Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined ex...Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined extensively.We used immunohistochemistry and immunofluorescence staining to analyze the forebrain tissue slices of Alzheimer’s disease patients.Widespread axonal amyloidosis with distinctive axonal enlargement was observed in patients with Alzheimer’s disease.On average,amyloid-β-positive axon diameters in Alzheimer’s disease brains were 1.72 times those of control brain axons.Furthermore,axonal amyloidosis was associated with microtubule-associated protein 2 reduction,tau phosphorylation,lysosome destabilization,and several blood-related markers,such as apolipoprotein E,alpha-hemoglobin,glycosylated hemoglobin type A1C,and hemin.Lysosome destabilization in Alzheimer’s disease was also clearly identified in the neuronal soma,where it was associated with the co-expression of amyloid-β,Cathepsin D,alpha-hemoglobin,actin alpha 2,and collagen type IV.This suggests that exogenous hemorrhagic protein intake influences neural lysosome stability.Additionally,the data showed that amyloid-β-containing lysosomes were 2.23 times larger than control lysosomes.Furthermore,under rare conditions,axonal breakages were observed,which likely resulted in Wallerian degeneration.In summary,axonal enlargement associated with amyloidosis,micro-bleeding,and lysosome destabilization is a major defect in patients with Alzheimer’s disease.This finding suggests that,in addition to the well-documented neural soma and synaptic damage,axonal damage is a key component of neuronal defects in Alzheimer’s disease.展开更多
Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mecha...Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.展开更多
Background:Neurological disorders(NDs),including ischemic stroke(IS),Parkinson’s disease(PD),and Alzheimer’s disease(AD),are major contributors to global morbidity and mortality.Boswellia extract has demonstrated ne...Background:Neurological disorders(NDs),including ischemic stroke(IS),Parkinson’s disease(PD),and Alzheimer’s disease(AD),are major contributors to global morbidity and mortality.Boswellia extract has demonstrated neuroprotective properties,yet a comprehensive systematic review assessing its efficacy remains absent.This study aims to evaluate the efficacy of Boswellia extract in treating NDs,with a particular focus on its effects in AD and its potential for long-term neurorestoration,thereby supporting further investigation into Boswellia’s therapeutic role in ND management.Methods:A systematic literature search was performed in PubMed,Web of Science,ScienceDirect,and Google Scholar for English-language studies published up to March 2024.Eighteen studies met the inclusion criteria and were included in the meta-analysis.The study protocol was registered on PROSPERO(CRD42024524386).Eligible studies involved rodent models of IS,PD,or AD with post-operative interventions using Boswellia extract.Data extraction focused on mechanisms of action,dosages,treatment durations,and therapeutic outcomes.Studies were excluded if they involved non-ND models,combined treatments,or had incomplete data.Two researchers independently conducted literature screening and data extraction.Statistical analyses were conducted using Stata(version 17)and RevMan(version 5.4),employing fixed or random-effects models based on heterogeneity assessments.Result s:Boswellia extract significantly improved the mean effect size for NDs(ES=1.28,95%CI(1.05,1.51),P<0.001).Specifically,it reduced cerebral infarct volume in IS(SMD=−2.87,95%CI(−3.42,−2.32))and enhanced behavioral outcomes in AD(SMD=3.26,95%CI(2.07,5.14))and PD(SMD=5.37,95%CI(3.93,6.80)).Subgroup analyses revealed that Boswellia extract exhibited superior efficacy in AD when administered orally and via intra-cerebroventricular injection.Long-term treatment with Boswellia extract suggested potential neurorestorative effects.Additionally,Boswellia extract was more effective than its monomeric constituents,highlighting its promising role in ND treatment.Conclusion:Boswellia extract demonstrates significant neuroprotective effects across various NDs,particularly in AD and in promoting long-term neurorestoration.These findings support the need for further research into Boswellia’s potential as a therapeutic agent in the management of neurological disorders.展开更多
