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American Journal of Reproductive... Jul 2024The decidualization process conditions monocytes to the immunosuppressive and tolerogenic dendritic cell (DC)-10 profile, a DC subset with high IL-10 production. Since...
PROBLEM
The decidualization process conditions monocytes to the immunosuppressive and tolerogenic dendritic cell (DC)-10 profile, a DC subset with high IL-10 production. Since the implantation process implies an embryo-endometrium-immune crosstalk, here we focused on the ability of embryonic soluble factors to modify decidual DC conditioning accordingly with its quality.
METHOD OF STUDY
Human endometrial stromal cell line (HESC) decidualized with medroxyprogesterone and dibutyryl-cAMP (Dec) was stimulated with human embryo-conditioned media (ECM), classified as normal (ND) or impaired developed (ID) for 48 h (n = 18/group). Monocytes isolated from six healthy women were differentiated to DCs with rhGM-CSF+rhIL-4 in the presence/absence of conditioned media (CM) from decidualized cells stimulated with ECM or nontreated.
RESULTS
We found that decidualized cells stimulated with ECM sustain a myeloid regulatory cell profile on monocyte-derived culture with increased frequency of CD1aCD14 and CD83CD86 cells. ND-Dec sustained the higher expression of the DC-10 markers, HLA-G and IL-10 whereas ID-Dec diminished IL-10 production (ID-Dec: 135 ± 37.4 vs. Dec: 223.3 ± 49.9 pg/mL, p < 0.05). The treatment with ECM-Dec sustained a higher IL-10 production and prevented the increase of CD83/CD86 after LPS challenge regardless of embryo quality. Notably, TNF-α production increased in ID-Dec cultures (ID-Dec: 475.1 ± 134.7 vs. Dec: 347.5 ± 98 pg/mL, p < 0.05).
CONCLUSIONS
Although remaining in a tolerogenic profile compatible with DC-10, DCs can differentially respond to decidual secreted factors based on embryo quality, changing their secretome. These results suggest that in the presence of arrested embryo, DCs could differentially shape the immunological microenvironment, contributing to arrested embryo clearance during the menstrual phase.
Topics: Humans; Female; Dendritic Cells; Embryo Implantation; Immune Tolerance; Decidua; Cell Differentiation; Culture Media, Conditioned; Interleukin-10; Adult; Stromal Cells; Cells, Cultured; Embryo, Mammalian; Endometrium; Cell Line; Monocytes; Pregnancy
PubMed: 38958250
DOI: 10.1111/aji.13891 -
Journal of Computational Chemistry Jul 2024Cocrystals are assemblies of more than one type of molecule stabilized through noncovalent interactions. They are promising materials for improved drug formulation in...
Cocrystals are assemblies of more than one type of molecule stabilized through noncovalent interactions. They are promising materials for improved drug formulation in which the stability, solubility, or biocompatibility of the active pharmaceutical ingredient (API) is improved by including a coformer. In this work, a range of density functional theory (DFT) and density functional tight binding (DFTB) models are systematically compared for their ability to predict the lattice enthalpy of a broad range of existing pharmaceutically relevant cocrystals. These range from cocrystals containing model compounds 4,4'-bipyridine and oxalic acid to those with the well benchmarked APIs of aspirin and paracetamol, all tested with a large set of alternative coformers. For simple cocrystals, there is a general consensus in lattice enthalpy calculated by the different DFT models. For the cocrystals with API coformers the cocrystals, enthalpy predictions depend strongly on the DFT model. The significantly lighter DFTB models predict unrealistic values of lattice enthalpy even for simple cocrystals.
PubMed: 38958249
DOI: 10.1002/jcc.27454 -
Journal of the American Heart... Jul 2024Endothelial cell (EC) dysfunction involves reduced nitric oxide (NO) bioavailability due to NO synthase uncoupling linked to increased oxidation and reduced cofactor...
BACKGROUND
Endothelial cell (EC) dysfunction involves reduced nitric oxide (NO) bioavailability due to NO synthase uncoupling linked to increased oxidation and reduced cofactor availability. Loss of endothelial function and NO bioavailability are associated with inflammation, including leukocyte activation. Eicosapentaenoic acid (EPA) administered as icosapent ethyl reduced cardiovascular events in REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) in relation to on-treatment EPA blood levels. The mechanisms of cardiovascular protection for EPA remain incompletely elucidated but likely involve direct effects on the endothelium.
