Cancer cachexia is a multi-organ syndrome and closely related to changes in signal communication between organs,which is mediated by cancer cachexia factors.Cancer cachexia factors,being the general name of inflammato...Cancer cachexia is a multi-organ syndrome and closely related to changes in signal communication between organs,which is mediated by cancer cachexia factors.Cancer cachexia factors,being the general name of inflammatory factors,circulating proteins,metabolites,and microRNA secreted by tumor or host cells,play a role in secretory or other organs and mediate complex signal communication between organs during cancer cachexia.Cancer cachexia factors are also a potential target for the diagnosis and treatment.The pathogenesis of cachexia is unclear and no clear effective treatment is available.Thus,the treatment of cancer cachexia from the perspective of the tumor ecosystem rather than from the perspective of a single molecule and a single organ is urgently needed.From the point of signal communication between organs mediated by cancer cachexia factors,finding a deeper understanding of the pathogenesis,diagnosis,and treatment of cancer cachexia is of great significance to improve the level of diagnosis and treatment.This review begins with cancer cachexia factors released during the interaction between tumor and host cells,and provides a comprehensive summary of the pathogenesis,diagnosis,and treatment for cancer cachexia,along with a particular sight on multi-organ signal communication mediated by cancer cachexia factors.This summary aims to deepen medical community’s understanding of cancer cachexia and may conduce to the discovery of new diagnostic and therapeutic targets for cancer cachexia.展开更多
Cancer,a complex and multifactorial disease,presents a significant challenge to global health.Despite significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment...Cancer,a complex and multifactorial disease,presents a significant challenge to global health.Despite significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment outcomes,drug therapy continues to serve as a key therapeutic strategy.However,the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects,and thus there remains a critical need to develop novel cancer therapeutics.One promising strategy that has received widespread attention in recent years is drug repurposing:the identification of new applications for existing,clinically approved drugs.Drug repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective,proven to be safe,and can significantly expedite the drug development process due to their already established safety profiles.In light of this,the present review offers a comprehensive overview of the various methods employed in drug repurposing,specifically focusing on the repurposing of drugs to treat cancer.We describe the antitumor properties of candidate drugs,and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor microenvironment.In addition,we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug delivery.We also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy regimen.To conclude,we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.展开更多
Dear Editor,Gastric cancer(GC)is among the most prevalent gastrointestinal malignancies.The occurrence of local deep infiltration or distant metastasis in GC is commonly associated with weak treatment and poor prognos...Dear Editor,Gastric cancer(GC)is among the most prevalent gastrointestinal malignancies.The occurrence of local deep infiltration or distant metastasis in GC is commonly associated with weak treatment and poor prognosis.1 Although,N4-Acetylcytidine(ac4C)represents one of the extensive chemical modifications in mRNAs that plays a pivotal role in modulating mRNA stability and the mRNA translation process(Fig.1b).展开更多
Recent insights collectively suggest the important roles of lysyl oxidase(LysOX)in the pathological processes of several acute and chronic neurological diseases,but the molecular regulatory mechanisms remain elusive.H...Recent insights collectively suggest the important roles of lysyl oxidase(LysOX)in the pathological processes of several acute and chronic neurological diseases,but the molecular regulatory mechanisms remain elusive.Herein,we explore the regulatory role of LysOX in the seizure-induced ferroptotic cell death of neurons.Mechanistically,LysOX promotes ferroptosis-associated lipid peroxidation in neurons via activating extracellular regulated protein kinase(ERK)-dependent 5-lipoxygenase(Alox5)signaling.In addition,overexpression of LysOX via adeno-associated viral vector(AAV)-based gene transfer enhances ferroptosis sensitivity and aggravates seizure-induced hippocampal damage.Our studies show that pharmacological inhibition of LysOX withβ-aminopropionitrile(BAPN)significantly blocks seizure-induced ferroptosis and thereby alleviates neuronal damage,while the BAPN-associated cardiotoxicity and neurotoxicity could further be reduced through encapsulation with bioresponsive amorphous calcium carbonate-based nanocarriers.These findings unveil a previously unrecognized LysOX-ERK-Alox5 pathway for ferroptosis regulation during seizure-induced neuronal damage.Suppressing this pathway may yield therapeutic implications for restoring seizure-induced neuronal injury.展开更多
Patients with coronavirus disease 2019 (COVID-19) often succumb to neurological manifestations such as loss of smell, headache, disturbed consciousness, seizure, and stroke. In a recent paper published in Nature, Yang...Patients with coronavirus disease 2019 (COVID-19) often succumb to neurological manifestations such as loss of smell, headache, disturbed consciousness, seizure, and stroke. In a recent paper published in Nature, Yang et al.[1] reported substantial cellular perturbations in the choroid plexus and cortex, notably an infiltration of peripheral T cells into the parenchyma and microglial activation and astrogliosis with distinct transcriptional profiles. These findings provide a complex view of the cellular and molecular processes underlying COVID-19-related neurological abnormalities.展开更多
基金supported by the High-Level Talent Introduction Funds from the First Hospital of Lanzhou University.
