Search Results (1,550)

Background/Objectives: Late-onset neonatal sepsis (LOS) remains a leading cause of morbidity and mortality in very low birth weight (VLBW) infants (<1500 g and/or gestational age <32 weeks), with limited preventive strategies. We evaluated whether early enteral bovine lactoferrin (bLf), given its antimicrobial, immunomodulatory, and antioxidant properties, reduces LOS and improves immunologic, antioxidant, and hematologic markers in these infants. Methods: In this randomized, double-blind, placebo-controlled trial, 103 VLBW infants received bLf (150 mg/kg/day; n = 50) or the placebo (n = 53) within 72 h of birth for four weeks or until discharge. Outcomes included culture-confirmed LOS, mortality, and major morbidities. Risk ratios (RRs) were calculated, adjusting for gestational age, human milk intake, and ventilatory support when ≥25 events occurred. Pre/post changes in cytokines, total antioxidant capacity (TAC), and hemoglobin (Hb) were analyzed for interaction effects (time x intervention). Results: bLf reduced LOS (adjusted RR 0.54; 95% CI 0.31–0.93; p = 0.028), without differences in other morbidities or mortality. bLf preserved MCP-1 levels, declining in the placebo group (interaction p = 0.022). Among LOS infants receiving bLf, IL-6 remained stable and MCP-1 increased, while both declined in other groups (interaction p = 0.007 for IL-6; p = 0.052 for MCP-1). Although TAC showed a non-significant interaction, the placebo group declined (p = 0.002), while bLf remained stable (p = 0.400) in the post hoc analysis. In non-transfused infants, bLf increased Hb by 0.9 g/dL vs. controls (p = 0.028). Conclusions: Early bLf supplementation safely reduces LOS in VLBW infants and may support immunologic, antioxidant, and hematologic stability. Full article

Candida auris has emerged as a global public health threat due to its high mortality rates, multidrug resistance, and rapid transmission in healthcare settings. This study reports the first documented cases of C. auris candidemia in Portugal, comprising eight isolates from candidemia and colonised patients admitted to a major hospital in northern Portugal in 2023. Whole-genome sequencing (WGS) was performed to determine the phylogenetic relationships of the isolates, which were classified as belonging to Clade I. Genome sequencing also enabled the detection of missense mutations in antifungal resistance genes, which were correlated with antifungal susceptibility profiles determined according to EUCAST (European Committee on Antimicrobial Susceptibility Test) protocols and guidelines. All isolates exhibited resistance to fluconazole and amphotericin B according to the recently established EUCAST epidemiological cut-offs (ECOFFs). Most of the isolates showed a resistant phenotype to anidulafungin and micafungin. All isolates were resistant to caspofungin. Missense mutations identified included Y132F in ERG11, E709D in CDR1, A583S in TAC1b, K52N and E1464K in SNQ2, K74E in CIS2, M192I in ERG4, a novel mutation S237T in CRZ1, and variants in GCN5, a gene involved in chromatin remodelling and stress-response regulation. Identifying known and novel mutations highlights the evolution of antifungal resistance mechanisms in C. auris. These findings underscore the need for further research to understand C. auris resistance pathways and to guide effective clinical management strategies. Full article

Background/Objectives: Tacrolimus is the most used immunosuppressive agent in solid organ transplantation due to its efficacy in preventing acute rejection, but it has a narrow therapeutic range, and overexposure often leads to toxicities, including neurological side effects like tremors. Tremor affects up to 54% of renal transplant patients under tacrolimus. Extended-release tacrolimus (LCPT) has demonstrated efficacy in reducing tremor severity, as evidenced by studies employing quality of life (QoL) questionnaires, the Fahn–Tolosa–Marin (FTM) scale, and Accelerometer devices. The objectives of this study were to evaluate the benefits of the conversion to LCPT formulation in kidney transplant recipients experiencing tremors on prolonged-release tacrolimus (PR-TAC) treatment and to validate the DyCare device, a wearable wireless sensor for tremors. Results: The DyCare device measured tremor frequencies of 8.74 ± 0.11 Hz and 1.36 ± 0.08° and 17.38 ± 1.16°, as root mean square (RMSx100 for accelerometer and Gyroscope, respectively) in PR-TAC patients. After switching ten patients to LCPT, tremor severity significantly decreased, as confirmed by DyCare and the QoL in the Essential Tremor Questionnaire (QUEST). Additionally, LCPT allowed a 34% reduction in tacrolimus dosage while maintaining therapeutic trough concentrations. Immunological and pharmacodynamic biomarkers (p-miR-210-3p, p-IL10, p-IL12p70, p-IFNγ uCXCL10, NFAT-regulated gene expression) confirmed stable immunosuppression post-conversion. Conclusions: The conversion to the LCPT formulation significantly reduced tremors in kidney transplant recipients without altering their immunological status, as confirmed through a panel of immunologic and pharmacodynamic biomarkers. The DyCare device enables a precise quantification of tremors in transplant recipients, allowing physicians to optimize treatment strategies. Full article

