Search Results (7,546)

Regenerative medicine and tissue engineering aim to restore or replace impaired organs and tissues using cell transplantation supported by scaffolds. Recently scientists are focusing on developing new biomaterials that optimize cellular attachment, migration, proliferation, and differentiation. Nanoparticles, such as graphene oxide (GO), have emerged as versatile materials due to their high surface-to-volume ratio and unique chemical properties, such as electrical conductivity and flexibility. However, GO faces challenges such as cytotoxicity at high concentrations, a negative surface charge, and potential inflammatory responses; for these reasons, variations in synthesis have been studied. A GO derivative, Graphene Oxide-Polyethylenimine (GO-PEI), shows controlled porosity and structural definition, potentially offering better support for cell growth. Human amniotic fluid stem cells (hAFSCs) are a promising candidate for regenerative medicine due to their ability to differentiate into mesodermic and ectodermic lineages, their non-immunogenic nature, and ease of isolation. This study investigates the effects of GO and GO-PEI on hAFSCs, focusing on the effects on adhesion, proliferation, and metabolic features. Results indicate that GO-PEI restores cell proliferation and mitochondrial activity to control levels, with respect to GO that appeared less biocompatible. Both materials also influence the miRNA cargo of hAFSC-derived microvesicles, potentially influencing also cell-to-cell communication. Full article

Eryptotic erythrocytes are prone to adhere to the vascular endothelium, provoking atherosclerosis. As statins do not prevent eryptosis compounds with anti-eryptotic effects could help treated hypercholesterolemic subjects in decreasing cardiovascular disease risk. Plant sterols (PSs) have shown this anti-eryptotic effect ex vivo, along with their cholesterol-lowering activity. A parallel double-blind placebo-controlled randomized trial was conducted using a PS-food supplement (2 g of PS/day) (case, n = 13) or a placebo supplement (control, n = 13) in statin-treated hypercholesterolemic subjects. Blood samples were extracted before (T0) and after (T1) a 6-week treatment, and erythrocytes were isolated for biochemical determination, phosphatidylserine externalization (EPHS), cell size and reduced glutathione (GSH) analyses, and endothelium adhesion evaluation. A reduction in glucose (4.3%) and LDL cholesterol (9.2%) was observed only in the control group, whereas in the case group, an increase in ApoA1 (6.4%) was observed. Neither EPHS, cell size nor GSH were modified by the treatment with any of the supplements, whilst endothelium adhesion was reduced (55.1%) only in the case group. These results suggest that the PS supplement may improve some cardiovascular health parameters in the target population even though eryptosis status is not modified by this treatment. Full article

Chlorogenic acid (CGA), a polyhydroxy phenolic acid, has been extensively studied for its antimicrobial properties. Staphylococcus aureus (S. aureus) threatens food safety by forming biofilms. This study aimed to investigate the mechanism of CGA against S. aureus and its biofilm. The anti-bacterial activity of CGA was assessed using crystal violet staining, TEM, SEM, a CLSM, and using metabolomics and molecular docking to elucidate the mechanism. The results indicated that the minimum inhibitory concentration of CGA against S. aureus was 2.5 mg/mL. CGA disrupts the integrity of bacterial cell membranes, leading to increased hydrophobicity, morphological changes, scattering, and reduced spreading. This disruption decreases biofilm adhesion and bacterial count. Metabolomics and molecular docking analyses revealed that CGA down-regulates key amino acids. It forms hydrogen bonds with penicillin-binding protein 4 (PBP4), Amidase, glutamate synthetase B, and glutamate synthetase A. By inhibiting amino acid metabolism, CGA prevents biofilm formation. CGA interacts with amino acids such as aspartic acid, glutamine, and glutamate through hydroxyl (-OH) and carbonyl (-C=O) groups. This interaction reduces cell viability and biofilm cohesion. The novel findings of this study, particularly the extension of the shelf life of pasteurized milk by inhibiting S. aureus growth, highlight the potential of CGA as a promising anti-biofilm strategy and preservative in the dairy industry. Full article

