Adhesion Capacity Research Articles

Development of an Ionic Conductive Elastomer from the Photocopolymerization of a Ternary Polymerizable Deep Eutectic Solvent for Human Motions Sensing.

Polymerizable deep eutectic solvents (PDES) represent a novel class of ionic liquids characterized by the presence of polymerizable groups in their hydrogen-bond donor or acceptor components. Within the realm of flexible electronics, PDES is emerged as a promising material for the fabrication of sensors that exhibit both flexibility and stretchability. This research employs the UV-initiated photocopolymerization of a ternary PDES composed of choline chloride (ChCl), 2-hydroxyethyl acrylate (HEA), and itaconic acid (IA), to synthesize an ionic conductive elastomer (ICE) that boasts desirable comprehensive performances, which can be controlled by meticulously adjusting the ratios of these components. The fabrication process is streamlined and efficient, utilizing cost-effective and eco-friendly materials. This elastomer exhibits favorable ionic conductivity (1.70 × 10-2-5.45 × 10-2 S m-1), mechanical strength (0.48-1.21MPa stress at break, 395-701% elongation at break), adhesion capacity (49-120kPa adhesion strength), and sensing sensitivity toward human motions.

WD-repeat containing protein-61 regulates endometrial epithelial cell adhesion indicating an important role in receptivity.

Endometrial receptivity is crucial for successful embryo implantation during early pregnancy. The human endometrium undergoes remodeling within each menstrual cycle to prepare or become receptive to an implanting blastocyst in the mid-secretory phase. However, the mechanisms behind these changes are not fully understood. Recently, using hormone treated endometrial organoids to model receptivity, we identified that the transcriptional regulator WD-repeat-containing protein-61 (WDR61) was reduced in organoids derived from infertile women. In this study, we aimed to determine the role of WDR61 in endometrial receptivity. Here we demonstrated that WDR61 immunolocalizes in the nuclei and cytosol of endometrial glandular epithelium, luminal epithelium and stroma. The staining intensity of WDR61 was significantly higher during the receptive mid-secretory phase compared to the non-receptive proliferative phase in fertile women. In a functional experiment to model blastocyst adhesion to the endometrial epithelium, we found that adhesion of cytotrophoblast progenitor spheroids was blocked when siRNA was used to knockdown WDR61 in primary endometrial epithelial cells. Similarly, in Ishikawa cells (a receptive human endometrial epithelial cell line), siRNA knockdown of WDR61 significantly reduced the cell adhesive and proliferative capacities. qPCR revealed that WDR61 knockdown reduced expression of key genes involved in receptivity including HOXD10, MMP2 and CD44. Chromatin immunoprecipitation sequencing demonstrated that WDR61 directly targeted 2,022 genes in Ishikawa cells, with functions including focal adhesion, intracellular signaling and epithelial-mesenchymal transition. Overall, these findings suggest that WDR61 promotes endometrial receptivity by modulating epithelial cell focal adhesions, proliferation and epithelial-mesenchymal transition.

Evaluation of Mixing Temperature in the Preparation of Plant-Based Bigels

Understanding gel structures and behavior is a prerequisite for attaining the desired food application characteristics. The mixing temperature is crucial when incorporating thermolabile active compounds into gels. This study evaluated the effect of mixing temperature on the physical and chemical properties of a bigel system prepared using a carnauba wax/canola oil oleogel and Arabic gum hydrogels. The results showed that bigels prepared at lower temperatures (30 and 40 °C) resulted in a solid-like state under crystallization temperature, resulting in matrices with larger hydrogel droplets, softer texture, and lower adhesiveness, spreadability, and solvent binding capacity. In contrast, bigels prepared at higher temperatures (50 and 60 °C), around crystallization temperature but with no solid state, resulted in matrices with smaller hydrogel droplets and higher firmness, adhesiveness, and spreadability. These bigels had a higher apparent viscosity, especially at lower shear rates, and solid-like behavior in the linear viscosity range. During the bigel preparation process, adjusting the mixture temperature had no effect on the samples’ oxidative stability, FTIR spectra, or thermal properties. The results highlighted the importance of hydrogel droplet size on the microstructure of the formed bigels, and smaller droplets could act as effective fillers to reinforce the matrix without making chemical changes.

