Search Results (1,042)

Background/Objectives: Breast cancer is the most commonly diagnosed cancer among women worldwide, with triple-negative breast cancer (TNBC) being a highly aggressive subtype characterized by early recurrence, limited targeted therapies, and poor clinical outcomes. Despite advances in chemotherapy, therapeutic resistance remains a major challenge, underscoring the need for alternative therapeutic approaches. Natural products continue to serve as important sources of bioactive compounds for cancer drug discovery. Tiliacora triandra, a Thai medicinal plant traditionally used to manage inflammatory and metabolic disorders, has not been extensively investigated for its potential against TNBC. In this study, we evaluated the anti-cancer effects of T. triandra extracts and its major flavonoid constituent, pectolinarigenin, in triple-negative breast cancer, MDA-MB-231 cells. Methods: An 80% ethanolic root extract was sequentially partitioned into hexane, dichloromethane, and ethyl acetate fractions. High-performance liquid chromatography identified pectolinarigenin as a predominant component of the dichloromethane fraction (TT-DCM), with a quantified content of 14.24 ± 2.32 mg/g extract. The anti-cancer effect of TT-DCM and pectolinarigenin on MDA-MB-231 cells were investigated using colony formation, cell cycle analysis, PI/Annexin V staining, and Western blot analysis. Results: Both TT-DCM and pectolinarigenin significantly reduced MDA-MB-231 cell viability and clonogenic growth. Treatment resulted in G0/G1 phase accumulation, accompanied by decreased expression of cyclin D1, CDK2, and CDK4. Apoptotic induction was observed, as evidenced by lower expression levels of Bcl-xL, Bcl-2, and surviving proteins, together with increased caspase-9 and caspase-3 activities. Additionally, TT-DCM and pectolinarigenin were associated with reduced phosphorylation of ERK1/2, JNK1/2, and p38 MAPKs. Conclusions: Collectively, these findings demonstrate that pectolinarigenin derived from T. triandra exerts potent anti-cancer activity in MDA-MB-231 TNBC cells through coordinated modulation of cell cycle progression, apoptotic signaling, and MAPK pathway activity. Further studies are warranted to validate these effects in additional TNBC models. Full article

Objective: Adequate sleep is vital for children’s growth and well-being. This study investigates serum amino acid and fatty acid metabolic indicators in children with sleep disorders, identifies independent factors, and develops a predictive model. Methods: A total of 143 children diagnosed with sleep disorders (n = 143) were compared to 120 typically developing children (n = 120). Serum levels of 12 amino acids and 7 fatty acids were measured using liquid chromatography–tandem mass spectrometry. Differences between groups were assessed using t-tests or Mann–Whitney U tests. Independent factors were identified via multivariate logistic regression, leading to the construction of a predictive model. Its diagnostic efficacy was evaluated through receiver operating characteristic analysis, calibration curves, and decision curve analysis (DCA). Subgroup analysis of different sleep disorder subtypes was also performed to explore metabolic characteristic differences. Results: Significant differences in multiple metabolic indicators were found (p < 0.05) between these two groups. Seven amino acids were elevated, including glutamine and tryptophan, while linoleic acid and taurine levels were reduced. Analysis of four sleep disorder subtypes revealed no significant differences in most metabolic indicators among subtypes, with only taurine levels showing notable heterogeneity, the highest in parasomnia and the lowest in insomnia. Multivariate analysis revealed that arachidonic acid (OR = 0.75, 95% CI: 0.649–0.866), the ratio of cerotic acid to behenic acid (OR = 0.39, 95% CI: 0.186–0.816), aspartic acid (OR = 1.1, 95% CI: 1.040–1.164), glutamine (OR = 1.009, 95% CI: 1.004–1.014), taurine (OR = 0.985, 95% CI: 0.974–0.995), and phenylalanine (OR = 1.047, 95% CI: 1.018–1.078) were identified as independent factors for the development of sleep disorders (p < 0.05). The predictive model achieved the area under the ROC curve of 0.935 (95% CI: 0.904–0.967), with a threshold of 0.748 yielding sensitivity of 0.881 and specificity of 0.867. Ten-fold cross-validation confirmed robust generalizability (AUC: 0.927–0.916), and adjustable thresholds enabled flexible clinical application. Calibration curves and DCA demonstrated good agreement and clinical utility. Conclusions: Children with sleep disorders exhibit notable serum metabolic disturbances. The developed predictive model provides high diagnostic value and practicality for early screening and targeted interventions. Full article

