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Dissolvable microneedle-based wound dressing transdermally and continuously delivers anti-inflammatory and pro-angiogenic exosomes for diabetic wound treatment

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Bioactive Materials 2024年第12期42卷 32-51页

作者： Yanpeng Cao Bei Chen Qixing liu Yiyang Mao Yusheng He xiaoren liu Xin Zhao Yaowu Chen Xiying Li Yabei Li Liang liu Chengwu Guo Shiyu liu Fenghua Tan Hongbin Lu Jun liu Can Chen Department of Limbs(Foot and Hand)Microsurgery Chenzhou No.1 People’s HospitalThe First Clinical Medical College Affiliated to Southern Medical UniversityChenzhouHunanChina Department of Orthopedics Xiangya HospitalCentral South UniversityChangshaHunanChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunanChina Department of Sports Medicine Xiangya HospitalCentral South University ChangshaHunanChina Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan ProvinceChangshaHunanChina

Due to overactive inflammation and hindered angiogenesis,self-healing of diabetic wounds(DW)remains challenging in the ***-derived exosomes(PLT-Exos),a novel exosome capable of anti-inflammation and pro-angiogenesis,show great potential in DW ***,previous administration of exosomes into skin wounds is topical daub or intradermal injection,which cannot intradermally deliver PLT-Exos into the dermis layer,thus impeding its long-term efficacy in anti-inflammation and ***,a dissolvable microneedle-based wound dressing(PLT-Exos@ADMMA-MN)was developed for transdermal and long-term delivery of ***,a photo-crosslinking methacrylated acellular dermal matrix-based hydrogel(ADMMA-GEL),showing physiochemical tailorability,fast-gelling performance,excellent biocompatibility,and pro-angiogenic capacities,was synthesized as a base material of our *** endowing the dressing with anti-inflammation and pro-angiogenesis,PLT-Exos were encapsulated into ADMMA-GEL with a minimum effective concentration determined by our in-vitro ***,in-vitro results show that this dressing exhibits excellent properties in anti-inflammation and ***,in-vivo experiments showed that this dressing could continuously and transdermally deliver PLT-Exos into skin wounds to switch local macrophage into M2 phenotype while stimulating neovascularization,thus proving a low-inflammatory and pro-angiogenic microenvironment for DW ***,this study provides a novel wound dressing capable of suppressing inflammation and stimulating vascularization for DW treatment.

关键词： Acellular dermal matrix Diabetic wound Exosomes Microneedle Transdermal delivery

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短期血糖水平升高与18F-FDG PET/CT显像异常肌肉摄取的关系

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中国医学影像学杂志 2022年第5期30卷 505-508,513页

作者：李原郭昊刘晓任王茜北京大学人民医院核医学科北京100044

目的通过评估血糖短期变化情况,预测^(18)F-FDG PET/CT显像的肌肉异常摄取。资料与方法回顾性分析2019年1月—2020年6月于北京大学人民医院就诊的高血糖症PET/CT受检者100例,收集检查前3 d内基线空腹血糖(BGL_(基线))、检查前空腹血糖(B... 详细信息

目的通过评估血糖短期变化情况,预测^(18)F-FDG PET/CT显像的肌肉异常摄取。资料与方法回顾性分析2019年1月—2020年6月于北京大学人民医院就诊的高血糖症PET/CT受检者100例,收集检查前3 d内基线空腹血糖(BGL_(基线))、检查前空腹血糖(BGL_(检查前))测定结果,计算变化率(K),使用受试者工作特征(ROC)曲线分析获得K值最佳截止点,通过K值预测患者出现肌肉异常摄取,并将其预测效能与指南中BGL_(检查前)≥11.0 mmol/L的标准进行比较。结果BGL_(检查前)>11.0 mmol/L者出现肌肉异常摄取的比例为56.3%(10/16),BGL_(检查前)8.3~11.0 mmol/L者出现肌肉异常摄取比例为23.8%(20/84)。ROC曲线分析显示,以K值≥20.0%判断PET/CT显像发生异常肌肉摄取,其敏感度、特异度、阳性预测值、阴性预测值及准确度分别为90.0%(27/30)、87.1%(61/70)、75.0%(27/36)、95.3%(61/64)和88.0%(88/100),敏感度、阴性预测值及准确度均优于指南标准(χ^(2)=18.049、8.715、6.368,P=0.000、0.003、0.012)。结论通过比较患者BGL_(基线)及BGL_(检查前),可以更好地预测PET显像出现肌肉异常摄取的风险,推荐临床采用。

