In Vitro Human Endometrial Cells and In Vivo Rat Model Studies Suggest That Ulipristal Acetate Impacts Endometrial Compatibility for Embryo Implantation.

BACKGROUND: Ulipristal acetate (UPA) and levonorgestrel are used as emergency hormonal contraceptives. Although both are highly effective in preventing pregnancy, UPA shows efficacy even when taken up to 120 h after unprotected sexual intercourse. AIMS: To investigate whether the mechanism of UPA's contraceptive action involves post-fertilization effects. METHODS: In vitro and in vivo studies using cultured human endometrial cells and a pre-clinical rat model. RESULTS: Endometrial cells treated with UPA showed changes in the expression of receptivity gene markers and a significant decrease in trophoblast spheroids attached to the cultured cells. In addition, administration of UPA to female unmated rats decreased the expression of implantation-related genes in the endometrium and inhibited the number of implantation sites in the mated group compared to the non-treated group. CONCLUSIONS: These results support that UPA as an emergency contraceptive might have post-fertilization effects that may affect embryo implantation.

Cellulose acetate scaffold coated with a hydroxyapatite/graphene oxide nanocomposite for application in tissue engineering.

The objective of this study was to synthesize and characterize porous Cellulose Acetate (CA) scaffolds using the electrospinning technique and functionalize the surface of the scaffolds obtained through the dip-coating method with a Hydroxyapatite (HA) nanocomposite and varying concentrations of graphene oxide (GO) for application in tissue engineering regeneration techniques. The scaffolds were divided into four distinct groups based on their composition: 1) CA scaffolds; 2) CAHAC scaffolds; 3) CAHAGOC 1.0% scaffolds; 4) CAHAGOC 1.5% scaffolds. Scaffold analyses were conducted using X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Raman Spectroscopy, Scanning Electron Microscopy with Energy Dispersive Spectroscopy (SEM/EDS), and in vitro cell viability assays (WST). For the biological test analysis, Variance (two-way) was used, followed by Tukey's post-test (α = 0.05). The XRD results revealed the predominant presence of CaP phases in the CAHAC, CAHAGOC 1.0%, and CAHAGOC 1.5% groups, emphasizing the presence of HA in the scaffolds. FTIR demonstrated characteristics of cellulose and PO4 bands in the groups containing HA, confirming the presence of CaP in the synthesized materials, as also indicated by XRD. Raman spectroscopy showed the presence of D and G bands, consistent with GO, confirming the successful incorporation of the HAGO nanocomposite into the scaffolds. The micrographs displayed overlapping electrospun fibers, forming the three-dimensional structure in the produced scaffolds. It was possible to observe hydroxyapatite crystals filling some of these pores, creating a suitable structure for cell adhesion, proliferation, and nutrition, as corroborated by the results of in vitro tests. All scaffolds exhibited high cell viability, with significant cell proliferation. Even after 48 h, there was a slight reduction in the number of cells, but a noteworthy increase in cell proliferation was evident in the CAHAGOC 1.5% group after 48 h (p < 0.05). In conclusion, it can be affirmed that the produced scaffolds demonstrated physical and biological characteristics and properties capable of promoting cell adhesion and proliferation. Therefore, they represent significant potential for application in tissue engineering, offering a new perspective regarding techniques and biomaterials applied in regenerative therapies.

Development of biopolymer films loaded with fluconazole and thymol for resistant vaginal candidiasis.

Vulvovaginal candidiasis (VVC) is an opportunistic infection caused by a fungus of the Candida genus, affecting approximately 75 % of women during their lifetime. Fungal resistance cases and adverse effects have been the main challenges of oral therapies. In this study, the topical application of thin films containing fluconazole (FLU) and thymol (THY) was proposed to overcome these problems. Vaginal films based only on chitosan (CH) or combining this biopolymer with pectin (PEC) or hydroxypropylmethylcellulose acetate succinate (HPMCAS) were developed by the solvent casting method. In addition to a higher swelling index, CH/HPMCAS films showed to be more plastic and flexible than systems prepared with CH/PEC or only chitosan. Biopolymers and FLU were found in an amorphous state, contributing to explaining the rapid gel formation after contact with vaginal fluid. High permeability rates of FLU were also found after its immobilization into thin films. The presence of THY in polymer films increased the distribution of FLU in vaginal tissues and resulted in improved anti-Candida activity. A significant activity against the resistant C. glabrata was achieved, reducing the required FLU dose by 50 %. These results suggest that the developed polymer films represent a promising alternative for the treatment of resistant vulvovaginal candidiasis, encouraging further studies in this context.

