate analyzer (Roche), which is based on multiple electrode impedance aggregometry. Platelet aggregation was induced using adenosine diphosphate (ADP), and the area under the curve (AUC) served as the primary endpoint. In addition, platelet counts and C-reactive protein (CRP) levels were measured. To further evaluate nitric oxide (NO)-mediated inhibition of platelet aggregation, blood samples were incubated with the NO donor, sodium nitroprusside (SNP), and the phosphodiesterase 5A (PDE5A) inhibitor, sildenafil. Results: A total of 60 patients undergoing HD and 67 healthy controls were included in the analysis. Patients receiving HD treatment had significantly lower platelet counts compared to healthy controls (226.9 ± 53.47 vs. 246.7 ± 47.21 G/L, p = 0.029). Platelet aggregation was markedly reduced in patients undergoing HD compared to controls (462.0 ± 266.54 vs. 644.5 ± 254.44 AU × min, p < 0.001) with a significant correlation for platelet count (r = 0.42, p = 0.001) and systemic inflammation as indicated by CRP levels (r = 0.28, p = 0.035). Following SNP and sildenafil administration, inhibition of platelet aggregation remained more pronounced in patients undergoing HD. However, the change in platelet aggregation after SNP/sildenafil treatment did not differ significantly between the groups. Conclusions: Patients undergoing HD exhibit altered platelet function, indicated by reduced aggregation and platelet counts, as well as an association with systemic inflammation. Multiple electrode impedance aggregometry appears to be a feasible method for detecting platelet function alterations in patients receiving HD treatment. Responsiveness to NO donors was preserved in patients undergoing HD. Further studies are needed to identify the underlying mechanisms, particularly the role of NO signaling in platelet dysfunction in patients undergoing HD. Full article

Platelets play critical roles in haemostasis and thrombosis. The platelet activation process is driven by agonist-induced rises in cytosolic [Ca²⁺]_i, where the patterns of Ca²⁺ responses are still incompletely understood. In this study, we developed a number of techniques to model the [Ca²⁺]_i curves of platelets from a single blood donor. Fura-2-loaded platelets were quasi-simultaneously stimulated with various agonists, i.e., thrombin, collagen, or CRP, in the presence or absence of extracellular Ca²⁺ entry, secondary mediator effects, or Ca²⁺ reuptake into intracellular stores. To understand the calibrated time curves of [Ca²⁺]_i rises, we developed two non-linear models, a multilayer perceptron (MLP) network and an autoregressive network with exogenous inputs (NARX). The trained networks accurately predicted the [Ca²⁺]_i curves for combinations of agonists and inhibitors, with the NARX model achieving an R² of 0.64 for the trend prediction of unforeseen data. In addition, we used the same dataset for the construction of a partial least square (PLS) linear regression model, which estimated the explained variance of each input. The NARX model demonstrated that good fits could be obtained for the nanomolar [Ca²⁺]_i curves modelled, whereas the PLS model gave useful interpretable information on the importance of each variable. These modelling results can be used for the development of novel platelet [Ca²⁺]_i-inhibiting drugs, such as the drug 2-aminomethyl diphenylborinate, blocking Ca²⁺ entry in platelets, or for the evaluation of general platelet signalling defects in patients with a bleeding disorder. Full article

Despite notable advancements in clinical care, cardiovascular disease (CVD) remains a leading global cause of mortality. Encompassing a wide range of heart and blood vessel disorders, CVD requires targeted prevention and treatment strategies to mitigate its public health impact. In recent years, extracellular vesicles (EVs) have emerged as crucial mediators of intercellular communication, influencing key processes such as vascular remodeling, inflammation, and immune responses in CVDs. EVs, including exosomes and microvesicles, carry bioactive molecules such as miRNAs, proteins, and lipids that contribute to disease progression. They are released by various cell types, including platelets, erythrocytes, leukocytes, endothelial cells, and cardiomyocytes, each playing distinct roles in cardiovascular homeostasis and pathology. Given their presence in circulating blood and other body fluids, EVs are increasingly recognized as promising non-invasive biomarkers for CVD diagnosis and prognosis. Furthermore, EV-based therapeutic strategies, including engineered EVs for targeted drug delivery, are being explored for treating atherosclerosis, myocardial infarction, heart failure, and hypertension. However, challenges remain regarding the standardization of EV isolation and characterization techniques, which are critical for their clinical implementation. This review highlights the diverse roles of EVs in CVD pathophysiology, their potential as diagnostic and prognostic biomarkers, and emerging therapeutic applications, clearing the way for their integration into cardiovascular precision medicine. Full article

