three-dimensional-printing-assisted-physician-modified-fenestrated

Three-Dimensional Printing Assisted Physician-Modified Fenestrated Endografts for Thoracic Endovascular Aortic Aneurysm Repair in Zone 1

Aortic arch aneurysm is a life-threatening cardiovascular disorder that requires timely medical intervention. Aneurysms in Zone 1 typically involve ...

Nanjing University

: Since primary prostate cancer (PCa) can advance to the life-threatening metastatic PCa, exploring the molecular mechanisms underlying PCa metastasis is crucial for developing the novel targeted preventive strategies for decreasing the mortality of PCa. RNA N-methyladenosine (mA) is an emerging regulatory mechanism for gene expression and its specific roles in PCa progression remains elusive.  Western blotting, quantitative real-time PCR and immunohistochemical analyses were used to detect target gene expression in PCa cells  and prostate tissues from patients. RNA immunoprecipitation was conducted to analyze the specific binding of mRNA to the target protein. Migration and invasion assays were used to assess the migratory capacities of cancer cells. The correlation between target gene expression and survival rate of PCa patients was analyzed based the TCGA database.  We found that total RNA N-methyladenosine (mA) modification levels were markedly upregulated in human PCa tissues due to increased expression of methyltransferase like 3 (METTL3). Further studies revealed that the migratory and invasive capacities of PCa cells were markedly suppressed upon METTL3 knockdown. Mechanistically, METTL3 mediates mA modification of USP4 mRNA at A2696, and mA reader protein YTHDF2 binds to and induces degradation of  mRNA by recruiting RNA-binding protein HNRNPD to the mRNA. Decrease of USP4 fails to remove the ubiquitin group from ELAVL1 protein, resulting in a reduction of ELAVL1 protein. Lastly, downregulation of ELAVL1 in turn increases ARHGDIA expression, promoting migration and invasion of PCa cells.  Our findings highlight the role of METTL3 in modulating invasion and metastasis of PCa cells, providing insight into promising therapeutic strategies for hindering PCa progressing to deadly metastases.

Silencing of METTL3 effectively hinders invasion and metastasis of prostate cancer cells.

N-methyladenosine (mA), the methylation targeting the N position of adenosine, is the most common internal modification of mRNA in eukaryotes. Considering the roles of mA in regulating gene expression, the investigation of mA roles in the biological processes including cell renewal, differentiation, apoptosis, and invasion of cancer cells has become a hot research topic. There are three kinds of protein involved in mA regulation. The methyltransferases and demethylases cooperatively regulate the mA levels, while the mA reading proteins recognize the mA sites and mediate multiple mA-dependent biological functions including mRNA splicing, transfer, translation, and degradation. At present, a large number of studies have found that the changes of mA levels in tumor cells play a very important role in the occurrence and development of tumors, as well as metastasis and invasion of tumor cells. This review summarizes the different roles of mA modification in the occurrence and development of various cancers, and discusses the possibility of choosing the mA related proteins as potential therapeutic targets.

Advances in the functional roles of N6-methyladenosine modification in cancer progression: mechanisms and clinical implications.

Asthenozoospermia, characterized by poor sperm motility, is a common cause of male infertility. Improving energy metabolism and alleviating oxidative stress through drug regimens are potential therapeutic strategies. In this study, we observed upregulated miR-24-3p levels in asthenozoospermia spermatozoa, contributing to energy metabolism disorder and oxidative stress by reducing GSK3β expression. Thus, reducing miR-24-3p levels using drugs is expected to improve sperm motility. The blood-testis barrier (BTB) protects the testis from xenobiotics and drugs. In this study, we found that Sertoli cell-derived small extracellular vesicles (SC-sEV) can traverse the BTB and enter germ cells. We successfully loaded miR-24-3p inhibitor into SC-sEV, creating the nano-drug SC-sEV@miR-24-3p inhibitor, which effectively delivers miR-24-3p inhibitor into germ cells. In a gossypol-induced mouse asthenozoospermia model, administration of SC-sEV@miR-24-3p inhibitor significantly improved sperm motility, in vitro fertilization success, and blastocyst formation rates. As anticipated, it also improved the litter size of asthenozoospermia mice. These results suggest that SC-sEV@miR-24-3p inhibitor holds promise as a potential clinical treatment for asthenospermia.

Sertoli cell-derived extracellular vesicles traverse the blood-testis barrier and deliver miR-24-3p inhibitor into germ cells improving sperm mobility.

[This corrects the article DOI: 10.7150/thno.61178.].

Erratum: Silencing of METTL3 effectively hinders invasion and metastasis of prostate cancer cells: Erratum.

Stanford Type B Aortic Dissection (TBAD), a critical aortic disease, has exhibited stable mortality rates over the past decade. However, diagnostic approaches for TBAD during routine health check-ups are currently lacking. This study focused on developing a model to improve the diagnosis in a population.

Article	Year
Silencing of METTL3 effectively hinders invasion and metastasis of prostate cancer cells. Theranostics\| PubMed ID: 34335955	2021
Advances in the functional roles of N6-methyladenosine modification in cancer progression: mechanisms and clinical implications. Molecular biology reports\| PubMed ID: 35025029	2022
Sertoli cell-derived extracellular vesicles traverse the blood-testis barrier and deliver miR-24-3p inhibitor into germ cells improving sperm mobility. Journal of controlled release : official journal of the Controlled Release Society\| PubMed ID: 37595666	2023
Erratum: Silencing of METTL3 effectively hinders invasion and metastasis of prostate cancer cells: Erratum. Theranostics\| PubMed ID: 39659567	2024
Development and Validation of a Diagnostic Model for Stanford Type B Aortic Dissection Based on Proteomic Profiling. Journal of inflammation research\| PubMed ID: 39816951	2025

Jianhang Hu

Biography

JoVE Journal Publications

Other Publications