METHODS AND RESULTS
In this study, human ECs were treated with EPA and challenged with the cytokine IL-6 (interleukin-6). Proinflammatory responses in the ECs were confirmed by ELISA capture of sICAM-1 (soluble intercellular adhesion molecule-1) and TNF-α (tumor necrosis factor-α). Global protein expression was determined using liquid chromatography-mass spectrometry tandem mass tag. Release kinetics of NO and peroxynitrite were monitored using porphyrinic nanosensors. IL-6 challenge induced proinflammatory responses from the ECs as evidenced by increased release of sICAM-1 and TNF-α, which correlated with a loss of NO bioavailability. ECs pretreated with EPA modulated expression of 327 proteins by >1-fold (<0.05), compared with IL-6 alone. EPA augmented expression of proteins involved in NO production, including heme oxygenase-1 and dimethylarginine dimethylaminohydrolase-1, and 34 proteins annotated as associated with neutrophil degranulation. EPA reversed the endothelial NO synthase uncoupling induced by IL-6 as evidenced by an increased [NO]/[peroxynitrite] release ratio (<0.05).
CONCLUSIONS
These direct actions of EPA on EC functions during inflammation may contribute to its distinct cardiovascular benefits.
PubMed: 38958135
DOI: 10.1161/JAHA.123.034076 -
Chemical Biology & Drug Design Jul 2024To develop novel bovine lactoferrin (bLF) peptides targeting bLF-tumour necrosis factor (TNF) receptor-associated factor 6 (TRAF6) binding sites, we identified two...
To develop novel bovine lactoferrin (bLF) peptides targeting bLF-tumour necrosis factor (TNF) receptor-associated factor 6 (TRAF6) binding sites, we identified two peptides that could target bLF-TRAF6 binding sites using structural analysis. Moreover, another peptide that could bind to the TRAF6 dimerization area was selected from the bLF sequence. The effects of each peptide on cytokine expression in lipopolysaccharide (LPS)-stimulated osteoblasts (ST2) and on osteoclastogenesis were examined using an LPS-treated co-culture of primary bone marrow cells (BMCs) with ST2 cells and a single culture of osteoclast precursor cells (RAW-D) treated with soluble receptor activator of NF-κB ligand. Finally, the effectiveness of these peptides against LPS-induced alveolar bone destruction was assessed. Two of the three peptides significantly suppressed LPS-induced TNF-α and interleukin-1β expression in ST2 cells. Additionally, these peptides inhibited and reversed LPS-induced receptor activator of NF-κB ligand (RANKL) upregulation and osteoprotegerin (OPG) downregulation, respectively. Furthermore, both peptides significantly reduced LPS-induced osteoclastogenesis in the BMC-ST2 co-culture and RANKL-induced osteoclastogenesis in RAW-D cells. In vivo, topical application of these peptides significantly reduced the osteoclast number by downregulating RANKL and upregulating OPG in the periodontal ligament. It is indicated that the novel bLF peptides can be used to treat periodontitis-associated bone destruction.
Topics: Animals; Lactoferrin; Lipopolysaccharides; Rats; Peptides; Osteoclasts; RANK Ligand; Male; Alveolar Bone Loss; Cattle; Mice; Osteoblasts; Rats, Sprague-Dawley; Osteogenesis; Tumor Necrosis Factor-alpha; Binding Sites; Coculture Techniques; Osteoprotegerin; Disease Models, Animal
PubMed: 38958121
DOI: 10.1111/cbdd.14574 -
Dalton Transactions (Cambridge, England... Jul 2024The shuttle effect of soluble lithium polysulfide (LiPS) is a major obstacle to the practical application of lithium-sulfur (Li-S) batteries. In order to reduce the...
The shuttle effect of soluble lithium polysulfide (LiPS) is a major obstacle to the practical application of lithium-sulfur (Li-S) batteries. In order to reduce the negative impact of the shuttle effect, Nd-MOF was combined with carbon nanofibers (CNFs) so that Nd-MOF was embedded in the CNFs and the NdO-C/CNF composite was realized as a separation modification material. This embedded structure made the combination between NdO-C and CNFs tighter, and it exhibited better synergistic effects to inhibit the shuttle effect of polysulfides while also enhancing the tensile strength of the separator and improving the safety performance of the battery. Based on these advantages, a lithium-sulfur coin cell with the NdO-C/CNF-modified separator exhibited excellent electrochemical performance.
PubMed: 38958052
DOI: 10.1039/d4dt01193g -
Tribological Effects of Quaternary Ammonium-Functionalized Montmorillonite as Water-Based Additives.Langmuir : the ACS Journal of Surfaces... Jul 2024In this study, a water-soluble quaternary ammonium salt (QAS)-functionalized montmorillonite (MMT) was fabricated using a mechanochemical method as a high-performance...