Mesomycoplasma (Mycoplasma) ovipneumoniae dihydrolipoamide dehydrogenase is an immunogenic plasminogen binding protein and a putative adhesin

The interaction of Mesomycoplasma (Mycoplasma) ovipneumoniae (M. ovipneumoniae) with host cells is a pivotal step in the infection process, underlining the necessity to develop vaccines and therapeutic approaches targeting the pathogen's key invasion mechanisms. The bacterium's capacity for adherence, invasion, and subsequent evasion of the host immune response underpins its pathogenicity, rendering adherence genes feasible vaccine targets. This study focuses on pyruvate dehydrogenase complex component E3 (PdhD), a membrane-anchored surface protein implicated in these pathogenic processes. Bioinformatics analysis reveals the conservation of PdhD sequence within M. ovipneumoniae. Membrane protein extraction, immunoblotting and ELISA assay have confirmed the presence of PdhD on the M. ovipneumoniae surface and cytoplasm, suggesting its multifunctionality. Our research employed antibody inhibition assays to characterize the bacterial adhesion suppression by anti-PdhD antibodies, complemented by bactericidal complement assays, supporting its candidacy as a putative vaccine target. The ELISA binding assay substantiated that PdhD binded to plasminogen (Plg) in a dose-dependent manner. Notably, PdhD is also involved in biofilm formation. The inhibitory effect of anti-PdhD sera on biofilm formation is congruent with novel therapeutic strategies targeting related mycoplasmas. This study reports the characterization of the first virulence-associated protein PdhD of M. ovipneumoniae and suggests its potential as a vaccine target to combat M. ovipneumoniae infection.

3D-printed laponite bioceramic triply periodic minimal surface scaffolds with excellent bioactivity for bone regeneration

Laponite (LAP) is a promising biomaterial for bone regeneration due to its reliable biocompatibility and excellent osteoinductivity in bone tissue engineering. However, the personalized manufacture of LAP bioceramic scaffolds with controlled complex architecture and high porosity remains challenging. This study used vat photopolymerization (VPP) to manufacture LAP bioceramic scaffolds with high precision and biological activity. We first selected a 40 wt% LAP bioceramic slurry for subsequent VPP printing based on stability experiments and viscosity characterization results. The curing parameters of the photosensitive bioceramic slurry and the degassing sintering process were studied to ensure the quality of the ceramic green bodies. Then, we characterized the effects of different sintering temperatures (1150°C, 1200°C, 1250°C) on the crystalline phase composition, microstructure, and mechanical properties of the LAP bioceramic. The research showed that the densification and compressive strength of the LAP bioceramic sintered at 1250°C reached 2.51 g/cm3 and 15 Mpa, respectively. Finally, the bioceramic scaffolds with different sintering temperatures were co-cultured with rat bone marrow mesenchymal stem cells to detect biocompatibility. The results showed that the three groups of scaffolds enhanced cell proliferation, adhesion, and osteogenic capacity. In conclusion, the LAP bone scaffolds by VPP presented the potential for bone repair.

Environmentally stable and multi-functional conductive gelatin/PVA/black wattle bark tannin based organogel as strain, temperature and bioelectric sensor for multi-mode sensing

Conductive hydrogels are regarded as ideal candidates for the application of flexible sensors owing to their excellent flexibility, portability and conductivity. However, it is still challenging and meaningful to prepare multifunctional (self-healing, adhesion, anti-freezing, biocompatibility, antibacterial and conductivity properties) and multi-mode sensing hydrogel-based sensors. Herein, we developed an environmentally stable and multi-functional conductive organogel via dynamic crosslinks based on biomass materials gelatin, black wattle bark tannin and PVA in the propylene glycol/water binary solvent system. Thanks to the dynamic interactions in the system, the good mechanical strength and self-healing performance of the obtained organogel are simultaneously realized. Meanwhile, the organogel integrates many crucial properties such as adhesion, environmental stability (anti-freezing and water retention), biocompatibility, antibacterial behavior and conductivity capacity. Significantly, the organogel can be assembled as three-mode sensors for strain, bioelectricity and temperature sensing. This three-mode sensor can effectively monitor human health data, resulting in providing supplement human health information and conditions. This work displays an interesting approach to construct an intelligent multi-functional conductive biomass organogel based multi-mode flexible sensors.

