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20 pages, 549 KB  
Article
Candidate Circulating microRNAs in Patients with Sarcopenic Obesity: Results of a Pilot Screening
by Nela Chobolová, Zdeněk Švagera, David Stejskal and Marek Bužga
Biomedicines 2026, 14(6), 1377; https://doi.org/10.3390/biomedicines14061377 - 18 Jun 2026
Viewed by 455
Abstract
Background/Objectives: Sarcopenic obesity (SO) represents a severe clinical phenotype characterized by the coexistence of reduced skeletal muscle mass and excess adiposity, and is associated with insulin resistance, dyslipidemia, and systemic inflammation. However, easily accessible biomarkers that capture early molecular changes underlying SO [...] Read more.
Background/Objectives: Sarcopenic obesity (SO) represents a severe clinical phenotype characterized by the coexistence of reduced skeletal muscle mass and excess adiposity, and is associated with insulin resistance, dyslipidemia, and systemic inflammation. However, easily accessible biomarkers that capture early molecular changes underlying SO are lacking. The aim of this pilot study was to compare circulating microRNA (miRNA) profiles in patients with severe obesity and a sarcopenic obesity phenotype with those of healthy controls and to identify candidate miRNAs suitable for further validation. To the best of our knowledge, this represents one of the first broad screening studies of circulating miRNAs specifically conducted in patients with severe obesity and DXA-confirmed sarcopenic obesity. Methods: In this single-center pilot study conducted in the Czech Republic, fasting plasma samples from 12 adult participants (6 with severe obesity and sarcopenic obesity phenotype, body mass index > 45 kg/m2; 6 healthy controls; age 18–65 years) were analyzed using an RT-qPCR panel comprising 384 assays, including technical controls and 352 target circulating miRNAs. Following predefined quality control and filtering criteria, 224 miRNAs were retained for the final statistical analysis. Six patients with severe obesity were classified according to the ESPEN/EASO 2022 consensus criteria for sarcopenic obesity, while EWGSOP2-based assessment was used for functional evaluation of sarcopenia. Differential expression was evaluated using fold change and exploratory statistical testing. Results: We identified a set of miRNAs with significantly altered expression in SO, including increased muscle-enriched miR-486-5p and hepatocyte-enriched miR-122-5p, and decreased vascular miR-145-5p, as well as several additional miRNAs related to myogenesis, lipid metabolism and inflammatory signaling. miR-451a, a recognized marker of hemolysis, was also increased but was interpreted with caution. Conclusions: Despite the limited sample size, the results of this study suggest that specific circulating miRNAs may reflect key pathophysiological pathways in SO and could serve as promising biomarkers to support risk stratification and monitoring in larger, hypothesis-driven studies. Full article
(This article belongs to the Section Molecular Genetics and Genetic Diseases)
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11 pages, 967 KB  
Article
Association of Hemodynamic Parameters with Clinical Outcomes in Cardiogenic Shock: Insights from Full-Flow Micro-Axial Flow Pump Data in a Retrospective Single-Center Study
by Julia Riebandt, Roxana Moayedifar, Lukas Ruoff, Hebe Al Asadi, Sanja Söllner, Rabab Saleh, Oliver Seibert, Barbara Karner, Anne-Kristin Schaefer, Daniel Zimpfer and Thomas Schlöglhofer
J. Clin. Med. 2026, 15(8), 3071; https://doi.org/10.3390/jcm15083071 - 17 Apr 2026
Viewed by 465
Abstract
Objectives: The Impella 5.5 (J&J MedTech, USA) is increasingly used for refractory cardiogenic shock (CS), yet early predictors of mortality and recovery remain unclear. This study aimed to evaluate early patient characteristics and device-related parameters in relation to clinical outcomes; to compare outcome-based [...] Read more.
