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Cell Biology and Toxicology May 2024MYBL1 is a strong transcriptional activator involved in the cell signaling. However, there is no systematic study on the role of MYBL1 in atherosclerosis. The aim of...
MYBL1 is a strong transcriptional activator involved in the cell signaling. However, there is no systematic study on the role of MYBL1 in atherosclerosis. The aim of this study is to elucidate the role and mechanism of MYBL1 in atherosclerosis. GSE28829, GSE43292 and GSE41571 were downloaded from NCBI for differentially expressed analysis. The expression levels of MYBL1 in atherosclerotic plaque tissue and normal vessels were detected by qRT-PCR, Western blot and Immunohistochemistry. Transwell and CCK-8 were used to detect the migration and proliferation of HUVECs after silencing MYBL1. RNA-seq, Western blot, qRT-PCR, Luciferase reporter system, Immunofluorescence, Flow cytometry, ChIP and CO-IP were used to study the role and mechanism of MYBL1 in atherosclerosis. The microarray data of GSE28829, GSE43292, and GSE41571 were analyzed and intersected, and then MYBL1 were verified. MYBL1 was down-regulated in atherosclerotic plaque tissue. After silencing of MYBL1, HUVECs were damaged, and their migration and proliferation abilities were weakened. Overexpression of MYBL1 significantly enhanced the migration and proliferation of HUVECs. MYBL1 knockdown induced abnormal autophagy in HUVEC cells, suggesting that MYBL1 was involved in the regulation of HUVECs through autophagy. Mechanistic studies showed that MYBL1 knockdown inhibited autophagosome and lysosomal fusion in HUVECs by inhibiting PLEKHM1, thereby exacerbating atherosclerosis. Furthermore, MYBL1 was found to repress lipid accumulation in HUVECs after oxLDL treatment. MYBL1 knockdown in HUVECs was involved in atherosclerosis by inhibiting PLEKHM1-induced autophagy, which provided a novel target of therapy for atherosclerosis.
Topics: Animals; Humans; Atherosclerosis; Autophagy; Cell Movement; Cell Proliferation; Down-Regulation; Human Umbilical Vein Endothelial Cells; Membrane Glycoproteins; Plaque, Atherosclerotic; Trans-Activators
PubMed: 38797732
DOI: 10.1007/s10565-024-09873-6 -
Bioscience Reports May 2024Varicose vein disease (VVD) is a common health problem worldwide. Microfibril-associated protein 5 (MFAP5) is one of the potential key players in its pathogenesis. Our...
Varicose vein disease (VVD) is a common health problem worldwide. Microfibril-associated protein 5 (MFAP5) is one of the potential key players in its pathogenesis. Our previous microarray analysis revealed the cg06256735 and cg15815843 loci in the regulatory regions of the MFAP5 gene as hypomethylated in varicose veins which correlated with its up-regulation. The aim of this work was to validate preliminary microarray data, estimate the level of 5-hydroxymethylcytosine (5hmC) at these loci, and determine the methylation status of one of them in different layers of the venous wall. For this, methyl- and hydroxymethyl-sensitive restriction techniques were used followed by real-time PCR and droplet digital PCR, correspondingly, as well as bisulfite pyrosequencing of +/- oxidized DNA. Our microarray data on hypomethylation at the cg06256735 and cg15815843 loci in whole varicose vein segments were confirmed and it was also demonstrated that the level of 5hmC at these loci is increased in VVD. Specifically, among other layers of the venous wall, tunica (t.) intima is the main contributor to hypomethylation at the cg06256735 locus in varicose veins. Thus, it was shown that hypomethylation at the cg06256735 and cg15815843 loci takes place in VVD, with evidence to suggest that it happens through their active demethylation leading to up-regulation of the MFAP5 gene, and t. intima is most involved in this biochemical process.
Topics: Varicose Veins; Humans; DNA Methylation; Male; Female; Middle Aged; 5-Methylcytosine; Adult; Aged; Regulatory Sequences, Nucleic Acid; Genetic Loci
PubMed: 38743016
DOI: 10.1042/BSR20231938 -
Nature Communications May 2024Microfibril-associated glycoprotein 4 (MFAP4) is a 36-kDa extracellular matrix glycoprotein with critical roles in organ fibrosis, chronic obstructive pulmonary...
