Search Results (163)

Chronic respiratory diseases claim nearly four million lives annually, making them the third leading cause of death worldwide. Extracorporeal membrane oxygenation (ECMO) is often the last line of support for patients with severe lung failure. Still, its performance is limited by an incomplete understanding of gas exchange in hollow fiber membrane (HFM) oxygenators. Computational fluid dynamics (CFD) has become a robust oxygenator design and optimization tool. However, most models oversimplify O₂ and CO₂ transport by ignoring their physiological coupling, instead relying on fixed saturation curves or constant-content assumptions. For the first time, this study introduces a novel physiologically informed CFD model that integrates the Bohr and Haldane effects to capture the coupled transport of oxygen and carbon dioxide as functions of local pH, temperature, and gas partial pressures. The model is validated against in vitro experimental data from the literature and assessed against established CFD models. The proposed CFD model achieved excellent agreement with experiments across blood flow rates (100–500 $\mathrm{mL}/\min$ ), with relative errors below 5% for oxygen and 10–15% for carbon dioxide transfer. These results surpassed the accuracy of all existing CFD approaches, demonstrating that a carefully formulated single-phase model combined with physiologically informed diffusivities can outperform more complex multiphase simulations. This work provides a computationally efficient and physiologically realistic framework for oxygenator optimization, potentially accelerating device development, reducing reliance on costly in vitro testing, and enabling patient-specific simulations. Full article

Background/Objectives: Combination therapies using traditional Chinese medicine and Western drugs have gained attention for their enhanced therapeutic effects and reduced side effects. Toujie Quwen Granules (TQG), known for its antiviral properties, particularly against respiratory viruses, could offer new treatment strategies when combined with antiviral drugs like arbidol, especially for diseases such as Coronavirus disease. This study investigates the synergistic mechanisms between arbidol and components from TQG against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (M^pro). Methods: We identified compounds from TQG via existing data. Multi-ligand molecular docking, pharmacokinetic/toxicity screening, and preliminary simulations were performed to assess potential synergistic compounds with arbidol. UPLC-Q-Exactive Orbitrap-MS verified the presence of these compounds. Extended simulations and in vitro assays, including Luciferase and surface plasmon resonance, validated the findings. Results: Five compounds interacted with arbidol in synergy based on docking and preliminary dynamics simulation results. Only Baicalein (HQA004) could be identified in the herbal remedy by untargeted metabolomics, with ideal pharmacokinetic properties, and as a non-toxic compound. Extended simulations revealed that HQA004 enhanced arbidol’s antiviral activity via a “Far” Addition Mechanism #2, with an optimal 2:1 arbidol:HQA004 ratio. The movements of arbidol (diffusion and intramolecular conformational shifts) in the system were significantly reduced by HQA004, which may be the main reason for the synergism that occurred. In vitro experiments confirmed an increased inhibition of M^pro by the combination. Conclusions: HQA004 demonstrated synergistic potential with arbidol in inhibiting M^pro. The development of combination therapies integrating Western and herbal medicine is supported by these findings for effective antiviral treatments. Full article

Quercetin (Que) is widely recognized for its antioxidant and neuroprotective properties; however, its clinical potential remains limited due to poor solubility and low oral bioavailability. Nasal powders have emerged as a promising strategy to overcome these limitations, taking advantage of nose-to-brain delivery, offering a direct, non-invasive route to the central nervous system while bypassing first-pass metabolism. This study aims to extend previous work by systematically investigating the impact of different preparation methods (spray drying vs. lyophilization) and the incorporation of hydroxypropyl methylcellulose (HPMC) and mannitol/lecithin microparticles (MLMPs) on the physicochemical characteristics, structural properties, and in vitro diffusion behavior of HPβCD-based nasal powder formulations of Que. Thermal behavior and stability were analyzed using TGA, while morphology and particle distribution were assessed via Scanning Electron Microscopy. In vitro diffusion studies using Franz cells and regenerated cellulose membranes were conducted under simulated nasal conditions. Among all tested formulations, the spray-dried HPβCD/Que powder (F4) showed the highest permeation (0.11 ± 0.01 mg/cm² at 120 min). The inclusion of HPMC improved thermal stability but reduced Que diffusion, likely due to increased viscosity and matrix formation. Blending with MLMPs enhanced powder flow and dose placement, although it modestly reduced diffusion efficiency. Overall, this study highlights the potential of HPβCD-based spray-dried powders for nasal Que delivery and demonstrates how HPMC and MLMPs can be strategically employed to tailor performance characteristics. Full article

