Overview and research infrastructure As one of the leading laboratories in the interdisciplinary field of additive manufacturing and bio-3D printing,the Bio-Manufacturing Center at Tsinghua University is highly dedica...Overview and research infrastructure As one of the leading laboratories in the interdisciplinary field of additive manufacturing and bio-3D printing,the Bio-Manufacturing Center at Tsinghua University is highly dedicated to conducting cutting-edge research in the emerging field of bio-manufacturing.The latter is comprised of research involving biomaterials,living cells,proteins,and/or other biological compounds as basic building blocks to fabricate biomimetic structures,in vitro functional biological models and/or cellular systems with application to tissue engineering,regenerative medicine,disease pathogenesis,drug screening,and tissue/organ-on-a-chip.展开更多
Crosstalk between the nervous system and cancer plays an important role in tumor metastasis yet is poorly understood.Recently,Padmanaban et al.demonstrated a novel mechanism for nerve-induced metastasis.Sensory nerve-...Crosstalk between the nervous system and cancer plays an important role in tumor metastasis yet is poorly understood.Recently,Padmanaban et al.demonstrated a novel mechanism for nerve-induced metastasis.Sensory nerve-derived substance P could induce apoptosis in breast cancer cells that overexpressed tachykinin receptors.Single-stranded RNAs(ssRNAs)leaking from dying cells subsequently interact with toll-like receptor 7(TLR7)on other cancer cells and finally promoted metastasis.This notable study displays a delicate loop between the nervous system and cancer and,more importantly,amplifies the conception of apoptosis-induced metastasis.Over the past years,a mass of breakthrough studies have proven the pivotal role of the nervous system in tumorigenesis and cancer progression thereby contributing to the creation of a new disciplinecancer neuroscience[1].Hanahan and Monje discussed in detail the interactions between the nervous system and tumors based on the theoretical framework of the cancer hallmarks,focused on nerve-mediated proliferation,angiogenesis,immune evasion,cell death resistance,and metastasis[2].展开更多
Cancer neuroscience is an emerging discipline that is developing at a high speed.Its main field lies in studying the interaction between tumors and the nervous system,thereby offering new perspective on cancer initiat...Cancer neuroscience is an emerging discipline that is developing at a high speed.Its main field lies in studying the interaction between tumors and the nervous system,thereby offering new perspective on cancer initiation and progression.In this editorial,we briefly reviewed the origin and development process of cancer neuroscience,and gave a brief introduction to its research contents.Finally,we discussed the future development directions of this discipline.展开更多
Glioblastoma(GBM)is one of the most aggressive and treatment-resistant brain cancers.Despite years of research and clinical trials,especially using immune checkpoint inhibitors,therapeutic gains remain minimal[1,2].A ...Glioblastoma(GBM)is one of the most aggressive and treatment-resistant brain cancers.Despite years of research and clinical trials,especially using immune checkpoint inhibitors,therapeutic gains remain minimal[1,2].A recent study published in Nature by Faust Akl and colleagues begins to lift the veil on this mystery,uncovering a previously unknown mechanism of immune evasion in GBM[3].展开更多
Background:Oral cancer,a malignancy that is prevalent worldwide,is often diagnosed at an advanced stage.MicroRNAs(miRNAs)in circulating exosomes have emerged as promising cancer biomarkers.The role of miRNA let-7c-5p ...Background:Oral cancer,a malignancy that is prevalent worldwide,is often diagnosed at an advanced stage.MicroRNAs(miRNAs)in circulating exosomes have emerged as promising cancer biomarkers.The role of miRNA let-7c-5p in oral cancer remains underexplored,and its potential involvement in tumorigenesis warrants comprehensive investigation.Methods:Serum samples from 30 patients with oral cancer and 20 healthy controls were used to isolate exosomes and quantify their RNA content.Isolation of the exosomes was confirmed through transmission electron microscopy.Quantitative PCR was used to assess the miRNA profiles.The effects of let-7c-5p and TAGLN overexpression on oral cancer cell viability,migration,and invasion were analyzed via CCK-8 and Transwell assays.Moreover,we conducted mRNA sequencing of exosomal RNA from exosomes overexpressing let-7c-5p to delineate the gene expression profile and identify potential let-7c-5p target genes.Results:let-7c-5p was upregulated in serumderived exosomes of patients with oral cancer.Overexpression of let-7c-5p in the TCA8113 and CAL-27 cell lines enhanced their proliferative,migratory,and invasive capacities,and overexpression of let-7c-5p cell-derived exosomes promoted oral cancer cell invasiveness.Exosomal mRNA sequencing revealed 2,551 differentially expressed genes between control cell-derived exosomes and overexpressed let-7c-5p cell-derived exosomes.We further identified TAGLN as a direct target of let-7c-5p,which has been implicated in modulating the oncogenic potential of oral cancer cells.Overexpression of TAGLN reverses the promoting role of let-7c-5p on oral cancer cells.Conclusion:Our findings highlight the role of exosomal let-7c-5p in enhancing oral cancer cell aggressiveness by downregulating TAGLN expression,highlighting its potential as a diagnostic and therapeutic strategy.展开更多