Background/Objectives: Anorexia nervosa (AN) is a chronic eating disorder with the highest mortality rate among psychiatric conditions. Malnutrition and starvation lead to long-term impairments in metabolic processes, hormonal regulation, and immune function, offering potential diagnostic and prognostic value. This study aimed to identify immune–metabolic–hormonal markers associated with treatment response and nutritional rehabilitation. Methods: Fifty hospitalized female patients with AN were included. Anthropometric measurements and venous blood samples were collected at admission and discharge, following partial nutritional recovery. Blood analyses included complete blood count, serum levels of total cholesterol, LDL and HDL, triglycerides, glucose, NT-pro-BNP, TSH, free thyroxine (fT4), sodium, chloride, potassium, calcium, iron, and vitamin D. Composite immune-inflammatory indices calculated were neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte (PLR); neutrophil-to-high-density lipoprotein (NHR), monocyte-to-high-density lipoprotein (MHR), platelet-to-high-density lipoprotein (PHR) and lymphocyte-to-high-density lipoprotein (LHR) ratios; systemic immune-inflammation (SII), and systemic inflammation response (SIRI) indexes. Results: Responders (R) and non-responders (NR) differed significantly at baseline in levels of sodium, chloride, fT4, monocyte count, MCV, NLR, MLR, SII, and SIRI (all: R < NR; p < 0.05). Predictive ability for treatment response was confirmed by AUC values (95%CI): sodium = 0.791 (0.622–0.960), chloride = 0.820 (0.690–0.950), fT4 = 0.781 (0.591–0.972), monocytes = 0.785 (0.643–0.927), MCV = 0.721 (0.549–0.892), NLR = 0.745 (0.578–0.913), MLR = 0.785 (0.643–0.927), SII = 0.736 (0.562–0.911), SIRI = 0.803 (0.671–0.935). The lower levels of inflammation and chloride are particularly predictive of better nutritional recovery, accounting for 26% of the variability in treatment response. Conclusions: The study demonstrated important insights into the hematological, metabolic, hormonal, and immune-inflammatory mechanisms associated with nutritional recovery in AN. Full article

Background and Objectives: Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder with diverse subtypes. Recent evidence has suggested a link between vitamin D deficiency and IBS; however, the associations between vitamin D levels, IBS subtypes, and hematological–biochemical parameters remain unclear. The aim of this research was to investigate the associations between vitamin D status, IBS subtypes, and sex, along with their relationships with biochemical and hematological parameters. Materials and Methods: This retrospective study included 240 patients diagnosed with IBS according to the Rome IV criteria at Van Yüzüncü Yıl University Medical Faculty Hospital. The patients were classified as diarrhea-predominant (IBS-D), constipation-predominant (IBS-C), or mixed-type (IBS-M). The patients’ serum vitamin D levels and hematological (hemoglobin, white blood cell and platelet counts, and mean corpuscular volume) and biochemical (ferritin, iron, calcium, magnesium, and vitamin B12 levels) parameters were evaluated at baseline and after vitamin D supplementation. Sex-related differences were assessed. Results: Baseline vitamin D levels were low in all IBS subtypes, with no significant differences between the groups. Vitamin D supplementation resulted in a significant increase in serum vitamin D levels across all subtypes (p = 0.001). No significant correlations were identified between vitamin D levels and hematological or biochemical parameters. Sex differences in vitamin D levels were only significant in the IBS-M group, both at baseline and post-treatment (p < 0.05). Conclusions: Vitamin D deficiency is prevalent among all IBS subtypes and significantly improves with supplementation, independently of the subtype. Although no associations were found between vitamin D levels and laboratory parameters, the observed sex differences in patients with IBS-M highlight the need for further research into potential sex-related pathophysiological mechanisms. These findings support the integration of routine vitamin D assessment and supplementation into the clinical management of IBS, especially in patients with the IBS-M subtype and female sex, to potentially improve patient outcomes. Full article

Platelets are attributed an increasing role in the post-traumatic immune response. The exact mechanisms, particularly the link between immune response and hemostasis, have not been conclusively established. This study aimed to investigate the activity marker CD63 on platelets after polytrauma and its significance for hemostasis. A non-interventional, prospective clinical study was conducted, in which the blood of 20 polytraumatized patients was analyzed at nine time points within 10 days following trauma. Peripheral blood platelets were analyzed using flow cytometry to determine CD63 expression and rotational thromboelastometry (ROTEM^®) for hemostatic platelet function. Additionally, the clinical parameters of age, gender, and injury severity were correlated to the experimental outcomes. During the observation period, an increase in platelet count and CD63 expression was observed. Simultaneously, a hemostasiological dysfunction with reduced platelet maximum clot firmness (MCF) was observed. The factors of age, gender, and injury severity showed no significant influence on immunological activation or coagulation function. These results suggest that polytrauma induces a platelet response and CD63 activation while simultaneously impairing hemostasis. This reveals a novel perspective on post-traumatic coagulation disorders, indicating that immunologically active platelets may lose their ability to contribute effectively to blood clotting. Consequently, these findings emphasize the critical role of platelet immunology in hemostatic regulation. Full article