Anxiety disorders are the most prevalent mental health conditions worldwide, yet current treatments remain suboptimal, with benzodiazepines carrying risks of tolerance and dependence. These limitations motivate the search for novel anxiolytics. Tropical marine macroalgae represent a promising source of neuroactive metabolites. Here, we investigate the anxiolytic potential of Stypopodium zonale using a neuroproteomics-based approach in Drosophila melanogaster. Crude organic extracts were prepared via ultrasonic-assisted extraction and administered acutely to adult flies for six hours. Proteins from fly heads were quantified and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), revealing 66 significantly differentially abundant proteins (fold change ≥ |1.5|, p ≤ 0.05), 72.7% of which were less abundant in the extract-treated group. Principal component analysis demonstrated clear separation between control and experimental samples. Ingenuity Pathway Analysis (IPA) mapped 33 of the differentially abundant proteins to human orthologs and identified significant predicted inhibition of the Protein Kinase A (PKA) signaling pathway. An IPA Interaction Network enabled the construction of a preliminary working model, suggesting that the extract may antagonize Drosophila’s Dop1R2 (DAMB). Overall, this study integrates natural product drug discovery with neuroproteomics in an invertebrate model system, providing a foundation for future behavioral validation and isolation of bioactive compounds from S. zonale. Full article

Cannabis seed (CS), also known as hemp seed, is a nutrient-dense plant-derived food material rich in polyunsaturated fatty acids and bioactive components with reported anti-inflammatory properties. However, potential nutritional effects of CS on acute pancreatitis (AP), an inflammation-driven disease with limited dietary management strategies, have not yet been investigated. In this study, we examined the effects of dietary CS extract in a cerulein-induced AP mouse model. CS extract (5, 10, or 50 mg/kg) or vehicle (dimethyl sulfoxide) was orally administered 1 h prior to cerulein injection, and mice were euthanized 6 h after the final challenge. Oral supplementation with CS significantly attenuated AP severity, indicated by reducing pancreatic weight-to-body weight ratio, serum amylase and lipase activities, histopathological pancreatic injury, and pancreatic myeloperoxidase activity. CS administration alleviated AP-associated acute lung injury; markedly suppressing pancreatic mRNA expression of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. High-performance liquid chromatography analysis identified α-linolenic acid, an omega-3 polyunsaturated fatty acid, as a major nutritional component of CS extract. Collectively, these findings suggest that CS supplementation may contribute to nutritional modulation of inflammatory responses and systemic organ injury in experimental AP, supporting its potential as a functional food ingredient in inflammation-associated pancreatic disorders. Full article

Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder requiring safe, multitarget therapeutic strategies. Marine macroalgae represent an underexplored source of bioactives with pleiotropic metabolic effects. This study investigated the antidiabetic potential of an ultrasound-assisted ethanolic extract of Caulerpa racemosa (UAECr) and its key phytosterol, campesterol, through an integrative framework combining metabolomics, network pharmacology, molecular docking, molecular dynamics simulation, and in vitro validation. Untargeted ultra-high-performance liquid chromatography–high-resolution mass spectrometry (UHPLC–HRMS) metabolomics characterized UAECr constituents, followed by in silico bioactivity prediction, target-network analysis, molecular docking, and 100 ns molecular dynamics simulation of the peroxisome proliferator-activated receptor gamma (PPARγ)–campesterol complex. Functional validation was performed in differentiated 3T3-L1 adipocytes assessing glucose uptake, PPARγ expression, dipeptidyl peptidase 4 (DPP-4) inhibition, and cytotoxicity. Metabolomics identified campesterol as a prominent bioactive. Network pharmacology highlighted PPARγ as a central hub, supported by strong docking affinity of campesterol toward PPARγ (−11.4 kcal/mol) and DPP-4 (−8.3 kcal/mol). Molecular dynamics simulations demonstrated stable PPARγ–campesterol interactions, with preserved protein compactness and low residue fluctuation. In vitro, UAECr and campesterol significantly enhanced glucose uptake (up to 134% vs. control, p < 0.001), upregulated PPARγ expression (4-fold, p < 0.0001), and moderately inhibited DPP-4 activity (p < 0.01) without cytotoxicity. C. racemosa-derived extracts and campesterol exert antidiabetic effects primarily via stable PPARγ-mediated insulin sensitization with complementary DPP-4 modulation, supporting its potential as a marine-derived functional food candidate. Full article