Lactobacillus delbrueckii CIDCA 133 fermented milk modulates inflammation and gut microbiota to alleviate acute colitis.

Lactobacillus delbrueckii subsp. lactis CIDCA 133 is a health-promoting bacterium that can alleviate gut inflammation and improve the epithelial barrier in a mouse model of mucositis. Despite these beneficial effects, the protective potential of this strain in other inflammation models, such as inflammatory bowel disease, remains unexplored. Herein, we examined for the first time the efficacy of Lactobacillus delbrueckii CIDCA 133 incorporated into a fermented milk formulation in the recovery of inflammation, epithelial damage, and restoration of gut microbiota in mice with dextran sulfate sodium-induced colitis. Oral administration of Lactobacillus delbrueckii CIDCA 133 fermented milk relieved colitis by decreasing levels of inflammatory factors (myeloperoxidase, N-acetyl-ß-D-glucosaminidase, toll-like receptor 2, nuclear factor-κB, interleukins 10 and 6, and tumor necrosis factor), secretory immunoglobulin A levels, and intestinal paracellular permeability. This immunobiotic also modulated the expression of tight junction proteins (zonulin and occludin) and the activation of short-chain fatty acids-related receptors (G-protein coupled receptors 43 and 109A). Colonic protection was effectively associated with acetate production and restoration of gut microbiota composition. Treatment with Lactobacillus delbrueckii CIDCA 133 fermented milk increased the abundance of Firmicutes members (Lactobacillus genus) while decreasing the abundance of Proteobacteria (Helicobacter genus) and Bacteroidetes members (Bacteroides genus). These promising outcomes influenced the mice's mucosal healing, colon length, body weight, and disease activity index, demonstrating that this immunobiotic could be explored as an alternative approach for managing inflammatory bowel disease.

Flexible Force Sensor Based on a PVA/AgNWs Nanocomposite and Cellulose Acetate.

Nanocomposites are materials of special interest for the development of flexible electronic, optical, and mechanical devices in applications such as transparent conductive electrodes and flexible electronic sensors. These materials take advantage of the electrical, chemical, and mechanical properties of a polymeric matrix, especially in force sensors, as well as the properties of a conductive filler such as silver nanowires (AgNWs). In this work, the fabrication of a force sensor using AgNWs synthesized via the polyol chemical technique is presented. The nanowires were deposited via drop-casting in polyvinyl alcohol (PVA) to form the active (electrode) and resistive (nanocomposite) sensor films, with both films separated by a cellulose acetate substrate. The dimensions of the resulting sensor are 35 mm × 40 mm × 0.1 mm. The sensor shows an applied force ranging from 0 to 3.92 N, with a sensitivity of 0.039 N. The sensor stand-off resistance, exceeding 50 MΩ, indicates a good ability to detect changes in applied force without an external force. Additionally, studies revealed a response time of 10 ms, stabilization of 9 s, and a degree of hysteresis of 1.9%. The voltage response of the sensor under flexion at an angle of 85° was measured, demonstrating its functionality over a prolonged period. The fabricated sensor can be used in applications that require measuring pressure on irregular surfaces or systems with limited space, such as for estimating movement in robot joints.

Mechanistic insights into C(sp2)-H activation in 1-Phenyl-4-vinyl-1H-1,2,3-triazole derivatives: a theoretical study with palladium acetate catalyst.

