RESUMEN
Diabetes is linked to male infertility, but the mechanisms and therapeutic options remain unclear. This study investigates the effects of semaglutide on testicular function in a diabetes mouse model. Clinical data shows that diabetes affects blood glucose, lipid levels, and sperm quality. Single-cell and transcriptome analyses reveal changes in testicular tissue cell proportions and activation of ferroptosis pathways in diabetic patients/rats. In the diabetes mouse model, sperm quality decreases significantly. Treatment with semaglutide (Sem) and the ferroptosis inhibitor ferrostatin-1 (Fer-1) alleviates testicular damage, as evidenced by improved lipid peroxidation and ferroptosis markers. Moreover, the diabetes-induced decrease in the TM-3 cell line's vitality, increased lipid peroxidation, ROS, ferrous ions, and mitochondrial membrane potential damage are all improved by semaglutide and ferrostatin-1 intervention. Overall, these findings highlight semaglutide's potential as a therapeutic approach for mitigating diabetes-induced testicular damage through modulation of the ferroptosis pathway.
Asunto(s)
Ferroptosis , Péptidos Similares al Glucagón , Testículo , Masculino , Ferroptosis/efectos de los fármacos , Animales , Testículo/efectos de los fármacos , Testículo/metabolismo , Testículo/patología , Péptidos Similares al Glucagón/farmacología , Péptidos Similares al Glucagón/uso terapéutico , Ratones , Humanos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Experimental/complicaciones , Línea Celular , Ratones Endogámicos C57BL , Peroxidación de Lípido/efectos de los fármacos , RatasRESUMEN
Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy, which is the most common and severe acute leukemia in adults. Its occurrence, development and prognosis are affected by many factors, and more research is still needed to further guide its treatment. Here, we found that roundabout3 (ROBO3) was associated with poor prognosis in AML through bioinformatics analysis. We then found that overexpression of ROBO3 promoted AML cell proliferation, adhesion and migration while knockdown of ROBO3 had opposite effects. We subsequently found that ROBO3 regulated CD34 expression in AML cells, and this regulatory effect may be achieved through the Hippo-YAP pathway. The inhibitors of this pathway, K-975 and verteporfin, showed an inhibitory effect on AML cells with high ROBO3 expression. ROBO3 was also found to be significantly increased in bone marrow samples from AML patients. Our research indicates that ROBO3 plays an important role in the development of AML, which suggests that ROBO3 can be a prognostic biomarker and potential therapeutic target for AML.