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Nature Communications Jun 2024Developing superporous hemostatic sponges with simultaneously enhanced permeability and mechanical properties remains challenging but highly desirable to achieve rapid...
Developing superporous hemostatic sponges with simultaneously enhanced permeability and mechanical properties remains challenging but highly desirable to achieve rapid hemostasis for non-compressible hemorrhage. Typical approaches to improve the permeability of hemostatic sponges by increasing porosity sacrifice mechanical properties and yield limited pore interconnectivity, thereby undermining the hemostatic efficacy and subsequent tissue regeneration. Herein, we propose a temperature-assisted secondary network compaction strategy following the phase separation-induced primary compaction to fabricate the superporous chitosan sponge with highly-interconnected porous structure, enhanced blood absorption rate and capacity, and fatigue resistance. The superporous chitosan sponge exhibits rapid shape recovery after absorbing blood and maintains sufficient pressure on wounds to build a robust physical barrier to greatly improve hemostatic efficiency. Furthermore, the superporous chitosan sponge outperforms commercial gauze, gelatin sponges, and chitosan powder by enhancing hemostatic efficiency, cell infiltration, vascular regeneration, and in-situ tissue regeneration in non-compressible organ injury models, respectively. We believe the proposed secondary network compaction strategy provides a simple yet effective method to fabricate superporous hemostatic sponges for diverse clinical applications.
Topics: Animals; Porosity; Chitosan; Hemostatics; Swine; Hemostasis; Permeability; Hemorrhage; Male
PubMed: 38937462
DOI: 10.1038/s41467-024-49578-2 -
AAPS PharmSciTech Jun 2024Our study aimed to explore the potential of using nanostructured lipid carriers (NLCs) to enhance the topical administration of β-sitosterol, a bioactive that is poorly...
Our study aimed to explore the potential of using nanostructured lipid carriers (NLCs) to enhance the topical administration of β-sitosterol, a bioactive that is poorly soluble in water. Here, we have taken advantage of the unique characteristics that cubosomes have to provide as a drug delivery system. These characteristics include a large surface area, thermal stability, and the capacity to encapsulate molecules that are hydrophobic, amphiphilic, and hydrophilic. The cubosomal formulation was optimized by building a central composite design. The optimum dispersion exhibited a particle size of 88.3 nm, a zeta potential of -43, a polydispersity index of 0.358, and drug entrapment of 95.6%. It was composed of 15% w/w oleic acid and 5% w/w pluronic F127. The optimized cubosome dispersion was incorporated into a sponge formulation. The optimized cubosome sponge achieved a higher drug release compared with the cubosome dispersion. The SEM micrograph of the selected sponge showed that it has an interwoven irregular fibrous lamellar structure with low density and high porosity. The in-vivo data revealed that topical application of the β-sitosterol cubosomal sponge showed significant higher wound closure percentage relative to the β-sitosterol product (Mebo)®.
Topics: Sitosterols; Animals; Chitosan; Drug Carriers; Particle Size; Burns; Drug Liberation; Wound Healing; Male; Drug Delivery Systems; Rats; Poloxamer; Hydrophobic and Hydrophilic Interactions; Nanostructures; Administration, Topical
PubMed: 38937387
DOI: 10.1208/s12249-024-02852-4 -
Investigative Ophthalmology & Visual... Jun 2024To assess the association of age-related macular degeneration (AMD) progression and statins, connected with AMD genetic risk, and if there is an interplay between...
PURPOSE
To assess the association of age-related macular degeneration (AMD) progression and statins, connected with AMD genetic risk, and if there is an interplay between statins and genetics.
METHODS
In this analysis, 682 subjects made two visits (6.5-year follow-up) of the Coimbra Eye Study. Subjects who started taking statins at any time point between the two visits were considered. Progressors were defined as not having AMD at baseline and having any AMD at follow-up. Genetic risk scores (GRSs) were calculated individually with 52 independent variants associated with AMD. Time to progression was estimated using unadjusted Kaplan-Meier curves. An extended Cox model was used for the association between statins and GRS with the risk for AMD progression. Multiplicative and additive interactions were assessed.