Vibrio species are among the primary pathogenic bacteria affecting abalone aquaculture, posing significant threats to farming practices. Current clinical control predominantly relies on antibiotics, which can result in antibiotic residues in both abalone and the surrounding marine environments. Lactobacillus plantarum (LP) has been shown to release bioactive antagonistic substances and exhibits potent inhibitory effects against marine pathogenic bacteria. This study aimed to screen and characterize the probiotic properties of LP strains isolated from rice wine lees to develop a novel biocontrol strategy against Vibriosis in abalone. The methods employed included selective media cultivation, streak plate isolation, and single-colony purification for strain screening, followed by Gram staining, 16S rDNA sequencing, and phylogenetic tree construction using MEGA11 for identification. The resilience, antimicrobial activity, and in vivo antagonistic efficacy of the strains were evaluated through stress tolerance assays, agar diffusion tests, and animal experiments. The results demonstrated the successful isolation and purification of four LP strains (NDMJ-1 to NDMJ-4). Phylogenetic analysis revealed closer genetic relationships between NDMJ-3 and NDMJ-4, while NDMJ-1 and NDMJ-2 were found to be more distantly related. All strains exhibited γ-hemolytic activity, bile salt tolerance (0.3–3.0%), and resistance to both acid (pH 2.5) and alkali (pH 8.5), although they were temperature sensitive (inactivated above 45 °C). The strains showed susceptibility to most of the 20 tested antibiotics, with marked variations in hydrophobicity (1.91–93.15%) and auto-aggregation (13.29–60.63%). In vitro antibacterial assays revealed that cell-free supernatants of the strains significantly inhibited Vibrio parahaemolyticus, V. alginolyticus, and V. natriegens, with NDMJ-4 displaying the strongest inhibitory activity. In vivo experiments confirmed that NDMJ-4 significantly reduced mortality in abalone infected with V. parahaemolyticus. In conclusion, the LP strains isolated from rice wine lees (NDMJ-1 to NDMJ-4) possess robust stress resistance, adhesion capabilities, and broad antibiotic susceptibility. Their metabolites exhibit significant inhibition against abalone-pathogenic Vibrios, particularly NDMJ-4, which demonstrates exceptional potential as a candidate strain for developing eco-friendly biocontrol agents against Vibriosis in abalone aquaculture. Full article

Background/Objectives: Difenoconazole (DFC) is a broad-spectrum fungicide. However, its application is limited due to poor aqueous solubility. Drugs with low solubility can be better absorbed using nanostructured lipid carriers (NLCs). Hence, the application of DFC in an NLC delivery system is proposed. Methods: Difenoconazole-loaded nanostructured lipid carriers (DFC-NLCs) with different solid–liquid lipid ratios were prepared by solvent diffusion method. Key physicochemical parameters, including particle diameter, surface charge (zeta potential), drug encapsulation efficiency, and morphological characteristics, were systematically characterized. Using Rhizoctonia solani (R. solani) as the model strain, inhibitory efficiency of DFC-NLC dispersion was compared with that of commercial dosage forms, such as 25% DFC emulsifiable concentrate (DFC-EC) and 40% DFC suspension concentrate (DFC-SC). Additionally, uptakes of DFC-NLC dispersions in R. solani were further observed by fluorescence probe technology. The safety profiles of DFC-NLCs and commercial dosage forms were evaluated using zebrafish as the model organism. Acute toxicity studies were conducted to determine the maximum non-lethal concentration (MNLC) and 10% lethal concentration (LC₁₀). Developmental toxicity studies were performed to observe toxic phenotypes. Results: DFC-NLC dispersions were in the nanometer range (≈200 nm) with high zeta potential, spherical in shape with encapsulation efficiency 69.1 ± 1.8%~95.0 ± 2.6%, and drug loading 7.1 ± 0.3%~9.7 ± 0.6% determined by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Compared with commercial dosage forms, the antifungal effect of the DFC-NLC on R. solani was significantly improved in in vitro antibacterial experiments (p < 0.05). The 50% effective concentration (EC₅₀) values were 0.107 mg·L⁻¹ (DFC-NLC), 0.211 mg·L⁻¹ (DFC-EC), and 0.321 mg·L⁻¹ (DFC-SC), respectively. The uptakes of FITC-labeled DFC-NLC demonstrated that an NLC was appropriate to deliver DFC into pathogen to enhance the target effect. In safety assessment studies, DFC-NLCs exhibited a superior safety profile compared with commercial formulations (p < 0.05). Conclusions: This study investigates the feasibility of NLCs as delivery systems for poorly water-soluble fungicides, demonstrating their ability to enhance antifungal efficacy and reduce environmental risks. Full article