Background: Seminal plasma is an important component of semen and has a significant effect on sperm function. However, the relationship between seminal plasma and sperm freezing capacity has not been fully studied. Purpose: Exploring metabolites and proteins related to the boar sperm freezing capacity in seminal plasma, by metabolomic and proteomic approaches, and directly verifying the protective effect of seminal plasma on the cryopreservation of boar sperm using high and low freezability seminal plasma as base freezing extender. Methods: Semen samples were collected from 30 different boars, 11 high and 11 low freezing-resistant boars were selected after freezing 2~4 times, and seminal plasma was selected at the same time. Sperm motility and movement parameters were analyzed using a CASA system. Reproductive hormones (Testosterone, progesterone, estradiol, prolactin, prostaglandin F2α, luteinoid hormone) in seminal plasma were detected by ELISA. Analysis of proteins and metabolites in high and low freezing-resistant seminal plasma by proteomics and metabolomics techniques. Results: The six reproductive hormones tested were not significantly associated with sperm freezing resistance. A total of 13 differentially expressed metabolites (DEMs) and 38 differentially expressed proteins (DEPs) were identified, while a total of 348 metabolites and 1000 proteins were identified. These DEMs were related to energy metabolism, drugs, or environmental pollutants, while the DEPs were mainly involved in the cytoskeletal dynamics and cell adhesion processes. There were 33 metabolites and 70 proteins significantly associated with mean progress motility (PM) at 10 min and 2 h after thawing. The 70 related proteins were associated with cell division and cycle regulation in gene ontology (GO) terms, as well as KEGG pathways, thermogeneration, and pyruvate metabolism. Using highly freezable boar SP as a base freezing extender made no difference from using lowly freezable boar SP, and both were not as good as the commercial control. Conclusion: There were significant differences in seminal plasma with different freezability, but the similarity was much greater than the difference. The protection effect of seminal plasma is not remarkable, and it does not exhibit superior cryoprotective properties compared to commercial semen cryoelongators. Significance: This study provides a deeper understanding of how seminal plasma composition affects sperm freezabilty. It provides potential biomarkers and targets for improving sperm cryopreservation techniques. Full article

Electrospun poly(ε-caprolactone) (PCL)-based scaffolds are widely used in tissue engineering. However, low cell adhesion remains the key drawback of PCL scaffolds. It is well known that nitrogen-doped diamond-like carbon (N-DLC) coatings deposited on the surface of various implants are able to enhance their biocompatibility and functional properties. Herein, we report the utilization of the pulsed vacuum arc deposition (PVAD) technique for the fabrication of thin N-DLC coatings on the surface of electrospun PCL scaffolds. The effect of N-DLC coating deposition under various nitrogen pressures on the morphological, mechanical, physico-chemical, and biological properties of PCL scaffolds was investigated. It was established that an increase in nitrogen pressure in the range from 5 × 10⁻³ to 5 × 10⁻¹ Pa results in up to a 10-fold increase in the nitrogen content and a 2-fold increase in the roughness of the PCL fiber surface. These factors provided the conditions for the enhanced adhesion and proliferation of human mesenchymal stem cells (MMSCs) on the surface of the modified PCL scaffolds. Importantly, the preservation of N-DLC coating properties determines the shelf life of a coated medical device. The elemental composition, tensile strength, and surface human MMSC adhesion were studied immediately after fabrication and after 6 months of storage under normal conditions. The enhanced MMSC adhesion was preserved after 6 months of storage of the modified PCL-based scaffolds under normal conditions. Full article