RESULTS
Median survival time was 7.50 years for subjects not taking statins and 7.62 for subjects taking statins (P < 0.001). Statin intake reduced the risk for progression to AMD in 48%, adjusting for age, sex, body mass index, smoking, and diabetes (model 1) and GRS (model 2). The combined effects of not taking statins and having high GRS increased the progression risk fourfold compared to taking statins and having low GRS (hazard ratio [HR] = 4.25; 95% confidence interval [CI], 1.62-11.16; P = 0.003). For subjects not taking statins, an increased risk of progression was found for those subjects with high GRS compared to subjects with low GRS (HR = 1.80; 95% CI, 1.13-2.85; P = 0.013). No statistically significant multiplicative or additive interactions were found.
CONCLUSIONS
Statins seem to be protective against AMD progression, and genetics may play a role in treatment response.
Topics: Humans; Male; Female; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Aged; Disease Progression; Macular Degeneration; Follow-Up Studies; Risk Factors; Middle Aged; Aged, 80 and over; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease
PubMed: 38935028
DOI: 10.1167/iovs.65.6.38 -
Tidsskrift For Den Norske Laegeforening... Jun 2024
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cardiovascular Diseases; History, 20th Century; History, 21st Century
PubMed: 38934304
DOI: 10.4045/tidsskr.24.0165 -
Nutrients Jun 2024Free radicals and reactive oxygen species initiate when the oxidative stress arises. (1) Background: The effect of natural molecules on oxidative stress in...
Free radicals and reactive oxygen species initiate when the oxidative stress arises. (1) Background: The effect of natural molecules on oxidative stress in hyperlipidemic rats, taking statins, was observed. (2) Methods: One hundred and twelve white Wistar rats, males and females, were divided into seven: Group I received 20 mg of atorvastatin while groups II and III received a combination of 20 mg of atorvastatin and 100 mg of Sea buckthorn and grape extract. Groups IV and V received 100 mg of Sea buckthorn and grape extract, while groups VI and VII received only high-fat diet (HFD) and normal rodents' fodder. After two and six months, rats were euthanized, and blood was gathered to measure the main paraclinical values and total antioxidant capacity (TAC). Also, the liver and kidney were stored for the organs' cytoarchitecture. For statistics, two-way analysis of variance (ANOVA), was performed. (3) Results: HFD produced hyperlipidemia, accompanied by augmented serum and hepatic oxidative stress markers, in addition to a reduction in antioxidant enzyme activities and glutathione levels. Polyphenolic substances proven efficient against HFD caused oxidative stress. (4) Conclusions: Atorvastatin heightened the histological injuries caused by the fatty diet, but these were diminished by taking atorvastatin in combination with 100 mg/kg of plant extracts.
Topics: Animals; Atorvastatin; Oxidative Stress; Rats, Wistar; Hyperlipidemias; Male; Hippophae; Vitis; Plant Extracts; Female; Antioxidants; Diet, High-Fat; Liver; Rats; Biomarkers; Kidney
PubMed: 38931308
DOI: 10.3390/nu16121954 -
Medicina (Kaunas, Lithuania) Jun 2024: Although statins are recommended for secondary prevention of acute ischemic stroke, some population-based studies and clinical evidence suggest that they might be used...