CONTEXT: The activation of C-H bonds is a fundamental process in synthetic organic chemistry, which enables their replacement by highly reactive functional groups. Coordination compounds serve as effective catalysts for this purpose, as they facilitate chemical transformations by interacting with C-H bonds. A comprehensive understanding of the mechanism of activation of this type of bond lays the foundation for the development of efficient protocols for cross-coupling reactions. We explored the activation of C(sp2)-H bonds in 1-Phenyl-4-vinyl-1H-1,2,3-triazole derivatives with CH3, OCH3, and NO2 substituents in the para position of the phenyl ring, using palladium acetate as catalyst. The studied reaction is the first step for subsequent conjugation of the triazoles with naphthoquinones in a Heck-type reaction to create a C-C bond. The basic nitrogen atoms of the 1,2,3-triazole coordinate preferentially with the cationic palladium center to form an activated species. A concerted proton transfer from the terminal vinyl carbon to one of the acetate ligands with low activation energy is the main step for the C(sp2)-H activation. This study offers significant mechanistic insights for enhancing the effectiveness of C(sp2)-H activation protocols in organic synthesis. METHODS: All calculations were performed using the Gaussian 09 software package and density functional theory (DFT). The structures of all reaction path components were fully optimized using the CAM-B3LYP functional with the Def2-SVP basis set. The optimized geometries were analyzed by computing the second-order Hessian matrix to confirm that the corresponding minimum or transition state was located. To account for solvent effects, the Polarizable Continuum Model of the Integral Equation Formalism (IEFPCM) with water as the solvent was used.

Corrigendum: Random cellulose acetate nanofibers: a breakthrough for cultivated meat production.

[This corrects the article DOI: 10.3389/fnut.2023.1297926.].

Sodium acetate increases the productivity of HEK293 cells expressing the ECD-Her1 protein in batch cultures: experimental results and metabolic flux analysis.

Human Embryonic Kidney cells (HEK293) are a popular host for recombinant protein expression and production in the biotechnological industry. This has driven within both, the scientific and the engineering communities, the search for strategies to increase their protein productivity. The present work is inserted into this search exploring the impact of adding sodium acetate (NaAc) into a batch culture of HEK293 cells. We monitored, as a function of time, the cell density, many external metabolites, and the supernatant concentration of the heterologous extra-cellular domain ECD-Her1 protein, a protein used to produce a candidate prostate cancer vaccine. We observed that by adding different concentrations of NaAc (0, 4, 6 and 8 mM), the production of ECD-Her1 protein increases consistently with increasing concentration, whereas the carrying capacity of the medium decreases. To understand these results we exploited a combination of experimental and computational techniques. Metabolic Flux Analysis (MFA) was used to infer intracellular metabolic fluxes from the concentration of external metabolites. Moreover, we measured independently the extracellular acidification rate and oxygen consumption rate of the cells. Both approaches support the idea that the addition of NaAc to the culture has a significant impact on the metabolism of the HEK293 cells and that, if properly tuned, enhances the productivity of the heterologous ECD-Her1 protein.

Relationship between microstructure formation and in vitro starch digestibility in baked gluten-starch matrices.

Increased prevalence of diabetes prompts the development of foods with reduced starch digestibility. This study analyzed the impact of adding soluble dietary fiber (inulin-IN; polydextrose-PD) to baked gluten-starch matrices (7.5-13%) on microstructure formation and in vitro starch digestibility. IN and PD enhanced water-holding capacity, the hardness of baked matrices, and lowered water activity in the formulated matrices, potentially explaining the reduced starch gelatinization degree as IN or PD concentration increased. A maximum gelatinization decrease (26%) occurred in formulations with 13% IN. Micro-CT analysis showed a reduction in total and open porosity, which, along with the lower gelatinization degree, may account for the reduced in vitro starch digestibility. Samples with 13% IN exhibited a significantly lower rapidly available glucose fraction (8.56 g/100 g) and higher unavailable glucose fraction (87.76 g/100 g) compared to the control (34.85 g/100 g and 47.59 g/100 g, respectively). These findings suggest the potential for developing healthier, starch-rich baked foods with a reduced glycemic impact.

Enhancing mouthguard longevity: Impact of surface treatment against aging from brushing and disinfectant exposure.

