RESUMO
Prostate cancer is one of the most common malignancies and a leading cause of death in men. Owing to its excellent anti-tumor effects, androgen deprivation therapy (ADT) is widely used in the treatment of prostate cancer. However, its use is controversial because of its potential for inducing cognitive decline. In this review, we summarized the findings of preclinical and clinical studies investigating the effects of ADT on cognitive function in prostate cancer. We discussed the methods used to assess cognitive function in these studies, elucidated the mechanisms through which ADT affects cognitive function, and highlighted recent advancements in cognitive assessment methods. The findings of this review serve as a valuable reference for examining the relationship between ADT and cognitive function in future studies. Besides, the findings may help clinicians understand the advantages and disadvantages of ADT and optimize the treatment plan so as to minimize the adverse effects of ADT.
Assuntos
Antagonistas de Androgênios , Cognição , Neoplasias da Próstata , Humanos , Antagonistas de Androgênios/efeitos adversos , Neoplasias da Próstata/tratamento farmacológico , Masculino , Cognição/efeitos dos fármacos , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/etiologia , Fatores de RiscoRESUMO
BACKGROUND: Dysregulation of long noncoding RNA (lncRNA) expression is related to aging and age-associated neurodegenerative diseases, and the lncRNA expression profile in the aging hippocampus is not well characterized. In the present investigation, the changed mRNAs and lncRNAs were confirmed via deep RNA sequencing. GO and KEGG pathway analyses were conducted to investigate the principal roles of the clearly dysregulated mRNAs and lncRNAs. Subsequently, through the prediction of miRNAs via which mRNAs and lncRNAs bind together, a competitive endogenous RNA network was constructed. RESULTS: A total of 447 lncRNAs and 182 mRNAs were upregulated, and 385 lncRNAs and 144 mRNAs were downregulated. Real-time reverse transcription-polymerase chain reaction validated the reliability of mRNA and lncRNA sequencing. KEGG pathway and GO analyses revealed that differentially expressed (DE) mRNAs were associated with cell adhesion molecules (CAMs), the p53 signaling pathway (SP), phagosomes, PPAR SP and ECM-receptor interactions. KEGG pathway and GO analyses showed that the target genes of the DE lncRNAs were related to cellular senescence, the p53 signaling pathway, leukocyte transendothelial migration and tyrosine metabolism. Coexpression analyses showed that 561 DE lncRNAs were associated with DE mRNAs. A total of 58 lncRNA-miRNA-mRNA target pairs were confirmed in this lncRNAâmiRNAâmRNA network, comprising 10 mRNAs, 13 miRNAs and 38 lncRNAs. CONCLUSIONS: We found specific lncRNAs and mRNAs in the hippocampus of natural aging model rats, as well as abnormal regulatory ceRNA networks. Our outcomes help explain the pathogenesis of brain aging and provide direction for further research.
Assuntos
MicroRNAs , RNA Longo não Codificante , Envelhecimento , Animais , Redes Reguladoras de Genes , Hipocampo/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/genética , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Ratos , Reprodutibilidade dos Testes , Proteína Supressora de Tumor p53/genética , TirosinaRESUMO
Ferroptosis is a new type of cell death found in recent years, which is characterized by iron overload, excessive accumulation of lipid peroxide and destruction of mitochondrial structure. Testicular spermatogenic dysfunction (TSD) is an important factor affecting the health and quality of life of middle-aged and elderly men. Studies show that ferroptosis plays an important role in the development and progression of TSD, mainly involved in the mechanisms of abnormal iron metabolism, lipid peroxidation, oxidative stress response and mitochondrial damage. It is believed that ferroptosis can induce a series of symptoms, such as sperm quality and quantity reduction and spermatogenesis disorder. Therefore, inhibiting the development of ferroptosis can provide a new basis for the study of the mechanisms of the disease. This review focuses on the concept and characteristics of ferroptosis and the advances in the studies of the its mechanism in regulating TSD, with the purpose of introducing the clinical application prospect of targeted inhibition of ferroptosis in the prevention and treatment of TSD and expanding the ideas for the treatment of TSD and other male reproductive diseases.