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Millifluidics, the manipulation of liquid flow in millimeter-sized channels, has been a revolutionary concept in chemical processing and engineering. The solid channels that contain the liquids, though, are not flexible in their design and modification, and prevent contact with the external environment. All-liquid constructs, on the other hand, while flexible and open, are imbedded in a liquid environment. Here, we provide a route to circumvent these limitations by encasing the liquids in a hydrophobic powder in air that jams on the surface, containing and isolating flowing fluids, offering flexibility and adaptability in design, as manifest in the ability to reconfigure, graft, and segment the constructs. Along with the open nature of these powder-contained channels that allow arbitrary connections/disconnections and substance addition/extraction, numerous applications can be opened in the biological, chemical, and material arenas.
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BACKGROUND: Sustained release of bioactive BMP2 (bone morphogenetic protein-2) is important for bone regeneration, while the intrinsic short half-life of BMP2 at protein level cannot meet the clinical need. In this study, we aimed to design Bmp2 mRNA-enriched engineered exosomes, which were then loaded into specific hydrogel to achieve sustained release for more efficient and safe bone regeneration. RESULTS: Bmp2 mRNA was enriched into exosomes by selective inhibition of translation in donor cells, in which NoBody (non-annotated P-body dissociating polypeptide, a protein that inhibits mRNA translation) and modified engineered BMP2 plasmids were co-transfected. The derived exosomes were named ExoBMP2+NoBody. In vitro experiments confirmed that ExoBMP2+NoBody had higher abundance of Bmp2 mRNA and thus stronger osteogenic induction capacity. When loaded into GelMA hydrogel via ally-L-glycine modified CP05 linker, the exosomes could be slowly released and thus ensure prolonged effect of BMP2 when endocytosed by the recipient cells. In the in vivo calvarial defect model, ExoBMP2+NoBody-loaded GelMA displayed great capacity in promoting bone regeneration. CONCLUSIONS: Together, the proposed ExoBMP2+NoBody-loaded GelMA can provide an efficient and innovative strategy for bone regeneration.
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Exossomos , Hidrogéis , Regeneração Óssea , Preparações de Ação Retardada/metabolismo , Exossomos/metabolismo , Hidrogéis/farmacologia , Osteogênese , RNA Mensageiro/metabolismo , Proteína Morfogenética Óssea 2/metabolismoRESUMO
Mycoplasma pneumoniae causes respiratory tract infections, affecting both children and adults, with varying degrees of severity ranging from mild to life-threatening. In recent years, a new class of regulatory RNAs called long non-coding RNAs (lncRNAs) has been discovered to play crucial roles in regulating gene expression in the host. Research on lncRNAs has greatly expanded our understanding of cellular functions involving RNAs, and it has significantly increased the range of functions of lncRNAs. In lung cancer, transcripts associated with lncRNAs have been identified as regulators of airway and lung inflammation in a process involving protein complexes. An excessive immune response and antibacterial immunity are closely linked to the pathogenesis of M. pneumoniae. The relationship between lncRNAs and M. pneumoniae infection largely involves lncRNAs that participate in antibacterial immunity. This comprehensive review aimed to examine the dysregulation of lncRNAs during M. pneumoniae infection, highlighting the latest advancements in our understanding of the biological functions and molecular mechanisms of lncRNAs in the context of M. pneumoniae infection and indicating avenues for investigating lncRNAs-related therapeutic targets.
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Purpose: Forming a compact biological seal between the gingiva and the implant interface around the percutaneous parts of an implant is one of the key issues in preventing peri-implantitis. Methods: In this study, since microRNA-21 (miR-21) has been approved to promote fibroblast proliferation and collagen formation in skin fibrosis, we prepared miR-21-loaded chitosan (CS)/tripolyphosphate (TPP)/hyaluronic acid (HA) nanoparticles (CTH NPs) and cross-linked them to smooth Ti surfaces with 0.2% gel solution for reverse transfection, after which isolated human gingival fibroblasts were cultured on the miR-21-functionalized Ti substrates. Results: An optimal CS:TPP:HA ratio (1:0.15:0.1) and N/P ratio (20:1) were chosen to produce appropriate nanoparticles. Finally, the CTH/miR-21 nanoparticle-coated smooth Ti surfaces demonstrated increased fibroblast adhesion, proliferation and expression of extracellular matrix-related genes along with similar cytotoxicity and cell spreading on the miR-21-functionalized Ti surface and the unmodified smooth Ti surface. Conclusion: The chitosan-based nanoparticles might be an efficient nonviral miRNA vector to form a stable biological seal in percutaneous areas of Ti for clinical use.
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Quitosana , MicroRNAs , Nanopartículas , Fibroblastos , Gengiva/metabolismo , Humanos , Ácido Hialurônico/farmacologia , MicroRNAs/genética , MicroRNAs/metabolismo , Propriedades de Superfície , Titânio/farmacologiaRESUMO
Spiroplasma mirum, small motile wall-less bacteria, was originally isolated from a rabbit tick and had the ability to infect newborn mice and caused cataracts. In this study, the whole genome and antigen proteins of S. mirum were comparative analyzed and investigated. Glycolysis, pentose phosphate pathway, arginine metabolism, nucleotide biosynthesis, and citrate fermentation were found in S. mirum, while trichloroacetic acid, fatty acids metabolism, phospholipid biosynthesis, terpenoid biosynthesis, lactose-specific PTS, and cofactors synthesis were completely absent. The Sec systems of S. mirum consist of SecA, SecE, SecDF, SecG, SecY, and YidC. Signal peptidase II was identified in S. mirum, but no signal peptidase I. The relative gene order in S. mirum is largely conserved. Genome analysis of available species in Mollicutes revealed that they shared only 84 proteins. S. mirum genome has 381 pseudogenes, accounting for 31.6% of total protein-coding genes. This is the evidence that spiroplasma genome is under an ongoing genome reduction. Immunoproteomics, a new scientific technique combining proteomics and immunological analytical methods, provided the direction of our research on S. mirum. We identified 49 proteins and 11 proteins (9 proteins in common) in S. mirum by anti-S. mirum serum and negative serum, respectively. Forty proteins in S. mirum were identified in relation to the virulence. All these proteins may play key roles in the pathogeny and can be used in the future for diagnoses and prevention.
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Rare therapeutic genes or agents are reported to control orthodontic bone remodeling. MicroRNAs have recently been associated with bone metabolism. Here, we report the in vitro and in vivo effects of miR-34a on osteogenic differentiation under orthodontic force using an N-acetyl-L-leucine-modified polyethylenimine (N-Ac-l-Leu-PEI) carrier. N-Ac-l-Leu-PEI exhibited low cytotoxicity and high miR-34a transfection efficiency in rat bone mineral stem cells and local alveolar bone tissue. After transfection, miR-34a enhanced the osteogenic differentiation of Runx2 and ColI, Runx2 and ColI protein levels, and early osteogenesis function under orthodontic strain in vitro. MiR-34a also enhanced alveolar bone remodeling under orthodontic force in vivo, as evidenced by elevated gene and protein expression, upregulated indices of alveolar bone anabolism, and diminished tooth movement. We determined that the mechanism miR-34a in osteogenesis under orthodontic force may be associated with GSK-3ß. These results suggested that miR-34a delivered by N-Ac-l-Leu-PEI could be a potential therapeutic target for orthodontic treatment.