Study On The Dynamics Of Inflammation And Cancer Gene Regulatory Network Mediated By P53 And NF-κB

The inflammatory response plays a decisive role in different stages of tumor develop-ment,including initiation,promotion,malignant transformation,invasion and metastasis.Inflammation can also affect immune surveillance and response to treatment.The oscil-lation mechanism of tumor suppressor p53 and inflammatory factor NF-κB plays an important role in the field of medical research.Inflammation is generally regarded as an adaptive response to infection,tissue damage and other harmful stimuli and drugs,includ-ing various physiological and pathological processes,with the aim of limiting its adverse effects.However,more and more studies have shown that chronic inflammation itself is dangerous,especially in terms of cancer risk.The activation of NF-κB itself is the root cause of chronic inflammation and is a common basic feature of tumors.The loss of p53activity is also a feature of most tumors.Therefore,the system dynamics mechanism of p53 and NF-κB and the crosstalk between the two has become a hot topic in current research,which has attracted the attention of many experts and scholars.However,few people pay attention to the inevitable transcription and translation time delays of gene expression on the behaviors of the system.Therefore,it is of practical significance to study the influence of time delay on the system dynamics behaviorThis article mainly studies the effect of gene expression and drug response time delays,important parameters,and the combined effects of time delays and parameters on the dynamics of p53 and NF-κB systems.Firstly,the research background,significance,development status and main work of p53 and NF-κBsystem are described.Secondly,transcriptional translation time delays and drug response time delay(dou-ble time delays)were introduced on the basis of the mathematical model established by H¨unziker et al.,and the effects of time delay on the p53 system were studied by combining theoretical analysis and numerical simulation.The results show that the system oscillates when the time delay is greater than the critical value,and is stable when the time delay is less than the critical value.When Mdm2,p53,the degradation rate and time delay of Mdm2 in p53-Mdm2 acted on the p53 system together,the dynamic behavior of p53system would be significantly changed.Thirdly,the influence of time delay and important parameters on the oscillation mech-anism of NF-κB system proposed by H¨eltberg et al is studied.The results show that the time delay bifurcation diagram of NF-κB has Hopf bifurcation at the critical value.The theoretical analysis and numerical simulation are similar to the treatment methods in Chapter 2.The difference is that the third chapter mainly considers the induction level of T NF,the amount of total NF-κB,the half maximum effective concentration,the self-inactivation rate of IKK_a,the nuclear input rate of NF-κB and the conversion rate of IKK_nto IKK_awhen the NF-κB system is applied,and the supercritical or subcritical Hopf bifurcations occur in NF-κB.Finally,based on the model proposed by B¨orchsenius et al.,p53 and NF-κB model are correlated.The specific model proposed by P¨uszynski et al is used to study the ef-fects of time delay,parameters and their combined effects on p53 and NF-κB crostalk system,and the results show that they have an impact on the dynamic behavior of the sys-tem.The results of this study are helpful to further understand the relationship between inflammation and cancer,and have a clear guiding significance for clinical treatment.