Background: Cisplatin (CP), a platinum-based chemotherapeutic agent, is widely used to treat cancer but causes nephrotoxicity. Riociguat, a soluble guanylate cyclase (sGC) stimulator that enhances the nitric oxide–sGC–cGMP signaling pathway, was investigated for its potential protective effects against cisplatin-induced nephrotoxicity. Materials and Methods: Rats were randomly divided into four equal groups (six rats each) and treated for nine consecutive days. The first and second groups were given oral carboxymethylcellulose 0.5% (vehicle) for 9 days, and on day 6 were injected intraperitoneally with saline or CP, respectively. The third and fourth groups were treated orally with two doses of riociguat (3 and 10 mg/kg/day) for 9 days, and received intraperitoneal injections of CP on day 6. Blood, urine, and kidney tissues were analyzed 24 h after the last treatment. Results: CP significantly elevated the markers of kidney function, including uric acid, serum creatinine, and urea. CP also caused histological kidney damage. Antioxidant markers, including catalase (CAT), glutathione reductase (GR), superoxide dismutase (SOD), and total antioxidant capacity (TAC) were significantly reduced, while inflammatory cytokines (IL-1β, IL-6, and TNF-α) and lipid peroxidation (MDA) were markedly increased. Riociguat improved kidney structure and significantly reduced kidney function markers, MDA, and inflammatory cytokines while restoring GR, TAC, SOD, and CAT activities. Conclusions: These results indicate that riociguat exerts protection of the kidneys from CP-caused kidney damage by antioxidation and anti-inflammation. Riociguat may have potential as an adjunct therapy to mitigate CP-associated nephrotoxicity. Full article

This multidisciplinary comparative study investigates consumption patterns, health-related properties, and quality attributes of trademarked and local extra virgin olive oil (EVOO) samples. It highlights the importance of localization in promoting agricultural sustainability, strengthening regional economies, and enhancing socio-economic impacts within EVOO production and consumption systems. In terms of quality characteristics, significant differences were observed in color parameters (L*, a*, b*, Chroma, Hue angle) among EVOO samples (p < 0.05). Regarding nutritional and functional properties, total phenolic content (TPC) measured with the Folin–Ciocalteu method ranged from 58.15 to 176.29 mg of gallic acid equivalents/kg of oil, while total antioxidant capacity (TAC) measured by CUPRAC and DPPH assays varied between 3.42 and 6.54 and 8.56–10.71 µmol of Trolox equivalents/g of oil, respectively. TPC and TAC were also evaluated for their stability during in vitro gastro-intestinal digestion, demonstrating that EVOO’s bioactive potential remains stable under gastric and intestinal conditions. Local samples exhibited significantly higher TACs than trademarked products across undigested, gastric, and intestinal phases (p < 0.05). Concurrently, a face-to-face consumer survey assessed purchasing behaviors and preferences, revealing that 71.3% of consumers preferred local EVOO and showed a low tendency to purchase commercial brands (p < 0.05). Cooperatives were identified as the main distribution channel, playing a crucial role in sustaining local production systems. This study offers valuable insights into EVOO’s bioactive content and consumer behavior, providing a foundation for developing both localized and commercial products that support health outcomes. Additionally, the findings contribute to policy development concerning sustainable food systems and geographical indications. Full article