Crack-growth inhibition by designing dendritic pattern for soft adhesives

Soft adhesive layers show promise in various engineering applications, including biomedicine, automotive, semiconductor, and aerospace industries. However, cavities trapped at the interface due to poor contact will significantly inhibit their adhesion capacity, leading to rapid crack-growth failure. Significant efforts in these applications within a confined contact area are focused on mitigating the effects and enhancing the debonding work of the interface without changing the materials, such as using bioinspired micropillars. However, soft adhesives with isolated contact elements face limitations due to manufacturing complexity and the collision of micropillars under large deformation. This study proposes a simple and effective method to reduce the hydrostatic pressure around the crack tips by designing a dendritic pattern within the confined area. This approach inhibited interface crack growth well and improved adhesive performance. As a result, the crack failure was delayed, with the stretch ratio enhanced by more than 36 %, while the debonding work increased by 85 % compared with the circular adhesive layer. This study demonstrates that adhesion capacity can be significantly improved while reducing material usage by designing dendritic patterns.

Micromechanism of interparticle normal magnetic attraction effect in magnetorheological suspensions based on magnetic-dipole theory

In order to reveal adsorption-regulation micromechanism and debonding micromechanism between wall surface and magnetorheological (MR) wall-climbing robot legs, an interparticle normal magnetic attraction (NMA) mechanics model was constructed based upon the magnetic-dipole theory. According to analysis of NMA mechanics, it was confirmed that the interparticle NMA could be intensified with enhancing magnetic-particle diameter but was weakened with ratio of adjacent magnetic-particles distance to magnetic-particle radius. It means that the adhesive capacity between MR wall-climbing robot legs and wall surface could be strengthened by increasing magnetic-particle size and decreasing interparticle distance. Furthermore, it was found that the NMA of the first particle in the magnetic chain was positively related to magnetic-particles number until the magnetic-particles number reached a critical value. Consequently, the adsorption ability between MR wall-climbing robot legs and wall surface could be effectively controlled by changing magnetic-particles number. Besides, the strongest NMA appeared at the middle of the magnetic chain. However, the weakest NMA locates at both ends of the magnetic chain. Thus, it could be concluded that the end of the magnetic chain would be separated from wall surface rather than fracture occurred in the middle of the magnetic chain when the MR wall-climbing robot legs divorced from wall surface.

The Impact of Subinhibitory Concentrations of Ɛ-polylysine, Hydrogen Peroxide, and Lauric Arginate on Listeria monocytogenes Virulence

Recent studies on the use of plant-derived and other bioactive compounds and antimicrobials in food have challenged the idea that exposure to antimicrobials at sublethal or subinhibitory concentrations (SICs) increases the virulence potential of bacterial pathogens including Listeria monocytogenes. The objective of this study was to determine the effect of exposure to SICs of Ɛ-polylysine (EPL), hydrogen peroxide (HP), and lauric arginate (LAE) on L. monocytogenes virulence. For all assays, L. monocytogenes strains Scott A and 2014L-6025 were grown to mid-log phase in the presence of SICs of EPL, HP, or LAE. Motility was determined by spot inoculating cultures on soft brain heart infusion agar (0.3% agar). Cultures grown in SICs of antimicrobials were also inoculated onto Caco-2 cells (10:1 MOI) to determine the effects on subsequent adhesion and invasion. Last, the relative expression of key virulence genes (prfA, plcB, hlyA, actA, inlA, inlB, sigB, and virR) following growth in SICs was determined by RT-qPCR. Results indicate that L. monocytogenes growth in the presence of SICs of EPL, HP, or LAE did not affect the motility, adhesion, or invasion capacity of either strain. Changes in gene expression were observed for both L. monocytogenes strains. More specifically, SICs of EPL and LAE reduced hlyA expression in Scott A, whereas SICs of EPL and HP increased the expression of virR. The upregulation of sigB and actA in the presence of EPL and LAE, respectively, was observed in strain 2014L-6025. These findings indicate that exposure to SICs of these antimicrobials has varying effects on L. monocytogenes that differ by strain. Although no phenotypic effects were observed in terms of motility, adhesion, and invasion, the observed changes in virulence gene expression warrant further investigation.

Isolated prolapse of the posterior mitral valve leaflet: phenotypic refinement, heritability and genetic etiology.