Objectives: The Impella 5.5 (J&J MedTech, USA) is increasingly used for refractory cardiogenic shock (CS), yet early predictors of mortality and recovery remain unclear. This study aimed to evaluate early patient characteristics and device-related parameters in relation to clinical outcomes; to compare outcome-based phenotypic groups (native heart recovery (NHR), heart replacement therapy (HRT), and death on the device (DEC)); and to analyze P-level impact on hemolysis and acute kidney injury. Methods: This retrospective single-center study included 28 CS patients supported with Impella 5.5 between May 2023 and August 2024. Data included intensive care unit (ICU) hemodynamics, vasoactive-inotropic score (VIS), lab markers, and pump parameters. Primary analysis evaluated early (first 24 h) parameters as potential indicators associated with mortality on the device and recovery, while secondary analyses compared hemodynamic and pump performance parameters across outcome groups, evaluated the association between P-level and hemolysis, and assessed the impact of shock etiology on clinical outcomes. Results: Among 28 patients (mean age 56 years, 10.7% female, body mass index (BMI) 27.7 kg/m2), NHR occurred in 39.3% and bridged to HRT in 42.9%. Non-survivors (17.8%) had significantly higher lactate (3.1 vs. NHR: 1.9 vs. HRT: 1.4 mmol/L, p < 0.001) and VIS (307.0 vs. NHR: 18.8 vs. HRT: 12.6, p < 0.001) at implantation. Higher VIS values (>69) were strongly associated with mortality on the device, with 100% sensitivity and 77% specificity (area under the curve (AUC) = 0.86); VIS < 9.9 was related to NHR (AUC = 0.63, 94% sensitivity, 45% specificity). P-levels were not linked to hemolysis index (r = −0.03, p = 0.64) or lactate dehydrogenase (r = −0.06, p = 0.37). Conclusions: Early vasoactive burden was associated with clinical outcomes in Impella 5.5-supported patients. No association between P-levels and the analyzed hemolysis surrogates was detected in this cohort. Distinct phenotypes across recovery outcomes may guide personalized management, but prospective validation of this exploratory and hypothesis-generating analysis is needed. Full article
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18 pages, 1495 KB  
Article
Production of Surface-Active Metabolites by Bacillus sp. from Vegetable Oil-Impacted Soil: Ecological Implications and Screening Limitations
by Eugenia Guadalupe Ortiz-Lechuga, Verónica Almaguer-Cantú, Hiram Herrera-Barquín, Karla Katiushka Solís-Arévalo, Ramón Alberto Batista-García and Katiushka Arévalo-Niño
Microbiol. Res. 2026, 17(4), 76; https://doi.org/10.3390/microbiolres17040076 - 8 Apr 2026
Viewed by 691
Abstract
Biosurfactant-producing microorganisms play an important ecological role in soils impacted by hydrophobic contaminants by enhancing substrate bioavailability and influencing microbial interactions. In this study, we critically evaluated the reliability of commonly used screening methods for biosurfactant detection. A total of 71 microbial isolates [...] Read more.
Biosurfactant-producing microorganisms play an important ecological role in soils impacted by hydrophobic contaminants by enhancing substrate bioavailability and influencing microbial interactions. In this study, we critically evaluated the reliability of commonly used screening methods for biosurfactant detection. A total of 71 microbial isolates (16 bacteria and 55 fungi) were obtained from vegetable oil-contaminated soil and screened using a multi-step approach combining enzymatic assays (lipolytic and hemolytic activity) and physicochemical methods, including drop-collapse, oil spreading, emulsification index (E24), and surface tension reduction. Although 21 isolates exhibited lipolytic activity and 9 showed hemolysis, inconsistent responses among assays revealed significant limitations of individual screening methods. Only two bacterial isolates consistently tested positive across all criteria. When cultivated in mineral salt medium supplemented with hydrophobic substrates, both isolates produced stable emulsions and significantly reduced surface tension (from 54.26 mN/m to 31.46 mN/m). Substrate-dependent variation was observed for isolate C3, which showed reduced surface tension (39.63 mN/m) when grown with biodiesel. These findings highlight the risk of relying on single assays and emphasize the need for integrated screening strategies to ensure reliable detection of biosurfactant-producing microorganisms. Full article
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15 pages, 942 KB  
Article
Hemolytic Activity of Vaginal Candida albicans Isolates and Antifungal Effects of Quinalizarin with Hemolysis Modulation
by Monika Janeczko and Elżbieta Kochanowicz
Pathogens 2026, 15(4), 401; https://doi.org/10.3390/pathogens15040401 - 8 Apr 2026
Viewed by 558
Abstract
This study evaluated the hemolytic activity of Candida albicans isolates from the female reproductive tract and investigated the in vitro effects of quinalizarin on fungal growth, hemolysis, and ECE1 expression. Ninety-four clinical C. albicans isolates and three ATCC reference strains were analyzed. Hemolytic [...] Read more.
This study evaluated the hemolytic activity of Candida albicans isolates from the female reproductive tract and investigated the in vitro effects of quinalizarin on fungal growth, hemolysis, and ECE1 expression. Ninety-four clinical C. albicans isolates and three ATCC reference strains were analyzed. Hemolytic activity was quantified in culture supernatants and normalized per 107 cells. Antifungal susceptibility and the effect of quinalizarin on hemolysis were assessed using broth microdilution and hemolysis assays. Expression of the ECE1 gene was evaluated by quantitative real-time PCR in three selected hemolytic strains. Drug interactions between quinalizarin and fluconazole were determined using the fractional inhibitory concentration index (FICI). Among the 97 tested strains, 78 exhibited hemolytic activity with variable intensity. Quinalizarin demonstrated antifungal activity, with MIC values ranging from 2 µg/mL to 256 µg/mL, and showed synergistic effects with fluconazole in selected strains. Exposure to quinalizarin at subinhibitory concentrations reduced ECE1 transcript levels to 22.8–73.6% of controls (p < 0.05) in the analyzed strains. However, the phenotypic effect on hemolysis was limited, with residual activity remaining high: 82% (p < 0.05), 93.7% (p < 0.05), and 83% (p < 0.05) relative to untreated controls in C. albicans ATCC 10231, ATCC 90028, and a clinical isolate, respectively. FICI analysis confirmed synergistic interactions between quinalizarin and fluconazole. This preliminary in vitro study highlights the need for further investigation into the relationship between ECE1 expression, candidalysin-mediated damage, and the antifungal potential of quinalizarin. Full article
(This article belongs to the Special Issue Insights into Fungal Infections)
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11 pages, 239 KB  
Article
Early Vascular Aging and Subclinical Myocardial Deformation in Children with β-Thalassemia Major: The Role of Asymmetric Dimethylarginine
by Pelin Kosger, Zeynep Canan Özdemir, Ayse Sulu, Özcan Bör and Birsen Uçar
Children 2026, 13(4), 461; https://doi.org/10.3390/children13040461 - 27 Mar 2026
Viewed by 528
Abstract
Background: Children with β-thalassemia major (β-TM) survive longer due to advances in transfusion and chelation therapy; however, cardiovascular complications have emerged as a leading cause of long-term morbidity. Chronic hemolysis, oxidative stress, and iron overload may promote early endothelial dysfunction and premature vascular [...] Read more.