Background: The rapid emergence of antibiotic resistance in Acinetobacter baumannii has led the World Health Organization (WHO) to designate it as a “high priority” pathogen. The emergence of multidrug-resistant (MDR) and pandrug-resistant (PDR) strains poses considerable treatment challenges. As antimicrobial resistance (AMR) escalates toward a post-antibiotic era, innovative therapeutic solutions are urgently needed. Objectives: To clone, over-express, and characterize a novel endolysin, LysTAC1, from Acinetobacter phage TAC1 for its antibacterial efficacy against multidrug-resistant bacteria. Methods: A 24 kDa endolysin featuring a glycoside hydrolase Family 19 chitinase domain was tested against carbapenem-resistant Acinetobacter baumannii clinical isolates and various Escherichia coli strains following outer membrane permeabilization with Ethylenediaminetetraacetic acid (EDTA). Stability assays and molecular docking studies were performed. Results: LysTAC1 demonstrated potent lytic activity against Gram-negative bacteria but showed no activity against Gram-positive bacteria (Staphylococcus aureus ATCC 29213 and Enterococcus gallinarum HCD 28-1). LysTAC1 maintained activity across pH 6–9 and temperatures 4–65 °C, with differential sensitivity to metal ions where K⁺ showed no inhibitory effect at any concentration (0.1–100 mM), and Fe²⁺ was non-inhibitory at lower concentrations (0.1–1 mM), while Mg²⁺ and Ca²⁺ demonstrated concentration-dependent inhibition across the tested range (0.1–100 mM). Molecular docking revealed LysTAC1 interactions with chitinase substrates 4-nitrophenyl N-acetyl-β-D-glucosaminide and 4-nitrophenyl N, N-Diacetyl-β-D-chitobioside, with binding energies of −5.82 and −6.85 kcal/mol, respectively. Conclusions: LysTAC1 shows significant potential as a targeted therapeutic agent against A. baumannii with robust stability under physiological conditions. Full article

Background and Objectives: Cardiovascular disease remains a leading cause of mortality in Diabetes mellitus (DM), where chronic hyperglycemia induces oxidative stress, mitochondrial dysfunction, and hypoxia in cardiomyocytes. Liraglutide (Lir), a glucagon-like peptide-1 receptor agonist, is widely used for type 2 DM management and has been shown to exert cardioprotective and antioxidant effects. This study aimed to evaluate whether Lir mitigates hyperglycemia-induced oxidative and hypoxic stress in H9c2 cardiomyoblasts while preserving cellular ultrastructure. Materials and Methods: H9c2 cells were cultured under normoglycemic (5.5 mM) or hyperglycemic (30 mM) conditions, with or without Lir. Cell viability was assessed using MTT assay. Ultrastructural changes were examined by transmission electron microscopy (TEM). Hypoxia-inducible factor-1α (HIF-1α), lipid peroxidation markers (LOOH, MDA), advanced oxidation protein products (AOPP), and total antioxidant capacity (TAC) were quantified by spectrophotometric assays. Results: MTT assays revealed that Lir significantly improved cell viability under hyperglycemic conditions and the EC₅₀ was 1.05 ± 0.06 μM after 48 h of treatment. Under HG, HIF-1α, lipid hydroperoxides (LOOH), malondialdehyde (MDA) and advanced oxidation protein products (AOPP) increased and total antioxidant capacity (TAC) decreased (p < 0.001, for all); Lir significantly reversed these changes, restoring values to near-NG levels. Ultrastructural analysis of HG + Lir-treated cells revealed reduced granules, increased vacuolization, and slight rough endoplasmic reticulum dilatation, though mitochondria appeared normal. Conclusions: Lir significantly attenuated oxidative stress and cellular injury in cardiomyocytes under hyperglycemic conditions, improving viability, modulating HIF-1α expression, and restoring antioxidant balance. These findings support a dual role for Lir in diabetic cardiomyopathy: glucose-independent cytoprotection and regulation of mitochondrial and hypoxia pathways, highlighting its therapeutic potential beyond glycemic control. Full article