BACKGROUND Crohn’s disease(CD)is a chronic inflammatory bowel disease with unknown etiology.Inflammatory chemical mediators synthesized from arachidonic acid,an n-6 polyunsaturated fatty acid(PUFA),have been shown to...BACKGROUND Crohn’s disease(CD)is a chronic inflammatory bowel disease with unknown etiology.Inflammatory chemical mediators synthesized from arachidonic acid,an n-6 polyunsaturated fatty acid(PUFA),have been shown to activate CD.Additionally,n-3 PUFAs are metabolized by the same enzyme as n-6 PUFAs and known to inhibit the arachidonic acid cascade.Our previous study noted that the presence of erythrocyte membrane fatty acids is a characteristic finding in Japanese CD patients.It was thus speculated that FADS2 gene polymorphisms,which induce PUFA metabolizing enzymes,are involved in the pathogenesis of CD,though no such relationship was found.AIM To investigate the relationship of FADS2 polymorphisms with serum and erythrocyte membrane fatty acid composition ratios,and disease activity.METHODS Using previously reported findings regarding FADS2 genetic polymorphisms,the records of 52 CD patients undergoing treatment at Jikei University Kashiwa Hospital were analyzed.Mutations noted were divided into three groups;wild-type(GG),heterozygous mutants(GA),and homozygous(AA),with the activities of delta-6 and delta-5 desaturases compared using redefined d6d index(rd.d6di)and d5d index(d5di).Additionally,comparisons of serum and erythrocyte membranes for fatty acid composition,and also gene polymorphisms and CD activity index(CDAI)were performed.RESULTS The presence of the rs174538 mutation in FADS2 resulted in reduction of only rd.d6di in the erythrocyte membrane(P<0.01).In contrast,that mutation was found to be associated with d5di induced by FADS1 in serum(P=0.019)as well as the erythrocyte membrane(P<0.0001),and also with reduction in the fatty acid composition of arachidonic acid in both serum(P<0.0001)and the erythrocyte membrane(P<0.01).Regarding disease activity,a positive correlation of CDAI score with rd.d6di in both serum(P<0.05)and the erythrocyte membrane(P<0.05)was found only in the rs174538 wild-type group.In contrast,there was no correction between CDAI and d5di in either serum or erythrocyte membrane samples.CONCLUSION The rs174538 mutation alters the fatty acid profile through strong linkage to the FADS1 gene.In wild-type individuals,rd.d6di was positively correlated with CDAI,suggesting predictive utility of disease severity.展开更多
Background:A significant proportion of patients still cannot benefit from existing targeted therapies and immunotherapies,making the search for new treatment strategies extremely urgent.In this study,we combined integ...Background:A significant proportion of patients still cannot benefit from existing targeted therapies and immunotherapies,making the search for new treatment strategies extremely urgent.In this study,we combined integrate public data analysis with experimental validation to identify novel prognostic biomarkers and therapeutic targets for lung adenocarcinoma(LUAD).Methods:We analyzed RNA and protein databases to assess the expression levels of cytochrome C oxidase 5B(COX5B)in LUAD.Several computational algorithms were employed to investigate the relationship between COX5B and immune infiltration in LUAD.To further elucidate the role of COX5B in LUAD,we utilized multiple experimental approaches,including quantitative reverse transcription PCR assays,western blot,immunohistochemistry,electron microscopy,flow cytometry,and EdU proliferation assays.Results:We revealed that COX5B was significantly elevated in LUAD and positively correlated with poor prognosis of LUAD patients.Analysis of co-expression network indicated that COX5B may take part in the intracellular