Microfibril-associated glycoprotein 4 (MFAP4) is a 36-kDa extracellular matrix glycoprotein with critical roles in organ fibrosis, chronic obstructive pulmonary disease, and cardiovascular disorders, including aortic aneurysms. MFAP4 multimerises and interacts with elastogenic proteins, including fibrillin-1 and tropoelastin, and with cells via integrins. Structural details of MFAP4 and its potential interfaces for these interactions are unknown. Here, we present a cryo-electron microscopy structure of human MFAP4. In the presence of calcium, MFAP4 assembles as an octamer, where two sets of homodimers constitute the top and bottom halves of each octamer. Each homodimer is linked together by an intermolecular disulphide bond. A C34S missense mutation prevents disulphide-bond formation between monomers but does not prevent octamer assembly. The atomic model, built into the 3.55 Å cryo-EM map, suggests that salt-bridge interactions mediate homodimer assembly, while non-polar residues form the interface between octamer halves. In the absence of calcium, an MFAP4 octamer dissociates into two tetramers. Binding studies with fibrillin-1, tropoelastin, LTBP4, and small fibulins show that MFAP4 has multiple surfaces for protein-protein interactions, most of which depend upon MFAP4 octamer assembly. The C34S mutation does not affect these protein interactions or cell interactions. MFAP4 assemblies with fibrillin-1 abrogate MFAP4 interactions with cells.
Topics: Humans; Fibrillin-1; Tropoelastin; Cryoelectron Microscopy; Extracellular Matrix Proteins; Protein Multimerization; Protein Binding; Models, Molecular; Calcium; Mutation, Missense; Microfibrils; HEK293 Cells; Carrier Proteins; Glycoproteins; Adipokines
PubMed: 38740766
DOI: 10.1038/s41467-024-48377-z -
ACS Omega May 2024Cellulose nanofibrils (CNFs) with different charge densities were prepared and investigated by a combination of different complementary techniques sensitive to the...
Cellulose nanofibrils (CNFs) with different charge densities were prepared and investigated by a combination of different complementary techniques sensitive to the structure and molecular dynamics of the system. The morphology of the materials was investigated by scanning electron microscopy (SEM) and X-ray scattering (SAXS/WAXS). The latter measurements were quantitatively analyzed yielding to molecular parameters in dependence of the charge density like the diameter of the fibrils, the distance between the fibrils, and the dimension of bundles of nanofibrils, including pores. The influence of water on the properties and the charge density is studied by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and broadband dielectric spectroscopy. The TGA measurements reveal two mass loss processes. The one at lower temperatures was related to the loss of water, and the second process at higher temperatures was related to the chemical decomposition. The resulting char yield could be correlated to the distance between the microfibrils. The DSC investigation for hydrated CNFs revealed three glass transitions due to the cellulose segments surrounded by water molecules in different states. In the second heating scan, only one broad glass transition is observed. The dielectric spectra reveal two relaxation processes. At low temperatures or higher frequencies, the β-relaxation is observed, which is assigned to localized fluctuation of the glycosidic linkage. At higher temperatures and lower frequencies, the α-relaxation takes places. This relaxation is due to cooperative fluctuations in the cellulose segments. Both processes were quantitatively analyzed. The obtained parameters such as the relaxation rates were related to both the morphological data, the charge density, and the content of water for the first time.
PubMed: 38737077
DOI: 10.1021/acsomega.4c00255 -
Polymers May 2024Biopolymers are biodegradable and renewable and can significantly reduce environmental impacts. For this reason, biocomposites based on a plasticized starch and...
Biopolymers are biodegradable and renewable and can significantly reduce environmental impacts. For this reason, biocomposites based on a plasticized starch and cross-linker matrix and with a microfibrillated OCC cardboard cellulose reinforcement were developed. Biocomposites were prepared by suspension casting with varied amounts of microfibrillated cellulose: 0, 4, 8, and 12 wt%. Polyethylene glycol diglycidyl ether (PEGDE) was used as a cross-linking, water-soluble, and non-toxic agent. Microfibrillated cellulose (MFC) from OCC cardboard showed appropriate properties and potential for good performance as a reinforcement. In general, microfiber incorporation and matrix cross-linking increased crystallization, reduced water adsorption, and improved the physical and tensile properties of the plasticized starch. Biocomposites cross-linked with PEGDE and reinforced with 12 wt% MFC showed the best properties. The chemical and structural changes induced by the cross-linking of starch chains and MFC reinforcement were confirmed by FTIR, NMR, and XRD. Biodegradation higher than 80% was achieved for most biocomposites in 15 days of laboratory compost.