Liver steatosis, the hallmark component of metabolic dysfunction-associated steatotic liver disease (MASLD), is particularly common among individuals with type 2 diabetes mellitus (T2DM). Shared mechanisms such as insulin resistance, oxidative stress, and chronic inflammation contribute to the coexistence of these conditions and accelerate disease progression, emphasizing the need for effective therapeutic strategies. In this 12-month, randomized, double-blind, placebo-controlled trial, 227 obese individuals with T2DM were assigned to receive either 1500 mg of curcumin daily or placebo. Curcumin significantly reduced liver fat content, liver stiffness, and glycated hemoglobin (HbA1c) compared with placebo (all p < 0.001). Improvements were also noted in inflammatory mediators, including interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) (all p < 0.001), reflecting curcumin’s anti-inflammatory effects. Antioxidant benefits were evident, as total antioxidant capacity (TAC), glutathione peroxidase (GPx), and superoxide dismutase (SOD) increased, while malondialdehyde levels decreased (all p < 0.001). Systematic safety assessments, including liver and kidney function tests, revealed no clinically significant abnormalities. Mild gastrointestinal discomfort was the most common non-serious adverse event. Overall, these findings support curcumin as a safe and effective adjunctive therapy for improving liver steatosis in obese patients with T2DM. Full article

Background: Abnormal mitochondrial energy metabolism is a key factor in the development and progression of cardiac hypertrophy. Hopeaphenol (HP), a tetramer of the natural polyphenol resveratrol, exhibits higher biological activity than resveratrol, but its specific role in cardiac hypertrophy and underlying mechanisms remains unclear. Methods: This study explored the protective effect and mechanism of hopeaphenol on cardiac hypertrophy through in vivo and in vitro experiments. In in vivo experiments, transverse aortic constriction (TAC) was used to induce cardiac hypertrophy in mice; HE, Masson, and WGA staining were applied to observe myocardial changes, ELISA was used to detect animal serum indicators, and the Cellular Thermal Shift Assay (CETSA) was conducted to verify the interaction between hopeaphenol and AMPK. In in vitro experiments, angiotensin II (Ang II) was used to induce hypertrophy of HL-1 cardiomyocytes, and the AMPK-specific inhibitor Compound C was employed to confirm the role of the AMPK pathway. Results: In in vivo experiments, TAC-induced cardiac hypertrophy in mice was characterized by left ventricular cavity enlargement and decreased ejection fraction; hopeaphenol treatment significantly improved these cardiac function indices, and HE, Masson, and WGA staining confirmed that hopeaphenol could restore cardiomyocyte morphology and reduce fibrosis. ELISA results of animal serum showed that hopeaphenol could improve metabolic disorders in TAC mice. Furthermore, CETSA confirmed a direct interaction between hopeaphenol and AMPK. In in vitro experiments, hopeaphenol reduced Ang II-induced hypertrophy and apoptosis of HL-1 cardiomyocytes, enhanced mitochondrial membrane potential, and decreased reactive oxygen species (ROS) levels by activating the AMPK pathway; moreover, the AMPK-specific inhibitor Compound C blocked these effects. This suggests that hopeaphenol’s cardioprotective effect is largely mediated by AMPK activation. Conclusions: The protective effect of hopeaphenol on cardiac hypertrophy is highly dependent on the activation of the AMPK signaling pathway, with CETSA and molecular docking supporting direct binding between hopeaphenol and AMPK; this pathway improves mitochondrial dysfunction through AMPK, thereby alleviating heart failure caused by pressure overload. This finding identifies hopeaphenol as a potential candidate for further development in the prevention and treatment of heart failure. Full article

Tetrahydrofuran (THF) and methanol (MeOH) are widely used as organic solvents in chemical, pharmaceutical, and other industrial fields. The wastewater from producing 1,4-butanediol contains THF, MeOH, and water ternary azeotropic mixture. In this study, to protect the environment and improve economic feasibility, THF and MeOH from the wastewater must be recovered. Triple-column extractive distillation (TED), pressure-swing azeotropic distillation (PSAD) and reactive extractive dividing-wall column (REDWC) are introduced to separate this ternary system, and the NSGA-III algorithm is introduced to optimize the processes, taking the total annual cost (TAC), CO₂ emissions, and process route index (PRI) as objective functions. The results indicate that in comparison with TED process, TAC of PSAD and REDWC is reduced by 29.92% and 24.25%, respectively, and CO₂ emissions decreased by 18.01% and 25.13%, while PRI increased by 150.25% and 100.50%. This study can provide an insight for the design of ternary azeotropic system separation. Full article