Background: Children with β-thalassemia major (β-TM) survive longer due to advances in transfusion and chelation therapy; however, cardiovascular complications have emerged as a leading cause of long-term morbidity. Chronic hemolysis, oxidative stress, and iron overload may promote early endothelial dysfunction and premature vascular aging, yet their impact on myocardial deformation in pediatric patients remains incompletely characterized. Objectives: To evaluate subclinical myocardial dysfunction and arterial stiffness in children with β-TM and to investigate hemolysis-related changes in asymmetric dimethylarginine (ADMA) and L-arginine as biomarkers of endothelial dysfunction in relation to cardiovascular involvement. Methods: Twenty-four children with β-TM and 20 age-matched healthy controls were included. Cardiac structure and myocardial deformation were assessed by conventional echocardiography, tissue Doppler imaging, and speckle-tracking strain analysis. Arterial stiffness was evaluated using oscillometric pulse wave analysis and bilateral carotid intima–media thickness (CIMT). Serum ADMA and L-arginine levels were measured, and hemoglobin, reticulocyte count, and ferritin levels were recorded. Results: Children with β-thalassemia major demonstrated significantly increased arterial stiffness compared with controls, including higher PWV (4.61 ± 0.37 vs. 4.38 ± 0.31), AIx@75 (augmentation index at 75 bpm) (28.5 ± 8.34 vs. 22.8 ± 6.51), left CIMT [0.45 (0.39–0.51) vs. 0.41 (0.38–0.46)], and right CIMT [0.43 (0.39–0.54) vs. 0.40 (0.34–0.46)]. In addition, patients exhibited reduced global longitudinal strain (−19.3 ± 2.91 vs. −21.84 ± 1.91), prolonged isovolumetric relaxation time [53 (37–71) vs. 45 (37–55)], and elevated E/Em (8.44 ± 2.19 vs. 6.92 ± 1.10). ADMA levels were significantly higher in patients (0.54 ± 0.19 vs. 0.39 ± 0.22) and were positively associated with reticulocyte counts and inversely correlated with hemoglobin levels. In addition, both ADMA and ferritin levels were positively correlated with arterial stiffness indices and left ventricular filling pressures. Conclusions: Children with β-thalassemia major exhibit features suggestive of early cardiovascular aging, including impaired myocardial deformation, diastolic involvement, and increased arterial stiffness. The observed association between ADMA levels and markers of hemolysis, vascular stiffness, and myocardial deformation highlights the potential involvement of endothelial dysfunction in premature myocardial–vascular remodeling. These findings suggest that ADMA may serve as a promising biomarker for early cardiovascular risk in pediatric β-thalassemia major; however, further longitudinal and multi-center studies are needed to confirm its clinical utility for risk stratification. Full article
(This article belongs to the Section Pediatric Cardiology)
27 pages, 6817 KB  
Article
Benzyl-Naphthoquinones as Selective Anticancer Agents for Oral Squamous Cell Carcinoma via Apoptosis Induction
by Antonio Mendonça Marconi-Nicolau, Rebeca Gripp de Sá, Caroline Reis Santiago Paschoal, Lethícia Andrade de Almeida, Gabriel Ouverney, Ana Caroline dos Santos-Diniz, Anamel Blaudt Meira, João Pedro da Costa Faria Brunhosa, Luiz Carlos da Silva Pinheiro, Paula Alvarez Abreu, Vinicius Rangel Campos and Bruno Kaufmann Robbs
Biomedicines 2026, 14(4), 757; https://doi.org/10.3390/biomedicines14040757 - 26 Mar 2026
Viewed by 741
Abstract
Background: Oral squamous cell carcinoma (OSCC) is an aggressive cancer closely associated with smoking and alcohol consumption, with a higher incidence in men. Despite changes in treatment strategies, poor survival persists in most patients, highlighting the need for novel and improved therapeutic [...] Read more.