Isolated posterior leaflet mitral valve prolapse (PostMVP), a common form of MVP, often referred as fibroelastic deficiency, is considered a degenerative disease. PostMVP patients are usually asymptomatic and often undiagnosed until chordal rupture. The present study aims to characterize familial PostMVP phenotype and familial recurrence, its genetic background, and the pathophysiological processes involved. We prospectively enrolled 284 unrelated MVP probands, of whom 178 (63%) had bi-leaflet MVP and 106 had PostMVP (37%). Familial screening within PostMVP patients allowed the identification of 20 families with inherited forms of PostMVP for whom whole genome sequencing was carried out in probands. Functional in vivo and in vitro investigations were performed in zebrafishand in Hek293T cells. In the 20 families with inherited form of PostMVP, 38.8% of relatives had a MVP/prodromal form, mainly of the posterior leaflet, with transmission consistent with an autosomal dominant mode of inheritance. Compared with control relatives, PostMVP family patients have clear posterior leaflet dystrophy on echocardiography. Patients with PostMVP present a burden of rare genetic variants in ARHGAP24. ARHGAP24 encodes the filamin A binding RhoGTPase-activating protein FilGAP and its silencing in zebrafish leads to atrioventricular regurgitation. In vitro functional studies showed that variants of FilGAP, found in PostMVP families, are loss-of-function variants impairing cellular adhesion and mechano-transduction capacities. PostMVP should not only be considered an isolated degenerative pathology but as a specific heritable phenotypic trait with genetic and functional pathophysiological origins. The identification of loss-of-function variants in ARHGAP24 further reinforces the pivotal role of mechano-transduction pathways in the pathogenesis of MVP. Isolated posterior mitral valve prolapse (PostMVP), often called fibro-elastic deficiency MVP, is at least in some patients, a specific inherited phenotypic traitPostMVP has both genetic and functional pathophysiological origins Genetic variants in the ARHGAP24 gene, which encodes for the FilGAP protein, cause progressive Post MVP in familial cases, and impair cell adhesion and mechano-transduction capacities.

Anti-Cancer Potential of Linear β-(1→6)-D-Glucan from Agaricus bisporus on Estrogen Receptor-Positive (ER+) Breast Cancer Cells

Mushroom β-D-glucans can be isolated from several species, including the widely consumed Agaricus bisporus. Besides immunomodulatory responses, some β-D-glucans may exhibit direct antitumoral effects. It was previously observed that a β-(1→6)-D-glucan (BDG16) has indirect cytotoxicity on triple-negative breast cancer cells. In this study, the cytotoxicity of this same glucan was observed on estrogen receptor-positive (ER+) breast cancer cells (MCF-7). Cell viability was determined by multiple methods to assess metabolic activity, lysosomal membrane integrity, and adhesion capacity. Assays to evaluate cell respiration, cell cycle, apoptosis, necroptosis, and oxidative stress were performed to determine the action of BDG16 on MCF-7 cells. A gradual and significant cell viability reduction was observed when the cells were treated with BDG16 (10–1000 µg/mL). This result could be associated with the inhibition of the basal state respiration after incubation with the β-D-glucan. The cells showed a significant arrest in G1 phase population at 1000 µg/mL, with no induction of apoptosis. However, an increase in necrosis and necroptosis at the same concentration was observed. No difference in oxidative stress-related molecules was observed. Altogether, our findings demonstrate that BDG16 directly induces toxicity in MCF-7 cells, primarily by impairing mitochondrial respiration and promoting necroptosis. The specific mechanisms that mediate this action are being investigated.

Pre-vascularized porous gelatin-coated β-tricalcium phosphate scaffolds for bone regeneration: an in vivo and in vitro investigation.

Vascularization is vital in bone tissue engineering, supporting development, remodeling, and regeneration. Lack of vascularity leads to cell death, necessitating vascularization strategies. Angiogenesis, forming new blood vessels, provides crucial nutrients and oxygen. Pre-vascularized gelatin-coated β-tricalcium phosphate (G/β-TCP) scaffolds show promise in bone regeneration and vascularization. Our study evaluates G/β-TCP scaffolds' osteogenic and angiogenic potential in vitro and a canine model with vascular anastomosis. Channel-shaped G/β-TCP scaffolds were fabricated using foam casting and sintering of a calcium phosphate/silica slurry-coated polyurethane foam, then coated with cross-linked gelatin. Buccal fat pad-derived stem cells (BFPdSCs) were seeded onto scaffolds and assessed over time for adhesion, proliferation, and osteogenic capacity using scanning electron microscopy (SEM), 4,6-diamidino-2-phenylindole (DAPI) staining, Alamar blue, and alkaline phosphatase (ALP) assays. Scaffolds were implanted in a canine model to evaluate osteogenesis and angiogenesis by histology and CT scans at 12 wk. Our studies showed preliminary results for G/β-TCP scaffolds supporting angiogenesis and bone regeneration. In vitro analyses demonstrated excellent proliferation/viability, with BFPdSCs adhering and increasing on the scaffolds. ALP activity and protein levels increased, indicating osteogenic differentiation. Examination of tissue samples revealed granulation tissue with a well-developed vascular network, indicating successful angiogenesis and osteogenesis was further confirmed by a CT scan. In vivo, histology revealed scaffold resorption. However, scaffold placement beneath muscle tissue-restricted bone regeneration. Further optimization is needed for bone regeneration applications.

