The present application relates to a kind of FOXM1 proteinphosphorylation modification interfering peptide and its application, belong to the field of biological medicine technology. Specifically, the present application is found in research, the transcriptional activity of FOXM1 protein depends on the condensate formed by its polymerization, destroying the polymerization of FOXM1 can effectively inhibit the occurrence and development of tumor, and the phosphorylation of the 376th amino acid of FOXM1 protein can also inhibit polymerization to some extent, thereby inhibiting the transcriptional activation of FOXM1 protein. Therefore, the present application designs an interfering peptide, and introduces phosphorylation modification in appropriate position, obtains a kind of phosphorylation modification interfering peptide FIP4 targeted to FOXM1 protein polymerization domain, the interfering peptide plays a significant role in inhibiting the transcriptional activation of FOXM1 protein in cell and animal in vivo, and can be used for treating tumor-related diseases.
This invention belongs to the field of biomedicine and regenerative medicine technology. It discloses a chimeric polypeptide, related biomaterials, and their application in inducing cardiomyocytes. The chimeric polypeptide is obtained through family homologous domain substitution and is selected from the following groups: (1) a MEF2 chimeric polypeptide with MEF2C protein as the backbone, wherein the N-terminal and C-terminal transcriptional activation domains are replaced by homologous regions of MEF2B and MEF2D, respectively; (2) a GATA chimeric polypeptide with GATA4 protein as the backbone, wherein the N-terminal transcriptional activation domain is replaced by homologous regions of GATA1 and GATA6. This invention also provides the nucleic acid encoding the polypeptide, the construct, and a method for efficiently inducing fibroblastreprogramming into cardiomyocytes under in vitro conditions. When the chimeric polypeptide of this invention is used alone or in combination, the induced cells exhibit calciumion oscillations earlier and have higher maturity.
This invention relates to the field of gene editing technology, specifically to a gene circuit-based specific gene expression system and module, a pharmaceutical composition, and its applications. The system includes a first vector and a second vector. The first vector includes a first expression cassette containing a cell-specific promoter, a coding sequence encoding a transcriptionally activated fusion protein, and a regulatory region sequence downstream of the coding sequence. The regulatory region sequence is configured to form a response element in the 3' untranslated region of the fusion protein's mRNA after transcription. This response element binds to a specific long non-coding RNA within the silenced cell, leading to the degradation of the fusion protein's mRNA. The second vector includes a second expression cassette containing an associated promoter that can be activated by the transcriptionally activated fusion protein, and a target gene downstream of the associated promoter. Advantages: This ensures that the target protein is expressed only in target cells and not in cancer cells, avoiding adverse effects on non-target cells or tissues, and reducing treatment risks and side effects.
This invention discloses a stable A549 expression cell line constructed based on a dCas9-VP64 transcriptional activation system and its applications. Based on the dCas9-VP64 transcriptional activation system, this invention yielded a stable A549 expression cell line with the highest relative expression level of dCas9 protein after puromycin selection. Subsequently, by introducing sgRNAs targeting one or more genes into this cell line, the expression of endogenous genes in lungcancer cells can be activated, and related functional gene studies can be conducted. Furthermore, this invention prepares an A549 cell line with significantly reduced proliferation rate by introducing sgRNA targeting the TP53 binding site in the LTR5Hs sequence into this cell line. This invention is the first to discover a novel target for lungcancer treatment, which is of great significance for the treatment and mechanistic research of lungcancer.
This invention provides a triptolide sustained-release hydrogel targeting the FOSB and TGFB1 axes and its applications, belonging to the field of biomedical materials and drug delivery technology. The sustained-release hydrogel is a core-shell structured sequential release hydrogel. The outer layer is a 40 mg / mL low-concentration gelatinmethacrylamide hydrogel loaded with stromal cell-derived factor-1α (SDF-1α), and the inner layer is a 60 mg / mL high-concentration GelMA hydrogel loaded with triptolide. This invention is the first to clearly demonstrate that the transcription factor FOSB constitutes a core driving pathway for endometriosisfibrosis by transcribing and activating TGFB1. Triptolide can directly bind to FOSB and promote its ubiquitination-mediated degradation, thereby blocking the TGF-β / Smad signaling pathway and mesenchymal-myofibroblast transformation. Through a synergistic recruitment-targeted inhibition strategy using core-shell hydrogels, SDF-1α rapidly recruits myofibroblasts in the lesion area, and tripterygium wilfordii achieves local sustained release over 14 days. While significantly inhibiting fibrosis and reducing the size of endometriosis lesions, it avoids the hepatotoxicity and off-target damage of free drugs.