BACKGROUND/AIMS: The study aimed to assess the surface characteristics of sports mouthguards under mechanical stresses during cleaning, either by brushing or immersion in disinfectant solutions. MATERIAL AND METHODS: Ethylene-vinyl acetate samples, 4 mm thick, were randomly assigned to cleaning methods: control (C-no cleaning), brushing with water (B.W), brushing with neutral liquid soap (B.S), brushing with toothpaste (B.T), immersion in distilled water for 10 min (I.W), immersion in 2.25% sodium hypochlorite solution for 10 min (I.SH), and immersion in sodium bicarbonate solution for 5 min (I.SB). All cleaning methods were applied for 28 days. Surface roughness average (Ra) and wettability were measured at baseline for the control group (n = 9), and after cleaning for all the other groups. RESULTS: One-way ANOVA with Tukey tests (5% significance) indicated significant differences among groups (p < .05). The I.SB group had higher surface roughness than B.S and B.T (p < .05). B.W showed the lowest wettability, significantly lower than B.T, I.W, and I.SB (p < .05). I.SB exhibited the highest wettability, significantly different from sodium hypochlorite, neutral liquid soap, brushing with water, and control groups (p < .05). The sodium bicarbonate immersion group (I.SB) demonstrated greater statistical variation, displaying higher susceptibility to aging compared to brushing with neutral liquid soap. CONCLUSION: Cleaning mouthguards with a toothbrush, water, and neutral liquid soap emerged as the most promising method, causing minimal surface changes in the material.

The effect of antiangiogenic agent aflibercept on surgically induced endometriosis in a rat model.

OBJECTIVE: The aim of the study is to show for the first time how aflibercept affects endometriosis lesions. MATERIAL AND METHODS: Surgically induced endometriosis in Wistar albino female rats. Rats with endometriosis were randomly divided into three groups: control (Co), aflibercept (Af), and leuprolide acetate (Le). Then, Af, aflibercept, and Le received leuprolide acetate. The control group was not treated. The weights and changes in intra-abdominal adhesions of the rats before and after treatment were recorded according to the Blauer adhesion score. Blood extracted for sacrifice was analyzed. Endometriotic lesions were evaluated for size, volume, histology, and immunohistochemistry (vascular endothelial growth factor [VEGF] and CD31). Significance level was accepted as p < 0.05. RESULTS: Aflibercept significantly reduced endometrial implant volume (p = 0.002). The explant epithelial histological score showed a significant difference between aflibercept and leuprolide acetate (p = 0.006) and between aflibercept and control groups (p = 0.002). Aflibercept decreased VEGF-H and CD31 expression (p = 0.001) more than leuprolide acetate. Aflibercept improved adhesions (p = 0.006). CONCLUSION: Aflibercept is more successful than leuprolide acetate in the treatment of endometriosis.

OBJETIVO: Mostrar por primera vez cómo afecta aflibercept a las lesiones de endometriosis. MATERIAL Y MÉTODOS: Endometriosis inducida quirúrgicamente en ratas hembras albinas Wistar. Las ratas con endometriosis se dividieron aleatoriamente en tres grupos: control (Co), aflibercept (Af) y acetato de leuprolida (Le). Luego, Af, aflibercept y Le recibieron acetato de leuprolida. El grupo de control no fue tratado. Los pesos y cambios en las adherencias intraabdominales de las ratas antes y después del tratamiento se registraron de acuerdo con la puntuación de adherencia de Blauer. La sangre extraída para el sacrificio fue analizada. Las lesiones endometriósicas se evaluaron en tamaño, volumen, histología e inmunohistoquímica (factor de crecimiento endotelial vascular [VEGF] y CD31). El nivel de significación se aceptó como p < 0.05. RESULTADOS: Aflibercept redujo significativamente el volumen del implante endometrial (p = 0.002). La puntuación histológica epitelial (EHS) del explante mostró una diferencia significativa entre aflibercept y acetato de leuprolida (p = 0.006) y entre los grupos de aflibercept y control (p = 0.002). Aflibercept disminuyó la expresión de VEGF-H y CD31 (p = 0.001) más que el acetato de leuprolida. Aflibercept mejoró las adherencias (p = 0.006). CONCLUSIÓN: Aflibercept tiene más éxito que el acetato de leuprolide en el tratamiento de la endometriosis.

Highly transparent sustainable biogel electrolyte based on cellulose acetate for application in electrochemical devices.