adenosine triphosphate(ATP)synthesis through the oxidative phosphorylation pathway.There was a negative correlation between COX5B expression and immune infiltration in LUAD.Furthermore,we validated that COX5B levels were significantly elevated in both LUAD tissues and cell lines.Specifically,immunohistochemistry(IHC)assays revealed a 2.32-fold increase of COX5B in tumor tissues compared to that in adjacent normal tissues(p=0.0044).Additionally,COX5B knockdown disrupted the redox homeostasis,ultimately suppressed the proliferation of LUAD cells.Subsequent investigations demonstrated that berberine effectively targeted COX5B,diminishing its protein expression and consequently inhibiting cell proliferation and tumor growth in LUAD.Conclusions:This study established that upregulated COX5B was positive associated with poor patient prognosis in LUAD,elucidating the mechanisms by which berberine targets COX5B to inhibit tumor growth,thereby providing a novel therapeutic target and strategy for the clinical management of LUAD.展开更多
The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evi...The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evidence highlights that these diseases share similar pathophysiological features,including insulin resistance and chronic inflammation,which contribute to their rapid progression(Chen et al.,2022).Insulin resistance,a hallmark of T2DM,has been suggested to exacerbate neurodegeneration in AD.Similarly,chronic low-grade inflammation in T2DM parallels with neuroinflammation,which is observed in AD,suggesting overlapping pathophysiological mechanisms in T2DM and AD.展开更多
In the pre-biologic era,immunomodulators such as azathioprine,6-mercaptopurine,and methotrexate(MTX)were widely used as first-line maintenance therapies in Crohn’s disease.However,in the current era shaped by biologi...In the pre-biologic era,immunomodulators such as azathioprine,6-mercaptopurine,and methotrexate(MTX)were widely used as first-line maintenance therapies in Crohn’s disease.However,in the current era shaped by biologics,their role has shifted toward adjunctive use,primarily in combination with anti-tumor necrosis factor agents to reduce immunogenicity.Amid growing concerns about thiopurine-associated risks,MTX is receiving renewed attention for its favorable safety profile;however,this agent remains inconsistently utilized in gastroenterology despite its frontline status in rheumatology.This discrepancy was highlighted in a recent nationwide survey by Bonnaud et al published in the World Journal of Gastroenterology,which offers timely insights into MTX prescribing behaviors among French gastroenterologists.Although 71%of respondents reported using MTX,primarily via subcutaneous injection,it is still perceived as a secondary choice after thiopurines.Importantly,this underuse appears to be driven more by clinical inertia and limited guidance rather than by lack of efficacy or safety concerns.Clinicians increasingly recognize the value of MTX,particularly in patients with joint involvement,Epstein-Barr virus negativity,or increased malignancy risk.Notably,even non-prescribers viewed the drug favorably,suggesting that usage barriers may be modifiable.In light of evolving treatment goals that prioritize safety,cost-effectiveness,and individualized care,this editorial argues that MTX should no longer be viewed as a fallback but as a strategic first-line option in well-defined high-risk populations.The survey underscores a persistent gap between guidelines and real-world practice,reinforcing the urgent need for clearer algorithms and education to support the repositioning of MTX in modern Crohn’s disease management.展开更多
基金supported by the National Natural Science Foundation of China,No.81472235(to HF)the Shanghai Jiao Tong University Medical and Engineering Project,Nos.YG2021QN53(to HF),YG2017MS71(to HF)+1 种基金the International Cooperation Project of the National Natural Science Foundation of China,No.82020108017(to DC)the Innovation Group Project of the National Natural Science Foundation of China,No.81921002(to DC).