Background: Oral squamous cell carcinoma (OSCC) is an aggressive cancer closely associated with smoking and alcohol consumption, with a higher incidence in men. Despite changes in treatment strategies, poor survival persists in most patients, highlighting the need for novel and improved therapeutic options. Naphthoquinone analogs are being investigated because of their active redox structure and broad pharmacological profile; they demonstrate cytotoxic antitumor activity, making them potential candidates for new drug agents. Objective: This study investigated new benzyl-naphthoquinone compounds as potential anticancer agents for various genotypes of oral squamous cell carcinoma (OSCC) and other cancer cells. Methods: This study reports the synthesis and evaluation of a series of eight benzyl-naphthoquinone compounds against oral squamous cell carcinoma. Results: Four compounds 14 showed the best cytotoxic profiles, with a selectivity index ≥ 3 for all OSCC cell lines tested. Compound 1 was the most selective compound in all OSCC models, showing a higher selectivity index than both carboplatin and shikonin. Furthermore, compound 1 induced DNA fragmentation, cell-cycle arrest, and caspase-3/7 activation, changes consistent with apoptosis, and time-lapse imaging corroborated the apoptotic phenotype. Hemolysis assays showed minimal toxicity in human erythrocytes, and acute in vivo evaluation in mice revealed no evident adverse effects under the conditions tested, indicating low acute toxicity, although more detailed histopathological and biochemical studies will be required to fully establish the safety profile. Molecular modeling suggested that compound 1 may interact with topoisomerase II, RSK2, and PKM2, which could contribute to the activation of apoptotic pathways, although these interactions remain predictive and require biochemical validation. Finally, in silico analysis of physicochemical and ADMET parameters indicated properties compatible with oral absorption and systemic exposure, together with predicted low toxicity; however, these results are model-based and should be confirmed experimentally. Conclusions: Based on these findings, compound 1 emerges as a promising lead candidate for the development of a novel chemotherapeutic agent against OSCC, with potential therapeutic efficacy against other cancer types. Full article
(This article belongs to the Special Issue Drug Resistance and Novel Targets for Cancer Therapy—Third Edition)
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19 pages, 2736 KB  
Article
Rationally Engineered D-Amino Acid Peptide DT7-3 Combats Multidrug-Resistant Helicobacter pylori via a Novel “Triple-Hit” Mechanism
by Shiying Yan, Xin Yan, Jiarui Zhao, Yue Zhou, Changyi Huang, Yiping Chen, Jia Wang, Jian Zhang, Chaoyi Han, Yu Gao, Tianlan Jiang, Hansheng Zhu, Hao Shi, Fosheng Li, Jian Zhao and Mei Cao
Microorganisms 2026, 14(4), 744; https://doi.org/10.3390/microorganisms14040744 - 26 Mar 2026
Viewed by 822
Abstract
Helicobacter pylori (H. pylori) is the primary etiological agent for chronic gastritis, peptic ulcers, and gastric adenocarcinoma. The alarming rise in multidrug-resistant (MDR) strains, particularly against clarithromycin (CLR), metronidazole (MNZ), and levofloxacin (LVX), has severely compromised standard therapies. Thus, there is [...] Read more.
Helicobacter pylori (H. pylori) is the primary etiological agent for chronic gastritis, peptic ulcers, and gastric adenocarcinoma. The alarming rise in multidrug-resistant (MDR) strains, particularly against clarithromycin (CLR), metronidazole (MNZ), and levofloxacin (LVX), has severely compromised standard therapies. Thus, there is an urgent clinical need for novel antimicrobial agents that operate through distinct mechanisms to bypass resistance pathways and mitigate gastric cancer risk. We designed and synthesized a series of antimicrobial peptides, focusing on the proteolytically stable all-D-amino acid enantiomer, DT7-3, derived from a probiotic-sourced template. Minimum inhibitory concentrations (MICs) were determined against standard strains and 11 clinical MDR isolates via the broth microdilution method. Antimicrobial mechanisms were elucidated using scanning electron microscopy (SEM) for morphology, fluorescence-based assays for anti-adhesion activity, and real-time qPCR to quantify virulence gene expression (babA, ureA, and vacA). Biocompatibility was assessed using defibrinated sheep erythrocytes, gastric epithelial cells (GES-1), and representative beneficial gut microbiota. Analysis of the clinical isolates revealed resistance rates of 63.6% for CLR/LVX and 81.8% for MNZ, with 54.5% identified as MDR. DT7-3 exhibited superior potency (MIC 1–32 µg/mL) against all strains, significantly outperforming its L-enantiomer counterparts. Mechanistic studies unveiled a “triple-hit” mechanism: (1) rapid membrane disruption; (2) potent inhibition of bacterial adhesion to host cells (~60% reduction at 0.5 × MIC); (3) significant downregulation of critical virulence factors (babA, ureA, and vacA). Furthermore, DT7-3 showed an excellent safety profile, with negligible hemolysis (<5% at 32 µg/mL) and minimal cytotoxicity toward GES-1 cells, yielding a high selectivity index (SI, MHC/MIC) > 32 relative to mammalian cells. Crucially, DT7-3 showed high selectivity for the pathogen over beneficial gut microbiota (MIC > 128 µg/mL, SI > 16). Crucially, DT7-3 maintained potent bactericidal activity (MIC ≤ 16 µg/mL) even under cholesterol-enriched conditions. The engineered D-peptide DT7-3 is a potent candidate for combating MDR H. pylori. Its multifaceted mechanism, targeting bacterial viability while suppressing core virulence factors, positions it as a robust lead compound for next-generation eradication therapies aimed at reducing the burden of H. pylori-associated diseases. Full article
(This article belongs to the Section Antimicrobial Agents and Resistance)
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12 pages, 1649 KB  
Article
Antitumor-Directed Fractionation of Lophocereus marginatus Extracts Against Murine L5178Y-R Lymphoma Cells
by Ángel David Torres-Hernández, César Iván Romo-Sáenz, Ramiro Quintanilla-Licea, Diana Elia Caballero-Hernández, Jesica María Ramírez-Villalobos, Diana Laura Clark-Pérez, Celia María Quiñonez-Flores, Joel Horacio Elizondo-Luevano, Patricia Tamez-Guerra and Ricardo Gomez-Flores
Pharmaceuticals 2026, 19(3), 369; https://doi.org/10.3390/ph19030369 - 26 Feb 2026
Viewed by 678
Abstract
Background/Objectives: Cancer has been associated with significant morbidity and mortality worldwide, particularly related to chemotherapy resistance. Therefore, it is essential to investigate alternative sources of non-toxic antitumor compounds. The cactus Lophocereus marginatus is native to Mexico and is commonly used to treat [...] Read more.