In this study, an easy and low-cost production method for a cellulose acetate-based gel polymer containing lithium perchlorate and propylene carbonate is described, as well as the investigation of its properties for potential use as an electrolyte in electrochemical devices. Cellulose acetate, a biopolymer derived from natural matrix, is colourless and transparent, as confirmed by the UV-Vis spectroscopy, with 85 % transparency in visible spectrum. The gels were prepared and tested at different concentrations and proportions to optimise their properties. Thermogravimetry, XRD, and FTIR analyses revealed crucial characteristics, including a substantial 90 % mass loss between 150 and 250 °C, a semi-crystalline nature with complete salt dissociation within the polymer matrix, and a decrease in intensity at 1780 cm-1 with increasing Li+ ion concentration, suggesting an improvement in ionic conduction capacity. In terms of electrochemical performance, the gel containing 10 % by mass of cellulose acetate and 1.4 M of LiClO4 emerged as the most promising. It exhibited a conductivity of 2.3 × 10-4 S.cm-1 at 25 °C and 3.0 × 10-4 S.cm-1 at 80 °C. Additionally, it demonstrated an ideal shape of cyclic voltammetry curves and stability after 400 cycles, establishing its suitability as an electrolyte in electrochemical devices.

Hydroxytakakiamide and Other Constituents from a Marine Sponge-Associated Fungus Aspergillus fischeri MMERU23, and Antinociceptive Activity of Ergosterol Acetate, Acetylaszonalenin and Helvolic Acid.

An unreported prenylated indole derivative hydroxytakakiamide (4) was isolated, together with the previously described ergosterol (1), ergosterol acetate (2), and (3R)-3-(1H-indol-3-ylmethyl)-3, 4-dihydro-1H-1,4-benzodiazepine-2,5-dione (3), from the column fractions of the crude ethyl acetate extract of the culture of a marine sponge-associated fungus, Aspergillus fischeri MMERU 23. The structure of 4 was elucidated by the interpretation of 1D and 2D NMR spectral data and high-resolution mass spectrum. The absolute configuration of the stereogenic carbon in 3 was proposed to be the same as those of the co-occurring congeners on the basis of their biogenetic consideration and was supported by the comparison of its sign of optical rotation with those of its steroisomers. The crude ethyl acetate extract and 2 were evaluated, together with acetylaszonalenin (5) and helvolic acid (6), which were previously isolated from the same extract, for the in vivo antinociceptive activity in the mice model. The crude ethyl acetate extract exhibited antinociceptive activity in the acetic acid-induced writhing and formalin tests, while 2, 5, and 6 displayed the effects in the late phase of the formalin test. On the other hand, neither the crude ethyl acetate extract nor 2, 5, and 6 affected the motor performance of mice in both open-field and rotarod tests. Additionally, docking studies of 2, 5, and 6 were performed with 5-lipoxygenase (5-LOX) and phosphodiesterase (PDE) enzymes, PDE4 and PDE7, which are directly related to pain and inflammatory processes. Molecular docking showed that 6 has low affinity energy to PDE4 and PDE7 targets while retaining high affinity to 5-LOX. On the other hand, while 2 did not display any hydrogen bond interactions in any of its complexes, it achieved overall better energy values than 6 on the three antinociceptive targets. On the other hand, 5 has the best energy profile of all the docked compounds and was able to reproduce the crystallographic interactions of the 5-LOX complex.

1H NMR spectroscopy as a tool to probe potential biomarkers of the drying-salting process: A proof-of-concept study with the Amazon fish pirarucu.

Dry-salted pirarucu (Arapaima gigas) plays an important cultural role in the Amazon region - South America. In this study, we explored the changes in the chemical composition of pirarucu meat following the drying-salting process via 1H NMR spectroscopy. Combining multivariate and univariate statistical analyses yielded a robust differentiation of metabolites involved in the process. VIP score (>1), p-value (<0.05), and AUC (>0.7) were considered to selecting compounds that had significant fluctuations in their contents along the process. Our results pointed out acetate, lactate, succinate, and creatinine as metabolites undergoing significant changes during the drying-salting process. Creatinine was not detected in fresh samples. The investigation of multiple components delves deeper into the molecular nuances of the salting-drying process's impact on fish meat, providing a more comprehensive understanding of the possible chemical transformations and how the matrix's quality control and nutritional aspects should be addressed.

Development and characterization of 3D printed ethylene vinyl acetate (EVA) as drug delivery device for the treatment of overactive bladder.