: Although statins are recommended for secondary prevention of acute ischemic stroke, some population-based studies and clinical evidence suggest that they might be used with an increased risk of intracranial hemorrhage. In this nested case-control study, we used Taiwan's nationwide universal health insurance database to investigate the possible association between statin therapy prescribed to acute ischemic stroke patients and their risk of subsequent intracerebral hemorrhage and all-cause mortality in Taiwan. : All data were retrospectively obtained from Taiwan's National Health Insurance Research Database. Acute ischemic stroke patients were divided into a cohort receiving statin pharmacotherapy and a control cohort not receiving statin pharmacotherapy. A 1:1 matching for age, gender, and index day, and propensity score matching was conducted, producing 39,366 cases and 39,366 controls. The primary outcomes were long-term subsequent intracerebral hemorrhage and all-cause mortality. The competing risk between subsequent intracerebral hemorrhage and all-cause mortality was estimated using the Fine and Gray regression hazards model. : Patients receiving statin pharmacotherapy after an acute ischemic stroke had a significantly lower risk of subsequent intracerebral hemorrhage ( < 0.0001) and lower all-cause mortality rates ( < 0.0001). Low, moderate, and high dosages of statin were associated with significantly decreased risks for subsequent intracerebral hemorrhage (adjusted sHRs 0.82, 0.74, 0.53) and all-cause mortality (adjusted sHRs 0.75, 0.74, 0.74), respectively. : Statin pharmacotherapy was found to safely and effectively reduce the risk of subsequent intracerebral hemorrhage and all-cause mortality in acute ischemic stroke patients in Taiwan.
Topics: Humans; Taiwan; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Female; Male; Cerebral Hemorrhage; Aged; Middle Aged; Case-Control Studies; Retrospective Studies; Ischemic Stroke; Big Data; Aged, 80 and over; Data Analysis; Risk Factors; Propensity Score
PubMed: 38929556
DOI: 10.3390/medicina60060939 -
International Journal of Molecular... Jun 2024Chitosan is a natural polymer with numerous biomedical applications. The cellular activity of chitosan has been studied in various types of cancer, including melanoma,...
Chitosan is a natural polymer with numerous biomedical applications. The cellular activity of chitosan has been studied in various types of cancer, including melanoma, and indicates that these molecules can open new perspectives on antiproliferative action and anticancer therapy. This study analyzes how different chitosan conformations, such as α-chitosan (CH) or β-oligochitosan (CO), with various degrees of deacetylation (DDA) and molar mass (MM), both in different concentrations and in CH-CO mixtures, influence the cellular processes of SK-MEL-28 melanocytes, to estimate the reactivity of these cells to the applied treatments. The in vitro evaluation was carried out, aiming at the cellular metabolism (MTT assay), cellular morphology, and chitinase-like glycoprotein YKL-40 expression. The in vitro effect of the CH-CO mixture application on melanocytes is obvious at low concentrations of α-chitosan/β-oligochitosan (1:2 ratio), with the cell's response supporting the hypothesis that β-oligo-chitosan amplifies the effect. This oligochitosan mixture, favored by the β conformation and its small size, penetrates faster into the cells, being more reactive when interacting with some cellular components. Morphological effects expressed by the loss of cell adhesion and the depletion of YKL-40 synthesis are significant responses of melanocytes. β-oligochitosan (1.5 kDa) induces an extension of cytophysiological effects and limits the cell viability compared to α-chitosan (400-900 kDa). Statistical analysis using multivariate techniques showed differences between the CH samples and CH-CO mixtures.
Topics: Chitosan; Melanocytes; Humans; Chitin; Oligosaccharides; Chitinase-3-Like Protein 1; Cell Survival; Cell Proliferation; Cell Line, Tumor; Melanoma
PubMed: 38928474
DOI: 10.3390/ijms25126768 -
International Journal of Molecular... Jun 2024Bosentan, an endothelin receptor antagonist (ERA), has potential anti-atherosclerotic properties. We investigated the complementary effects of bosentan and atorvastatin...