This systematic review examines the combined use of electroencephalography (EEG) and transcranial electrical stimulation (tES) in both clinical and healthy populations. The review focuses on EEG’s role in guiding, monitoring, and evaluating tES interventions and assesses the generalizability of EEG responses to different tES protocols. A comprehensive search across Google Scholar, PubMed, Scopus, IEEE Xplore, ScienceDirect, and Web of Science identified 162 relevant studies using the query: “EEG AND (tDCS OR transcranial direct current stimulation OR tACS OR transcranial alternating current stimulation OR tRNS OR transcranial random noise stimulation OR tPCS OR transcranial pulsed current stimulation)”. Quality was assessed using the Quality Assessment Tool for Quantitative Studies (QATQS). Most studies used EEG post tES to assess neuromodulatory effects, with fewer studies using EEG for protocol design or incorporating real-time EEG for adaptive stimulation. Some studies integrated EEG both before and after stimulation, but considerable heterogeneity in tES parameters and EEG metrics limited reproducibility and comparability. Many studies reported non-significant EEG changes despite standardized approaches. Methodological quality was generally low, and the link between EEG changes and clinical outcomes remains unclear. The findings underscore the potential of EEG-informed, personalized tES protocols, though the use of real-time closed-loop systems remains a limited approach in current research. Full article

This study reports the successful fabrication and characterization of two-dimensional (2D) vertical heterostructures composed of a semiconducting molybdenum disulfide (MoS₂) layer stacked with semimetallic platinum dichalcogenides (PtSe₂ and PtTe₂). The heterostructures were created using a versatile fabrication method that combines chemical vapor deposition (CVD) to grow high-quality MoS₂ nanolayers with thermally assisted conversion (TAC) for the synthesis of the Pt-based layers. The final MoS₂/PtSe₂ and MoS₂/PtTe₂ heterostructures were then assembled via a dry transfer process, ensuring high structural integrity. The quality and properties of these heterostructures were investigated using a range of advanced spectroscopic techniques. Raman spectroscopy confirmed the presence of characteristic vibrational modes for each material, validating successful formation. X-ray photoelectron spectroscopy (XPS) analysis further confirmed the elemental composition and oxidation states, though it also revealed the presence of elemental Pt⁰ and oxidized Te⁺⁴ in the PtTe₂ layer, suggesting an incomplete conversion. Importantly, the photoluminescence (PL) spectra showed a significant quenching effect, a clear sign of strong interlayer charge transfer, which is essential for optoelectronic applications. Finally, UV-Vis-NIR spectrophotometry demonstrated the combined optical properties of the stacked layers, with the Pt-based layers causing broadening and a blue-shift in the MoS₂ exciton peaks, indicating altered electronic and optical behavior. This research provides valuable insights into the synthesis and fundamental properties of MoS₂/PtX₂ heterostructures, highlighting their potential for next-generation electronic and optoelectronic devices. Full article

Cabbage is one of the most popular vegetables all over the world, with white cabbage generally being more popular than red cabbage. This study aimed at a comparison of the antioxidant properties of fresh and fermented white and red cabbage. Total phenolic content, the content of anthocyanins and carotenoids, and the Total Antioxidant Capacity (TAC) assayed by ABTS^• scavenging, DPPH^• scavenging, FRAP, and ORAC of fresh white and red cabbage, fermented white and red cabbage (sauerkraut), and sauerkraut juice were compared. The TAC of fresh and fermented red cabbage, and of red sauerkraut juice (110.3 ± 8.9, 47.4 ± 4.6 and 48.9 ± 5.7 mmol Trolox equivalents/kg, respectively) was significantly higher than the TAC of fresh and fermented white cabbage and white sauerkraut juice (5.1 ± 0.2, 7.9 ± 0.9 and 6.6 ± 0.9 mmol TE/kg, respectively, when assayed by ORAC). The TAC of white sauerkraut and white sauerkraut juice could be elevated by fermentation with 20% of black carrots (to 16.4 ± 1.2 and 10.5 ± 0.8 mmol TE/kg, respectively) but the TAC of red sauerkraut and red sauerkraut juice was diminished by a mixture of either orange or black carrots, which are of lower anthocyanin content than the red cabbage (41.8 ± 3.0 and 29.2 ± 3.1 mmol TE/kg, respectively). These results may justify the promotion of the broad consumption of red cabbage, both fresh and fermented, and encourage the usage of red cabbage as a promising material for functional foods. Full article