Psidium cattleyanum Sabine (strawberry guava, araçá) is an ethnomedicinal plant with reputed health benefits; however, its potential for treating skin disorders remains underexplored. This study aimed to characterize the phytochemical profile of P. cattleyanum leaves from Cabo Verde and evaluate their bioactivity relevant to skin health. Phytochemical analysis was performed using high-performance liquid chromatography-mass spectrometry (LC-MS) and spectrophotometric assays. Key biological activities were assessed in vitro, including antioxidant capacity (free radical scavenging assays), anti-aging enzyme inhibition (collagenase, elastase, and tyrosinase), and antibacterial activity against skin pathogens (agar diffusion, minimum inhibitory concentration, and combination studies with standard antibiotics). Cytotoxicity was evaluated using Vero cells (MTT assay). Additionally, a topical cream containing the leaf extract was formulated and subjected to physicochemical stability and sensory testing. LC-MS revealed a rich polyphenolic composition in the leaf extract, including abundant phenolic acids (gallic and ellagic acid derivatives) and flavonoid glycosides. The extract exhibited a high total phenolic content and strong antioxidant activity in DPPH/ABTS assays. It showed potent inhibition of collagenase, elastase, and tyrosinase, indicating an anti-aging effect against wrinkle formation and hyperpigmentation. The extract also demonstrated broad antimicrobial efficacy against skin-associated bacteria, such as Staphylococcus aureus and Cutibacterium acnes, with no antagonism and partial synergism observed when combined with certain antibiotics. The P. cattleyanum extract was successfully incorporated into a cream formulation that remained physically and chemically stable (no phase separation, consistent droplet size, and pH) over 90 days, with good homogeneity and acceptable sensory characteristics (neutral odor, smooth texture, and good spreadability). P. cattleyanum leaves from Cabo Verde are a rich source of bioactive compounds with multifunctional dermatological benefits. This study demonstrates that the P. cattleyanum leaf extract exhibits significant antioxidant, antimicrobial, and anti-aging activities in vitro, supporting its potential use as a natural ingredient for skin care. Full article

Background: Fatty acid oxidation disorders (FAOD) are rare inborn errors of metabolism that impair mitochondrial β-oxidation and energy production. Management includes fasting avoidance for all FAOD types. Patients with long-chain FAOD are advised to restrict long-chain triglycerides (LCTs) to 10% of total energy intake and supplement medium-chain triglycerides (MCTs). The impact of such dietary modification on fat-soluble vitamin status has not yet been studied. Methods: In this cross-sectional study, serum concentrations of vitamins A, 25(OH)D, E, and β-carotene were measured in 36 FAOD patients and 36 healthy controls matched for age and sex. Vitamins A, E, and β-carotene were quantified using high-performance liquid chromatography and vitamin 25(OH)D through an immunoassay. FAOD patients were further divided into fat-modified (LCT-restricted) and standard-fat diet subgroups based on dietary management. Results: FAOD patients had significantly higher vitamin A concentrations than controls (p < 0.05), while there was no difference in vitamins 25(OH)D, E, and β-carotene. Within the FAOD cohort, the fat-modified group had higher levels of vitamins A and 25(OH)D but lower levels of vitamin E and β-carotene than the standard-fat group (all p < 0.05). Vitamin 25(OH)D deficiency (<20 ng/mL) was more frequent in the standard-fat group (p = 0.03). Conclusions: Fat-modified diets influence fat-soluble vitamin status in FAOD, emphasising the importance of ongoing monitoring and tailored supplementation. Future work should focus on optimising nutritional management, including modifications to formula composition, and on addressing the currently limited evidence on nutritional status and vitamin deficiencies in patients with FAOD. Full article