Background: Conventional approaches in treating psoriasis demonstrate several complications. methotrexate (MTX) has been frequently used for its efficacy in managing moderate to severe psoriasis. However, MTX acts as an antagonist in regular dosage, which creates a patient compliance issue with undesirable consequences for patients, which necessitates development of an innovative approach to enhance skin permeation. Therefore, this study examines the improved topical administration of MTX utilizing a transferosome-loaded microneedle (MNs) array patch for the management of psoriasis. Methods: A design of experiment was used assess the effect of phospholipid content and edge activator type on vesicle size and entrapment efficiency (EE) to fabricate and optimize transferosome-loaded MTX. Furthermore, the MTX was incorporated within MNs and assessed for in vitro-ex vivo-in vivo parameters. Results: The morphology result revealed vesicles mean diameter of 169.4 ± 0.40 nm and EE of 69 ± 0.48 (%). Compared to traditional formulations (MTX patch and gel), the optimized transferosome-loaded dissolving MN array patch showed a substantial increase in diffusion of MTX tested over rat skin. Furthermore, an enhanced therapeutic benefit at the application site through cumulative drug release profiles suggested sustained release of MTX over 24 h. Moreover, in vivo experiments showed that the MN array patch exhibited higher accumulation, compared to conventional formulation tested. In addition, the plasma concentration measurements demonstrated a reduction in systemic exposure to MTX, diminishing the possibility of intricacy while preserving localized therapeutic efficacy. The capability of the MN array patch to lance the epidermal layers was proven by histological assessments. Conclusions: Thus, transferosome-loaded MNs is a viable method of delivering MTX topically with prolonged drug release and reduced systemic toxicity. Full article

This study investigated the role of synthetic mucus coatings in enhancing the physiological relevance of in vitro nasal spray deposition assessments using 3D-printed nasal cavity models. Synthetic mucus solutions, representing normal (0.25% w/v xanthan gum) and diseased (1% w/v xanthan gum) nasal conditions, were developed to mimic the viscoelastic properties of human nasal mucus. Their physical properties, including viscosity, surface tension, contact angle, and adhesivity on dry and synthetic mucus-coated stereolithography (SLA) surfaces, were systematically characterized. Comparative experiments evaluated the behavior of saline drops and liquid films on dry versus synthetic mucus-coated SLA surfaces at inclinations of 30°, 45°, and 60°. Observational deposition experiments using anatomically accurate nasal models were conducted under a 45° backward-tilted head position with gentle sniff airflow across uncoated, 0.25% w/v mucus-coated, and 1% w/v mucus-coated surfaces. Synthetic mucus coatings significantly influenced saline spray deposition patterns. On uncoated surfaces, deposition consisted of scattered droplets and limited film formation, mainly in the anterior and turbinate regions. In contrast, synthetic mucus coatings facilitated broader and more uniform liquid distribution due to diffusion and lubrication effects. These findings highlight the value of synthetic mucus coatings for better simulating nasal environments, offering insights to optimize nasal spray formulations and delivery devices. Full article