Background/Objectives: Tacrolimus dosing remains challenging due to its narrow therapeutic index and high inter- and intra-patient variability. The extended-release once-daily tacrolimus (LCP-Tac) formulation provides enhanced bioavailability and a sustained pharmacokinetic profile compared to the immediate-release twice-daily tacrolimus (IR-Tac) formulation. Although a general conversion ratio of 1:0.7 is widely recommended when switching between formulations, current guidelines do not account for pharmacogenetic variability. This study aimed to determine whether CYP3A5 genotype influences the conversion ratio in Caucasian renal transplant recipients using population pharmacokinetic (PopPK) modeling. Methods: A PopPK model was developed in NONMEM using full PK profiles (10–18 samples per patient) from 30 stable renal transplant patients treated with both IR-Tac and LCP-Tac. Results: Tacrolimus pharmacokinetics were best described by a two-compartment model with first-order absorption and linear elimination with distinct absorption rate constants and lag times for each formulation. Including circadian rhythm in the apparent clearance (CL/F) and Ka of IR-Tac significantly improved the model. CYP3A5 polymorphism was the most powerful covariate explaining variability on CL/F. CYP3A5*1 expressers showed higher clearance and lower exposure requiring a more pronounced dose reduction upon conversion to LCP-Tac. Simulations indicated optimal conversion ratios of 1:0.6 for CYP3A5*1 expressers and 1:0.7 for non-expressers. Conclusions: These findings highlight the need to move beyond a one-size-fits-all conversion ratio and adopt genotype-informed strategies. LCP-Tac’s enhanced bioavailability requires dose reduction, greater in expressers when switching from IR-Tac. These genotype-specific recommendations provide clinically actionable guidance to complement therapeutic drug monitoring and support more individualized conversion protocols in renal transplantation. Full article

Background and Objectives: Diabetes mellitus (DM) is associated with impaired wound healing and increased oxidative stress, posing a significant challenge in dental wound healing. Low-level laser therapy (LLLT) has emerged as a potential regenerative treatment to enhance tissue repair. This study aims to investigate the effects of LLLT on oral mucosal wound healing and oxidative stress markers in rats with DM. Materials and Methods: Male Wistar rats (n = 108) were divided into six equal groups (healthy and diabetic, with or without mucosal ulcers, with or without LLLT). DM was induced with alloxan, and standardized mucosal ulcers were created. Every other day for 10 days, LLLT (6 J/cm²) was applied, and tissue samples were collected after 3, 7, and 10 days. Wound healing was assessed by planimetry, while systemic biochemical analyses included total oxidative status (TOS), total antioxidant capacity (TAC), superoxide dismutase (SOD) activity, and oxidative stress index (OSI). Results: LLLT significantly accelerated oral ulcer closure and showed between-group differences in redox markers. In healthy rats, LLLT increased wound closure on day 7 (p = 0.018). In diabetic rats, LLLT improved closure on day 3 (p = 0.035) and on day 7 (p = 0.001). Across groups, oxidative markers differed significantly (e.g., TOS on day 10 overall, p = 0.011; OSI on day 10 overall, p = 0.047; SOD p < 0.001 at all time points). In diabetic rats, on day 10, median TOS was lower with LLLT (p = 0.004). Conclusions: LLLT enhances oral wound healing and restores redox balance in diabetic rats, which supports the potential usage of LLLT as an adjunctive therapy for managing oral lesions in diabetic patients. Full article