期刊文献+
任意字段
题名或关键词
题名
关键词
摘要
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息
共找到1,073篇文章
< 1 2 … 54 >
每页显示 20 50 100
已选0条
引用分析
参考文献
引证文献
 统计分析
检索结果
已选文献
显示方式：
Anti-and non-tumor necrosis factor-α-targeted therapies effects on insulin resistance in rheumatoid arthritis,psoriatic arthritis and ankylosing spondylitis 认领 引用 被引量：5
1
作者 Chrong-Reen Wang Hung-Wen Tsai 《World Journal of Diabetes》 SCIE 2021年第3期238-260,共23页
In addition toβ-cell failure with inadequate insulin secretion,the crucial mechanism leading to establishment of diabetes mellitus(DM)is the resistance of target cells to insulin,i.e.insulin resistance(IR),indicating... In addition toβ-cell failure with inadequate insulin secretion,the crucial mechanism leading to establishment of diabetes mellitus(DM)is the resistance of target cells to insulin,i.e.insulin resistance(IR),indicating a requirement of beyond-normal insulin concentrations to maintain euglycemic status and an ineffective strength of transduction signaling from the receptor,downstream to the substrates of insulin action.IR is a common feature of most metabolic disorders,particularly type II DM as well as some cases of type I DM.A variety of human inammatory disorders with increased levels of proinflammatory cytokines,including tumor necrosis factor(TNF)-α,interleukin(IL)-6 and IL-1β,have been reported to be associated with an increased risk of IR.Autoimmunemediated arthritis conditions,including rheumatoid arthritis(RA),psoriatic arthritis(PsA)and ankylosing spondylitis(AS),with the involvement of proinflammatory cytokines as their central pathogenesis,have been demonstrated to be associated with IR,especially during the active disease state.There is an increasing trend towards using biologic agents and small molecule-targeted drugs to treat such disorders.In this review,we focus on the effects of anti-TNF-α-and non-TNF-α-targeted therapies on IR in patients with RA,PsA and AS.Anti-TNF-αtherapy,IL-1 blockade,IL-6 antagonist,Janus kinase inhibitor and phosphodiesterase type 4 blocker can reduce IR and improve diabetic hyper-glycemia in autoimmune-mediated arthritis. 展开更多
关键词 Insulin resistance Diabetes mellitus Tumor necrosis factor-α-targeted therapy Non-tumor necrosis factor-α-targeted therapy Rheumatoid arthritis Psoriatic arthritis
暂未订购 下载PDF
Integrative study reveals NR1D1 mediates Hedyotis diffusa’s antifibrosis via hypoxia inducible factor-1/ammonia axis 认领 引用 被引量：1
2
作者 Si-Wei Xia Huan Liu +7 位作者 Kai-Yao Yang Yi-Jie Gao Meng-Ru Zhang Jing-Wen Zhou De-Song Kong Hong-Yan Wu Feng Zhang Li Chen 《World Journal of Gastroenterology》 SCIE CAS 2026年第10期116-133,共18页
BACKGROUND Reversal of hepatic fibrosis(HF)represents a potential cure for chronic liver pathologies;however,clinically approved agents targeting this process remain scarce.Emerging evidence from traditional Chinese m... BACKGROUND Reversal of hepatic fibrosis(HF)represents a potential cure for chronic liver pathologies;however,clinically approved agents targeting this process remain scarce.Emerging evidence from traditional Chinese medicine(TCM)suggests that Hedyotis diffusa(HD),a botanical agent related to TCM principles of liver pathogenesis,may exert therapeutic effects against fibrotic liver damage.Despite its historical use,the molecular mechanisms underlying its antifibrotic properties and regulatory pathways require systematic elucidation.AIM To elucidate the efficacy and potential mechanism of HD against HF and to explore potential therapeutic targets.METHODS Liquid chromatograph mass spectrometer revealed six bioactive components of HD injection(HDI)that enter the blood and liver.Network pharmacology using these components predicted related signaling pathways.A HF mouse model was induced by administration of 10%carbon tetrachloride for 8 weeks to validate the efficacy of HDI.Integrated Gene Expression Omnibus(GEO)mining and liver proteomics revealed the antifibrotic mechanism of HD,which was confirmed via target gene interference to elucidate up-stream-downstream regulatory relationships.RESULTS Network pharmacology analysis suggests that HDI may ameliorate HF through the modulation of circadian rhythm,urea metabolism,and hypoxia inducible factor-1(HIF-1)signaling.GEO data mining and hepatic proteomic profiling in a fibrotic mouse model confirmed the close associations between disease progression and dysregulation of these pathways.HDI intervention significantly restored expression of the circadian regulator NR1D1.Further mechanistic investigations revealed NR1D1 as an upstream regulator of HIF-1 signaling,urea cycle function,and ammonia metabolism.In vitro experiments demonstrated that ammonium chloride-induced ammonia accumulation promoted LX2 cell activation,which is potentially associated with mitochondrial dysfunction.CONCLUSION HD demonstrates unequivocal efficacy in combating HF,potentially by modulating HIF-1 and the urea cycle through its influence on circadian rhythm genes,with NR1D1 as a prominent representative target. 展开更多
关键词 Hedyotis diffusa Hepatic fibrosis NR1D1 Hypoxia inducible factor-1 Urea cycle Ammonia metabolism
暂未订购 下载PDF
Developing potent anti-inflammatory IRAK4-targeting PROTACs with simplified CRBN ligands 认领 引用
3
作者 Zhen Li Peilu Song +3 位作者 Yujie Liu Xiuyun Sun Xin Zhai Yu Rao 《Chinese Chemical Letters》 SCIE CAS CSCD 2026年第3期565-571,共7页
