The nervous system is the dominant regulatory system in the human body.The traditional theory is that tumors lack innervation.However,an increasing number of studies have shown complex bidirectional interactions betwe...The nervous system is the dominant regulatory system in the human body.The traditional theory is that tumors lack innervation.However,an increasing number of studies have shown complex bidirectional interactions between tumors and the nervous system.Globally,colorectal cancer(CRC)is the third most common cancer.With the rise of tumor neuroscience,the role of nervous system imbalances in the occurrence and development of CRC has attracted increasing amounts of attention.However,there are still many gaps in the research on the interactions and mechanisms involved in the nervous system in CRC.This article systematically reviews emerging research on the bidirectional relationships between the nervous system and CRC,focusing on the following areas:(1)Effects of the nervous system on colon cancer.(2)Effects of CRC on the nervous system.(3)Treatment of CRC associated with the nervous system.展开更多
Epilepsy,one of the most common neurological disorders,is characterized by spon-taneous recurrent seizures.Temporal lobe epilepsy(TLE)is one of the most common medically intractable seizure disorders.Traf2-and NcK-int...Epilepsy,one of the most common neurological disorders,is characterized by spon-taneous recurrent seizures.Temporal lobe epilepsy(TLE)is one of the most common medically intractable seizure disorders.Traf2-and NcK-interacting kinase(TNIK)has recently attracted attention as a critical modulation target of many neurological and psychiatric disorders,but its role in epilepsy remains unclear.In this study,we hypothesized the involvement of TNIK in epilepsy and investigated TNIK expression in patients with intractable TLE and in a pilocarpineinduced rat model of epilepsy by western blotting,immunofluorescence,and immunohistochemistry.A pentylenetetrazole(PTZ)-induced epilepsy rat model was used to determine the effect of the TNIK inhibitor NCB-0846 on behavioral manifestations of epilepsy.Coimmunoprecipitation(Co-IP)/mass spectrometry(MS)was used to identify the potential mechanism.Through Co-IP,we detected and confirmed the main potential TNIK interactors.Subcellular fractionation was used to establish the effect of NCB-0846 on the expression of the main interactors in postsynaptic density(PSD)fractions.We found that TNIK was primarily located in neurons and decreased significantly in epilepsy model rats and TLE patients compared with controls.NCB-0846 delayed kindling progression and decreased seizure severity.Co-IP/MS identified 63 candidate TNIK interactors in rat hippocampi,notably CaMKIl.Co-IP showed that TNIK might correlate with endogenous GRIA1,SYN2,PSD-95,CaMKIV,GABRG1,and GABRG2.In addition,the significant decrease in GRIA1 in hippocampal total lysate and PSDs after NCB-0846 treatment might help modify the progression of PTZ kindling.Our results suggest that TNIK contributes to epileptic pathology and is a potential antiepileptic drug target.展开更多
基金supported by the National Natural Science Foundation of China(81901324)the Youth Innovation Technology Project of Higher School in Shandong Province(2023KJ261).
文摘The nervous system is the dominant regulatory system in the human body.The traditional theory is that tumors lack innervation.However,an increasing number of studies have shown complex bidirectional interactions between tumors and the nervous system.Globally,colorectal cancer(CRC)is the third most common cancer.With the rise of tumor neuroscience,the role of nervous system imbalances in the occurrence and development of CRC has attracted increasing amounts of attention.However,there are still many gaps in the research on the interactions and mechanisms involved in the nervous system in CRC.This article systematically reviews emerging research on the bidirectional relationships between the nervous system and CRC,focusing on the following areas:(1)Effects of the nervous system on colon cancer.(2)Effects of CRC on the nervous system.(3)Treatment of CRC associated with the nervous system.
基金supported by grants from the National Natural Science Foundation of China(No.81901324,82001378,82071395)China Postdoctoral Science Foundation(No.2021M693246)+4 种基金joint project of Chongqing Health Commission and Science and Technology Bureau(Chongqing,China)(No.2023QNXM009)Science and Technology Research Program of Chongqing Education Commission of China(No.KJQN202200435)Chongqing Talents:Exceptional Young Talents Project(Chongqing,China)(No.CQYC202005014)Natural Science Foundation of Chongqing,China(No.cstc2021ycjh-bgzxm0035,CSTB2022NSCQ-LZX0038)Key Research and Development Projects of Jining City,Shandong,China(No.2021YXNS057).
文摘Epilepsy,one of the most common neurological disorders,is characterized by spon-taneous recurrent seizures.Temporal lobe epilepsy(TLE)is one of the most common medically intractable seizure disorders.Traf2-and NcK-interacting kinase(TNIK)has recently attracted attention as a critical modulation target of many neurological and psychiatric disorders,but its role in epilepsy remains unclear.In this study,we hypothesized the involvement of TNIK in epilepsy and investigated TNIK expression in patients with intractable TLE and in a pilocarpineinduced rat model of epilepsy by western blotting,immunofluorescence,and immunohistochemistry.A pentylenetetrazole(PTZ)-induced epilepsy rat model was used to determine the effect of the TNIK inhibitor NCB-0846 on behavioral manifestations of epilepsy.Coimmunoprecipitation(Co-IP)/mass spectrometry(MS)was used to identify the potential mechanism.Through Co-IP,we detected and confirmed the main potential TNIK interactors.Subcellular fractionation was used to establish the effect of NCB-0846 on the expression of the main interactors in postsynaptic density(PSD)fractions.We found that TNIK was primarily located in neurons and decreased significantly in epilepsy model rats and TLE patients compared with controls.NCB-0846 delayed kindling progression and decreased seizure severity.Co-IP/MS identified 63 candidate TNIK interactors in rat hippocampi,notably CaMKIl.Co-IP showed that TNIK might correlate with endogenous GRIA1,SYN2,PSD-95,CaMKIV,GABRG1,and GABRG2.In addition,the significant decrease in GRIA1 in hippocampal total lysate and PSDs after NCB-0846 treatment might help modify the progression of PTZ kindling.Our results suggest that TNIK contributes to epileptic pathology and is a potential antiepileptic drug target.