Programmable adhesion through triangular and hierarchical cuts in metamaterial adhesives.

Metamaterial design approaches, which integrate structural elements into material systems, enable the control of uncommon behaviours by decoupling local and global properties. Leveraging this conceptual framework, metamaterial adhesives incorporate nonlinear cut architectures into adhesive films to achieve unique combinations of adhesion capacity, release, and spatial tunability by controlling how cracks propagate forward and in reverse directions during separation. Here, metamaterial adhesive designs are explored with triangular cut features while integrating hierarchical and secondary cut patterns among primary nonlinear cuts. Both cut geometry and secondary cut features tune adhesive force capacity and energy of separation. Importantly, the size and spacing of cut features must be designed around a critical length scale. When secondary cut features are greater than a critical length, cracks can be steered in multiple directions, going both forward and backwards within a primary attachment element. This control over crack dynamics enhances the work of separation by a factor of 1.5, while maintaining the peel force relative to a primary cut. If hierarchical cut features are too small or too compliant, they interact and do not distinctly modify crack behaviour. This work highlights the importance of adhesive length scales and stiffness for crack control and attachment characteristics in adhesive films.This article is part of the theme issue 'Origami/Kirigami-inspired structures: from fundamentals to applications'.

Dysregulated miR-124-3p in endometrial epithelial cells reduces endometrial receptivity by altering polarity and adhesion

The endometrium undergoes substantial remodeling in each menstrual cycle to become receptive to an implanting embryo. Abnormal endometrial receptivity is one of the major causes of embryo implantation failure and infertility. MicroRNA-124-3p is elevated in both the serum and endometrial tissue of women with chronic endometritis, a condition associated with infertility. MicroRNA-124-3p also has a role in cell adhesion, a key function during receptivity to allow blastocysts to adhere and implant. In this study, we aimed to determine the function of microRNA-124-3p on endometrial epithelial adhesive capacity during receptivity and effect on embryo implantation. Using a unique inducible, uterine epithelial-specific microRNA overexpression mouse model, we demonstrated that elevated uterine epithelial microRNA-124-3p impaired endometrial receptivity by altering genes associated with cell adhesion and polarity. This resulted in embryo implantation failure. Similarly in a second mouse model, increasing microRNA-124-3p expression only in mouse uterine surface (luminal) epithelium impaired receptivity and led to implantation failure. In humans, we demonstrated that microRNA-124-3p was abnormally increased in the endometrial epithelium of women with unexplained infertility during the receptive window. MicroRNA-124-3p overexpression in primary human endometrial epithelial cells (HEECs) impaired primary human embryo trophectoderm attachment in a 3-dimensional culture model of endometrium. Reduction of microRNA-124-3p in HEECs from infertile women normalized HEEC adhesive capacity. Overexpression of microRNA-124-3p or knockdown of its direct target IQGAP1 reduced fertile HEEC adhesion and its ability to lose polarity. Collectively, our data highlight that microRNA-124-3p and its protein targets contribute to endometrial receptivity by altering cell polarity and adhesion.

Insights into sex differences in perioperative outcomes of non-small cell lung cancer patients.