Interleukin-1 receptor-associated kinase 4(IRAK4),a key target with both enzymatic and non-enzymatic functions,plays a pivotal role in autoimmune diseases.Previous studies have demonstrated that proteolysis-targeting ... Interleukin-1 receptor-associated kinase 4(IRAK4),a key target with both enzymatic and non-enzymatic functions,plays a pivotal role in autoimmune diseases.Previous studies have demonstrated that proteolysis-targeting chimera(PROTAC)molecules targeting IRAK4 can effectively eliminate both its enzymatic and non-enzymatic functions,showing promising therapeutic potential.However,the development of highly potent,synthetically accessible IRAK4-targeting degraders remains a challenge.In this work,through three rounds of PROTAC library construction,screening,and optimization,we successfully identified a representative compound,LZ-07,which proved to be a highly potent degrader with a half-maximal degradation concentration(DC50)value of 1.14 nmol/L.Notably,compared with KT-474,LZ-07 demonstrated comparable degradation activity and superior inhibition of cytokine production,while featuring a simpler synthetic route with optimized IRAK4 and cereblon(CRBN)ligands.LZ-07-induced degradation of IRAK4 led to marked suppression of key cytokines,including interleukin-6(IL-6),IL-1β,tumor necrosis factor alpha(TNF-α),and IL-10.This study presents LZ-07 as a novel,highly efficient,and synthetically straightforward IRAK4-targeting degrader,offering a promising tool compound for the study of the potential treatment of autoimmune diseases. 展开更多
关键词 IRAK4-targeting degraders Simplified CRBN ligands Non-enzymatic functions Inflammatory cytokines inhibition Autoimmune diseases
暂未订购 下载PDF
Abnormal expression of hypoxia inducible factor-1α and clinical values of molecular-targeted interference in hepatocellular carcinoma 认领 引用 被引量：3
4
作者 Shanshan Li Dengfu Yao +6 位作者 Zhizhen Dong Yajie Qian Dandan Yu Ninghua Yao Jie Chen Xiaodi Yan Chenglin Qin 《The Chinese-German Journal of Clinical Oncology》 2012年第3期125-129,共5页
Objective:The aim of this study was to analyze the expression features of hypoxia inducible factor-1α (HIF-1α) in hepatocellular carcinoma (HCC) and effects of HIF-1α silencing on HepG2 cells.Methods:HIF-1α expres... Objective:The aim of this study was to analyze the expression features of hypoxia inducible factor-1α (HIF-1α) in hepatocellular carcinoma (HCC) and effects of HIF-1α silencing on HepG2 cells.Methods:HIF-1α expression was analyzed in the self-control HCC specimens by immunohistochemistry.After HepG2 cells with miRNA transfection,the expression of HIF-1α was determined at mRNA or protein level by real-time polymerase chain reaction (PCR) or Western blotting.Vascular endothelial growth factor (VEGF) and angiopoietin-2 (ANG-2) were determined by ELISA.Alterations of cell cycles and apoptosis of HepG2 cells were measured using a flow cytometer.Results:Positive HIF-1α was brown and granule-like in the cytoplasm or nucleus.Significant difference was found between HCC (80%) and its surrounding tissues (100%,χ2=22.35,P < 0.001) and HIF-1α expression related to tumor size.At 72 h after miRNA transfection,the expression of HIF-1α in HepG2 cells was down-regulated by 87% at mRNA or 65% at protein level,with VEGF and ANG-2 decreased to 54% and 36%,respectively.After RNA interference combined with anti-cancer drug,the apoptotic rate of HepG2 cells was increasing from 22.46% ± 0.61% to 36.99% ± 0.88%,with up-regulation of G1 phase (65.68% ± 0.91%) and down-regulation of S phase (19.47 ± 1.34 %).Conclusion:Abnormal expression of HIF-1α is associated with development of HCC,and HIF-1α gene silencing can effectively inhibit HepG2 cell proliferation. 展开更多
关键词 hepatocellular carcinoma （HCC） hypoxia inducible factor-1α （HIF-1α） expression RNA interference gene silencing
暂未订购 下载PDF
S1PR1 knockdown protects endothelial cells from oxidized lowdensity lipoprotein-induced injury via reducing interleukin-1β and tumor necrosis factor-αexpression 认领 引用
5
作者 Fu-Ying Chu Meng-Han Yao +4 位作者 Le-Ming Gu Hua Cai Ya-Nan Li Xiang Chen Xin-Xin Xu 《World Journal of Cardiology》 2026年第5期90-102,共13页
BACKGROUND Coronary atherosclerotic heart disease(CAHD)is a prevalent cardiovascular condition.Recent research has uncovered the significant role of sphingosine-1-phosphate receptor 1(S1PR1)in cardiovascular disorders... BACKGROUND Coronary atherosclerotic heart disease(CAHD)is a prevalent cardiovascular condition.Recent research has uncovered the significant role of sphingosine-1-phosphate receptor 1(S1PR1)in cardiovascular disorders,including atherosclerosis,acute myocardial infarction,myocardial ischemia,and reperfusion.AIM To explore the clinical relevance,diagnostic utility,and molecular mechanisms of S1PR1 in CAHD.METHODS The expression of S1PR1 was examined by quantitative real-time polymerase chain reaction.Cytokines in serum were detected by flow cytometry using a twelve-cytokine detection kit.Receiver operating characteristic curves were employed to assess the diagnostic value of S1PR1,interleukin(IL)-1β,and tumor necrosis factor(TNF)-αin CAHD.The cell counting kit-8 assay was utilized to determine cell viability,and flow cytometry was used to detect cell apoptosis.Western blot analysis was conducted to detect the protein levels of S1PR1.RESULTS S1PR1 was highly expressed in CAHD,with significantly higher levels observed in the high Gensini score group(≥40)compared to the low score group(<40).Compared with the healthy control group,the CAHD group exhibited significantly increased levels of IL-1βand TNF-α,no significant difference in IL-2 and IL-6 levels,and a significant decrease in the levels of other cytokines.Furthermore,a correlation was observed between S1PR1 and both IL-1βand TNF-αin CAHD.The receiver operating characteristic curve analysis demonstrated that the combined detection of S1PR1,IL-1β,and TNF-αexhibited superior diagnostic value for CAHD compared to individual tests.Additionally,in oxidized low-density lipoprotein-treated human umbilical vein endothelial cells,the expressions of S1PR1,IL-1β,and TNF-αwere increased.However,knockdown of S1PR1 resulted in decreased expression of IL-1βand TNF-α,accompanied by enhanced cell viability and attenuated apoptosis.CONCLUSION S1PR1 could act as a new diagnostic and monitoring biomarker for CAHD.Knockdown of S1PR1 protected human umbilical vein endothelial cells from oxidized low-density lipoprotein-induced injury,which is mediated through regulation of IL-1βand TNF-αexpression. 展开更多