文摘Alzheimer’s disease is a multi-amyloidosis disease characterized by amyloid-βdeposits in brain blood vessels,microaneurysms,and senile plaques.How amyloid-βdeposition affects axon pathology has not been examined extensively.We used immunohistochemistry and immunofluorescence staining to analyze the forebrain tissue slices of Alzheimer’s disease patients.Widespread axonal amyloidosis with distinctive axonal enlargement was observed in patients with Alzheimer’s disease.On average,amyloid-β-positive axon diameters in Alzheimer’s disease brains were 1.72 times those of control brain axons.Furthermore,axonal amyloidosis was associated with microtubule-associated protein 2 reduction,tau phosphorylation,lysosome destabilization,and several blood-related markers,such as apolipoprotein E,alpha-hemoglobin,glycosylated hemoglobin type A1C,and hemin.Lysosome destabilization in Alzheimer’s disease was also clearly identified in the neuronal soma,where it was associated with the co-expression of amyloid-β,Cathepsin D,alpha-hemoglobin,actin alpha 2,and collagen type IV.This suggests that exogenous hemorrhagic protein intake influences neural lysosome stability.Additionally,the data showed that amyloid-β-containing lysosomes were 2.23 times larger than control lysosomes.Furthermore,under rare conditions,axonal breakages were observed,which likely resulted in Wallerian degeneration.In summary,axonal enlargement associated with amyloidosis,micro-bleeding,and lysosome destabilization is a major defect in patients with Alzheimer’s disease.This finding suggests that,in addition to the well-documented neural soma and synaptic damage,axonal damage is a key component of neuronal defects in Alzheimer’s disease.
基金supported by the National Science Foundation of China,Nos.82325031(to FX),82030059(to YC),82102290(to YG),U23A20485(to YC)Noncommunicable Chronic Diseases-National Science and Technology Major Project,No.2023ZD0505504(to FX),2023ZD0505500(to YC)the Key R&D Program of Shandong Province,No.2022ZLGX03(to YC).
文摘Global brain ischemia and neurological deficit are consequences of cardiac arrest that lead to high mortality.Despite advancements in resuscitation science,our limited understanding of the cellular and molecular mechanisms underlying post-cardiac arrest brain injury have hindered the development of effective neuroprotective strategies.Previous studies primarily focused on neuronal death,potentially overlooking the contributions of non-neuronal cells and intercellular communication to the pathophysiology of cardiac arrest-induced brain injury.To address these gaps,we hypothesized that single-cell transcriptomic analysis could uncover previously unidentified cellular subpopulations,altered cell communication networks,and novel molecular mechanisms involved in post-cardiac arrest brain injury.In this study,we performed a single-cell transcriptomic analysis of the hippocampus from pigs with ventricular fibrillation-induced cardiac arrest at 6 and 24 hours following the return of spontaneous circulation,and from sham control pigs.Sequencing results revealed changes in the proportions of different cell types,suggesting post-arrest disruption in the blood-brain barrier and infiltration of neutrophils.These results were validated through western blotting,quantitative reverse transcription-polymerase chain reaction,and immunofluorescence staining.We also identified and validated a unique subcluster of activated microglia with high expression of S100A8,which increased over time following cardiac arrest.This subcluster simultaneously exhibited significant M1/M2 polarization and expressed key functional genes related to chemokines and interleukins.Additionally,we revealed the post-cardiac arrest dysfunction of oligodendrocytes and the differentiation of oligodendrocyte precursor cells into oligodendrocytes.Cell communication analysis identified enhanced post-cardiac arrest communication between neutrophils and microglia that was mediated by neutrophil-derived resistin,driving pro-inflammatory microglial polarization.Our findings provide a comprehensive single-cell map of the post-cardiac arrest hippocampus,offering potential novel targets for neuroprotection and repair following cardiac arrest.