Collagen contributes to extracellular matrix formation and stiffness,providing a three-dimensional framework that supports the development and growth of solid tumors.By interacting with specific tumor cell receptors,c...Collagen contributes to extracellular matrix formation and stiffness,providing a three-dimensional framework that supports the development and growth of solid tumors.By interacting with specific tumor cell receptors,collagen influences tumor cell signaling pathways,promoting cancer progression and drug resistance.Recent advancements in understanding the tumor extracellular matrix have underscored collagen's role in fostering an immunosuppressive tumor microenvironment(TME)and acting as a barrier to immunotherapy.Understanding the immunosuppressive mechanisms of collagen in the TME has revealed novel therapeutic targets and opportunities.This review highlights the immunoregulatory functions of collagen in the TME and provides a comprehensive overview of integrating collagen scores with traditional immunoscore-based immunotyping methods to enhance response prediction.Additionally,we discuss recent therapeutic developments in collagen targeting and their clinical potential for enhancing anti-cancer immunity.展开更多
Tumors are complex,highly heterogeneous diseases that place an enormous burden on the world's healthcare systems.Updating understanding of tumor initiation and progression is critical and the current breakthrough ...Tumors are complex,highly heterogeneous diseases that place an enormous burden on the world's healthcare systems.Updating understanding of tumor initiation and progression is critical and the current breakthrough lies in cancer neuroscience,which focuses on the crosstalk between neural components and tumors.Neuropeptides are a class of highly potent peptides,that perform the physiological functions of neurotransmitters,neuromodulators,and endocrine hormones.Currently,many studies have shown that many cellular components of the tumor microenvironment express neuropeptides and their receptors and that neuropeptides may play an important role in their cellular communication.In addition,neuropeptides and their receptors affect cancer hallmarks such as proliferation,invasion and metastasis,angiogenesis,immune escape,metabolic reprogramming,and others.More importantly,neuropeptides may also affect some tumor comorbidities such as insomnia,depression,anorexia,cancer pain,and others.Targeting neuropeptides in combination with new therapeutic strategies may significantly advance anti-tumor therapy,not only for treating the tumor itself but also for improving the patient's quality of life.展开更多
Metabolic dysfunction-associated fatty liver disease(MAFLD)encompasses a spectrum of liver diseases ranging from metabolic dysfunction-associated fatty liver to metabolic dysfunction-associated steatohepatitis,which m...Metabolic dysfunction-associated fatty liver disease(MAFLD)encompasses a spectrum of liver diseases ranging from metabolic dysfunction-associated fatty liver to metabolic dysfunction-associated steatohepatitis,which may progress to liver cirrhosis and hepatocellular carcinoma.Several mechanisms,including obesity,insulin resistance,dyslipidemia,inflammation,apoptosis,mitochondrial dysfunction,and reactive oxygen species,have been proposed to underlie the progression of MAFLD.Transcription factors are proteins that specifically bind to DNA sequences to regulate the transcription of target genes.Numerous transcription factors regulate MAFLD by modulating the transcription of genes involved in steatosis,inflammation,apoptosis,and fibrosis.Here,we review the pathological factors associated with MAFLD,with a particular emphasis on the transcription factors that contribute to the progression of MAFLD and their therapeutic implications.展开更多
In the past period,due to the rapid development of next-generation sequencing technology,accumulating evidence has clarified the complex role of the human microbiota in the development of cancer and the therapeutic re...In the past period,due to the rapid development of next-generation sequencing technology,accumulating evidence has clarified the complex role of the human microbiota in the development of cancer and the therapeutic response.More importantly,available evidence seems to indicate that modulating the composition of the gut microbiota to improve the efficacy of anti-cancer drugs may be feasible.However,intricate complexities exist,and a deep and comprehensive understanding of how the human microbiota interacts with cancer is critical to realize its full potential in cancer treatment.The purpose of this review is to summarize the initial clues on molecular mechanisms regarding the mutual effects between the gut microbiota and cancer development,and to highlight the relationship between gut microbes and the efficacy of immunotherapy,chemotherapy,radiation therapy and cancer surgery,which may provide insights into the formulation of individualized therapeutic strategies for cancer management.In addition,the current and emerging microbial interventions for cancer therapy as well as their clinical applications are summarized.Although many challenges remain for now,the great importance and full potential of the gut microbiota cannot be overstated for the development of individualized anti-cancer strategies,and it is necessary to explore a holistic approach that incorporates microbial modulation therapy in cancer.