The presence of bile acids in the cystic fibrosis patient’s lungs contributes to an increase in the inflammatory response, in the dominance of pathogens, as well as in the decline in lung function, increasing morbidity. The aim of this study is to determine the effects of exposure of Pseudomonas aeruginosa to primary and secondary bile acids on the production of several virulence factors which are involved in its pathogenic power. The presence of bile acids in the bacterial culture medium had no effect on growth up to a concentration of 1 mM. However, a slight decrease in the adhesion index as well as a reduction in the virulence of the bacteria on the HT29 cell line could be observed. In this model, exposure of P. aeruginosa to bile acids showed a significant decrease in the production of LasB and AprA proteases due to the reduction in the expression of their genes. A decrease in pyocyanin production was also observed in relation to the effects of bile acids on the quorum sensing regulators. In order to have an effect on gene expression, it is necessary for bile acids to enter the bacteria. P. aeruginosa harbors two potential homologs of the eukaryotic genes encoding the bile acid transporters NTCP1 and NTCP2 that are expressed in hepatocytes and enterocytes, respectively. By carrying out a comparative BLAST-P between the amino acid sequences of the PAO1 proteins and those of NTCP1 and NTCP2, we identified the products of the PA1650 and PA3264 genes as the unique homologs of the two eukaryotic genes. Exposure of the mutant in the PA1650 gene to chenodeoxycholic acid (CDCA) and lithocholic acid (LCA) showed a less significant effect on pyocyanin production than with the isogenic PAO1 strain. Also, no effect of CDCA on the PA3264 gene mutant was observed. This result indicated that CDCA should enter the bacteria by the transporter produced by this gene. The entry of LCA into bacteria seemed more complex and rather responded to a multifactorial system involving the product of the PA1650 gene but also the products of other genes encoding potential transporters. Full article

Granule secretion is an essential platelet function that contributes not only to haemostasis but also to wound healing, inflammation, and atherosclerosis. Granule secretion from platelets is facilitated, at least in part, by Soluble N-ethylmaleimide-Sensitive Factor (NSF) Attachment Protein Receptor (SNARE) complex-mediated granule fusion. Although α-synuclein is a protein known to modulate the assembly of the SNARE complex in other cells, its role in platelet function remains poorly understood. In this study, we provide evidence that α-synuclein is critical for haemostasis using α-synuclein-deficient (^−/−) mice. The genetic deletion of α-synuclein resulted in impaired platelet aggregation, secretion, and adhesion in vitro. In vivo haemostasis models showed that α-synuclein^−/− mice had prolonged bleeding times and activated partial thromboplastin times (aPTTs). Mechanistically, platelet activation induced α-synuclein serine (ser) 129 phosphorylation and re-localisation to the platelet membrane, accompanied by an increased association with VAMP 8, syntaxin 4, and syntaxin 11. This phosphorylation was calcium (Ca²⁺)- and RhoA/ROCK-dependent and was inhibited by prostacyclin (PGI₂). Our data suggest that α-synuclein regulates platelet secretion by facilitating SNARE complex formation. Full article

Cinnamon oil, an essential oil extracted from plants of the genus Cinnamomum, has been highly valued in ancient Chinese texts for its medicinal properties. This review summarizes the chemical composition, pharmacological actions, and various applications of cinnamon oil, highlighting its potential in medical and industrial fields. By systematically searching and evaluating studies from major scientific databases including Web of Science, PubMed, and ScienceDirect, we provide a comprehensive analysis of the therapeutic potential of cinnamon oil. Research indicates that cinnamon oil possesses a wide range of pharmacological activities, covering antibacterial, anti-inflammatory, anti-tumor, and hypoglycemic effects. It is currently an active ingredient in over 500 patented medicines. Cinnamon oil has demonstrated significant inhibitory effects against various pathogens comprising Staphylococcus aureus, Salmonella, and Escherichia coli. Its mechanisms of action include disrupting cell membranes, inhibiting ATPase activity, and preventing biofilm formation, suggesting its potential as a natural antimicrobial agent. Its anti-inflammatory properties are evidenced by its ability to suppress inflammatory markers like vascular cell adhesion molecules and macrophage colony-stimulating factors. Moreover, cinnamon oil has shown positive effects in lowering blood pressure and improving metabolism in diabetic patients by enhancing glucose uptake and increasing insulin sensitivity. The main active components of cinnamon oil include cinnamaldehyde, cinnamic acid, and eugenol, which play key roles in its pharmacological effects. Recently, the applications of cinnamon oil in industrial fields, including food preservation, cosmetics, and fragrances, have also become increasingly widespread. Despite the extensive research supporting its medicinal value, more clinical trials are needed to determine the optimal dosage, administration routes, and possible side effects of cinnamon oil. Additionally, exploring the interactions between cinnamon oil and other drugs, as well as its safety in different populations, is crucial. Considering the current increase in antibiotic resistance and the demand for sustainable and effective medical treatments, this review emphasizes the necessity for further research into the mechanisms and safety of cinnamon oil to confirm its feasibility as a basis for new drug development. In summary, as a versatile natural product, cinnamon oil holds broad application prospects and is expected to play a greater role in future medical research and clinical practice. Full article