The appreciation of sex differences is substantial for precise cancer management. Surgery is the main treatment for non-small cell lung cancer (NSCLC). We aimed to identify sex differences on perioperative outcomes in NSCLC patients and to uncover the origins of sex effect in outcomes using a Chinese cohort. We retrospectively enrolled patients undergoing NSCLC surgery in the Western China Lung Cancer Database from January 2014 to April 2021. We compared baseline characteristics and perioperative outcomes between male and female. Multivariable analyses were performed. We conducted causal mediation analysis to identify drivers to sex differences in perioperative outcomes. Altogether, data of 10,181 patients (5,738 women and 4,443 men) were analyzed. Women had lower incidence of complications (5.05% vs. 12.15%), shorter postoperative length of stays (4.92 vs. 6.41 days), and less hospitalization cost (50,713.69 vs. 54,580.85, Chinese Yuan). Multivariable regression analysis identified sex as an independent factor of perioperative complications [odds ratio (OR), 1.843, 95% confidence interval (CI): 1.476-2.294], as well as of postoperative length of hospital stays (beta 0.123, 95% CI: 0.099-0.148), and hospitalization cost (beta 0.026, 95% CI: 0.026-0.026). Mediation analysis revealed that age, body mass index, prevalence of chronic obstructive pulmonary disease, predicted diffusion capacity for carbon monoxide, tumor size, pleural adhesion, and surgery duration were identified as mediators for sex differences in outcomes, while smoking status, surgery type, and resection extent were not. Female NSCLC patients demonstrated lower incidence of complications, shorter postoperative length of stays, and less hospitalization cost after surgery. Those differences between men and women could be explained by their inherent biological differences and baseline health status. Perioperative management strategies for NSCLC should prioritize recognizing the potentially poorer outcomes among male patients and implementing tailored precautions accordingly.

Evaluation of the Mechanical Strength and Cell Adhesion Capacity of POSS Doped PVA/CMC Hernia Patch.

Peritoneal adhesion typically occurs in applications such as abdominal, pelvic, and vascular surgery. It is necessary to develop a mechanical barrier to prevent adhesion. In this study, a novel biomaterial as a mechanical barrier is developed by combining polyvinyl alcohol (PVA) and carboxymethyl cellulose (CMC), doped with polyhedral oligomeric silsesquioxane (POSS) to prevent peritoneal adhesion. Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) methods reveal that POSS nanoparticles in the PVA matrix disrupted the intramolecular hydroxyl groups and structure of the crystal region. Electron microscopy (EM) images reveal that high concentrations of POSS (2wt.%) cause irregular clustering in the composite matrix. As the concentration of POSS increases in the matrix, the degradation of the membranes increases, and protein adhesion decreases. In vitro cytotoxicity tests show a toxic effect on cells for PVA/CMC composite membranes, while on the other hand, the addition of POSS increases cell viability. According to the MMT test the POSS decreases cell adhesion of membranes. When comparing the POSS doped membrane to the undoped PVA/CMC membrane, an increase in the total antioxidant level and a decrease in the total oxidant level is observed.

Meibomian gland lipid alterations and ocular surface sequela in Awat2 knockout murine model of meibomian gland dysfunction and evaporative dry eye disease

PurposeThere is an urgent need for animal models of meibomian gland dysfunction (MGD) and evaporative dry eye disease (EDED) to understand their pathophysiology and investigate novel therapeutics. This study sought to further define the acyl-CoA: wax alcohol acyltransferase 2 knockout (Awat2 KO) mouse as a model of EDED using a combination of novel clinical, biochemical, and biophysical endpoints. MethodsWildtype and Awat2 KO mice between 1 and 18 months of age were used. Ocular examinations and advanced imaging were performed. The lipidomic composition and in situ melting temperature of meibum were determined. qPCR was performed to define ocular surface gene and pro-inflammatory transcript expression. Dynamic contact angle goniometry was performed to assess the adherence capability of the ocular surface. ResultsAwat2 KO mice have mild, white, hyperreflective corneal opacities of the anterior stroma and significantly enlarged apical epithelial cells (P=0.0004). In Awat2 KO meibum, wax esters were 9-10 times lower than in wildtype meibum. Additionally, meibum melting temperature increased from 32° to 47°C (P<0.0001), leading to impaired meibum secretion and dilation of the central duct. Awat2 KO corneal epithelia had significantly decreased mucin expression (Muc1 and Muc4, P=0.0043) and increased interferon-γ production (P=0.0303). Awat2 KO globes have a significantly shortened time of droplet adherence to their ocular surface (P=0.0053), indicating a decreased tear film adherence capacity. Wildtype corneal epithelia does not express Awat2, indicating that the EDED phenotype is secondary to the loss of Awat2 from the meibomian glands. ConclusionsAwat2 KO mice recapitulate many of features of human MGD and EDED, representing a model to test novel therapeutics.

Physico-Chemical Characterization and Initial Evaluation of Carboxymethyl Chitosan-Hyaluronan Hydrocolloid Systems with Insulin Intended for Intranasal Administration.