Botryosphaeria dieback, a significant grapevine trunk disease (GTD) caused by various pathogens, represents a serious threat to viticulture. Biocontrol emerges as a promising sustainable alternative to chemical control, aligning toward environmentally friendly viticultural practices. This study evaluated the in vitro, in vivo, and in situ biocontrol potential of Chilean native bacteria isolated from wild flora and endophytic communities of grapevine against Neofusicoccum parvum. In vitro biocontrol assays screened 15 bacterial strains at 10, 22, and 30 °C, identifying four Pseudomonas strains with >30% mycelial growth inhibition. In diffusible agar and double plate assays, plant growth-promoting bacteria AMCR2b and GcR15a, which were isolated from native flora, achieved significant inhibition of N. parvum growth, with reductions of up to ~50% (diffusible agar) and up to ~46% (double plate). In vivo experiments on grapevine cuttings revealed that strains AMCR2b and GcR15a inhibited mycelial growth (17–90%); younger grapevines (1–5 years) were more susceptible to N. parvum. In situ trials using Vitis vinifera L. cv. Cabernet Sauvignon and Sauvignon Blanc demonstrated higher fungal susceptibility in Sauvignon Blanc. These results highlight the potential of Pseudomonas sp. AMCR2b and GcR15a to be effective biocontrol agents against GTDs at a wide range of temperatures, contributing to sustainable viticulture. Full article

Background: Rutin is a natural flavonoid extracted primarily from plants with anti-inflammatory and antioxidant properties, and it is highly valuable in the cosmetics industry. However, the poor transdermal permeability of rutin limits its application via transdermal administration. Previous studies have predominantly focused on chemical methods for enhancing penetration. This study investigated the potential of ultrasound as a physical method by which to augment the transdermal absorption and anti-inflammatory effects of rutin. Method: Through in vitro diffusion experiments, we analyzed the effects of the ultrasonic frequency and intensity on percutaneous absorption. The optimal ultrasound parameters were determined based on the intradermal retention rate, which is defined as the proportion of intradermal retention to the total penetration. Parameters with higher retention rates were considered optimal. To validate the anti-inflammatory efficacy of rutin delivered using the ultrasound-assisted method, we employed a tape-stripping technique to induce inflammation in BALB/c nude mice. Eight mice were assigned to each treatment group: (A) self-repair (control group), (B) regular rutin treatment, and (C) ultrasound-assisted treatment. Results: The research findings indicate that ultrasound frequency and intensity of 1 MHz and 0.2 W/cm², as well as 3 MHz and 0.2 W/cm², result in the maximum proportion of rutin intradermal retention, exhibiting values 1.8 times (using porcine skin) and 2.63 times (using nude mouse skin) higher than those achieved without ultrasound, respectively. Group C showed the shortest recovery time and displayed complete skin barrier function restoration by the fourth day $(p<0.05)$, whereas group A exhibited the slowest recovery. Conclusions: This study offers an innovative approach for the transdermal delivery of rutin to facilitate skin barrier function repair. Full article

The nasal epithelium is the primary site for entry of respiratory viruses. In comparison to oral administration, nasal drug applications directed locally to the site of infection can serve as early interventional barriers against respiratory virus pathogenesis by limiting viral spread in the upper airway. Experiments on the diffusion of methylene blue and nanoparticles in both water and low pH conditions revealed that hydroxypropyl methylcellulose (HPMC) can act as an effective physical barrier. This study also evaluated the activity of HPMC as a barrier against common respiratory viruses, i.e., rhinovirus (RV) and influenza A virus (IAV) using the in vitro human nasal epithelial cell (hNEC) model. Utilizing the hNEC infection model, we assessed the protective effects of HPMC in pH 3.5 and pH 7 buffers against RV and IAV. Acidic and pH-neutral buffers and HPMC dissolved in acidic and pH-neutral buffers were administered for 4 h prior to virus infection and at 4 h post-infection (hpi). The apical supernatant was harvested at 24 hpi to determine the viral loads of RV and IAV (H1N1 and H3N2). HPMC was demonstrated to exert protective effects in the infected hNECs independent of acidic pH. Pre-treatment with HPMC in acidic buffer significantly diminished viral loads for both RV and IAV infections of hNECs. Similarly, direct treatment of HPMC in acidic buffer after infection (4 hpi) also effectively decreased viral loads of both RV and IAV. Moreover, treatment using HPMC in acidic buffer before or after infection did not affect the epithelial integrity and ciliary function of hNECs. This study demonstrates the protective effects of HPMC in acidic buffer against RV and IAV infections of the human nasal epithelium. Full article