Background/Objectives: Cancer has been associated with significant morbidity and mortality worldwide, particularly related to chemotherapy resistance. Therefore, it is essential to investigate alternative sources of non-toxic antitumor compounds. The cactus Lophocereus marginatus is native to Mexico and is commonly used to treat gastrointestinal infections and diabetes in traditional medicine. Methods: The in vitro antitumor activity of L. marginatus extract fractions against murine L5178Y-R lymphoma cells was evaluated. The crude extract and its solvent-derived fractions were evaluated for cytotoxicity, selectivity, and hemolytic activity. Results: The crude extract exhibited an IC50 of 9.09 μg/mL, demonstrating a high selectivity index (SI: 330.03), with no hemolytic activity observed at 1000 μg/mL. The LM-HP, LM-CP, and LM-MP partitions showed varying IC50 values (6.74, 7.93, and 45.38 μg/mL, respectively) and selectivity indices of 445.1, 378.31, and 66.1, respectively. Only LM-HP induced hemolysis at 200 μg/mL. The most promising fraction, CP-F8, exhibited an IC50 of 11.2 μg/mL, high selectivity index (354.29), and antioxidant activity, without hemolytic effects. Phytochemical analysis of CP-F8 identified phenolic compounds, triterpenes, and sterols, which are known for their anti-cancer and anti-inflammatory properties. In vivo tests showed no significant liver damage or changes in body weight, indicating the safety of CP-F8. Conclusions: These results suggest that CP-F8 is a promising antitumor candidate with selective cytotoxicity and minimal toxicity to normal cells. Full article
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27 pages, 9046 KB  
Article
Formulation, Characterization, and In Vitro Biological Evaluation of a Triple-Phytochemical Nano Delivery System for Colon Cancer Therapy—A Preliminary Feasibility Study
by Dhanalekshmi Unnikrishnan Meenakshi, Gurpreet Kaur Narde, Shah Alam Khan and Alka Ahuja
Pharmaceutics 2026, 18(2), 277; https://doi.org/10.3390/pharmaceutics18020277 - 23 Feb 2026
Viewed by 1258
Abstract
Background/Objectives: Poor oral bioavailability and limited intestinal permeation restrict the clinical translation of phytochemicals for colorectal cancer (CRC) therapy. The present preliminary study explored the development of a nanoparticle-based combinatorial formulation of resveratrol (Resv), acetyl-11-keto-β-boswellic acid (AKBA), and quercetin (Quer), to improve [...] Read more.
Background/Objectives: Poor oral bioavailability and limited intestinal permeation restrict the clinical translation of phytochemicals for colorectal cancer (CRC) therapy. The present preliminary study explored the development of a nanoparticle-based combinatorial formulation of resveratrol (Resv), acetyl-11-keto-β-boswellic acid (AKBA), and quercetin (Quer), to improve intestinal permeation and anti-cancer efficacy. Methods: A triple phytochemical nano formulation (designated as 3X) was developed and evaluated for morphology, particle size, zeta potential, encapsulation efficiency, and in vitro pharmaceutical characteristics. Safety was evaluated using in vitro cytotoxicity assays, while anticancer efficacy and apoptotic potential were preliminarily evaluated in Caco-2 CRC cell lines. Gene expression analysis was performed to examine the modulation of inflammation and cancer-related markers. Results: The 3X formulation exhibited a particle size of 198.5 nm with a polydispersity index of 0.492 and a zeta potential of −32.7, indicating good nanoscale stability. The encapsulation efficiencies were 90% for AKBA, 80% for Resv, and 75% for Quer. In vitro permeation studies demonstrated a controlled release mechanism. The formulation showed minimal hemolysis (3%) and had acceptable in vitro safety. The IC50 of the formulation was found to be 365 µg in the cytotoxicity assay. Treatment with the 3X nanoformulation significantly modulated anti-inflammatory and cancer-related gene expression in Caco2 cells, evidenced by downregulation of TGFβ (Transforming Growth Factor-beta) and COX-2 (cyclooxygenase-2), and upregulation of TNFα (Tumor necrosis factor-alpha) and nitric oxide (NO) and reduced IL-1β (Interleukins-1 beta) expression compared with control cells. Conclusions: The findings demonstrate that the developed 3X nano formulation exhibits favorable permeation characteristics and exerts anticancer activity against CRC. Based on preliminary findings, the formulation represents a promising phytochemical-based combination strategy for CRC, warranting further in vivo studies to validate its efficacy and elucidate the underlying molecular mechanisms. Full article
(This article belongs to the Special Issue Advanced Drug Delivery Systems for Natural Products)
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15 pages, 794 KB  
Article
Lipoprotein Combine Index Is Associated with Multi-Compartment Oxidative Stress in Clinically Stable Peritoneal Dialysis Patients: A Cross-Sectional Study
by Natalia Stepanova and Lesya Korol
Biomedicines 2026, 14(2), 456; https://doi.org/10.3390/biomedicines14020456 - 18 Feb 2026
Viewed by 718
Abstract
Background/Objectives: Background: Dyslipidaemia and oxidative stress (OS) are frequent in peritoneal dialysis (PD). The Lipoprotein Combine Index (LCI) integrates lipid parameters, but its relationship with peritoneal transport and OS is unclear. Methods: This cross-sectional study included 100 clinically stable adults on continuous [...] Read more.
