N6-methyladenosine (m6A) is the most prevalent internal RNA modification, especially within eukaryotic messenger RNAs (mRNAs). m6A modifications of RNA regulate splicing, translocation, stability, and translation into proteins. m6A modifications are catalyzed by RNA methyltransferases, such as METTL3, METTL14, and WTAP (writers); the modifications are removed by the demethylases fat mass and obesity-associated protein (FTO) and ALKBH5 (ALKB homolog 5) (erasers); and the modifications are recognized by m6A-binding proteins, such as YTHDF domain-containing proteins and IGF2BPs (readers). Abnormal changes in the m6A levels of these genes are closely related to tumor occurrence and development. In this paper, we review the role of m6A in human cancer and summarize its prospective applications in cancer.
12 January 2024 in ACS Applied Materials & Interfaces
Bacterial infection is currently considered to be one of the major reasons that leads to the failure of guided bone regeneration (GBR) therapy. Under the normal condition, the pH is neutral, while the microenvironment will become acid at the sites of infection. Here, we present an asymmetric microfluidic/chitosan device that can achieve pH-responsive drug release to treat bacterial infection and promote osteoblast proliferation at the same time. On-demand release of minocycline relies on a pH-sensitive hydrogel actuator, which swells significantly when exposed to the acid pH of an infected region. The PDMAEMA hydrogel had pronounced pH-sensitive properties, and a large volume transition occurred at pH 5 and 6. Over 12 h, the device enabled minocycline solution flowrates of 0.51–1.63 µg/h and 0.44–1.13 µg/h at pH 5 and 6, respectively. The asymmetric microfluidic/chitosan device exhibited excellent capabilities for inhibiting Staphylococcus aureus and Streptococcus mutans growth within 24 h. It had no negative effect on proliferation and morphology of L929 fibroblasts and MC3T3-E1 osteoblasts, which indicates good cytocompatibility. Therefore, such a pH-responsive drug release asymmetric microfluidic/chitosan device could be a promising therapeutic approach in the treatment of infective bone defects.
Background: Exosomes derived from bone marrow mesenchymal stem cells (BMSC-exos) have been shown triggering osteogenic differentiation and mineralization of MSCs, but exosomes administered via bolus injections are rapidly sequestered and cleared. Therefore, we considered the implant as a new organ of patient’s body and expected to find a method to treat implant with BMSC-exos in vivo directly. Methods: A fusion peptide (PEP), as a drug delivery system (DDS) which contained a titanium-binding peptide (TBP) possessing the ability to selectively bind to the titanium surface and another peptide CP05 being able to capture exosomes expertly, is constructed to modify the titanium surface. Results: Both in vitro and in vivo experiments prove PEP retains the ability to bind titanium and exosome simultaneously, and the DDS gain the ability to target exosomes to titanium implants surface following enhancing osseointegration post-implantation. Moreover, the DDS constructed by exosomes of diverse origins shows the similar combination rate and efficiency of therapy. Conclusion: This drug delivery system demonstrates the concept that EXO-PEP system can offer an accurate and efficient therapy for treating implants with long-term effect.
6 March 2024 in ACS Biomaterials Science & Engineering