关键词 Sphingosine-1-phosphate receptor 1 Coronary atherosclerotic heart disease Oxidized low-density lipoprotein Interleukin-1β Tumor necrosis factor-α
暂未订购 下载PDF
MicroRNA-206 suppresses hypoxia-inducible factor-1α/PFKFB3-mediated glycolysis to inhibit recurrence and metastasis of hepatocellular carcinoma after incomplete radiofrequency ablation 认领 引用
6
作者 Dong Lu Li-Jun Wang +2 位作者 Jie Chai Jun Jiang Yan-Lin Tang 《World Journal of Gastrointestinal Oncology》 SCIE 2026年第4期232-243,共12页
BACKGROUND Hepatocellular carcinoma(HCC)remains one of the leading causes of cancer-related deaths,with high recurrence and metastasis rates after treatment.Incomplete radiofrequency ablation(iRFA)leaves residual tumo... BACKGROUND Hepatocellular carcinoma(HCC)remains one of the leading causes of cancer-related deaths,with high recurrence and metastasis rates after treatment.Incomplete radiofrequency ablation(iRFA)leaves residual tumor tissue that creates a hypoxic microenvironment that favors tumor progression.Emerging evidence suggests that microRNA-206(miR-206)may act as a tumor suppressor by regulating hypoxia-inducible factor-1α(HIF-1α)and its downstream glycolytic target 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3).AIM To investigate whether miR-206 regulates the HIF-1α/PFKFB3/glycolysis axis in the recurrence and metastasis of HCC following iRFA.METHODS A clinical study was conducted in 45 patients with HCC undergoing RFA,comparing serum miR-206,HIF-1α,glucose,and pyruvate between complete(n=35)and incomplete ablation(n=10)groups.In vitro,tumor-derived endothelial cells(Td-ECs)exposed to sublethal thermal stress were evaluated for proliferation,migration,invasion,tube formation,and glycolysis after miR-206 mimic transfection or PFKFB3 knockdown.Dual-luciferase assays confirmed direct targeting of HIF-1αby miR-206.In vivo,a rabbit VX2 liver tumor model was used to compare angiogenesis,glycolysis,and molecular expression after complete or incomplete ablation.RESULTS Clinically,iRFA was associated with increased HIF-1αand pyruvate,decreased glucose,and altered miR-206 levels compared with complete ablation.In Td-ECs,thermal stimulation enhanced proliferation,migration,glycolysis,and HIF-1α/PFKFB3 expression,while miR-206 overexpression significantly attenuated these effects.Dual-luciferase assays confirmed that miR-206 directly binds the 3′UTR of HIF-1α.In animal models,incomplete ablation increased microvessel density,α-SMA,HIF-1α,and PFKFB3,while miR-206 expression was reduced.CONCLUSION miR-206 suppresses HIF-1α-driven PFKFB3-mediated glycolysis,thereby limiting angiogenesis,cell migration,and recurrence after iRFA.These findings suggest that miR-206 is a potential therapeutic target to reduce HCC recurrence and metastasis following ablation,although larger cohorts and in vivo rescue studies are warranted. 展开更多
关键词 MicroRNA-206 Hypoxia-inducible factor-1α 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 Glycolysis Incomplete radiofrequency ablation Hepatocellular carcinoma Tumor recurrence Angiogenesis
暂未订购 下载PDF
Tumor necrosis factor-α-stimulated gene 6 promotes hematoma clearance after intracerebral hemorrhage in a mouse model 认领 引用
7
作者 Xia Liu Dabao Yao +11 位作者 Yunjie Li Shiling Chen Yingxin Tang Jingyi Wang Jingfei Yang Jie Jing Jiahui Wang Ge Zhang Luwei Nie Yangyang Feng Gaigai Li Zhouping Tang 《Neural Regeneration Research》 SCIE CAS CSCD 2026年第8期3629-3640,共12页
The prognosis for patients who experience intracerebral hemorrhage is poor because of a lack of effective treatments.Tumor necrosis factor-α-stimulated gene 6(TSG6)is a secreted glycoprotein that exerts anti-inflamma... The prognosis for patients who experience intracerebral hemorrhage is poor because of a lack of effective treatments.Tumor necrosis factor-α-stimulated gene 6(TSG6)is a secreted glycoprotein that exerts anti-inflammatory effects in various inflammatory diseases.We previously showed that adipose-derived stem cells can inhibit inflammation by upregulating TSG6 secretion in an in vitro model of intracerebral hemorrhage.However,the direct effects of TSG6 on hematoma clearance in vivo remain largely unknown.The aim of this study was to determine how TSG6 affects hematoma absorption in mice subjected to intracerebral hemorrhage and to explore the potential underlying mechanisms.We first analyzed the gene profiles of patients with intracerebral hemorrhage from the GEO database and examined changes in TSG6 expression in the brain tissues of mice subjected to intracerebral hemorrhage.We found that TSG6 expression exhibited a transient increase following intracerebral hemorrhage,and that there was a negative correlation between the initial hematoma volume and TSG6 levels.Immunofluorescence analysis showed that TSG6 was primarily expressed in microglia and macrophages.Furthermore,we found that TSG6 promoted functional recovery in mice subjected to intracerebral hemorrhage by accelerating hematoma clearance,reducing the number of apoptotic cells and degenerated neurons,increasing the proportion of phagocytic