Temporomandibular disorders (TMDs) impact quality of life and present diagnostic and treatment challenges. Biomarkers may serve as an additional tool to support diagnosis and monitor disease progression, offering supplementary information for treatment strategies in specific and selected patients. This systematic review aimed to assess the role of biomarkers in diagnosing TMD and guiding personalized treatment. It also examined key biomarkers linked to chronic temporomandibular joint (TMJ) pain and how therapies affect biomarker levels and clinical outcomes. A comprehensive search was conducted in PubMed, Scopus, and Web of Science to identify observational and interventional studies assessing the role of biomarkers in synovial fluid/tissue, saliva, and blood. The research was registered in PROSPERO, adhered to PRISMA guidelines, and employed Cochrane Risk of Bias tools. To assess the effect, only studies examining biomarker levels were considered. A total of forty-six studies met the inclusion criteria: three randomized controlled trials were rated as having some concerns, as were most of the observational studies. Elevated levels of interleukins (1ß and 6), tumour necrosis factor alpha, and prostaglandin E2 in synovial fluid were correlated with temporomandibular joint (TMJ) inflammation. Increased matrix metalloproteinases (2, 7, and 9) indicated cartilage deterioration, while oxidative stress markers such as malondialdehyde were higher in TMD patients. Treatments including hyaluronic acid, platelet-rich plasma, and low-level laser therapy effectively reduced inflammatory biomarkers and improved symptoms. Biomarkers show potential to contribute to the understanding of pathophysiological mechanisms in TMD and may support future diagnostic and therapeutic strategies for selected patients. After high-quality studies confirm these findings, this approach will enable personalized medicine by tailoring treatments to individual patient profiles, ultimately leading to improved outcomes and quality of life. Full article

Background/Objectives: Postpartum depression (PPD), the most common and prevalent psychiatric disorder after birth, is a prevalent yet underdiagnosed psychiatric condition that remains insufficiently understood, particularly in terms of its biological basis. While epidemiological data are extensive, few studies have systematically investigated their underlying biological mechanisms. The purpose of this study was to explore the potential links between blood biomarker levels and postpartum depressive symptoms, contributing to the development of a unified biological model of PPD. Methods: We conducted a cross-sectional study between 2023 and 2025 at a tertiary academic hospital in Timisoara, Romania, involving 860 postpartum women recruited at hospital discharge (1–2 weeks after childbirth). The participants completed the Edinburgh Postnatal Depression Scale (EPDS) and provided peripheral blood samples, which were analyzed using standardized protocols. The blood levels of pregnancy-related hormones (estrogen and progesterone), vitamin D, biochemical markers of inflammatory response (white blood cell count, C-reactive protein, fibrinogen, neutrophil count, lymphocyte count, and ferritin), anemia indicators (hemoglobin, red blood cell count, hematocrit, and ferritin), thyroid hormones (TSH, FT3, and FT4) and markers of coagulation abnormalities (D-dimer, platelets, fibrinogen, APTT, and INR) were evaluated. The data were analyzed with JASP v0.19.3. The statistical methods included multivariate linear regression, the Kruskal–Wallis and Mann–Whitney U tests, and Spearman correlation, with significance set at p < 0.05. Results: The analysis revealed that postpartum depression (PPD) is associated with distinct biological profiles, reflecting the unique hormonal and physiological changes in the peripartum period. Significant associations were identified between EPDS scores and the levels of estrogen, progesterone, thyroid hormones (TSH, FT3, and FT4), inflammatory markers (CRP and ferritin), vitamin D, and coagulation parameters (APTT and INR). These findings support the notion that PPD has a multifactorial biological basis and highlight the potential of these biomarkers as early predictors of risk. Conclusions: Integrating biochemical assessments into postpartum care may enhance early identification and inform targeted preventive interventions, such as hormone monitoring, vitamin D and iron supplementation, or thyroid function correction. Full article

Inherited platelet disorders (IPDs) are a group of rare conditions affecting platelet number, function, or both. Clinical manifestations vary widely, from asymptomatic cases to patients with severe bleeding, syndromic features, or early-onset blood cancers. Some are diagnosed due to family history. Early and accurate diagnosis—through both clinical and molecular evaluation—is essential for effective patient management and to avoid inappropriate treatments due to misdiagnosis. Genetic confirmation aids in prognosis, follow-up planning, family screening, genetic counseling, and donor selection for stem cell transplantation if required. However, diagnosing IPD is still challenging due to the disorders’ complexity and the limitations of current lab tests. This review outlines the diagnostic process for IPD and provides evidence-based, practical recommendations informed by scientific literature and clinical experience. Full article