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
Lipids and glucose exert many essential physiological functions,such as providing raw materials or energy for cellular biosynthesis,regulating cell signal transduction,and maintaining a constant body temperature.Dysre...Lipids and glucose exert many essential physiological functions,such as providing raw materials or energy for cellular biosynthesis,regulating cell signal transduction,and maintaining a constant body temperature.Dysregulation of lipid and glucose metabolism can lead to glucolipid metabolic disorders linked to various metabolic diseases,such as obesity,diabetes,and cardiovascular disease.Therefore,intervention in glucolipid metabolism is a key therapeutic strategy for the treatment of metabolic diseases.Activating transcription factor 3(ATF3)is a transcription factor that acts as a hub of the cellular adaptive-response network and plays a pivotal role in the regulation of inflammation,apoptosis,DNA repair,and oncogenesis.Emerging evidence has illustrated the vital roles of ATF3 in glucolipid metabolism.ATF3 inhibits intestinal lipid absorption,enhances hepatic triglyceride hydrolysis and fatty acid oxidation,promotes macrophage reverse cholesterol transport,and attenuates the progression of western diet-induced nonalcoholic fatty liver disease and atherosclerosis.In addition to its role in lipid metabolism,ATF3 has also been identified as an important regulator of glucose metabolism.Here,we summarize the recent advances in the understanding of ATF3,mainly focusing on its role in glucose and lipid metabolism and potential therapeutic implications.展开更多
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
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
A recent research published in Science by Hsiue et al.1 introduced a CD3-targeting bispecific antibody that can bind to tumor cells by recognizing mutation-associated neoantigens and activate T cell-mediated tumor kil...A recent research published in Science by Hsiue et al.1 introduced a CD3-targeting bispecific antibody that can bind to tumor cells by recognizing mutation-associated neoantigens and activate T cell-mediated tumor killing by binding to CD3.The tumor suppressor gene TP53 is the most commonly mutated gene in various cancers.展开更多
Bromodomain and extra-terminal domain(BET)proteins,which function partly through MYC proto-oncogene(MYC),are critical epigenetic readers and emerging therapeutic targets in cancer.Whether and how BET inhibition simult...Bromodomain and extra-terminal domain(BET)proteins,which function partly through MYC proto-oncogene(MYC),are critical epigenetic readers and emerging therapeutic targets in cancer.Whether and how BET inhibition simultaneously induces metabolic remodeling in cancer cells remains unclear.Here we find that even transient BET inhibition by JQ-1 and other pan-BET inhibitors(pan-BETis)blunts liver cancer cell proliferation and tumor growth.BET inhibition decreases glycolytic gene expression but enhances mitochondrial glucose and glutamine oxidative metabolism revealed by metabolomics and isotope labeling analysis.Specifically,BET inhibition downregulates miR-30a to upregulate glutamate dehydrogenase 1(GDH1)independent of MYC,which producesα-ketoglutarate for mitochondrial oxidative phosphorylation(OXPHOS).Targeting GDH1 or OXPHOS is synthetic lethal to BET inhibi-tion,and combined BET and OXPHOS inhibition therapeutically prevents liver tumor growth in vitro and in vivo.Together,we uncover an important epigenetic-metabolic crosstalk whereby BET inhibition induces MYC-independent and GDH1-dependent glutamine metabolic remodeling that can be exploited for innovative combination therapy of liver cancer.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
文摘Overview and research infrastructure As one of the leading laboratories in the interdisciplinary field of additive manufacturing and bio-3D printing,the Bio-Manufacturing Center at Tsinghua University is highly dedicated to conducting cutting-edge research in the emerging field of bio-manufacturing.The latter is comprised of research involving biomaterials,living cells,proteins,and/or other biological compounds as basic building blocks to fabricate biomimetic structures,in vitro functional biological models and/or cellular systems with application to tissue engineering,regenerative medicine,disease pathogenesis,drug screening,and tissue/organ-on-a-chip.