microglia/macrophages,and decreasing iron deposition.Western blotting and immunofluorescence analysis indicated that TSG6 promoted M2 polarization of microglia/macrophages.In vitro phagocytosis experiments confirmed that TSG6 enhanced the ability of microglia to phagocytize red blood cells.Finally,we identified the signal transducer and activator of transcription 6/growth arrest-specific protein 6 signaling pathway as playing a critical role in TSG6-mediated hematoma absorption.In summary,our results demonstrate an essential role for TSG6 in promoting hematoma absorption in a mouse model of intracerebral hemorrhage.These findings suggest that TSG6 accelerates hematoma clearance and improves neurological function by promoting microglia/macrophage polarization to the M2 phenotype,activating the STAT6/GAS6 signaling pathway,and increasing phagocytic receptor expression on the surface of phagocytes,thereby enhancing their ability to phagocytize red blood cells. 展开更多
关键词 apoptosis growth arrest-specific protein 6 hematoma absorption inflammation intracerebral hemorrhage iron deposition microglia/macrophages polarization signal transducer and activator of transcription 6 tumor necrosis factor-α-stimulated gene 6
暂未订购 下载PDF
Cell type-dependent role of transforming growth factor-βsignaling on postnatal neural stem cell proliferation and migration 认领 引用 被引量：1
8
作者 Kierra Ware Joshua Peter +1 位作者 Lucas McClain Yu Luo 《Neural Regeneration Research》 SCIE CAS CSCD 2026年第3期1151-1161,共11页
Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents.While it is known transforming growth factor-βsignaling is important in embryonic neurogenesis,its role in postn... Adult neurogenesis continuously produces new neurons critical for cognitive plasticity in adult rodents.While it is known transforming growth factor-βsignaling is important in embryonic neurogenesis,its role in postnatal neurogenesis remains unclear.In this study,to define the precise role of transforming growth factor-βsignaling in postnatal neurogenesis at distinct stages of the neurogenic cascade both in vitro and in vivo,we developed two novel inducible and cell type-specific mouse models to specifically silence transforming growth factor-βsignaling in neural stem cells in(mGFAPcre-ALK5fl/fl-Ai9)or immature neuroblasts in(DCXcreERT2-ALK5fl/fl-Ai9).Our data showed that exogenous transforming growth factor-βtreatment led to inhibition of the proliferation of primary neural stem cells while stimulating their migration.These effects were abolished in activin-like kinase 5(ALK5)knockout primary neural stem cells.Consistent with this,inhibition of transforming growth factor-βsignaling with SB-431542 in wild-type neural stem cells stimulated proliferation while inhibited the migration of neural stem cells.Interestingly,deletion of transforming growth factor-βreceptor in neural stem cells in vivo inhibited the migration of postnatal born neurons in mGFAPcre-ALK5fl/fl-Ai9 mice,while abolishment of transforming growth factor-βsignaling in immature neuroblasts in DCXcreERT2-ALK5fl/fl-Ai9 mice did not affect the migration of these cells in the hippocampus.In summary,our data supports a dual role of transforming growth factor-βsignaling in the proliferation and migration of neural stem cells in vitro.Moreover,our data provides novel insights on cell type-specific-dependent requirements of transforming growth factor-βsignaling on neural stem cell proliferation and migration in vivo. 展开更多
关键词 adult neurogenesis doublecortin hippocampus migration neural stem cells proliferation transforming growth factor-β
暂未订购 下载PDF
Hypoxia-inducible factor-1:A new neuroprotective agent for the treatment of hyperglycemia after stroke 认领 引用
9
作者 María Isabel Hernández Jose L.Zugaza Abraham Martín 《Neural Regeneration Research》 SCIE CAS CSCD 2026年第9期4061-4067,共7页
Acute hyperglycemia in ischemic stroke occurs in almost half of cases,inducing a worsening of the underlying pathophysiology.Hence,the management of acute hyperglycemia during the first hours following ischemic stroke... Acute hyperglycemia in ischemic stroke occurs in almost half of cases,inducing a worsening of the underlying pathophysiology.Hence,the management of acute hyperglycemia during the first hours following ischemic stroke requires well-defined strategies.Furthermore,the effect of hyperglycemia on stroke remains an unresolved paradoxical process whose possible causes are still unknown.The ischemic process involves the activation of multiple signaling pathways related to cell death and survival,which can be acutely altered by hyperglycemia,causing subsequent worsening of the ischemic process.In search of potential biological targets to combat this medical burden,the role of hypoxia-inducible factor appears as a novel neuroprotective agent that needs further investigation.Furthermore,hypoxia-inducible factor protein targets multiple pathways changing depending on factors such as the severity of hypoxia,the time elapsed after reperfusion and the specific cell type.In fact,the poor prognosis of ischemic stroke associated with acute hyperglycemia has been linked to alterations in hypoxia-inducible factor-1αprotein function.Together,these findings support this transcription factor as a new therapeutic target to prevent the negative effect of hyperglycemia,opening new avenues for treatment in stroke. 展开更多
关键词 acute hyperglycemia hypoxia-inducible factor-1α ischemic stroke neuroprotective agents post-translational modifications
暂未订购 下载PDF
Hypoxia-inducible factor-1α/β-catenin axis:A conserved regulatory hub for enhancing stem cell function in tissue regeneration 认领 引用
10