Cystinosis is a rare autosomal recessive lysosomal storage disorder that is caused by mutations in the CTNS gene. The hallmark of this disease is the accumulation of cystine within lysosomes, which functions as a pivotal diagnostic and monitoring biomarker. Cysteamine therapy has been demonstrated to reduce lysosomal cystine and improve outcomes; however, it does not fully halt progression, particularly renal decline. Consequently, preclinical research relies on diverse in vitro and in vivo models to explore mechanisms and test new treatments. Accurate intracellular cystine quantification is vital for clinical and research purposes. Conventional granulocyte cystine measurement, the prevailing standard, is technically intricate and necessitates volumes of samples, which presents challenges for rodent models. Advancements in analytical chemistry, such as the use of liquid chromatography with tandem mass spectrometry (LC-MS/MS), have enhanced the sensitivity of analytical methods. However, the development of optimized methods for analyzing small volumes of biological samples remains a limitation. This study presents a novel micro-quantification protocol for measuring cystine in a minimal volume of whole blood from rodent models. This protocol enhances the sensitivity, reproducibility, and feasibility of longitudinal studies. Addressing this methodological gap is imperative for accelerating translational research and supporting the development of improved therapies for cystinosis. Full article

This study investigates the molecular interactions and interfacial behaviors of a carboxylate-sulfonate gemini surfactant (CSGS) with four heavy-oil components (SARA: saturates, aromatics, resins, and asphaltenes) using molecular dynamics (MD) simulations. To provide a comprehensive analysis, two distinct systems were constructed: a homogeneous bulk oil phase (System 1) and a solid–liquid interfacial system containing a calcite (CaCO₃) substrate (System 2). In System 1, results showed that CSGS remained well dispersed in the bulk heavy-oil phase and promoted a more uniform distribution of the SARA components. The differences in mobility among the components were mainly determined by molecular structure, resulting in a consistent diffusion trend in the CSGS-containing bulk system. In contrast, the introduction of a calcite substrate (System 2) shifted the distribution from a largely disordered bulk-like state to a confined interfacial organization, with clear layering and enrichment near the mineral surface. Compared with the CaCO₃-free system, molecular migration was noticeably restricted, indicating that the carbonate layer imposed additional constraints on mass transport. At the same time, CSGS preferentially accumulated in the SARA components–CaCO₃ region, consistent with competitive adsorption at the carbonate interface, and further reorganized the local interfacial structure. Full article

Background/Objectives: This study aimed to investigate plasma duloxetine concentrations, factors influencing these concentrations, and the relationship between plasma levels and clinical response in patients diagnosed with generalized anxiety disorder who were treated with duloxetine. Additionally, the study evaluated whether dose escalation resulted in proportional increases in plasma concentration and assessed the clinical utility of therapeutic drug monitoring (TDM) for duloxetine. Methods: In this study, plasma duloxetine levels were analyzed in 68 patients with generalized anxiety disorder who had been receiving duloxetine treatment for at least three months. A review of digital medical files revealed that duloxetine was initiated at 30 mg/day in all patients, and doses were increased to 60 or 90 mg/day in those with insufficient symptom improvement. Digital medical files indicated that participants had been on the final prescribed duloxetine dose for at least four weeks at the time of plasma level measurement. Baseline Hamilton Anxiety Rating Scale (HAM-A) and Generalized Anxiety Disorder-7 (GAD-7) scores were compared with scores obtained on the day of blood sampling. Plasma duloxetine concentrations were quantified using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Associations between dose, plasma concentration, and clinical response were statistically analyzed. Results: Plasma duloxetine concentrations increased significantly following dose escalation. However, no significant correlation was observed between plasma concentrations and percentage change in HAM-A scores. Although patients receiving 60 or 90 mg/day had higher plasma levels than those maintained on 30 mg/day, clinical improvement did not differ significantly between dose groups. In addition to dose, increasing age and non-smoking status were associated with higher plasma duloxetine concentrations. Conclusions: Duloxetine demonstrates a predictable dose–concentration relationship; however, in this response-guided titration setting, plasma concentrations were not consistently associated with clinical improvement. Accordingly, these findings suggest that routine therapeutic drug monitoring may not consistently predict clinical response to duloxetine in generalized anxiety disorder; nevertheless, considering the study’s limitations, it could still offer clinically relevant insights in selected pharmacokinetically sensitive or treatment-resistant cases. Full article