Background/Objectives: Background: Dyslipidaemia and oxidative stress (OS) are frequent in peritoneal dialysis (PD). The Lipoprotein Combine Index (LCI) integrates lipid parameters, but its relationship with peritoneal transport and OS is unclear. Methods: This cross-sectional study included 100 clinically stable adults on continuous ambulatory PD with preserved ultrafiltration and adequate dialysis. LCI was calculated as (total cholesterol × triglycerides × LDL-C)/HDL-C and analyzed by tertiles. Lipid peroxidation and antioxidant markers were measured in serum, erythrocytes, urine, and spent dialysate. Multivariable regression models examined associations between LCI, peritoneal solute transport, and dialysate OS markers. Results: Higher LCI was independently associated with lower peritoneal solute transport. LCI correlated inversely with the 4 h dialysate-to-plasma creatinine ratio (ρ = −0.32, p = 0.001) and remained significant after adjustment (adjusted R2 = 0.224, p < 0.001). Increasing LCI was associated with higher malondialdehyde levels in serum, urine, and dialysate (all p ≤ 0.008) and impaired antioxidant defenses, including lower total peroxidase activity in erythrocytes and dialysate (both p = 0.001), reduced serum sulfhydryl groups (p = 0.011), decreased oxidative resistance of erythrocytes, and increased peroxide-induced hemolysis (both p = 0.001). In adjusted models, logLCI was independently associated with higher dialysate malondialdehyde (p < 0.001) and lower dialysate peroxidase activity (p = 0.005). Conclusions: In clinically stable PD patients, higher lipid burden assessed by LCI is independently associated with lower peritoneal solute transport and a marked increase in systemic and local OS. Our findings suggest that dyslipidaemia may contribute to early metabolic and oxidative changes even before overt peritoneal membrane dysfunction develops. Full article
(This article belongs to the Topic Oxidative Stress and Inflammation, 3rd Edition)
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17 pages, 2629 KB  
Article
Simulated Oxygen Supply Efficiency Assessment to Represent Stored Red Blood Cells Quality
by Zongtang Chu, Guoxing You, Weidan Li, Peilin Shu, Dong Qin, Lian Zhao, Hong Zhou and Ying Wang
Life 2026, 16(2), 205; https://doi.org/10.3390/life16020205 - 26 Jan 2026
Viewed by 603
Abstract
Hemolysis rate is usually used as the acceptance criterion for stored red blood cells (RBCs) in clinical practice. However, there is a current lack of parameters for the characterization of hemoglobin quality. This study aimed to incorporate oxygen affinity, cooperativity, and the Bohr [...] Read more.