作者 Hui-Fang Wang Peng-Yu Yan +2 位作者 Shoaib Muhammad Yu-Xiang Liu Chun Liu 《World Journal of Stem Cells》 SCIE 2026年第5期1-8,共8页
This article provides an in-depth commentary on the study by Wang et al,which elucidates that the hypoxia-inducible factor-1α(HIF-1α)/β-catenin axis serves as a core hub regulating the function of peripheral blood ... This article provides an in-depth commentary on the study by Wang et al,which elucidates that the hypoxia-inducible factor-1α(HIF-1α)/β-catenin axis serves as a core hub regulating the function of peripheral blood mesenchymal stem cells(PBMSCs)under hypoxic conditions.The research confirms that in a hypoxic environment,HIF-1αacts as an upstream regulator by directly binding to and activating the transcription ofβ-catenin,a relationship that is unidirectional and irreversible.This axis enhances the therapeutic potential of PBMSCs through a dual mechanism:On one hand,it regulates anti-apoptotic proteins while inhibiting pro-apoptotic molecules,significantly improving cell survival and self-renewal capacity;on the other hand,it promotes the secretion of factors such as vascular endothelial growth factor,thereby enhancing angiogenic activity.In a rat myocardial infarction model,PBMSCs overexpressing HIF-1αshowed significantly improved retention in the infarcted area,reduced infarct size,and promoted neovascularization-effects that were abolished upon knockdown ofβ-catenin.This discovery provides a key target for optimizing stem cell therapy for myocardial infarction.By pre-activating this axis in vitro(e.g.,via lentiviral vectors or small-molecule regulators),it is possible to standardize and enhance the survival and reparative capacity of PBMSCs in ischemic tissues,holding important translational medical value. 展开更多
关键词 Hypoxia-inducible factor-1α β-catenin Stem cell Tissue regeneration Conserved regulatory hub
暂未订购 下载PDF
Letter to the Editor:Tumor necrosis factor-α signaling and β-cell apoptosis in acute pancreatitis-integrating molecular mechanisms and metabolic implications 认领 引用
11
作者 Lara Lizzi Mara Massimi 《World Journal of Gastroenterology》 SCIE CAS 2026年第27期176-179,共4页
The recent study by Chen et al,published in the World Journal of Gastroenterology,provides valuable evidence that tumor necrosis factor-α(TNF-α)contributes to acute metabolic disorder after acute pancreatitis throug... The recent study by Chen et al,published in the World Journal of Gastroenterology,provides valuable evidence that tumor necrosis factor-α(TNF-α)contributes to acute metabolic disorder after acute pancreatitis through Bax/Bcl-2-mediated β-cell apoptosis.Their study elegantly combines clinical observations with experimental data,but the biological framework underlying TNF-α signaling in β-cell damage is more complex than a single apoptotic pathway.TNF-α appears to function as a central hub,linking nuclear factor kappa B(NF-κB)activation,oxidative and endoplasmic reticulum stress,and cytokine cross-talk,all of which influence β-cell survival.The apoptotic cascade described by Chen et al can be viewed as one effector branch of this wider network.Moreover,TNF-α affects key metabolic aspects of β-cell function,including mitochondrial activity and GLUT2-dependent glucose handling,suggesting that metabolic dysfunction and apoptosis may arise together as part of an integrated stress response.By briefly outlining these additional mechanisms,this article places TNF-α within a broader inflammatory-metabolic context that complements and extends their interpretation. 展开更多
关键词 Tumor necrosis factor-α β-cell apoptosis Oxidative stress Endoplasmic reticulum stress Glucose metabolism Acute pancreatitis Post-pancreatitis diabetes mellitus Inflammatory signaling
暂未订购 下载PDF
Nuclear factor-κB as a key inflammatory mediator in psychiatric diseases:A narrative review 认领 引用
12
作者 Fei Fan Bo Wang +3 位作者 Qiong Wang Zi-Lin Chen Wei-Feng Li Fei Han 《World Journal of Psychiatry》 SCIE 2026年第8期36-46,共11页
Nuclear factor-κB(NF-κB)is a central transcription factor that links peripheral immune activation to neuroinflammatory responses in the brain,playing a key role in the pathophysiology of several psychiatric disorder... Nuclear factor-κB(NF-κB)is a central transcription factor that links peripheral immune activation to neuroinflammatory responses in the brain,playing a key role in the pathophysiology of several psychiatric disorders.This review examines the aberrant activation of NF-κB in major depressive disorders,schizophrenia,post-traumatic stress disorder,bipolar disorder,and autism spectrum disorder.It delves into the cell-type-specific mechanisms through which NF-κB modulates neuroinflammation,synaptic plasticity,and neuronal function in microglia,astrocytes,and neurons,and explore its interactions with other key pathways,such as nuclear factor erythroid 2-related factor 2,hypoxia-inducible factor 1-alpha,and NOD-like receptor family pyrin domain containing 3.Furthermore,we summarize current indirect and direct therapeutic strategies targeting NF-κB signaling and discuss the potential of biomarker-guided personalized medicine. 展开更多
关键词 Nuclear factor-κB Psychiatric diseases Neuroinflammation Microglia Astrocytes Synaptic plasticity Immune dysregulation
暂未订购 下载PDF
Research Progress of Insulin-like Growth Factor-1 in the Diagnosis and Efficacy Prediction of Sarcopenia in the Elderly 认领 引用
13
作者 Yang Liao Shujin Guo 《Journal of Clinical and Nursing Research》 2026年第2期69-74,共6页