基金supported by the National Natural Science Foundation of China,specifically through grants(No.8227431382304947)Key Research and Development Project of Shaanxi Province(2023GHZD43).Peer re v iew information。
文摘Background:Neurological disorders(NDs),including ischemic stroke(IS),Parkinson’s disease(PD),and Alzheimer’s disease(AD),are major contributors to global morbidity and mortality.Boswellia extract has demonstrated neuroprotective properties,yet a comprehensive systematic review assessing its efficacy remains absent.This study aims to evaluate the efficacy of Boswellia extract in treating NDs,with a particular focus on its effects in AD and its potential for long-term neurorestoration,thereby supporting further investigation into Boswellia’s therapeutic role in ND management.Methods:A systematic literature search was performed in PubMed,Web of Science,ScienceDirect,and Google Scholar for English-language studies published up to March 2024.Eighteen studies met the inclusion criteria and were included in the meta-analysis.The study protocol was registered on PROSPERO(CRD42024524386).Eligible studies involved rodent models of IS,PD,or AD with post-operative interventions using Boswellia extract.Data extraction focused on mechanisms of action,dosages,treatment durations,and therapeutic outcomes.Studies were excluded if they involved non-ND models,combined treatments,or had incomplete data.Two researchers independently conducted literature screening and data extraction.Statistical analyses were conducted using Stata(version 17)and RevMan(version 5.4),employing fixed or random-effects models based on heterogeneity assessments.Result s:Boswellia extract significantly improved the mean effect size for NDs(ES=1.28,95%CI(1.05,1.51),P<0.001).Specifically,it reduced cerebral infarct volume in IS(SMD=−2.87,95%CI(−3.42,−2.32))and enhanced behavioral outcomes in AD(SMD=3.26,95%CI(2.07,5.14))and PD(SMD=5.37,95%CI(3.93,6.80)).Subgroup analyses revealed that Boswellia extract exhibited superior efficacy in AD when administered orally and via intra-cerebroventricular injection.Long-term treatment with Boswellia extract suggested potential neurorestorative effects.Additionally,Boswellia extract was more effective than its monomeric constituents,highlighting its promising role in ND treatment.Conclusion:Boswellia extract demonstrates significant neuroprotective effects across various NDs,particularly in AD and in promoting long-term neurorestoration.These findings support the need for further research into Boswellia’s potential as a therapeutic agent in the management of neurological disorders.
文摘BACKGROUND Crohn’s disease(CD)is a chronic inflammatory bowel disease with unknown etiology.Inflammatory chemical mediators synthesized from arachidonic acid,an n-6 polyunsaturated fatty acid(PUFA),have been shown to activate CD.Additionally,n-3 PUFAs are metabolized by the same enzyme as n-6 PUFAs and known to inhibit the arachidonic acid cascade.Our previous study noted that the presence of erythrocyte membrane fatty acids is a characteristic finding in Japanese CD patients.It was thus speculated that FADS2 gene polymorphisms,which induce PUFA metabolizing enzymes,are involved in the pathogenesis of CD,though no such relationship was found.AIM To investigate the relationship of FADS2 polymorphisms with serum and erythrocyte membrane fatty acid composition ratios,and disease activity.METHODS Using previously reported findings regarding FADS2 genetic polymorphisms,the records of 52 CD patients undergoing treatment at Jikei University Kashiwa Hospital were analyzed.Mutations noted were divided into three groups;wild-type(GG),heterozygous mutants(GA),and homozygous(AA),with the activities of delta-6 and delta-5 desaturases compared using redefined d6d index(rd.d6di)and d5d index(d5di).Additionally,comparisons of serum and erythrocyte membranes for fatty acid composition,and also gene polymorphisms and CD activity index(CDAI)were performed.RESULTS The presence of the rs174538 mutation in FADS2 resulted in reduction of only rd.d6di in the erythrocyte membrane(P<0.01).In contrast,that mutation was found to be associated with d5di induced by FADS1 in serum(P=0.019)as well as the erythrocyte membrane(P<0.0001),and also with reduction in the fatty acid composition of arachidonic acid in both serum(P<0.0001)and the erythrocyte membrane(P<0.01).Regarding disease activity,a positive correlation of CDAI score with rd.d6di in both serum(P<0.05)and the erythrocyte membrane(P<0.05)was found only in the rs174538 wild-type group.In contrast,there was no correction between CDAI and d5di in either serum or erythrocyte membrane samples.CONCLUSION The rs174538 mutation alters the fatty acid profile through strong linkage to the FADS1 gene.In wild-type individuals,rd.d6di was positively correlated with CDAI,suggesting predictive utility of disease severity.
基金supported by grants from the Guangxi Natural Science Foundation(2024GXNSFAA010150)the Guangdong Basic and Applied Basic Research Foundation(2022A1515111167).