Hemolysis rate is usually used as the acceptance criterion for stored red blood cells (RBCs) in clinical practice. However, there is a current lack of parameters for the characterization of hemoglobin quality. This study aimed to incorporate oxygen affinity, cooperativity, and the Bohr effect into a parameter system to monitor oxygen supply efficiency in stored RBCs, potentially serving as a basis for quality assessment. Han Chinese blood from plains, Tibetan blood from plateau, bovine hemoglobin (bHb), and a dextran–bovine hemoglobin conjugate (Dex20-bHb) were analyzed using the BLOODOX-2018. Oxygen affinity (P50) was determined by oxygen dissociation curves (ODCs) at pH = 7.4. Cooperativity was assessed through the Hill coefficient, calculated from the fitting range of the Hill equation. The Bohr effect was evaluated by the acid-base sensitivity index (SI) under simulated pH conditions of the lungs (pH = 7.6) and tissues (pH = 7.2) to calculate corresponding P50 values. Oxygen partial pressures (PO2) simulating lungs (PO2 = 100 mmHg for plains and 60 mmHg for plateau) and tissues (PO2 = 40 mmHg for plains and 30 mmHg for plateau) were used to calculate theoretical oxygen-release capacities in both environments. Multiple regression analysis explored relationships among parameters, constructing a system to assess changes in rat RBCs during storage. Optimized test methods determined P50, Hill coefficient, SI, and theoretical oxygen-release capacities for Han Chinese blood, Tibetan blood, bHb, and Dex20-bHb samples in various environments. We constructed a parameter system to characterize blood’s oxygen supply efficiency, revealing the significant influence of the Bohr effect. This influence varied with environmental changes in oxygen affinity. We validated the system using stored rat RBCs, finding consistent P50 trends with predictions, and initial increases in Hill coefficient and SI followed by decreases. Theoretical oxygen-release capacities varied significantly between plateau and plain environments. These results support using oxygen supply efficiency to assess RBC storage quality for developing transfusion strategies. P50, Hill coefficient, SI, and theoretical oxygen-release capacity in different environments can be incorporated into blood oxygen supply efficiency characterization systems to assess the quality changes in RBCs during storage. Full article
(This article belongs to the Section Physiology and Pathology)
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10 pages, 1857 KB  
Article
Algorithm for Reporting Free Hemoglobin in ECMO Patients: Need for a Multidisciplinary Approach
by Ivana Baršić Lapić, Ljiljana Zaninović, Daniel Lovrić, Ana Lončar Vrančić, Dora Rebrek and Dunja Rogić
J. Clin. Med. 2026, 15(2), 867; https://doi.org/10.3390/jcm15020867 - 21 Jan 2026
Viewed by 765
Abstract
Background: Intravascular hemolysis is a common complication in patients undergoing extracorporeal membrane oxygenation (ECMO), with plasma free hemoglobin (pfHb) serving as a biomarker for detection. Without standardized protocols, laboratories face challenges in interpreting and reporting results. Hemolysis indices may enhance reporting accuracy. Methods: [...] Read more.
Background: Intravascular hemolysis is a common complication in patients undergoing extracorporeal membrane oxygenation (ECMO), with plasma free hemoglobin (pfHb) serving as a biomarker for detection. Without standardized protocols, laboratories face challenges in interpreting and reporting results. Hemolysis indices may enhance reporting accuracy. Methods: This retrospective observational study at University Hospital Center Zagreb included 61 lithium heparin plasma samples from ECMO patients. pfHb was measured using the Harboe method (fHb) and estimated from hemolysis indices on Abbott Alinity c analyzer (efHb). Total and conjugated bilirubin, hemolysis, icterus, and lipemia indices (HIL) were recorded. Method comparison used Passing-Bablok regression and Bland–Altman analysis. An algorithm for pfHb reporting accounting for HIL interferences was developed. Results: Significant differences were observed between methods, with Harboe yielding higher median fHb (261 mg/L) versus efHb (58 mg/L). Regression analysis showed constant negative bias of −91 mg/L (95% CI: −143 to −16) for efHb relative to fHb. Bland–Altman analysis demonstrated wide limits of agreement. Correlation between fHb and efHb was moderate (Spearman’s rho = 0.618, p < 0.001). The delta between methods increased with higher bilirubin concentrations. An algorithm integrating HIL indices with the Harboe method was developed to guide result validation and reporting. Conclusions: Accurate hemolysis assessment in ECMO patients requires careful interpretation, appropriate method selection, and laboratory–clinician collaboration. The proposed algorithm improves the clinical utility of pfHb testing by accounting for analytical interferences and supporting informed decision-making. Full article
(This article belongs to the Special Issue Clinical Guidelines in Critical Care Medicine)
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16 pages, 2811 KB  
Article
Construction of Flexible Kaolin/Chitin Composite Aerogels and Their Properties
by Meng He, Yujia Huang, Zhicheng Cui, Ziyue Cheng, Weiwei Cao, Gan Wang, Wei Yao and Mengna Feng
Gels 2026, 12(1), 76; https://doi.org/10.3390/gels12010076 - 15 Jan 2026
Cited by 8 | Viewed by 671
Abstract
In this work, kaolin/chitin (K/Ch) composite aerogels with different mass ratios were successfully fabricated via a freeze–drying approach. The influence of kaolin content on the microstructure, properties and hemostatic performance of the composite aerogels was systematically investigated. The results demonstrated that the incorporation [...] Read more.