PubMed: 38732758
DOI: 10.3390/polym16091290 -
American Journal of Translational... 2024Triple-negative breast cancer (TNBC) is characterized by significant heterogeneity, presenting a formidable challenge with a poor prognosis and a deficiency of...
OBJECTIVES
Triple-negative breast cancer (TNBC) is characterized by significant heterogeneity, presenting a formidable challenge with a poor prognosis and a deficiency of efficacious treatment options.
METHODS
In this comprehensive study, we investigated the multifaceted role of Microfibril-associated glycoprotein 2 (MFAP2) in TNBC using a combination of bioinformatics analysis involving Gene Expression Omnibus (GEO), OncoDB, UALCAN, Human Protein Atlas (HPA), TIMER, STRING, DAVID, and GSCA databases and in vitro experiments, such as cell culture, MFAP2 gene knockdown, RT-qPCR, western Blot, colony formation, Cell counting kit-8, and wound healing assays.
RESULTS
Our findings demonstrated a significant up-regulation of MFAP2 mRNA in TNBC cell lines, emphasizing its potential as a diagnostic biomarker. Validation across multiple datasets further affirmed the elevated expression of MFAP2 in TNBC tissues, underscoring its prognostic relevance. Notably, our study revealed a correlation between MFAP2 expression and immune cell infiltration, suggesting its role in shaping the tumor microenvironment. STRING analysis unveiled interactions with proteins involved in elastic fibers and extracellular matrix constituents. Furthermore, KEGG pathway analysis highlighted enrichment in the TGF-beta signaling pathway, implicating MFAP2 in key cancer-related processes. Drug sensitivity analysis identified potential therapeutic targets, supporting MFAP2's utility in personalized treatment strategies. In vitro experiments corroborated the oncogenic impact of MFAP2, demonstrating its influence on TNBC cell proliferation and migration.
CONCLUSION
These comprehensive findings position MFAP2 as a promising biomarker and therapeutic target in TNBC, offering valuable insight for future research and clinical application.
PubMed: 38715831
DOI: 10.62347/BLDG4505 -
Journal of Dentistry May 2024This laboratory study assessed the performance of a novel fluoride dentifrice containing micro-fibrillated cellulose (MFC) and entrapped silica.
OBJECTIVES
This laboratory study assessed the performance of a novel fluoride dentifrice containing micro-fibrillated cellulose (MFC) and entrapped silica.
METHODS
Removal of extrinsic stains was assessed using the pellicle cleaning ratio (PCR) method, and radioactive dentin abrasivity (RDA) was measured, to calculate a cleaning efficiency index (CEI). Fluoride efficacy was evaluated using widely used remineralization and fluoride uptake methods. The test product (Protegera™) was compared to common dentifrices (Crest - Cavity Protection™ and ProHealth™, Sensodyne Pronamel™, Arm & Hammer™ Advanced Whitening, Crest ProHealth™, and Colgate Optic White™).
RESULTS
The PCR for the MFC dentifrice (141) was comparable to three known marketed stain-removing dentifrices (Arm & Hammer™ Advanced Whitening, Crest ProHealth™, and Colgate Optic White™) but it had a significantly lower RDA (88 ± 6) than 5 other products. This gave it the highest CEI of the tested products (2.0). In a 10-day pH cycling study, the fluoride efficacy of the MFC product was comparable to Sensodyne Pronamel and Crest Cavity Protection. The MFC dentifrice was superior for promoting fluoride uptake into incipient enamel lesions compared to the USP reference dentifrice.
CONCLUSION
The MFC dentifrice has low abrasion, but despite this, it is highly effective in removing stained pellicle. It also is an efficacious fluoride source when compared to relevant commercially available fluoride dentifrices with high dentin abrasivity.
CLINICAL SIGNIFICANCE
The addition of micro-fibrillated cellulose to a fluoride dentifrice gives a low abrasive product that can effectively remove external stains, and serve as an effective fluoride source. This combination of benefits seems well suited to enamel protection and caries prevention.