Bosentan, an endothelin receptor antagonist (ERA), has potential anti-atherosclerotic properties. We investigated the complementary effects of bosentan and atorvastatin on the progression and composition of the atherosclerotic lesions in diabetic mice. Forty-eight male mice were fed high-fat diet (HFD) for 14 weeks. At week 8, diabetes was induced with streptozotocin, and mice were randomized into four groups: (1) control/COG: no intervention; (2) ΒOG: bosentan 100 mg/kg/day per os; (3) ATG: atorvastatin 20 mg/kg/day per os; and (4) BO + ATG: combined administration of bosentan and atorvastatin. The intra-plaque contents of collagen, elastin, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-a (TNF-a), matrix metalloproteinases (MMP-2, -3, -9), and TIMP-1 were determined. The percentage of lumen stenosis was significantly lower across all treated groups: BOG: 19.5 ± 2.2%, ATG: 12.8 ± 4.8%, and BO + ATG: 9.1 ± 2.7% compared to controls (24.6 ± 4.8%, < 0.001). The administration of both atorvastatin and bosentan resulted in significantly higher collagen content and thicker fibrous cap versus COG ( < 0.01). All intervention groups showed lower relative intra-plaque concentrations of MCP-1, MMP-3, and MMP-9 and a higher TIMP-1concentration compared to COG ( < 0.001). Importantly, latter parameters presented lower levels when bosentan was combined with atorvastatin compared to COG ( < 0.05). Bosentan treatment in diabetic, atherosclerotic mice delayed the atherosclerosis progression and enhanced plaques' stability, showing modest but additive effects with atorvastatin, which are promising in atherosclerotic cardiovascular diseases.
Topics: Animals; Bosentan; Atorvastatin; Mice; Male; Atherosclerosis; Endothelin Receptor Antagonists; Diabetes Mellitus, Experimental; Drug Therapy, Combination; Collagen; Diet, High-Fat; Chemokine CCL2; Tumor Necrosis Factor-alpha; Plaque, Atherosclerotic; Mice, Knockout; Tissue Inhibitor of Metalloproteinase-1
PubMed: 38928320
DOI: 10.3390/ijms25126614 -
Scientific Reports Jun 2024The development of nanomaterials has been speedily established in recent years, yet nanoparticles synthesized by traditional methods suffer unacceptable toxicity and the...
The development of nanomaterials has been speedily established in recent years, yet nanoparticles synthesized by traditional methods suffer unacceptable toxicity and the sustainability of the procedure for synthesizing such nanoparticles is inadequate. Consequently, green biosynthesis, which employs biopolymers, is gaining attraction as an environmentally sound alternative to less sustainable approaches. Chitosan-encapsulated nanoparticles exhibit exceptional antibacterial properties, offering a wide range of uses. Chitosan, obtained from shrimp shells, aided in the environmentally friendly synthesis of high-purity zinc oxide nanoparticles (ZnO NPs) with desirable features such as the extraction yield (41%), the deacetylation (88%), and the crystallinity index (74.54%). The particle size of ZnO NPs was 12 nm, while that of chitosan-ZnO NPs was 21 nm, and the bandgap energies of these nanomaterials were 3.98 and 3.48, respectively. The strong antibacterial action was demonstrated by ZnO NPs, chitosan-ZnO NPs, and chitosan-ZnO/PVP, particularly against Gram-positive bacteria, making them appropriate for therapeutic use. The photocatalytic degradation abilities were also assessed for all nanoparticles. At a concentration of 6 × 10 M, chitosan removed 90.5% of the methylene blue (MB) dye, ZnO NPs removed 97.4%, chitosan-coated ZnO NPs removed 99.6%, while chitosan-ZnO/PVP removed 100%. In the case of toluidine blue (TB), at a concentration of 4 × 10 M, the respective efficiencies were 96.8%, 96.8%, 99.5%, and 100%, respectively. Evaluation of radical scavenger activity revealed increased scavenging of ABTS and DPPH radicals by chitosan-ZnO/PVP compared to individual zinc oxide or chitosan-ZnO, where the IC50 results were 0.059, 0.092, 0.079 mg/mL, respectively, in the ABTS test, and 0.095, 0.083, 0.061, and 0.064 mg/mL in the DPPH test, respectively. Moreover, in silico toxicity studies were conducted to predict the organ-specific toxicity through ProTox II software. The obtained results suggest the probable safety and the absence of organ-specific toxicity with all the tested samples.
Topics: Chitosan; Zinc Oxide; Anti-Bacterial Agents; Catalysis; Nanoparticles; Microbial Sensitivity Tests; Metal Nanoparticles; Biphenyl Compounds; Green Chemistry Technology
PubMed: 38926522
DOI: 10.1038/s41598-024-65579-z -
BMJ (Clinical Research Ed.) Jun 2024
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 38925802
DOI: 10.1136/bmj.q1424