Objectives: To evaluate the prognostic value of systemic inflammatory response (SIR) parameters in predicting the recurrence of cervical intraepithelial neoplasia (CIN2+) in women undergoing a loop electrosurgical excision procedure (LEEP). Methods: This retrospective study included women aged ≥18 years who underwent an LEEP at a tertiary center between 2013 and 2023. Patients who were pregnant and those who had malignancies, immune disorders, or prior cervical surgery were excluded. The data collected included age, parity, cervical cytology, HPV DNA status, histology, LEEP specimen size, and preoperative blood count parameters. Follow-up was performed every six months using cytology, colposcopy, and histology to assess recurrence. The SIR markers evaluated included the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and lymphocyte count. Statistical analyses included ROC curves and Cox regression. Results: Of the 1068 patients included, 726 had follow-up data, and 32 (4.4%) experienced a recurrence after a mean interval of 24 ± 20 months. Recurrence-negative patients had higher median lymphocyte counts (2.40 vs. 2.15, p = 0.031) and LMRs (4.57 vs. 3.86, p = 0.011). The disease-free survival period was longer in patients with high lymphocyte counts, a low NLR and PLR, and a high LMR. However, the discriminatory power of these markers was limited. In the multivariate analysis, only a PLR > 118.4 remained independently associated with an increased recurrence risk (HR 3.06, p = 0.011). Due to the small number of cases of recurrences and the small amount of HPV DNA results, the findings should be interpreted with caution. Conclusions: Preoperative SIR markers such as the PLR, NLR, LMR, and lymphocyte count showed statistical associations with CIN2+ recurrence after an LEEP, but their clinical utility appears to be limited. Further prospective studies are needed to validate these findings. Full article

Background: Transient tachypnea of the newborn (TTN) is traditionally viewed as a disorder of delayed lung fluid clearance, but emerging evidence suggests inflammatory involvement. Aim: This study investigated systemic inflammatory indices [(systemic immune-inflammation index (SII-i), systemic inflammation response index (SIR-i), neutrophil-to-lymphocyte ratio (NL-r), and platelet-to-lymphocyte ratio (PL-r)] and underlying mechanisms in TTN pathogenesis for the first time. Methods: This retrospective case–control study included 199 neonates (123 with TTN and 76 healthy controls) admitted between 2022 and 2025 to a tertiary care hospital. Complete blood count parameters were collected within the first two hours of life. Inflammatory indices were calculated and compared between groups. Subgroup analyses were conducted based on gestational age (late preterm vs. term) and mode of delivery (cesarean vs. vaginal). Results: Although not statistically significant, TTN infants showed a trend toward higher inflammatory indices with median NL-r (2.54 vs. 1.75, p = 0.197) and SII-i (729,307.83 vs. 373,593.50, p = 0.276). Term TTN infants had higher NL-r (3.08 vs. 2.04, p = 0.022) and SII-i (729,147.74 vs. 538,928.30, p = 0.133) than late preterm infants. SIR-i and NL-r values were higher in the full-term group than in the early-term and late-preterm groups (p = 0.014, p = 0.022, respectively). Cesarean births showed higher NL-r (3.20 vs. 2.33, p = 0.049) and SII-i (p = 0.040) than vaginal deliveries. Strong correlations existed between SII-I, NL-r (r = 0.886, p < 0.01), and SII-i, SIR-i (r = 0.817, p < 0.01). Conclusions: Elevated inflammatory indices in neonates with TTN, particularly in term infants and those delivered vaginally, suggest a supportive/potential role for systemic inflammation in TTN pathophysiology. These markers may serve as potential supplementary markers for risk stratification, though further prospective validation is required to confirm their clinical relevance. These findings suggest that the early assessment of systemic inflammatory indices may assist clinicians in identifying neonates at risk for TTN, thereby guiding initial respiratory support strategies. Full article

Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers characterized by the excessive production of blood cells in the bone marrow. These disorders arise from acquired genetic driver mutations, with or without underlying genetic predispositions, resulting in the uncontrolled production of red blood cells, white blood cells, or platelets. The excessive cell production and abnormal signaling from driver mutations cause chronic inflammation and a higher risk of blood clots and vascular complications. The primary goals of MPN treatment are to induce remission, improve quality of life and survival, as well as to reduce the risk of complications such as thrombosis, vascular events, and leukemic transformation. This review provides a comprehensive update on the diagnosis and therapeutic advancements in major MPN subtypes, including chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, and primary myelofibrosis. It examines these complex diseases from a molecular and evolutionary perspective, highlighting key clinical trials’ long-term follow-up and therapies targeting driver mutations that have transformed treatment strategies. Additionally, several important advancements in addressing challenges such as anemia in myelofibrosis, along with promising emerging therapies, are also discussed. Full article