Research progress of artificial intelligence-based small molecule generation models in drug discovery / 中国药科大学学报

@#Abstract: With the rapid development of artificial intelligence technology, small molecule generation models have emerged as a significant research direction in the field of drug discovery. These models, including Generative Adversarial Networks (GANs), Variational Autoencoders (VAEs), and diffusion models, have proven to possess remarkable capabilities in optimizing drug properties and generating complex molecular structures. This article comprehensively analyzes the application of the aforementioned advanced technologies in the drug discovery process, demonstrating how they supplement and enhance traditional drug design methods. At the same time, it addresses the challenges facing current methods in terms of data quality, model complexity, computational cost, and generalization ability, with a prospect of future research directions.

AKT inhibitor Hu7691 induces differentiation of neuroblastoma cells

While neuroblastoma accounts for 15% of childhood tumor-related deaths, treatments against neuroblastoma remain scarce and mainly consist of cytotoxic chemotherapeutic drugs. Currently, maintenance therapy of differentiation induction is the standard of care for neuroblastoma patients in clinical, especially high-risk patients. However, differentiation therapy is not used as a first-line treatment for neuroblastoma due to low efficacy, unclear mechanism, and few drug options. Through compound library screening, we accidently found the potential differentiation-inducing effect of AKT inhibitor Hu7691. The protein kinase B (AKT) pathway is an important signaling pathway for regulating tumorigenesis and neural differentiation, yet the relation between the AKT pathway and neuroblastoma differentiation remains unclear. Here, we reveal the anti-proliferation and neurogenesis effect of Hu7691 on multiple neuroblastoma cell lines. Further evidence including neurites outgrowth, cell cycle arrest, and differentiation mRNA marker clarified the differentiation-inducing effect of Hu7691. Meanwhile, with the introduction of other AKT inhibitors, it is now clear that multiple AKT inhibitors can induce neuroblastoma differentiation. Furthermore, silencing AKT was found to have the effect of inducing neuroblastoma differentiation. Finally, confirmation of the therapeutic effects of Hu7691 is dependent on inducing differentiation in vivo, suggesting that Hu7691 is a potential molecule against neuroblastoma. Through this study, we not only define the key role of AKT in the progression of neuroblastoma differentiation but also provide potential drugs and key targets for the application of differentiation therapies for neuroblastoma clinically.

Deubiquitinase JOSD2 stabilizes YAP/TAZ to promote cholangiocarcinoma progression

Cholangiocarcinoma (CCA) has emerged as an intractable cancer with scanty therapeutic regimens. The aberrant activation of Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are reported to be common in CCA patients. However, the underpinning mechanism remains poorly understood. Deubiquitinase (DUB) is regarded as a main orchestrator in maintaining protein homeostasis. Here, we identified Josephin domain-containing protein 2 (JOSD2) as an essential DUB of YAP/TAZ that sustained the protein level through cleavage of polyubiquitin chains in a deubiquitinase activity-dependent manner. The depletion of JOSD2 promoted YAP/TAZ proteasomal degradation and significantly impeded CCA proliferation

Research progress of small molecule inhibitors targeting PI3K-Akt-mTOR pathway / 中国生化药物杂志

Aberrant activation of the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(PKB,Akt)-mammalian target of rapamycin(mTOR) pathway is commonly observed in human cancer and is critical for cell survival, proliferation and differentiation.A variety of small molecule inhibitors targeting PI3K-Akt-mTOR pathway are under clinical studies.This review will summarize the recent studies in terms of the PI3K-Akt-mTOR signaling pathway and cancer,research progress of the antitumor activity possessed by PI3K-Akt-mTOR inhibitors,as well as the recent research in the related field conducted by our group.

Impact of quality care on interventions PICC catheter patient compliance and mental health status of tumors / 中国现代医生

Objective To investigate the patient compliance and mental health conditions of quality care interventions PICC catheter affect tumor. Methods 123 cases of cancer patients were selected from March 2012 to October 2013 in our hospital, they were divided into two groups according to nursing methods, 62 cases in the observation group, 61 cases in the control group. The control group received basic care , the observation group was implemented quality care interventions on the basis of the control group. The compliance, mental health, satisfaction of two groups were com-pared. Results The patients maintain compliance in the observation group were better than the control group , the satis-faction total scores,the quality of care, nursing service, nursing process and other items satisfaction scores were higher than the control group, there were significantly differences between two groups (P<0.05). SCL-90 in depression, anx-iety , mental , forced , paranoid , sensitive , horror , hostility , and somatization factor score of the observation group after PICC catheter were significantly lower than the control group, there were significantly differeces (P<0.05). Con-clusion Quality care measures for cancer chemotherapy patients underwent intervention can PICC catheter and main-taining compliance, nursing satisfaction and improve quality of life, relief adverse psychological.