Silicon oxycarbide (SiOC), Ca- and Mg-modified silicon oxycarbide (SiCaOC and SiMgOC) were synthesized via sol–gel processing with subsequent pyrolysis in an inert gas atmosphere. The physicochemical structures of the materials were characterized by XRD, SEM, FTIR, and ²⁹Si MAS NMR. Biocompatibility and in vitro bioactivity were detected by MTT, cell adhesion assay, and simulated body fluid (SBF) immersion test. Mg and Ca were successfully doped into the network structure of SiOC, and the non-bridging oxygens (NBO) were formed. The hydroxycarbonate apatite (HCA) was formed on the modified SiOC surface after soaking in simulated body fluid (SBF) for 14 days, and the HCA generation rate of SiCaOC was higher than that of SiMgOC. Accompanying the increase of bioactivity, the network connectivity (NC) of the modified SiOC decreased from 6.05 of SiOC to 5.80 of SiCaOC and 5.60 of SiMgOC. However, structural characterization and biological experiments revealed the nonlinear relationship between the biological activity and NC of the modified SiOC materials. Full article

Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by limited interests, difficulties in social interactions, repetitive behaviors, and impairments in social communication. ASD tends to run in families, and twin studies suggest a strong genetic basis for the disorder. However, the definition of a genetic profile that indicates a risk for ASD remains unclear. Methods: This analysis includes an investigation (Autism Dataset 4 from the NIMH repository, n = 2890) and a replication (Autism Dataset 3 from the NIMH repository, n = 1233) of trio samples with GWAS data. In Phase 1, a molecular pathway analysis is conducted on the investigation sample to test for the enrichment of specific Gene Ontology (GO) terms associated with autism. In Phase 2, the identified pathways are tested for enrichment in the replication sample. Permutation tests are performed to reduce the risk of false-positive findings. Quality assessment is conducted using QQ-plots and λ values, with Plink and R utilized for the Transmission Disequilibrium Test (TDT) and permutation tests. Results: The GO term GO:0007417 was found to be enriched in both the investigation and replication samples. SNPs associated with this pathway were observed at a frequency higher than expected in the replication sample. Conclusions: The GO term GO:0007417 (development of the nervous system) was associated with autism in both trio samples. Variations in the genes TMPRSS4, TRPC4, and PCDH9 were consistently linked to autism across the two independent samples, highlighting the role of calcium signaling and cell adhesion molecules in the risk of autism-related disorders. The pathways and variations associated with autism are described in detail, which can contribute to the engineering of new pharmacological treatments for ASD. Full article

Cell walls play essential roles in cell recognition, tissue adhesion, and wound response. In particular, pectins as cell-adhesive agents are expected to play a key role in the early stages of grafting. To test this premise, this study focused on examining the dynamics of the accumulation and degree of methyl-esterification of pectic polysaccharides at the graft junctions using tomato autografts as an experimental model. Monosaccharide analysis showed a marked increase in homogalacturonan from 25% to 32 or 34% at the junction zones early after grafting. In addition, a decrease in the degree of homogalacturonan methyl-esterification up to 38% in the scion and 64% in the rootstock was observed in the first few days after grafting, accompanied by an increase in pectin methyl-esterase activity of up to 20–30% in the tissues surrounding the graft junction. These results shed light on the role of homogalacturonan in grafting and reinforce the key function of pectin as one of the most relevant cell wall components during the grafting process. Full article