Sarcopenia in the elderly is a syndrome characterized by age-related progressive loss of muscle mass, decline in muscle strength, and deterioration of muscle function. Its high incidence significantly increases the ri... Sarcopenia in the elderly is a syndrome characterized by age-related progressive loss of muscle mass, decline in muscle strength, and deterioration of muscle function. Its high incidence significantly increases the risk of falls, fractures, disability, and mortality among the elderly, posing a global public health challenge for geriatric health. Insulin-like growth factor-1 (IGF-1), a key cytokine regulating muscle growth, repair, and metabolism, exhibits a progressive decline in serum levels with aging and is closely associated with the onset and progression of sarcopenia in the elderly. This study reviews the research progress of IGF-1 in the diagnosis and efficacy prediction of sarcopenia in the elderly, providing theoretical references for precise diagnosis, treatment, and prognosis assessment of sarcopenia in the elderly. 展开更多
关键词 Insulin-like growth factor-1 Sarcopenia in the elderly Diagnosis Efficacy prediction Research progress
暂未订购 下载PDF
Donor-Derived CD19-Targeted T Cell Infusion Eliminates B Cell Acute Lymphoblastic Leukemia Minimal Residual Disease with No Response to Donor Lymphocytes after Allogeneic Hematopoietic Stem Cell Transplantation 认领 引用 被引量：9
14
作者 Yifei Cheng Yuhong Chen +11 位作者 Chenhua Yan Yu Wang Xiangyu Zhao Yao Chen Wei Han Lanping Xu Xiaohui Zhang Kaiyan Liu Shasha Wang Lungji Chang Lei Xiao Xiaojun Huang 《Engineering》 SCIE EI CAS 2019年第1期150-155,共6页
Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after ... Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with BALL after allo-HSCT have a very short median survival. Minimal residual disease (MRD) is predictive of forthcoming hematological relapse after hematopoietic stem cell transplantation (HSCT);furthermore, eliminating MRD effectively prevents relapse. Donor lymphoblastic infusion (DLI) is the main established approach to treat B-ALL with MRD after allo-HSCT. However, about one-third of patients with MRD are non-responsive to DLI and their prognosis worsens. Although donor-derived cluster of differentiation (CD)19-directed chimeric antigen receptor-modified (CAR) T cells (CART19s) can potentially cure leukemia, the efficiency and safety of infusions with these cells have not yet been investigated in patients with MRD after HSCT. Between September 2014 and February 2018, six patients each received one or more infusions of CART19s from HSCT donors. Five (83.33%) achieved MRD-negative remission, and one case was not responsive to the administration of CAR T cells. Three of the six patients are currently alive without leukemia. No patient developed acute graft-versus-host disease (aGVHD), and no patient died of cytokine release syndrome. Donor-derived CAR T cell infusions seem to be an effective and safe intervention for patients with MRD in B-ALL after allo-HSCT and for those who were not responsive to DLI. 展开更多
关键词 Donor-derived CD19-targeted T cell infusion Hematopoietic stem cell transplantation B cell acute lymphoblastic leukemia Minimal residual disease
暂未订购 下载PDF
Opportunities and challenges of CD47-targeted therapy in cancer immunotherapy 认领 引用 被引量：7
15
作者 QIUQIANG CHEN XUEJUN GUO WENXUE MA 《Oncology Research》 SCIE 2024年第1期49-60,共12页
Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been id... Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment. 展开更多
关键词 CD47 Cancer immunotherapy CD47-targeted therapies Tumor microenvironment Macrophage Cancer cell Immune evasion Checkpoint inhibitors CAR T-cell therapy Cancer treatment outcomes
暂未订购 下载PDF
Exploring the mechanism of Shenhua tablet(肾华片)alleviating renal injury by regulating macrophage glycolysis via hypoxia-inducible factor-1α/pyruvate kinase M2 signaling pathway in diabetic kidney disease mice 认领 引用 被引量：1
16
作者 CHEN Yuanchun JING Jiaxing +5 位作者 LI Qingmin ZHOU Xiaohong JIN Xiaofei GAO Weijuan CHEN Xiangmei YU Wentao 《Journal of Traditional Chinese Medicine》 SCIE CAS CSCD 2025年第3期528-537,共10页
OBJECTIVE:To investigate the impact of Shenhua tablet(肾华片,SHT)on renal macrophage polarization and renal injury in mice with diabetic kidney disease(DKD)and to explore the potential mechanism involving the hypoxia-... OBJECTIVE:To investigate the impact of Shenhua tablet(肾华片,SHT)on renal macrophage polarization and renal injury in mice with diabetic kidney disease(DKD)and to explore the potential mechanism involving the hypoxia-inducible factor-1α(HIF-1α)and pyruvate kinase M2(PKM2)signaling pathway,along with the glycolysis metabolism pathway.METHODS:The animals were divided into the following groups:Model,Control,dapagliflozin,SHT low-dose,SHT medium-dose,and SHT high-dose.We assessed 24-hour urine protein(24 h-UTP)levels,urinary albuminto-creatinine ratio,and regularly monitored fasting blood glucose during the treatment period.After treatment,we examined renal tissue structure,renal function(urea nitrogen,uric acid,creatinine,cystatin C,β2-microglobulin),and glycolysis in renal macrophages.Additionally,we observed macrophage polarization in renal tissue and measured inflammatory factors(tumor necrosis factor-α,interleukin-1β,interleukin-6,interleukin-10,monocyte chemoattractant protein-1)to assess the immunoinflammatory status of the renal tissue.Finally,we investigated the expression of the HIF-1α/PKM2 signaling pathway in macrophages to explore its role in the glycolysis process.RESULTS:SHT shows a beneficial effect in treating DKD by reducing 24 h-UTP,regulating blood glucose levels,improving renal tissue structure,protecting renal function,inhibiting macrophage glycolysis,reducing macrophage transformation to the M1 state,and suppressing the expression of the HIF-1α/PKM2 signaling pathway.CONCLUSION:SHT may exert renoprotective effects by inhibiting macrophage glycolysis via the HIF-1α/PKM2 signaling pathway.This inhibition decreases macrophage M1 polarization and reduces immunoinflammatory injury in the renal tissue of DKD mice. 展开更多