The overactive bladder is a condition characterized by a sudden urge to urinate, even with small volumes of urine present in the bladder. The current treatments available for this pathology consist on conservative approaches and the continuous administration of drugs, which when made by conventional methods has limitations related to the first pass metabolism, bioavailability, severe side effects, and low patient adherence to treatments, ultimately leading to low effectiveness. Within this context, the present work proposes the design, manufacture, and characterization of an intravesical implant for the treatment of overactive bladder pathology, using EVA copolymer as a matrix and oxybutynin as a drug. The fabrication of devices through two manufacturing techniques (extrusion and additive manufacturing by fused filament fabrication, FFF) and the evaluation of the implants through characterization tests was proposed. The usability and functionality were evaluated through simulated insertion of the device/prototype in a bladder model through catheter insertion tests. The safety and effectiveness of the devices was investigated from mechanical testing as well as drug release assays. Drug release assays presented a burst release in the first 24 h, followed by a release of 1.8 and 2.8 mg/d, totalizing 32 d. Mechanical tests demonstrated an increase in the stiffness of the specimens due to the addition of the drug, showing a change in maximum stress and strain at break. The released dose was higher than that usually presented when considering the oral administration route, showing the optimization of the development of this implant has the potential to improve the quality of life of patients with overactive bladder.

Cellulose esters: Synthesis for further formation of films with magnetite nanoparticles incorporated.

This study investigated the homogeneous synthesis of cellulose acetate (CA) and propionate (CP) with varying degrees of substitution (DS) from sisal cellulose in a N, N-dimethylacetamide/lithium chloride (DMAc/LiCl) solvent system. These esters were used to prepare neat (CADSF/CPDSF) and nanocomposite films (CADSFFe/CPDSFFe) from prior synthesized magnetite nanoparticles (NPs, Fe3O4, 5.1 ± 0.5 nm). Among the CA and CP series, the composite CA0.7FFe and the neat CP0.7F films exhibited the highest modulus of elasticity, 2105 MPa and 2768 MPa, respectively, probably a consequence of the continuous fibrous structures present on the surface of these films. Microsphere formation on the film's surface was observed in scanning electron microscopy micrographs. This points to applications in the controlled release of targeted substances. The VSM analysis showed that the cellulosic matrices preserved the superparamagnetic characteristics of the NPs. This study suggested a reduced coupling effect between nanoparticles inside polymeric films due to magnetic saturation at low fields. CA0.7FFe and CA1.3FFe composite films reached a saturation magnetization (MSAT) of 46 emu/g around 7 kOe field. Hosting magnetite nanoparticles in cellulose ester matrices may be an interesting way to develop new functional cellulose-based materials, which have the potential for diverse applications, including microelectromechanical systems and microsensors.

Flavonoids, biphenyls and xanthones from the genus Clusia: chemistry, biological activities and chemophenetics relevance.

Clusia is one of the most important genera of the Clusiaceae family, comprising up to 400 species. This review describes the identification of twenty-two flavonoids from Clusia species, which includes five flavonols (1-4 and 11), six flavones (5-10), one catechin (12), one flavanone (13), and nine biflavonoids (14-22). O- and C-glycosylation are frequently observed amongst these flavonoids. Furthermore, seven biphenyls (23-29) and nine xanthones (30-38) have been isolated from Clusia species. Biphenyls and xanthones show limited occurrence within the genus, but together with biosynthetic insights, they might offer important chemophenetics leads for the consolidation of the genus Clusia within the Clusiaceae family. Altogether, this work provides an overview of the chemistry of the genus Clusia in terms of flavonoids, biphenyls and xanthones, as well as it discusses biological activities and chemophenetics of the isolated compounds, when appropriate.

Egg white hydrolysate protects white adipose tissue against metabolic insult in deoxycorticosterone acetate-salt rats.