文摘Crosstalk between the nervous system and cancer plays an important role in tumor metastasis yet is poorly understood.Recently,Padmanaban et al.demonstrated a novel mechanism for nerve-induced metastasis.Sensory nerve-derived substance P could induce apoptosis in breast cancer cells that overexpressed tachykinin receptors.Single-stranded RNAs(ssRNAs)leaking from dying cells subsequently interact with toll-like receptor 7(TLR7)on other cancer cells and finally promoted metastasis.This notable study displays a delicate loop between the nervous system and cancer and,more importantly,amplifies the conception of apoptosis-induced metastasis.Over the past years,a mass of breakthrough studies have proven the pivotal role of the nervous system in tumorigenesis and cancer progression thereby contributing to the creation of a new disciplinecancer neuroscience[1].Hanahan and Monje discussed in detail the interactions between the nervous system and tumors based on the theoretical framework of the cancer hallmarks,focused on nerve-mediated proliferation,angiogenesis,immune evasion,cell death resistance,and metastasis[2].
基金supported by High-level talent introduction funds from the First Hospital of Lanzhou University.
文摘Cancer neuroscience is an emerging discipline that is developing at a high speed.Its main field lies in studying the interaction between tumors and the nervous system,thereby offering new perspective on cancer initiation and progression.In this editorial,we briefly reviewed the origin and development process of cancer neuroscience,and gave a brief introduction to its research contents.Finally,we discussed the future development directions of this discipline.
文摘Glioblastoma(GBM)is one of the most aggressive and treatment-resistant brain cancers.Despite years of research and clinical trials,especially using immune checkpoint inhibitors,therapeutic gains remain minimal[1,2].A recent study published in Nature by Faust Akl and colleagues begins to lift the veil on this mystery,uncovering a previously unknown mechanism of immune evasion in GBM[3].
文摘Background:Oral cancer,a malignancy that is prevalent worldwide,is often diagnosed at an advanced stage.MicroRNAs(miRNAs)in circulating exosomes have emerged as promising cancer biomarkers.The role of miRNA let-7c-5p in oral cancer remains underexplored,and its potential involvement in tumorigenesis warrants comprehensive investigation.Methods:Serum samples from 30 patients with oral cancer and 20 healthy controls were used to isolate exosomes and quantify their RNA content.Isolation of the exosomes was confirmed through transmission electron microscopy.Quantitative PCR was used to assess the miRNA profiles.The effects of let-7c-5p and TAGLN overexpression on oral cancer cell viability,migration,and invasion were analyzed via CCK-8 and Transwell assays.Moreover,we conducted mRNA sequencing of exosomal RNA from exosomes overexpressing let-7c-5p to delineate the gene expression profile and identify potential let-7c-5p target genes.Results:let-7c-5p was upregulated in serumderived exosomes of patients with oral cancer.Overexpression of let-7c-5p in the TCA8113 and CAL-27 cell lines enhanced their proliferative,migratory,and invasive capacities,and overexpression of let-7c-5p cell-derived exosomes promoted oral cancer cell invasiveness.Exosomal mRNA sequencing revealed 2,551 differentially expressed genes between control cell-derived exosomes and overexpressed let-7c-5p cell-derived exosomes.We further identified TAGLN as a direct target of let-7c-5p,which has been implicated in modulating the oncogenic potential of oral cancer cells.Overexpression of TAGLN reverses the promoting role of let-7c-5p on oral cancer cells.Conclusion:Our findings highlight the role of exosomal let-7c-5p in enhancing oral cancer cell aggressiveness by downregulating TAGLN expression,highlighting its potential as a diagnostic and therapeutic strategy.