In this study, a water-soluble quaternary ammonium salt (QAS)-functionalized montmorillonite (MMT) was fabricated using a mechanochemical method as a high-performance water lubrication additive. The intercalation of QAS into the MMT layer expands the layer spacing of MMT, but does not affect the hydrophilicity of MMT. The ultrathin layer QAS-functionalized montmorillonite (QAS-MMT) demonstrated excellent water-stable dispersion and can be used as a water-based lubrication additive. Only 0.1% addition can reduce the friction coefficient by more than 71.4% and the wear volume by about 58.8% when compared to water, demonstrating its excellent friction reduction and antiwear performance. The frictional mechanism indicates that the physical adsorption film, together with the chemical reaction film, endows the QAS-MMT additives with outstanding tribological performance, provides excellent lubrication for the contact of steel/steel pairs, and prevents the steel surface from being further worn.
PubMed: 38957946
DOI: 10.1021/acs.langmuir.4c01799 -
Green Chemistry : An International... Jul 2024Humins, (side-)products of the acid-catalysed dehydration of carbohydrates, will be produced in substantial quantities with the development of industrial biorefining...
Humins, (side-)products of the acid-catalysed dehydration of carbohydrates, will be produced in substantial quantities with the development of industrial biorefining processes. Most structural knowledge about such humins is based on synthetic model humins prepared at lab-scale from typical carbohydrate(-derived) compounds. Here, we report the first extensive characterisation study of an industrial humin. The soluble humin was generated from pilot plant-scale methanolic cyclodehydration of D-fructose to 5-methoxymethyl-2-furfural (MMF), as part of the Avantium YXY® process to produce FDCA. Purification of the industrial humin followed by fractionation allowed isolation of a water-insoluble, high molecular weight fraction (WIPIH) and a water-soluble, low-to-middle molecular weight soluble fraction (WES). Characterisation by elemental analysis, thermogravimetry, IR and NMR spectroscopy and size exclusion chromatography provided a detailed picture of the humin structure in both fractions. Aided by a comprehensive NMR spectral library of furanic model compounds, we identified the main furanic building blocks and inter-unit linkages and propose a structure for this industrial humin sample. The WIPIH and WES fractions were found to be composed of furanic rings interconnected by short aliphatic chains containing a wide range of functionalities including alcohols, ethers, carboxylic acids, esters, aldehydes and ketones. The low level of crosslinking and high functional group content of the industrial humin differ from the more extensively studied, (highly over-)condensed synthetic model humins, towards which they can be considered intermediates. The structural and compositional insights into the nature of an actual industrial humin open up a broad spectrum of valorisation opportunities.
PubMed: 38957875
DOI: 10.1039/d4gc00429a -
Frontiers in Plant Science 2024is the queen of the vines, being an ornamental plant with high economic value. Waterlogging stress reduces the ornamental value of the plant and limits its application....
is the queen of the vines, being an ornamental plant with high economic value. Waterlogging stress reduces the ornamental value of the plant and limits its application. Melatonin plays an important role in plant resistance to abiotic stresses. In this study, the physiological responses and gene expression levels of two wild species, namely, and , and two horticultural varieties, namely, 'Sen-No-Kaze' and 'Viva Polonia,' under waterlogging stress were analyzed to determine the effect of melatonin on waterlogging tolerance. The results showed that the waterlogging tolerances of and 'Sen-No-Kaze' were relatively poor, but were significantly improved by concentrations of 100 μmol·L and 50 μmol·L melatonin. and 'Viva Polonia' had relatively strong tolerance to waterlogging, and this was significantly improved by 200 μmol·L melatonin. Under waterlogging stress, the relative conductivity and HO content of increased significantly; the photosynthetic parameters and chlorophyll contents were significantly decreased; photosynthesis was inhibited; the contents of soluble protein and soluble sugars were decreased. Effective improvement of waterlogging tolerance after exogenous melatonin spraying, the relative conductivity was decreased by 4.05%-27.44%; the HO content was decreased by 3.84%-23.28%; the chlorophyll content was increased by 35.59%-103.36%; the photosynthetic efficiency was increased by 25.42%-45.86%; the antioxidant enzyme activities of APX, POD, SOD, and CAT were increased by 28.03%-158.61%; the contents of proline, soluble protein, and soluble sugars were enhanced, and cell homeostasis was improved. Transcription sequencing was performed on wild with differences in waterlogging tolerance, and nine transcription factors were selected that were highly correlated with melatonin and that had the potential to improve waterlogging tolerance, among which , and were significantly positively correlated with the antioxidant enzyme system, and , , and were significantly negatively correlated. Photosynthetic capacity was positively correlated with and while being significantly negatively correlated with , , , and . Melatonin could enhance the flooding tolerance of by improving photosynthetic efficiency and antioxidant enzyme activity. This study provides an important basis and reference for the application of melatonin in waterlogging-resistant breeding of .