In this work, kaolin/chitin (K/Ch) composite aerogels with different mass ratios were successfully fabricated via a freeze–drying approach. The influence of kaolin content on the microstructure, properties and hemostatic performance of the composite aerogels was systematically investigated. The results demonstrated that the incorporation of kaolin endowed the chitin-based aerogels with tunable porous structures, excellent water absorption capacity (up to 4282% for K0.25/Ch2), and enhanced water retention (73.7% for K2/Ch2 at 60 min). Moreover, the K/Ch composite aerogels exhibited good biodegradability, no cytotoxicity (cell viability > 91.9%), and no hemolysis (hemolysis rate < 1.5% at all test concentrations). In vitro hemostatic evaluations revealed that the composite aerogels exhibited rapid blood coagulation (blood clotting time of 16 s for K2/Ch2) with a blood coagulation index (BCI) as low as 0.5%, which was attributed to the synergistic effect of the physical adsorption of chitin and the coagulation cascade activation by kaolin. These findings indicated that the K/Ch composite aerogels could be used as novel natural hemostatic materials for potential effective and rapid hemostasis. Full article
(This article belongs to the Special Issue Recent Advances in Aerogels (2nd Edition))
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21 pages, 1579 KB  
Article
Popcorn-like Particles from an Amino Acid, Poly(L-Cysteine) as Drug Delivery System with Blood-Compatible, Bio-Compatible, Antibacterial, and Antioxidant Properties
by Nurettin Sahiner, Sahin Demirci, Betul Ari, Selin S. Suner, Mehtap Sahiner and Olgun Guven
Micro 2026, 6(1), 6; https://doi.org/10.3390/micro6010006 - 13 Jan 2026
Viewed by 983
Abstract
A facile and single-step synthesis of poly(L-Cysteine) (p(L-Cys)) particles through microemulsion polymerization using tetrakis(hydroxymethyl) phosphonium chloride (THPC) as crosslinker is accomplished for the first time. The L-Cys:THPC ratio in p(L-Cys) particles was calculated as 80:20% (by weight) with elemental analyses, and the generation [...] Read more.
A facile and single-step synthesis of poly(L-Cysteine) (p(L-Cys)) particles through microemulsion polymerization using tetrakis(hydroxymethyl) phosphonium chloride (THPC) as crosslinker is accomplished for the first time. The L-Cys:THPC ratio in p(L-Cys) particles was calculated as 80:20% (by weight) with elemental analyses, and the generation of p(L-Cys) particles was confirmed. SEM imaging revealed a popcorn-like morphology of the p(L-Cys) particles with a 1–20 µm particle size range. The isoelectric point of p(L-Cys) particles was determined at pH 1.15 via zeta potential measurements. The hydrolytic degradation of p(L-Cys) particles was determined as about 85% within 3 h (by weight). The p(L-Cys) particles displayed excellent blood compatibility with a hemolysis % ratio of <2.3% and a blood clotting index of 95% at 1 mg/mL concentration. Moreover, cell compatibility tests up to 50 mg/mL against L929 fibroblast cells exhibited about 90% cell viability for p(L-Cys) particles versus 58% for L-Cys molecule. The antimicrobial efficacy of the L-Cys molecules was notably enhanced in p(L-Cys) particles, exhibiting a 5-fold reduction in minimal bactericidal concentration (MBC) values against E. coli (Gram-negative, ATCC 8739) and a 2-fold reduction against S. aureus (Gram-positive, ATCC 6538). Additionally, the antioxidant capacity of p(L-Cys) particles was retained somewhat, measured as 0.14 ± 0.01 µM versus 2.25 ± 0.03 µM Trolox equivalent/g for L-Cys. Therefore, p(L-Cys) particles are versatile and offer a unique avenue for immense biomedical use. Full article
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16 pages, 805 KB  
Review
Highly Porous Cellulose-Based Scaffolds for Hemostatic Devices and Smart Platform Applications: A Systematic Review
by Nikita A. Shutskiy, Aleksandr R. Shevchenko, Ksenia A. Mayorova, Leonid L. Shagrov and Andrey S. Aksenov
Fibers 2026, 14(1), 9; https://doi.org/10.3390/fib14010009 - 5 Jan 2026
Cited by 1 | Viewed by 1849
Abstract
A promising application of smart materials based on natural polymers is the potential to solve problems related to hemostasis in cases of severe bleeding caused by injury or surgery. This can be a life-threatening situation. Cellulose and its modified derivatives represent one of [...] Read more.
A promising application of smart materials based on natural polymers is the potential to solve problems related to hemostasis in cases of severe bleeding caused by injury or surgery. This can be a life-threatening situation. Cellulose and its modified derivatives represent one of the most promising sources for creating effective hemostatic systems, as well as for various sensing applications related to disease detection, infection diagnosis, chronic condition monitoring, and blood analysis. The aim of this review was to identify key criteria for the efficiency of cellulose-based gels with hemostatic activity. Experimental studies aimed at evaluating new hemostatic devices were analyzed based on international sources using the PRISMA methodology. A total of 111 publications were identified. Following the identification and screening stages, 20 articles were selected for the final qualitative synthesis. The analyzed publications include experimental studies focused on the development and analysis of highly porous cellulose-based scaffolds in the form of aerogels and cryogels. The type and origin of cellulose, as well as the influence of additional components and synthesis conditions on gel formation, were investigated. Three major groups of key criteria that should be considered when developing new cellulose-based highly porous scaffolds with hemostatic functionality were identified: (I) physicochemical and mechanical properties (pore size distribution, compressive strength, and presence of functional groups); (II) in vitro tests (blood clotting index, red blood cell adhesion rate, hemolysis, cytocompatibility, and antibacterial activity); (III) in vivo hemostatic efficiency (hemostasis time and blood loss) in compliance with the 3Rs policy (replacement, reduction, refinement). The prospects for the development of highly porous cellulose-based scaffolds are not only focused on their hemostatic properties, but also on the development of smart platforms. Full article
(This article belongs to the Special Issue Nanocellulose Hydrogels and Aerogels as Smart Sensing Platforms)
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