基金supported by the National Natural Science Foundation of China(NSFC,No.82373899)the Science Fund Program for Distinguished Young Scholars(overseas,NSFC)+1 种基金the Special Funds for Basic Research of NSFCthe Shanghai Sailing Program(No.20YF1402800).
文摘Collagen contributes to extracellular matrix formation and stiffness,providing a three-dimensional framework that supports the development and growth of solid tumors.By interacting with specific tumor cell receptors,collagen influences tumor cell signaling pathways,promoting cancer progression and drug resistance.Recent advancements in understanding the tumor extracellular matrix have underscored collagen's role in fostering an immunosuppressive tumor microenvironment(TME)and acting as a barrier to immunotherapy.Understanding the immunosuppressive mechanisms of collagen in the TME has revealed novel therapeutic targets and opportunities.This review highlights the immunoregulatory functions of collagen in the TME and provides a comprehensive overview of integrating collagen scores with traditional immunoscore-based immunotyping methods to enhance response prediction.Additionally,we discuss recent therapeutic developments in collagen targeting and their clinical potential for enhancing anti-cancer immunity.
基金supported by the High-Level Talent Introduction Funds from the First Hospital of Lanzhou University(China).
文摘Tumors are complex,highly heterogeneous diseases that place an enormous burden on the world's healthcare systems.Updating understanding of tumor initiation and progression is critical and the current breakthrough lies in cancer neuroscience,which focuses on the crosstalk between neural components and tumors.Neuropeptides are a class of highly potent peptides,that perform the physiological functions of neurotransmitters,neuromodulators,and endocrine hormones.Currently,many studies have shown that many cellular components of the tumor microenvironment express neuropeptides and their receptors and that neuropeptides may play an important role in their cellular communication.In addition,neuropeptides and their receptors affect cancer hallmarks such as proliferation,invasion and metastasis,angiogenesis,immune escape,metabolic reprogramming,and others.More importantly,neuropeptides may also affect some tumor comorbidities such as insomnia,depression,anorexia,cancer pain,and others.Targeting neuropeptides in combination with new therapeutic strategies may significantly advance anti-tumor therapy,not only for treating the tumor itself but also for improving the patient's quality of life.
基金supported by the National Natural Science Foundation of China(No.32271218 to Y.X.).
文摘Metabolic dysfunction-associated fatty liver disease(MAFLD)encompasses a spectrum of liver diseases ranging from metabolic dysfunction-associated fatty liver to metabolic dysfunction-associated steatohepatitis,which may progress to liver cirrhosis and hepatocellular carcinoma.Several mechanisms,including obesity,insulin resistance,dyslipidemia,inflammation,apoptosis,mitochondrial dysfunction,and reactive oxygen species,have been proposed to underlie the progression of MAFLD.Transcription factors are proteins that specifically bind to DNA sequences to regulate the transcription of target genes.Numerous transcription factors regulate MAFLD by modulating the transcription of genes involved in steatosis,inflammation,apoptosis,and fibrosis.Here,we review the pathological factors associated with MAFLD,with a particular emphasis on the transcription factors that contribute to the progression of MAFLD and their therapeutic implications.
基金supported by the National Natural Science Foundation of China,No.82102998,No.82072688Sichuan Science and Technology Program,No.2021YFS0111.