文摘Background:A significant proportion of patients still cannot benefit from existing targeted therapies and immunotherapies,making the search for new treatment strategies extremely urgent.In this study,we combined integrate public data analysis with experimental validation to identify novel prognostic biomarkers and therapeutic targets for lung adenocarcinoma(LUAD).Methods:We analyzed RNA and protein databases to assess the expression levels of cytochrome C oxidase 5B(COX5B)in LUAD.Several computational algorithms were employed to investigate the relationship between COX5B and immune infiltration in LUAD.To further elucidate the role of COX5B in LUAD,we utilized multiple experimental approaches,including quantitative reverse transcription PCR assays,western blot,immunohistochemistry,electron microscopy,flow cytometry,and EdU proliferation assays.Results:We revealed that COX5B was significantly elevated in LUAD and positively correlated with poor prognosis of LUAD patients.Analysis of co-expression network indicated that COX5B may take part in the intracellular adenosine triphosphate(ATP)synthesis through the oxidative phosphorylation pathway.There was a negative correlation between COX5B expression and immune infiltration in LUAD.Furthermore,we validated that COX5B levels were significantly elevated in both LUAD tissues and cell lines.Specifically,immunohistochemistry(IHC)assays revealed a 2.32-fold increase of COX5B in tumor tissues compared to that in adjacent normal tissues(p=0.0044).Additionally,COX5B knockdown disrupted the redox homeostasis,ultimately suppressed the proliferation of LUAD cells.Subsequent investigations demonstrated that berberine effectively targeted COX5B,diminishing its protein expression and consequently inhibiting cell proliferation and tumor growth in LUAD.Conclusions:This study established that upregulated COX5B was positive associated with poor patient prognosis in LUAD,elucidating the mechanisms by which berberine targets COX5B to inhibit tumor growth,thereby providing a novel therapeutic target and strategy for the clinical management of LUAD.
基金supported by grants from NIH T32(DK007260,to WC)the Steno North American Fellowship awarded by the Novo Nordisk Foundation(NNF23OC0087108,to WC).
文摘The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evidence highlights that these diseases share similar pathophysiological features,including insulin resistance and chronic inflammation,which contribute to their rapid progression(Chen et al.,2022).Insulin resistance,a hallmark of T2DM,has been suggested to exacerbate neurodegeneration in AD.Similarly,chronic low-grade inflammation in T2DM parallels with neuroinflammation,which is observed in AD,suggesting overlapping pathophysiological mechanisms in T2DM and AD.
文摘In the pre-biologic era,immunomodulators such as azathioprine,6-mercaptopurine,and methotrexate(MTX)were widely used as first-line maintenance therapies in Crohn’s disease.However,in the current era shaped by biologics,their role has shifted toward adjunctive use,primarily in combination with anti-tumor necrosis factor agents to reduce immunogenicity.Amid growing concerns about thiopurine-associated risks,MTX is receiving renewed attention for its favorable safety profile;however,this agent remains inconsistently utilized in gastroenterology despite its frontline status in rheumatology.This discrepancy was highlighted in a recent nationwide survey by Bonnaud et al published in the World Journal of Gastroenterology,which offers timely insights into MTX prescribing behaviors among French gastroenterologists.Although 71%of respondents reported using MTX,primarily via subcutaneous injection,it is still perceived as a secondary choice after thiopurines.Importantly,this underuse appears to be driven more by clinical inertia and limited guidance rather than by lack of efficacy or safety concerns.Clinicians increasingly recognize the value of MTX,particularly in patients with joint involvement,Epstein-Barr virus negativity,or increased malignancy risk.Notably,even non-prescribers viewed the drug favorably,suggesting that usage barriers may be modifiable.In light of evolving treatment goals that prioritize safety,cost-effectiveness,and individualized care,this editorial argues that MTX should no longer be viewed as a fallback but as a strategic first-line option in well-defined high-risk populations.The survey underscores a persistent gap between guidelines and real-world practice,reinforcing the urgent need for clearer algorithms and education to support the repositioning of MTX in modern Crohn’s disease management.