关键词 diabetic kidney disease macrophages glycolysis hypoxia-inducible factor-1α pyruvate kinase M2 Shenhua tablet
暂未订购 下载PDF
Tumor necrosis factor-αpromotes abnormal glucose metabolism after acute pancreatitis by inducing isletβ-cell apoptosis via Bax/Bcl-2/caspase-3 signaling pathway 认领 引用 被引量：1
17
作者 Hai-Feng Chen Chen Gong +2 位作者 Ting-Ting Wang Jian-Xin Zhu Wei-Ping Li 《World Journal of Gastroenterology》 SCIE CAS 2025年第47期140-153,共14页
BACKGROUND Tumor necrosis factor-α(TNF-α)has been implicated in the development of diabetes following chronic pancreatitis.However,its role in abnormal glucose metabolism(AGM)after acute pancreatitis(AP)and post-pan... BACKGROUND Tumor necrosis factor-α(TNF-α)has been implicated in the development of diabetes following chronic pancreatitis.However,its role in abnormal glucose metabolism(AGM)after acute pancreatitis(AP)and post-pancreatitis diabetes mellitus remains unclear.AIM To investigate the role of TNF-αin AP-associated AGM and its effects on isletβ-cell apoptosis,focusing on the underlying molecular mechanisms.METHODS Clinical data were collected to assess AGM’s incidence and identify the characteristics in 369 AP patients.In vitro,AP models were established using lipopolysaccharide in 266-6 acinar cells and MIN-6β-cells.Cell proliferation,apoptosis,and protein expression were analyzed using the Cell Counting Kit-8 assay,terminal deoxynucleotidyl transferase dUTP nick-end labeling assay,and western blotting.The TNF-αand insulin concentration in co-culture medium was measured by enzyme-linked immunosorbent assay.In vivo,an AP mouse model was induced using sodium taurocholate,and pancreatic tissues were analyzed through hematoxylin and eosin staining,terminal deoxynucleotidyl transferase dUTP nick-end labeling,and western blotting.TNF-αlevels were assessed by enzyme-linked immunosorbent assay.A TNF-αinhibitor was applied to the AP cell model to reassess apoptosis and protein expression.RESULTS AGM occurred in 40.38%of AP patients.Body mass index,severity grade,recurrence frequency,and lung injury were significantly associated with AGM.AP models in 266-6 and MIN-6 cells showed reducedβ-cell proliferation,insulin secretion,and increased apoptosis,which correlated with inflammation severity.Similar findings ofβ-cell apoptosis were confirmed in the mouse model.TNF-αlevels were significantly elevated in AP models,with higher levels in severe inflammation.Increased Bax and caspase-3 expression and decreased Bcl-2 expression were observed in both in vitro and in vivo models.These changes intensified with increasing inflammation.TNF-αinhibition reduced apoptosis and altered protein expression patterns,decreasing Bax and caspase-3,while increasing Bcl-2 in MIN-6 cells.CONCLUSION TNF-αcontributes toβ-cell apoptosis and AGM in AP through the Bax/Bcl-2/caspase-3 signaling pathway,suggesting TNF-αas a potential therapeutic target for preventing AP-associated AGM. 展开更多
关键词 Tumor necrosis factor-α Abnormal glucose metabolism Acute pancreatitis Apoptosis Bax Bcl-2 Caspase-3
暂未订购 下载PDF
High hypoxia inducible factor-1αexpression is associated with reduced survival in patients with breast cancer:A meta-analysis 认领 引用
18
作者 Xue-Di Zheng Huan-Yu Li +2 位作者 Si-Yu Gao Qi Wang Jiang-Bo Liu 《World Journal of Clinical Oncology》 2025年第6期287-304,共18页
BACKGROUND Hypoxia-inducible factor 1α(HIF-1α)plays a crucial role in the prognosis of breast cancer,but the current evidence remains inconclusive.AIM To provide comprehensive evidence about the correlation of alter... BACKGROUND Hypoxia-inducible factor 1α(HIF-1α)plays a crucial role in the prognosis of breast cancer,but the current evidence remains inconclusive.AIM To provide comprehensive evidence about the correlation of altered HIF-1αexpression with overall survival(OS)and disease-free survival(DFS)in breast cancer patients.METHODS A systematic search was conducted in PubMed,Embase,and Web of Science databases to collect relevant articles that were published before April 8,2024.A meta-analysis was used to assess the impact of altered HIF-1αexpression on the OS and DFS of breast cancer patients.Subgroup and sensitivity analyses were also performed in this meta-analysis.RESULTS This meta-analysis included 40 studies.The average percentage of breast cancer patients with high HIF-1αexpression was 39.6%.The overall meta-analysis results demonstrated that high HIF-1αexpression is strongly linked to poor outcomes in patients of breast cancer.Compared with low HIF-1αexpression,the overall hazard ratio for OS in patients with high HIF-1αexpression was 1.47[95%confidence interval(CI):1.29-1.69],and the overall hazard ratio for DFS was 1.82(95%CI:1.56-2.12).Furthermore,both OS[1.18(95%CI:1.01-1.38)]and DFS[1.79(95%CI:1.03-3.11)]were markedly shorter in triple-negative breast cancer cases with high HIF-1αexpression.Subgroup analysis revealed that the antibody used to detect HIF-1αexpression affected only the correlation linking HIF-1αexpression to DFS in breast cancer patients(P=0.0004).Furthermore,the sensitivity analysis demonstrates that the overall conclusions of the meta-analysis were unaffected by the removal of individual studies.CONCLUSION Compared to patients with low HIF-1αexpression,those with high expression level had shorter OS and DFS.However,the prognostic significance of high HIF-1αexpression varies across molecularly stratified breast cancer cohorts needs to be further elucidated. 展开更多