文摘In the past period,due to the rapid development of next-generation sequencing technology,accumulating evidence has clarified the complex role of the human microbiota in the development of cancer and the therapeutic response.More importantly,available evidence seems to indicate that modulating the composition of the gut microbiota to improve the efficacy of anti-cancer drugs may be feasible.However,intricate complexities exist,and a deep and comprehensive understanding of how the human microbiota interacts with cancer is critical to realize its full potential in cancer treatment.The purpose of this review is to summarize the initial clues on molecular mechanisms regarding the mutual effects between the gut microbiota and cancer development,and to highlight the relationship between gut microbes and the efficacy of immunotherapy,chemotherapy,radiation therapy and cancer surgery,which may provide insights into the formulation of individualized therapeutic strategies for cancer management.In addition,the current and emerging microbial interventions for cancer therapy as well as their clinical applications are summarized.Although many challenges remain for now,the great importance and full potential of the gut microbiota cannot be overstated for the development of individualized anti-cancer strategies,and it is necessary to explore a holistic approach that incorporates microbial modulation therapy in cancer.
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the National Natural Science Foundation of China(32271218 to Y.X.)in part by grants from the National Natural Science Foundation of China(81670519 to J.L.)the Science and Technology Commission of Shanghai Municipality(22ZR1414300 to H.W.).
文摘Lipids and glucose exert many essential physiological functions,such as providing raw materials or energy for cellular biosynthesis,regulating cell signal transduction,and maintaining a constant body temperature.Dysregulation of lipid and glucose metabolism can lead to glucolipid metabolic disorders linked to various metabolic diseases,such as obesity,diabetes,and cardiovascular disease.Therefore,intervention in glucolipid metabolism is a key therapeutic strategy for the treatment of metabolic diseases.Activating transcription factor 3(ATF3)is a transcription factor that acts as a hub of the cellular adaptive-response network and plays a pivotal role in the regulation of inflammation,apoptosis,DNA repair,and oncogenesis.Emerging evidence has illustrated the vital roles of ATF3 in glucolipid metabolism.ATF3 inhibits intestinal lipid absorption,enhances hepatic triglyceride hydrolysis and fatty acid oxidation,promotes macrophage reverse cholesterol transport,and attenuates the progression of western diet-induced nonalcoholic fatty liver disease and atherosclerosis.In addition to its role in lipid metabolism,ATF3 has also been identified as an important regulator of glucose metabolism.Here,we summarize the recent advances in the understanding of ATF3,mainly focusing on its role in glucose and lipid metabolism and potential therapeutic implications.
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the Harbin Medical University Cancer Hospital(CN)Nn10 Project(Nn10py2017-01)。
文摘A recent research published in Science by Hsiue et al.1 introduced a CD3-targeting bispecific antibody that can bind to tumor cells by recognizing mutation-associated neoantigens and activate T cell-mediated tumor killing by binding to CD3.The tumor suppressor gene TP53 is the most commonly mutated gene in various cancers.
基金supported by the National Natural Science Foundation of China(82273223 to F.L.,32270798 to P.L.)the National Key Research and Development Program of China(2022YFA1103900 to F.L.).
文摘Bromodomain and extra-terminal domain(BET)proteins,which function partly through MYC proto-oncogene(MYC),are critical epigenetic readers and emerging therapeutic targets in cancer.Whether and how BET inhibition simultaneously induces metabolic remodeling in cancer cells remains unclear.Here we find that even transient BET inhibition by JQ-1 and other pan-BET inhibitors(pan-BETis)blunts liver cancer cell proliferation and tumor growth.BET inhibition decreases glycolytic gene expression but enhances mitochondrial glucose and glutamine oxidative metabolism revealed by metabolomics and isotope labeling analysis.Specifically,BET inhibition downregulates miR-30a to upregulate glutamate dehydrogenase 1(GDH1)independent of MYC,which producesα-ketoglutarate for mitochondrial oxidative phosphorylation(OXPHOS).Targeting GDH1 or OXPHOS is synthetic lethal to BET inhibi-tion,and combined BET and OXPHOS inhibition therapeutically prevents liver tumor growth in vitro and in vivo.Together,we uncover an important epigenetic-metabolic crosstalk whereby BET inhibition induces MYC-independent and GDH1-dependent glutamine metabolic remodeling that can be exploited for innovative combination therapy of liver cancer.
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.