Determining the concentration of fatty acid ethyl esters (FAEEs), ethyl sulfate (EtS), and ethyl glucuronide (EtG) is crucial for establishing the true scale of prenatal alcohol exposure (PAE) and enabling early diagnosis of fetal alcohol spectrum disorders. This study primarily aimed to compare two detection methods: retrospective maternal alcohol consumption surveys and chromatographic analysis of newborn meconium. Among 478 mothers, parallel survey data and meconium samples were collected. Nine FAEEs were measured by gas chromatography–mass spectrometry, and EtG and EtS by liquid chromatography–tandem mass spectrometry. The study also aimed to establish marker cut-offs and evaluate their clinical utility. While only 4% (approximately) of mothers reported alcohol consumption during pregnancy, the biomarker analysis suggested a significant underestimation of the actual PAE scale, highlighting the limitations of self-reported data. Analysis using the cumulative biomarker index for two biomarkers with a threshold of ≥5 indicated that alcohol consumption affected approximately 3% of the studied population, further demonstrating the low reliability of maternal self-reports. Ultimately, this study confirms that the combined EtG and EtS measurements provide the most reliable diagnostic information for PAE and underscores the necessity of objective meconium screening in clinical practice. Full article

Micropropagation is particularly relevant to A. xanthorrhiza because this crop is traditionally propagated by crown buds, with very low field multiplication rates and a high incidence of systemic pathogens, whereas in vitro culture enables rapid clonal multiplication, sanitation, and long-term conservation of elite and regional genotypes. Micropropagation of A. xanthorrhiza remains hindered by physiological disorders such as hyperhydricity and low shoot proliferation, often associated with limited gas exchange and inadequate culture systems. This study evaluated the effects of different gas exchange regimes and liquid culture methods on in vitro morphogenetic and structural responses. Forced ventilation at 81.3 gas exchanges per day reduced hyperhydricity to 8.3%, while sealed vessels exhibited a hyperhydricity rate of 65.8%. RITA^® bioreactors resulted in the highest shoot multiplication rate (6.5/explant), which is a 48.2% increase over semi-solid medium (4.4 shoots/explant). Additionally, RITA^® systems enhanced leaf expansion, reduced oxidative symptoms, and improved shoot morphology. These findings demonstrate that combining ventilation and immersion control is a promising strategy to improve micropropagation efficiency in A. xanthorrhiza, providing quantitative evidence that complements and extends prior qualitative studies on in vitro ventilation and liquid culture systems. Full article

Imperfect first-trimester screening for hypertensive disorders of pregnancy (HDP) means many high-risk women miss the window for preventive aspirin, and the biological heterogeneity of HDPs is overlooked. This study aimed to leverage first-trimester serum proteomics to create a more precise tool for predicting preeclampsia (PE) and differentiating it from other HDPs. A prospective nested case–control study (n = 172) was conducted using targeted liquid chromatography-multiple reaction monitoring-mass spectrometry (LC-MRM-MS) proteomic profiling of 115 proteins. Machine learning (ML) methods were used to develop classifiers from the proteomic data. The signature predictive of PE was characterized by dysregulation of the complement and coagulation cascades (F10, C8A, C1QA, SERPING1, VTN). The profile differentiating gestational hypertension (GAH) from chronic hypertension (CAH) was linked to lipid metabolism (HRG, APOA4, APOC2). An 18-protein support vector machine (SVM) model for predicting PE demonstrated exceptional performance, with 94% sensitivity and 100% specificity, significantly outperforming the standard Fetal Medicine Foundation (FMF) screening algorithm. Pathway analysis confirmed that PE is associated with early activation of innate immunity and coagulation pathways, while GAH is linked to a pregnancy-induced metabolic response. A targeted serum proteomic combined with ML approach represents a new perspective diagnostic tool with strong potential to personalize monitoring for women at the highest risk for specific hypertensive pregnancy complications. Full article