Background: Due to their antibacterial activities, essential oils can be potential alternatives to antibiotics in certain cases. West Indian lemongrass (Cymbopogon citratus) essential oil (LEO) is effective against a broad range of bacteria by inhibiting spore formation, and is considered safe. In this study, we demonstrated its therapeutical potential in the treatment of pitted keratolysis (PK), a superficial skin infection affecting the pressure-bearing areas of plantar surfaces. Methods: For in vitro antibacterial efficacy testing, LEO was mixed into different ointment bases, including Hydrogelum methylcellulose FoNo VIII., Ungentum oleosum FoNo VIII. (Ung. oleoso), Unguentum stearini FoNo VIII. (Ung. stearin), and Vaselinum cholesterinatum FoNo VIII. (Vasel. cholest.), at different concentrations of 1, 3, and 5%. These formulations were tested on representatives of three bacterial species associated with PK: Kytococcus sedentarius, Dermatophilus congolensis, and Bacillus thuringiensis. Results: In the in vitro tests, Hydrogelum methylcellulose (HM) gel best supported the antibacterial effects of LEO, reducing the number of living bacteria on agar plates by 4–5 orders of magnitude in a concentration-dependent manner during the 30 min exposure times. This was also confirmed by the Franz diffusion cell drug release test; after 30 min, several active compounds could be detected in the HM samples, in contrast to the other bases. Shelf-life experiments showed that the HM base supported the antibacterial features of 3% LEO for at least 2 years without significant loss of efficacy. Conclusions: Our study highlights that ointments containing essential oils potentially have a place in the treatment of PK. Therefore, antibiotics may potentially be replaced for the treatment of PK, thereby reducing environmental antibiotic pressure, which is one of the driving forces behind the spread of antibiotic resistance. Full article

Background: Diffuse intrinsic pontine glioma [DIPG] is a fatal pediatric disease characterized by a post-translational modification, a replacement of lysine by methionine in position 27 of the N-terminal [H3K27M] tail of histone 3 isoform-1 [H3.1] or histone 3 isoform-3 [H3.3], respectively, expressed in the DIPG-36 and DIPG-50 cells. We investigated the role of cation channels in DIPG cells for the first time and the effects of ATP-sensitive K⁺[KATP] and TRPV1 channel modulators. Methods: Experiments were performed using “in vitro” cytotoxic assays combined with the patch clamp technique, RT-PCR, Western blot, and flow cytometry assays. Results: The most effective anti-proliferative drugs were repaglinide and glibenclamide after short and long-term incubation [6–96 h]. These drugs reduced macroscopic currents of the DIPG cells recorded in whole-cell patch clamp. Repaglinide concentration dependently enhanced the target protein H3K27ac in Western blotting after 48 h of incubation. This drug reduced cell diameter and enhanced cleaved caspase-3 in DIPG cells; total AKT/mTOR levels and phospho-mTOR were downregulated in DIPG-36. Conclusions: KATP and TRPV1 channels are functionally expressed, and sulphonylureas are effective antiproliferative upregulating H3K27ac with apoptosis in DIPG cells and the sub-micromolar concentrations in DIPG-50. Full article