The purpose of this study was to investigate the effect of an egg white hydrolysate (EWH) to protect white adipose tissue damage from cardiometabolic changes induced by severe hypertension. Male Wistar rats were uninephrectomised and divided: SHAM (weekly subcutaneous vehicle (mineral oil + propylene glycol, 1:1)), SHAM + EWH (subcutaneous vehicle plus EWH via gavage, 1 g/kg per day), DOCA (deoxycorticosterone acetate diluted in vehicle subcutaneously weekly in subsequent doses of 20 mg/kg -1st week, 12 mg/kg - 2­3th week, and 6 mg/kg -4­8th week, respectively, plus 1 % NaCl and 0·2 % KCl in drinking water), and DOCA + EWH. Body weight gain, food and water intake, glucose and lipid metabolism were evaluated. Oxidative stress was assessed by biochemical assay and immunofluorescence for NOX-1, nuclear factor kappa B (NFκB), and caspase-3 in retroperitoneal white adipose tissue (rtWAT). Proinflammatory cytokines (IL-6 and 1ß), CD163+ macrophage infiltration, and immunohistochemistry for TNFα and uncoupling protein-1 were evaluated, as well as histological analysis on rtWAT. Glutathione peroxidase and reductase were also determined in plasma. EWH showed hypocholesterolemic, antioxidant, anti-inflammatory, and anti-apoptotic properties in the arterial hypertension DOCA-salt model. The results demonstrated the presence of functional changes in adipose tissue function by a decrease in macrophage infiltration and in the fluorescence intensity of NFκB, NOX-1, and caspase-3. A reduction of proinflammatory cytokines and restoration of antioxidant enzymatic activity and mitochondrial oxidative damage by reducing uncoupling protein-1 fluorescence intensity were also observed. EWH could be used as a potential alternative therapeutic strategy in the treatment of cardiometabolic complications associated with malignant secondary arterial hypertension.

Unravelling the role of anaerobic metabolism (pta-ackA) and virulence (misL and ssa) genes in Salmonella Heidelberg shedding using chicken infection model.

The mechanism of colonisation of the chicken intestine by Salmonella remains poorly understood, while the severity of infections vary enormously depending on the serovar and the age of the bird. Several metabolism and virulence genes have been identified in Salmonella Heidelberg; however, information on their roles in infection, particularly in the chicken infection model, remains scarce. In the present publication, we investigated three Salmonella Heidelberg mutants containing deletions in misL, ssa, and pta-ackA genes by using signature-tagged mutagenesis. We found that mutations in these genes of S. Heidelberg result in an increase in fitness in the chicken model. The exception was perhaps the pta-ackA mutant where colonisation was slightly reduced (2, 7, 14, and 21 days post-infection) although some birds were still excreting at the end of the experiment. Our results suggest that for intestinal colonisation of the chicken caecum, substrate-level phosphorylation is likely to be more important than the MisL outer membrane protein or even the secretion system apparatus. These findings validate previous work that demonstrated the contribution of ackA and pta mutants to virulence in chickens, suggesting that the anaerobic metabolism genes such as pta-ackA could be a promising mitigation strategy to reduce S. Heidelberg virulence.

Zein and hydroxypropyl methylcellulose acetate succinate microfibers combined with metronidazole benzoate and/or metronidazole-incorporated cellulose nanofibrils for potential periodontal treatment.

The development of flexible and porous materials to control antibacterial delivery is a pivotal endeavor in medical science. In this study, we aimed to produce long and defect-free fibers made of zein and hydroxypropyl methylcellulose acetate succinate (HPMCAS) to be used as a platform for the release of metronidazole (MDZ) and metronidazole benzoate (BMDZ) to be potentially used in periodontal treatment. Microfibers prepared via electrospinning under a 2:3 (w/w) zein to HPMCAS ratio, containing 0.5 % (w/w) poly(ethylene oxide) (PEO) and 1 % (w/w) cellulose nanofibril (CNF) were loaded with 40 % (w/w) MDZ, 40 % (w/w) BMDZ, or a combination of 20 % (w/w) of each drug. The addition of CNF improved the electrospinning process, resulting in long fibers with reduced MDZ and BMDZ surface crystallization. MDZ- and BMDZ-incorporated fibers were semicrystalline and displayed commendable compatibility among drugs, nanocellulose and polymeric chains. Release tests showed that zein/HPMCAS/PEO fibers without CNF and with 20 % (w/w) MDZ/ 20 % (w/w) BMDZ released the drug at a slower and more sustained rate compared to other samples over extended periods (up to 5 days), which is a favorable aspect concerning periodontitis treatment.