Thrombosis is a cardiovascular disease characterized by the pathological formation of a fibrin clot in blood vessels. Currently available fibrinolytic enzymes have some limitations, including severe side effects, high cost, short half-life, and low fibrin specificity. Proteins from microalgae and cyanobacteria have various biological effects and are emerging as promising sources for fibrinolytic enzymes. In this study, bioinformatics tools were used to evaluate the intrinsic disorder predisposition of microalgal fibrinolytic proteins, their capability to undergo liquid–liquid phase separation (LLPS), and the presence of disorder-based functional regions, and short linear motifs (SLiMs). Analysis revealed that these proteins are predominantly hydrophilic and exhibit acidic (pI 3.96–6.49) or basic (pI 8.05–11.0) isoelectric points. Most of them are expected to be moderately (61.4%) or highly disordered proteins (6.8%) and associated with LLPS, with nine proteins being predicted to behave as droplet drivers (i.e., being capable of spontaneous LLPS), and twenty-five proteins being expected to be droplet clients. These observations suggest that LLPS may be related to the regulation of the functionality of microalgal fibrinolytic proteins. The majority of these proteins belong to the blood coagulation inhibitor (disintegrin) 1 hit superfamily, which can inhibit fibrinogen binding to integrin receptors, preventing platelet aggregation. Furthermore, the SLiM-centered analysis indicated that the main motifs found in these proteins are MOD_GlcNHglycan and CLV_PCSK_SKI1_1, which can also play different roles in thrombolytic activity. Finally, Fisher and conservation analysis indicated that CLV_NRD_NRD_1, CLV_PCSK_FUR_1, CLV_PCSK_PC7_1, and MOD_Cter_Amidation motifs are enriched in intrinsically disordered regions (IDRs) of these proteins, showing significant conservation and suggesting compatibility with proteolytic activation and post-translational processing. These data provide important information regarding microalgal proteins with potential thrombolytic effects, which can be realized through protein–protein interactions mediated by SLiMs present in intrinsically disordered regions (IDRs). Additional analyses should be conducted to confirm these observations using experimental in vitro and in vivo approaches. Full article

Cardiovascular disease is a major cause of death worldwide and a global socio-economic problem. To date, there are numerous studies focused on finding new biomarkers of cardiovascular diseases. High-technological methods such as mass spectrometry (MS), high-performance liquid chromatography (HPLC), and nuclear magnetic resonance (NMR) spectroscopy enable us to record thousands of metabolites of organs and tissues. Studying organisms at a molecular level contributes to an in-depth understanding of preclinical conditions of various diseases. Metabolomics reflects the dynamics of metabolism distribution, including environmental influences, allowing us to create a metabolic profile of the patient. The aim of this review was to analyze current data on metabolomic and proteomic biomarkers in the diagnosis of cardiovascular diseases. The search databases were used to select studies on the potential clinical and diagnostic application of proteomic and metabolomic markers in cardiology. The selected sources were subjected to qualitative and thematic analysis. All biomarkers were grouped according to the pathophysiological process (inflammation, blood coagulation and lipid metabolism disorders, myocardial necrosis, etc.). The association of changes in metabolomic and proteomic profiles with the activation of pathogenic processes in the cardiovascular system was demonstrated. The use of these multivariate markers, individually or in combination, will increase the accuracy of early diagnosis and the effectiveness of treatment. This article also highlights the limitations of the method and possible ways to solve them. Full article