Background/Objectives: Since 2008, following clinical studies conducted on children that revealed the ability of the β-adrenergic antagonist propranolol to inhibit capillary growth in infantile hemangiomas (IHs), its oral administration has become the first-line treatment for IHs. Although oral propranolol therapy at a dosage of 3 mg/kg/die is effective, it can cause systemic adverse reactions. This therapy is not necessarily applicable to all patients. Topical skin applications could help maintain a high drug concentration at local sites and also represent a characteristically easy method of administration for pediatric patients. Because no topical propranolol dosage forms are commercially available, such formulations may be prepared at hospitals and pharmacies. Methods: In the present study, we identified a simple method for preparing topical propranolol hydrochloride formulations at 1% w/w with five commercial ready-to-use bases and evaluated the pharmaceutical profiles. The physical stability of the extemporaneous formulations was predicted by performing an accelerated centrifuge test and assessed by visual inspection after one month storage at 25 °C. The chemical stability of the drug in the five formulations was assessed by using a high-performance liquid chromatography (HPLC) method. In vitro drug-release and permeability experiments were conducted through synthetic membranes and the outer pavilion of a pig’s ear by utilizing Franz-type diffusion cells. Results: The results indicated that the release of the drug was significantly influenced by the internal structure and physicochemical properties of each base. Conclusions: Specifically, the formulations prepared with the hydrophilic bases could be easily prepared and yield satisfactory results, representing a potential effective therapy for IHs in pediatric patients. Full article

In order to sustain control over soybean root rot, wheat-straw-fiber-based mulch film (WFM) coated with carbendazim (C) and chitosan (CS) mixture (C-CS-WFM) were prepared through bar coating technology. The Box–Behnken design method was employed to investigate the effects of chitosan concentration, wet film thickness, and carbendazim loading on the dry tensile strength (DTS), wet tensile strength (WTS), and air permeance (AP) of C-CS-WFM. Eventually, the optimization process parameters were determined as follows: a chitosan concentration of 1.83–2.39%, a wet film thickness of 18–24 μm, and a carbendazim loading of 0.05–0.12 g/m². These parameters achieved the desired physical properties of C-CS-WFM, i.e., the DTS is not less than 3.5 kN/m, the WTS is not less than 0.8 kN/m, and the AP does not exceed 2.1 μm/(Pa·s). The results showed that after the introduction of the C-CS coating, the DTS and WTS of C-CS-WFM were enhanced by 11.4% and 14.9%, respectively. In contrast, the AP was reduced by 15.6%. FT-IR analysis indicated that carbendazim was embedded in the C-CS composite material without any chemical interaction. Through SEM and sustained-release kinetic analysis, it was found that the sustained-release mechanism of C-CS-WFM conformed to the Ritger–Peppas kinetic model, and its release mechanism was the physical diffusion and matrix erosion. The results of the in vitro antifungal test and pot experiment demonstrated that C-CS-WFM could effectively inhibit the growth of Fusarium solani and promote the growth of plants. This study provided new ideas for the comprehensive prevention and control of soybean root rot. Full article

One of the key factors of the interaction ‘osteoplastic material—organism’ is the state of the implant surface. Taking into account the fact that the equilibrium in regeneration conditions is reached only after the reparative histogenesis process is completed, the implant surface is constantly modified. This work is devoted to the numerical description of the dynamic bilateral material–medium interaction under close to physiological conditions, as well as to the assessment of the comparability of the model with in vitro and in vivo experimental results. The semi-empirical model obtained on the basis of chemical kinetics allows us to describe numerically the processes occurring in the in vitro systems and extrapolates well to assess the behavior of dicalcium phosphate dihydrate (DCPD) material under conditions of ectopic (subcutaneous) implantation in Wistar rats. It is shown that an experiment conducted using a perfusion–diffusion bioreactor in a cell culture medium with the addition of fetal bovine serum (FBS) allows for achieving morphologically and chemically identical changes in the surface of the material in comparison with the real organism. This fact opens up wide possibilities for the creation of an analog of a ‘laboratory-on-a-chip’ and the transition from classical in vivo models to more controlled and mathematically based in vitro systems. Full article