文摘Cancer cachexia is a multi-organ syndrome and closely related to changes in signal communication between organs,which is mediated by cancer cachexia factors.Cancer cachexia factors,being the general name of inflammatory factors,circulating proteins,metabolites,and microRNA secreted by tumor or host cells,play a role in secretory or other organs and mediate complex signal communication between organs during cancer cachexia.Cancer cachexia factors are also a potential target for the diagnosis and treatment.The pathogenesis of cachexia is unclear and no clear effective treatment is available.Thus,the treatment of cancer cachexia from the perspective of the tumor ecosystem rather than from the perspective of a single molecule and a single organ is urgently needed.From the point of signal communication between organs mediated by cancer cachexia factors,finding a deeper understanding of the pathogenesis,diagnosis,and treatment of cancer cachexia is of great significance to improve the level of diagnosis and treatment.This review begins with cancer cachexia factors released during the interaction between tumor and host cells,and provides a comprehensive summary of the pathogenesis,diagnosis,and treatment for cancer cachexia,along with a particular sight on multi-organ signal communication mediated by cancer cachexia factors.This summary aims to deepen medical community’s understanding of cancer cachexia and may conduce to the discovery of new diagnostic and therapeutic targets for cancer cachexia.
基金This study was supported by research grants from the National Natural Science Foundation of China to H.H.(82060442)the Foundation of the Education Department of Guizhou Province(no.[2022]214)+1 种基金the Undergraduate Teaching Engineering Construction Project of Guizhou College of Traditional Chinese Medicine to Y.X.(no.GZY-JG(2018)6)This work was funded in part by the China Scholarship Council(No.202008520053 to Y.X.).
文摘Cancer,a complex and multifactorial disease,presents a significant challenge to global health.Despite significant advances in surgical,radiotherapeutic and immunological approaches,which have improved cancer treatment outcomes,drug therapy continues to serve as a key therapeutic strategy.However,the clinical efficacy of drug therapy is often constrained by drug resistance and severe toxic side effects,and thus there remains a critical need to develop novel cancer therapeutics.One promising strategy that has received widespread attention in recent years is drug repurposing:the identification of new applications for existing,clinically approved drugs.Drug repurposing possesses several inherent advantages in the context of cancer treatment since repurposed drugs are typically cost-effective,proven to be safe,and can significantly expedite the drug development process due to their already established safety profiles.In light of this,the present review offers a comprehensive overview of the various methods employed in drug repurposing,specifically focusing on the repurposing of drugs to treat cancer.We describe the antitumor properties of candidate drugs,and discuss in detail how they target both the hallmarks of cancer in tumor cells and the surrounding tumor microenvironment.In addition,we examine the innovative strategy of integrating drug repurposing with nanotechnology to enhance topical drug delivery.We also emphasize the critical role that repurposed drugs can play when used as part of a combination therapy regimen.To conclude,we outline the challenges associated with repurposing drugs and consider the future prospects of these repurposed drugs transitioning into clinical application.
基金the National Natural Science Foundation of China(Grant no.81960273)Gansu Natural Science Foundation(No.18JR3RA343)+4 种基金Gansu Fund project for Distinguished Young Scholars(No.18JR3RA262)the Key Projects of Department of Science and Technology in Gansu Province,China(No.1602FKDA001)the Science and Technology Innovation and Development Special Funding of Gansu province,China(G.F.R[2018]No.32)the Science and Technology Bureau 2018 Fund of the Chengguan District(2018KJGG0037)National Key Research and Development Program of China(No.2017FYA0205302).
文摘Dear Editor,Gastric cancer(GC)is among the most prevalent gastrointestinal malignancies.The occurrence of local deep infiltration or distant metastasis in GC is commonly associated with weak treatment and poor prognosis.1 Although,N4-Acetylcytidine(ac4C)represents one of the extensive chemical modifications in mRNAs that plays a pivotal role in modulating mRNA stability and the mRNA translation process(Fig.1b).
基金supported by the National Natural Science Foundation of China (No. 81974502 and 81671293)the Natural Science Foundation of Hunan Province (No. 2020JJ3061, China)the Hunan Provincial Department of Education Innovation Platform Open Fund Project (No. 17K100, China)
文摘Recent insights collectively suggest the important roles of lysyl oxidase(LysOX)in the pathological processes of several acute and chronic neurological diseases,but the molecular regulatory mechanisms remain elusive.Herein,we explore the regulatory role of LysOX in the seizure-induced ferroptotic cell death of neurons.Mechanistically,LysOX promotes ferroptosis-associated lipid peroxidation in neurons via activating extracellular regulated protein kinase(ERK)-dependent 5-lipoxygenase(Alox5)signaling.In addition,overexpression of LysOX via adeno-associated viral vector(AAV)-based gene transfer enhances ferroptosis sensitivity and aggravates seizure-induced hippocampal damage.Our studies show that pharmacological inhibition of LysOX withβ-aminopropionitrile(BAPN)significantly blocks seizure-induced ferroptosis and thereby alleviates neuronal damage,while the BAPN-associated cardiotoxicity and neurotoxicity could further be reduced through encapsulation with bioresponsive amorphous calcium carbonate-based nanocarriers.These findings unveil a previously unrecognized LysOX-ERK-Alox5 pathway for ferroptosis regulation during seizure-induced neuronal damage.Suppressing this pathway may yield therapeutic implications for restoring seizure-induced neuronal injury.
基金supported by the National Natural Science Foundation of China(81671293 and 81974502)Natural Science Foundation of Hunan Province(2020JJ3061)。
文摘Patients with coronavirus disease 2019 (COVID-19) often succumb to neurological manifestations such as loss of smell, headache, disturbed consciousness, seizure, and stroke. In a recent paper published in Nature, Yang et al.[1] reported substantial cellular perturbations in the choroid plexus and cortex, notably an infiltration of peripheral T cells into the parenchyma and microglial activation and astrogliosis with distinct transcriptional profiles. These findings provide a complex view of the cellular and molecular processes underlying COVID-19-related neurological abnormalities.