关键词 Breast cancer Hypoxia-inducible factor-1α Prognosis Hypoxia Systematic review Meta-analysis
暂未订购 下载PDF
Antitumor effect of VEGFR2-targeted microbubble destruction with gemcitabine using an endoscopic ultrasound probe:In vivo mouse pancreatic ductal adenocarcinoma model 认领 引用 被引量：2
19
作者 Nana Shimamoto Masaki Ito +3 位作者 Masafumi Chiba Sadamu Honma Hiroo Imazu Kazuki Sumiyama 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS CSCD 2020年第5期478-485,共8页
Background:Ultrasound-targeted microbubble destruction(UTMD)induces cellular inflow of drugs at low intensity,while high intensity eradicates tumor vessels.Since vascular endothelial growth factor receptor 2(VEGFR2)is... Background:Ultrasound-targeted microbubble destruction(UTMD)induces cellular inflow of drugs at low intensity,while high intensity eradicates tumor vessels.Since vascular endothelial growth factor receptor 2(VEGFR2)is highly expressed in pancreatic ductal adenocarcinoma(PDAC),VEGFR2-targeted microbubble(MB)might additionally increase the tissue specificity of drugs and thus improve antitumor effects.In addition,fixing the dual pulse intensity could maximize MB properties.This study evaluated the one-off(experiment 1)and cumulative(experiment 2)treatment effect of UTMD by regulating the dual pulse output applied to PDAC using VEGFR2-targeted MB.Methods:C57BL/6 mice inoculated with Pan-02 cells were allocated to five groups:VEGFR2-targeted MB+gemcitabine(GEM),VEGFR2-targeted MB,non-targeted MB+GEM,GEM,and control groups.After injection of GEM or GEM and either VEGFR2-targeted or non-targeted MB,UTMD was applied for several minutes at low intensity followed by high intensity application.In experiment 1,mice were treated by the protocol described above and then euthanized immediately or at the tumor diameter doubling time(TDT).In experiment 2,the same protocol was repeated weekly and mice were euthanized at TDT regardless of protocol completion.Histological analysis by CD31 and VEGFR2 staining provided microvascular density(MVD)and VEGFR2 expression along vessels(VEGFR2v)or intra/peripheral cells(VEGFR2c).Results:In experiment 1,TDT was significantly longer in the VEGFR2-targeted MB+GEM group compared to the non-targeted MB+GEM,GEM,and control groups,while the VEGFR2-targeted MB group showed no statistical significance.MVD and VEGFR2v in the immediate euthanasia was significantly lower in the VEGFR2-targeted MB+GEM and VEGFR2-targeted MB groups than other conditions.In experiment 2,the VEGFR2-targeted MB+GEM group produced significantly longer TDT than the GEM or control groups,whereas the VEGFR2-targeted MB group showed no significant difference.Histology revealed significantly reduced VEGFR2v and VEGFR2c in the VEGFR2-targeted and non-targeted MB+GEM groups,while only VEGFR2v was significantly less in the VEGFR2-targeted MB group.Conclusions:UTMD-mediated GEM therapy with the dual pulse application using VEGFR2-targeted MB substantially suppresses PDCA growth. 展开更多
关键词 Ultrasound-targeted microbubble destruction VEGFR2-targeted microbubble Pancreatic ductal adenocarcinoma Gemcitabine
暂未订购 下载PDF
Abnormal expression and potential clinical value of oncogenic Krüppel-like factor-5 in lung squamous cell carcinoma 认领 引用
20
作者 Yang Shi Wen-Li Sai +4 位作者 Jin-Liang Chen Li-Wei Qiu Min Yao Jun Zhao Deng-Fu Yao 《World Journal of Clinical Oncology》 2025年第10期215-233,共19页
BACKGROUND Krüppel-like factor-5(KLF5)is a zinc-finger transcription factor related to tumor progression.However,the relationship between KLF5 and lung cancer remains to be identified.AIM To investigate the clini... BACKGROUND Krüppel-like factor-5(KLF5)is a zinc-finger transcription factor related to tumor progression.However,the relationship between KLF5 and lung cancer remains to be identified.AIM To investigate the clinical value of KLF5 and interference with KLF5 mRNA transcription on the effects of biological behaviors in lung squamous-cell carcinoma(LUSC).METHODS Lung KLF5 mRNA data were extracted from bioinformatics databases.Blood and tissues from a cohort of patients with benign or malignant lung diseases were collected with ethical committee consent to validate KLF5 expression via multiplex immunofluorescence and immunohistochemistry,Western blot,Enzyme Linked Immunosorbent Assay or quantitative polymerase chain reaction.Furthermore,KLF5 mRNA was silenced in lung A549 cells to validate biological behaviors in vitro and nude mouse xenograft growth in vivo,respectively.RESULTS A cohort of bioinformatics databases revealed high KLF5 mRNA expression in LUSC(P<0.001)but lower KLF5 mRNA expression in lung adenocarcinoma.Upregulated KLF5 in the lung or sera of patients with lung cancer(P<0.001)were confirmed that related to poor differentiation,lymph node or distant metastasis.Furthermore,the incidence of KLF5 levels greater than 500 ng/mL in LUSC patients was 86.7%,which was significantly greater(P<0.001)than that in cases with benign lung diseases(13.3%)or healthy controls.Functionally,silencing KLF5 mRNA with a specific shRNA significantly suppressed A549 cell proliferation,decreased cell migration,increased the ratio of G2 phase cells in vitro,and inhibited the growth of nude mouse xenografts in vivo.CONCLUSION KLF5 is a novel diagnostic biomarker or potential therapeutic target for LUSC. 展开更多
关键词 Targeted therapy Xenograft growth Biological behaviors Diagnostic biomarker Lung adenocarcinoma Lung squamous-cell carcinoma Lung cancer Oncogenic Krüppel-like factor-5
暂未订购 下载PDF
已选0条
引用分析
参考文献
引证文献
 统计分析
检索结果
已选文献
上一页 1 2 … 54 下一页 到第 页
在线咨询 使用帮助 返回顶部 意见反馈