PubMed: 38714242
DOI: 10.1016/j.jdent.2024.105038 -
Carbohydrate Polymers Aug 2024Microfibrillated cellulose (MFC) is a bio-material produced by disintegrating cellulose fibres into fibrillar components. MFC could offer a sustainable solution to... (Review)
Review
Microfibrillated cellulose (MFC) is a bio-material produced by disintegrating cellulose fibres into fibrillar components. MFC could offer a sustainable solution to packaging needs since it can form an excellent barrier to oxygen. However, a comprehensive understanding of how MFC characteristics impact barrier properties of MFC films or coatings is required. This article critically reviews how the extent of separation of fibres into fibrils-and any resulting changes to the crystallinity and degree of polymerisation of cellulose-influences gas barrier properties of MFC films or coatings. Findings from publications investigating the barrier performance of MFC prepared through different processes intending to increase the effectiveness of fibrillation are evaluated and compared. The effects of processing conditions or chemical pre-treatments on barrier properties of MFC films or coatings are then discussed. A comparison of reported results showed that morphology and size polydispersity of the cellulose strongly influence the barrier properties of MFC. However, changing the MFC production process to decrease fibril diameter and polydispersity can result in changes to cellulose crystallinity; reduction in fibril length; introduction of bulky functional groups; or increased fibril surface charge: all of which could have a negative impact on the barrier properties of the final films or coatings.
PubMed: 38710579
DOI: 10.1016/j.carbpol.2024.122085 -
Polymers Apr 2024Over the past few years, polymer nanocomposites have garnered a significant amount of interest from both the scientific community and industry due to their remarkable...
Over the past few years, polymer nanocomposites have garnered a significant amount of interest from both the scientific community and industry due to their remarkable versatility and wide range of potential uses in various fields, including automotive, electronics, medicine, textiles and environmental applications. In this regard, this study focuses on the influence of a compatibilizer rubber on a nanocomposite incorporating graphene nanoparticles (GNPs), with a polymer matrix based on a blend of polypropylene (PP) and polyethylene terephthalate (PET). This effect has been investigated on both isotropic samples and on anisotropic/spun fiber samples. The influence of the compatibilizer rubber on morphological, rheological and mechanical properties was analysed and discussed. Mechanical and morphological properties were evaluated on both isotropic samples obtained by compression moulding and melt-spun fibers. The addition of the rubbery compatibilizer increased the viscosity, improving interfacial adhesion, and the same effect was observed for the melt strength and breaking stretching ratios. Mechanical properties, including the elastic modulus, tensile strength and elongation at break, improved in both types of samples but more significantly in the fibers. These improvements were attributed to the orientation of the matrix, the formation of PET microfibrils, and the reduction in the size of graphene nanoparticles due to the action of the elongational flow. This reduction, facilitated by the elongation flow and the action of the compatibilizer, improved matrix-nanofiller adhesion due to the increased contact area between the two polymeric phases and between the filler and matrix. Finally, a transition from brittle to ductile behaviour was observed, particularly in the system with the compatibilizer, attributed to defect reduction and improved stress transmission.
PubMed: 38675011
DOI: 10.3390/polym16081092 -
Polymers Apr 2024As one of the most widely applied general-purpose plastics, high-density polyethylene (HDPE) exhibits good comprehensive performance. However, mechanical strength limits...
As one of the most widely applied general-purpose plastics, high-density polyethylene (HDPE) exhibits good comprehensive performance. However, mechanical strength limits its wider application. In this work, we introduced the engineering plastic PA6 as a dispersed phase to modify the HDPE matrix and applied multiple shears generated by vibration to the polymer melt during the packing stage of injection molding. SEM, 2D-WXRD and 2D-SAXS were used to characterize the morphology and structure of the samples. The results show that under the effect of a strong shear field, the dispersed phase in the composites can form in situ microfibers and numerous high-strength shish-kebab and hybrid shish-kebab structures are formed. Additionally, the distribution of fibers and high-strength oriented structures in the composites expands to the core region with the increase in vibration times. As a result, the tensile strength, tensile modulus and surface hardness of VIM-6 can reach a high level of 66.5 MPa, 981.4 MPa and 72, respectively. Therefore, a high-performance HDPE product is successfully prepared in this study, which is of great importance for expanding the application range of HDPE products.
PubMed: 38674952
DOI: 10.3390/polym16081032