PubMed: 38957603
DOI: 10.3389/fpls.2024.1385165 -
International Journal of Dentistry 2024To evaluate the solubility and the volumetric and morphological alterations of bioceramic filling material (Bio-CP) for primary teeth.
OBJECTIVE
To evaluate the solubility and the volumetric and morphological alterations of bioceramic filling material (Bio-CP) for primary teeth.
MATERIALS AND METHODS
Bio-CP, Calen thickened with zinc oxide (Calen-ZO), and with zinc oxide eugenol (ZOE) were placed in 1- or 2-mm-diameter polyethylene tubes and immersed in water or phosphate-buffered saline (PBS) for 30 days. The solubility (mass loss) was assessed using methodology modified from ISO 6876. Filling capacity, volumetric changes, and presence of voids were assessed by microcomputed tomography (micro-CT). The surface distribution of the chemical elements and the crystalline phases was evaluated by energy scattering X-ray scanning electron microscopy (SEM-EDX) and X-ray diffraction (XRD) to detect hydroxyapatite precipitate and components. The Shapiro-Wilk, Kruskal-Wallis, and Dunn's or two-way ANOVA and Tukey post hoc test were used ( = 0.05).
RESULTS
The solubility was ZOE > Calen-ZO = Bio-CP. Calen-ZO and Bio-CP were more soluble in water than in PBS. All the materials showed greater solubility in 2-mm tube diameter in both PBS and distilled water, except for Bio-CP in distilled water, which showed no difference between both tube diameters (1 and 2 mm). Only Calen-ZO and ZOE were analyzed by micro-CT, because Bio-CP separated into two phases during scanning. Calen-ZO had greater volumetric loss and presence of voids than ZOE in water, but there was no difference in PBS. The hydroxyapatite precipitate on the surface of Bio-CP and Calen-ZO was detected after immersion in PBS.
CONCLUSION
Although Bio-CP had acceptable solubility and filling capacity, its composition did not allow a proper volumetric and void assessment. From a clinical perspective, Bio-CP has the potential to become a suitable material for root canal filling in primary teeth. Nonetheless, its composition must first be revised to achieve better chemical stability prior to its recommendation.
PubMed: 38957372
DOI: 10.1155/2024/5945033 -
International Journal of Nanomedicine 2024Salidroside (SAL) is the most effective component of , a traditional Chinese medicine. Cryptotanshinone (CT) is the main fat-soluble extract of , exhibiting considerable...
BACKGROUND
Salidroside (SAL) is the most effective component of , a traditional Chinese medicine. Cryptotanshinone (CT) is the main fat-soluble extract of , exhibiting considerable potential for application in osteogenesis. Herein, a polycaprolactone/gelatin nanofiber membrane loaded with CT and SAL (PSGC membrane) was successfully fabricated via coaxial electrospinning and characterized.
METHODS AND RESULTS
This membrane capable of sustained and controlled drug release was employed in this study. Co-culturing the membrane with bone marrow mesenchymal stem cells and human umbilical vein endothelial cells revealed excellent biocompatibility and demonstrated osteogenic and angiogenic capabilities. Furthermore, drug release from the PSGC membrane activated the Wnt/β-catenin signaling pathway and promoted osteogenic differentiation and vascularization. Evaluation of the membrane's vascularization and osteogenic capacities involved transplantation onto a rat's subcutaneous area and assessing rat cranium defects for bone regeneration, respectively. Microcomputed tomography, histological tests, immunohistochemistry, and immunofluorescence staining confirmed the membrane's outstanding angiogenic capacity two weeks post-operation, with a higher incidence of osteogenesis observed in rat cranial defects eight weeks post-surgery.
CONCLUSION
Overall, the SAL- and CT-loaded coaxial electrospun nanofiber membrane synergistically enhances bone repair and regeneration.
Topics: Osteogenesis; Animals; Nanofibers; Gelatin; Polyesters; Glucosides; Phenols; Phenanthrenes; Humans; Neovascularization, Physiologic; Human Umbilical Vein Endothelial Cells; Mesenchymal Stem Cells; Rats, Sprague-Dawley; Rats; Male; Bone Regeneration; Membranes, Artificial; Coculture Techniques; Drug Liberation; Cell Differentiation
PubMed: 38957181
DOI: 10.2147/IJN.S461141