RESUMO
Although the composition and assembly of stress granules (SGs) are well understood, the molecular mechanisms underlying SG disassembly remain unclear. Here, we identify that heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) is associated with SGs and that its absence specifically enhances the disassembly of arsenite-induced SGs depending on the ubiquitination-proteasome system but not the autophagy pathway. hnRNPA2B1 interacts with many core SG proteins, including G3BP1, G3BP2, USP10, and Caprin-1; USP10 can deubiquitinate G3BP1; and hnRNPA2B1 depletion attenuates the G3BP1-USP10/Caprin-1 interaction but elevates the G3BP1 ubiquitination level under arsenite treatment. Moreover, the disease-causing mutation FUSR521C also disassembles faster from SGs in HNRNPA2B1 mutant cells. Furthermore, knockout of hnRNPA2B1 in mice leads to Sertoli cell-only syndrome (SCOS), causing complete male infertility. Consistent with this, arsenite-induced SGs disassemble faster in Hnrnpa2b1 knockout (KO) mouse Sertoli cells as well. These findings reveal the essential roles of hnRNPA2B1 in regulating SG disassembly and male mouse fertility.
Assuntos
Arsenitos , Masculino , Animais , Camundongos , Arsenitos/toxicidade , DNA Helicases , Proteínas de Ligação a Poli-ADP-Ribose , RNA Helicases , Proteínas com Motivo de Reconhecimento de RNA , Grânulos de Estresse , FertilidadeRESUMO
Blockchain technology is essentially a decentralized database maintained by relevant parties and has been widely used in various scenarios such as logistics and finance. In terms of applications in the medical field, it is becoming more and more important because the patient's symptoms may be related to a certain vaccine. Whether the patient has been vaccinated with this vaccine will lead to different diagnostic results by the doctor. However, in the current vaccination environment of many regions, the vaccination record (VR) can only be kept in the patient's vaccination booklet, which is easy to lose or destroy. Therefore, the doctor needs to retrieve the patient's VR through a centralized database maintained by the government, which is time-consuming and will increase the medical risk. This study proposes a traceable blockchain-based vaccination record storage and sharing system. In the proposed system, the patient gets the vaccination at any legal clinic and the VR can be saved accompanied by the signature into the blockchain center, which ensures traceability. When the patient visits the hospital for treatment, the doctor can obtain the detail of the VR from the blockchain center and then make a diagnosis. The security of the proposed system will be protected by the programmed smart contracts. Through mutual authentication, our system can also provide and guarantee data integrity and nonrepudiation. Moreover, the proposed system has resistance to replay and man-in-the-middle attacks, and the performance is good.
Assuntos
Blockchain , Gerenciamento de Dados , Registros Eletrônicos de Saúde , Humanos , Tecnologia , VacinaçãoRESUMO
Diabetic nephropathy (DN) is one of the chronic microvascular diseases of diabetes. Studies revealed that inflammation is involved in the development of DN. However, its mechanisms are not fully clear. Here, we screened DN-related mRNAs by RNA sequencing in the renal tissues of db/db DN mice and normal control mice. The Swiss-Model, ZDOCK 3.0.2 and PyMOL 2.3.2 were applied for bioinformatics analysis. In total, we obtained 6,820 mRNAs that were dysexpressed in DN. Among them, Receptor for Activated C Kinase 1 (Rack1) was focused on for its high fold changes and high values of fragments per kilobase million (FPKM) in both two groups (FPKM >100). Moreover, Rack1 was highly expressed in DN in vivo and in vitro. Results displayed that the expressions of pro-inflammatory cytokines Mcp-1 and Tnf-α were increased when Rack1 was overexpressed in cells cultured with low glucose while the expressions of Mcp-1 and Tnf-α were decreased when Rack1 was silenced in cells cultured with high glucose. Furthermore, results showed that the established DN inflammatory factor nuclear factor NF-kappa-B (NF-κB) was regulated by Rack1 via the direct interaction between Rack1 and NF-κB subunits P50 and P65. In summary, this identified Rack1 could play an important role in the inflammation of DN via NF-κB, which can provide new insight for DN research.