Transition (Ti, Zr) metal-substituted calcium hexaorthophosphate CaTi_4-zZr_z(PO₄)₆ coatings with an NaSICon structure were deposited by atmospheric plasma spraying (APS) onto Ti6Al4Veli substrates using a statistical design of experiments (SDE) methodology. Several coating properties were determined, including chemical composition, porosity, surface roughness, tensile adhesion strength, shear strength, and solubility in protein-free simulated body fluid (pf-SBF) and TRIS-HCl buffer solution. The biological performance evaluation involved cell proliferation and vitality studies and osseointegration tests of coated Ti6Al4Veli rods intramedullary implanted in sheep femora. After a 6 months observation time, a satisfactory gap-bridging potential was apparent as shown by a continuous, well-adhering layer of newly formed cortical bone. These tests suggest that the coatings possess a suitable osseoconductive potential and present an enhanced expression of bone growth-supporting non-collagenous proteins and cytokines, a high cell proliferation, spreading and vitality, and substantial osseointegration by strong bone apposition. The moderate intrinsic ionic conductivity of CaTi_4-zZr_z(PO₄)₆ compounds can be augmented by doping with highly mobile Na⁺ or Li⁺ ions to levels that suggest their use in electric bone growth stimulation (EBGS) devices, able to treat nonunion (pseudoarthrosis) and osteoporosis, and that may also support spinal stabilisation by vertebral fusion. Full article

Foam cell formation is a hallmark of atherosclerosis, yet the cellular complexity within foam cells in human plaques remains unexplored. Here, we integrate published single-cell RNA-sequencing, spatial transcriptomic, and chromatin accessibility sequencing datasets of human atherosclerotic lesions across eight distinct studies. Through this large-scale integration of patient-derived information, we identified foamy macrophages enriched for genes characteristic of the foamy signature. We further re-clustered the foamy macrophages into five unique subsets with distinct potential functions: (i) pro-foamy macrophages, exhibiting relatively high inflammatory and adhesive properties; (ii) phagocytic foamy macrophages, specialized in efferocytosis; (iii) high-efflux foamy macrophages marked by high NR1H3 expression; (iv) mature foamy macrophages prone to programmed cell death; and (v) synthetic subset. Trajectory analysis elucidated a bifurcated differentiation cell fate from pro-foam macrophages toward either the programmed death (iv) or synthetic (v) phenotype. The existence of these foamy macrophage subsets was validated by immunostaining. Moreover, these foamy macrophage subsets exhibited strong potential ligand–receptor interactions. Finally, we conducted Mendelian randomization analyses to identify a possible causal relationship between key regulatory genes along the programmed death pathway in foamy macrophages and atherosclerotic diseases. This study provides a high-resolution map of foam cell diversity and a set of potential key regulatory genes in atherosclerotic plaques, offering novel insights into the multifaceted pathophysiology underlying human atherosclerosis. Full article

PAK2 is a serine-threonine kinase and a member of the p21-activated kinase (PAK) family. PAK2 is activated by GTP-bound rho family GTPases, Rac, and Cdc42, and it regulates actin dynamics, cell adhesion to the extracellular matrix, and cell motility. In various types of cancers, PAK2 has been implicated in the regulation of cancer cell proliferation, cell cycle, and apoptosis. In addition, recent studies have shown that PAK2 plays an important role in cancer cell metastasis, indicating PAK2 as a potential therapeutic target. This review discusses recent discoveries on the functions of PAK2 in the regulation of various types of cancers. A better understanding of the mechanisms of function of PAK2 will facilitate future development of cancer therapies. Full article

Endoplasmic reticulum stress (ERS) can activate pyroptosis through CHOP and TXNIP; however, the correlation between this process and the formation of kidney stones has not been reported. The purpose is to investigate the effects of calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) on ERS and pyroptosis in HK-2 cells and to explore the formation mechanism of calcium oxalate stones. HK-2 cells were injured by 3 μm COM and COD. COM and COD significantly upregulated the expression levels of GRP78, CHOP, TXNIP, and pyroptosis-related proteins (NLRP3, caspase-1, GSDMD-N, and IL-1β). Fluorescence colocalization revealed that COM induced pyroptosis by inducing the interaction between TXNIP and NLRP3. Both COM and COD crystals can induce ERS and pyroptosis in HK-2 cells. COM induces the interaction with NLRP3 by the upregulation of CHOP and TXNIP and then promotes pyroptosis, while COD only promotes pyroptosis by the upregulation of CHOP. The cytotoxicity and the ability of COM to promote crystal adhesion and aggregation are higher than COD, suggesting that COM is more dangerous for calcium oxalate kidney stone formation. Full article