The nasal route of administration can bypass the blood-brain barrier in order to obtain a higher concentration in the brain, thus offering a feasible alternative route of administration for diseases associated with the central nervous system. The advantages of the intranasal administration and the potential favorable therapeutic effects of intranasally administered insulin led to the formulation of carboxymethyl chitosan (CMC) and sodium hyaluronate (NaHA) hydrocolloidal systems with insulin for nasal administration, targeting nose-to-brain delivery and the initial assessment of these systems. The influence of the formulation variables on the response parameters defined as surface properties, rheology, and in vitro release of insulin were analyzed using experimental design and statistical programs (Modde and Minitab software). The systems recorded good wetting and adhesion capacity, allowing the spread of the hydrocolloidal systems on the nasal mucosa. The samples had a pseudoplastic flow and the rapid release of the insulin was according to our objective. According to the physico-chemical characterization and preliminary assessment, these formulations are appropriate for administration on the nasal mucosa, but further studies are necessary to demonstrate the beneficial therapeutic actions and the safety of using intranasal insulin.

Virulence-Related Genes Expression in Planktonic Mixed Cultures of Candida albicans and Non-Albicans Candida Species

Introduction: Candida albicans is the most common opportunistic pathogen causing fungal infections worldwide, especially in high-risk patients. Its pathogenicity is related to virulence factors gene expression, such as hyphal growth (HWP1), cell adhesion (ALS3), and protease secretion (SAP1) during infection spreading mechanisms. In recent years, an increase in non-albicans Candida infections has been reported, which may present coinfection or competitive interactions with C. albicans, potentially aggravating the patient’s condition. This study aims to evaluate the expression of genes related to virulence factors of C. albicans and non-albicans Candida during planktonic stage. Methods: C. albicans (ATCC MYA-3573) as well as with three clinical strains (C. albicans DCA53, C. tropicalis DCT6, and C. parapsilosis DCP1) isolated from blood samples, were grown in 24-well plates at 37°C for 20 h, either in monocultures or mixed cultures. Quantitative real-time polymerase chain reaction was used to evaluate the expression levels of the genes HWP1, ALS3, and SAP1 in cells collected during the planktonic stage. In addition, hyphal filamentation was observed using a Scanning Electron Microscope. Results: The overexpression of HWP1 and ASL3 genes in mixed growth conditions between C. albicans and non-albicans Candida species suggests a synergistic relationship as well as an increased capacity for hyphal growth and adhesion. In contrast, C. parapsilosis versus C. tropicalis interaction shows an antagonistic relationship during mixed culture, suggesting a decreased virulence profile of C. parapsilosis during initial coinfection with C. tropicalis. Conclusion: The expression of HWP1, ALS3, and SAP1 genes associated with virulence factors varies under competitive conditions among species of the genus Candida during planktonic stage.

Antibacterial Activity and Prebiotic Properties of Six Types of Lamiaceae Honey.

Our work investigated the antimicrobial and prebiotic properties of basil, mint, oregano, rosemary, savory, and thyme honey. The potential antimicrobial action, assessed against the pathogens Acinetobacter baumannii, Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, and Staphylococcus aureus, evidenced the capacity of the honey to influence the pathogenic hydrophobicity and hemolytic activities. Honey inhibited pathogen biofilms, acting especially on the mature biofilms, with inhibition rates of up to 81.62% (caused by the presence of mint honey on L. monocytogenes). S. aureus biofilms were the most susceptible to the presence of honey, with inhibition rates up of to 67.38% in the immature form (caused by basil honey) and up to 80.32% in the mature form (caused by mint honey). In some cases, the amount of nuclear and proteic material, evaluated by spectrophotometric readings, if also related to the honey's biofilm inhibitory activity, let us hypothesize a defective capacity of building the biofilm scaffold or bacterial membrane damage or an incapability of producing them for the biofilm scaffold. The prebiotic potentiality of the honey was assessed on Lacticaseibacillus casei Shirota, Lactobacillus gasseri, Lacticaseibacillus paracasei subsp. paracasei, and Lacticaseibacillus rhamnosus and indicated their capacity to affect the whole probiotic growth and in vitro adhesive capacity, as well as the antioxidant and cytotoxic abilities, and to inhibit, mainly in the test performed with the L. casei Shirota, L. gasseri, and L. paracasei supernatants, the immature biofilm of the pathogens mentioned above.