关键词：高血糖症正电子发射断层显像术体层摄影术 X线计算机氟脱氧葡萄糖F18

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负压封闭引流技术对大鼠急性创面愈合过程中Ⅰ/Ⅲ型胶原比例变化的影响

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中国组织工程研究 2020年第32期24卷 5122-5127页

作者：赵鑫石新陈贝曹焱鹏陈耀武刘小仁何雨生何丽云李熙莹刘俊南方医科大学第一临床医学院广东省广州市510000 湖南省郴州市第一人民医院湖南省郴州市423000

背景:负压封闭引流技术可以促进各种急慢性创面的愈合。Ⅰ/Ⅲ型胶原比例在维持皮肤组织稳态及皮肤损伤后的修复过程中发挥着重要的作用,但是在负压封闭引流技术促进创面愈合过程中Ⅰ/Ⅲ型胶原比例的变化知之甚少。目的:观察负压封闭引... 详细信息

背景:负压封闭引流技术可以促进各种急慢性创面的愈合。Ⅰ/Ⅲ型胶原比例在维持皮肤组织稳态及皮肤损伤后的修复过程中发挥着重要的作用,但是在负压封闭引流技术促进创面愈合过程中Ⅰ/Ⅲ型胶原比例的变化知之甚少。目的:观察负压封闭引流技术促进创面愈合过程中Ⅰ/Ⅲ型胶原的比例变化,探讨其对大鼠急性创面的修复机制。方法:建立大鼠背部皮肤全层缺损模型,创面直径20 mm,建立创面模型以后随机分为负压封闭引流治疗组和空白对照组。创面愈合过程中于术后第1,3,7天对创面进行固定高度连续拍照,进而计算和比较创面愈合率;实时荧光定量PCR检测Ⅰ,Ⅲ型胶原mRNA的表达;免疫组织化学染色分析Ⅰ/Ⅲ型胶原比例;组织学检测创面组织肉芽组织再生和再上皮化长度的变化。结果与结论:①与空白对照组相比,负压封闭引流治疗组提高了Ⅰ,Ⅲ型胶原的m RNA和蛋白表达水平(P<0.05);②术后第3天开始,负压封闭引流治疗组的Ⅰ/Ⅲ型胶原比例高于空白对照组(P<0.05);③负压封闭引流治疗组的创面愈合率均高于空白对照组(P<0.05);④上述结果证实,负压封闭引流技术可能通过提高Ⅰ,Ⅲ型胶原蛋白表达和Ⅰ/Ⅲ型胶原比例,增加创面的抗拉伸强度,促进创面的早期愈合。

关键词：负压封闭引流急性创面模型 Ⅰ型胶原蛋白 Ⅲ型胶原蛋白 Ⅰ/Ⅲ型胶原比例再上皮化创面愈合肉芽组织创面愈合率

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不同亚型功能性消化不良患者的社会心理特征比较

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中华消化杂志 2017年第9期37卷 607-611页

作者：郑晓人吴文昭刘南华欧阳爱桂高镇松王增珍华中科技大学同济医学院公共卫生学院武汉430030 汕头市第四人民医院综合科汕头市第四人民医院精神科汕头市第四人民医院综合内科

的分析不同亚型功能性消化不良（FD）患者社会心理特征的差异。方法纳入2011年8月至2015年7月就诊的210例符合罗马Ⅲ标准的FD患者，分成单纯餐后不适综合征（PDS）组（69例）、单纯上腹痛综合征（EPS）组（74例）和PDS重叠EPS组（67例... 详细信息

的分析不同亚型功能性消化不良（FD）患者社会心理特征的差异。方法纳入2011年8月至2015年7月就诊的210例符合罗马Ⅲ标准的FD患者，分成单纯餐后不适综合征（PDS）组（69例）、单纯上腹痛综合征（EPS）组（74例）和PDS重叠EPS组（67例），采用汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）、生活事件量表（LES）和艾森克人格问卷（EPQ）进行评估分析。统计学方法采用卡方检验和最小显著性差异法。结果PDS重叠EPS组抑郁和焦虑发生率均为100.0%（67/67），高于单纯PDS组的84.1%（58/69）和91.3%（63/69），差异均有统计学意义（χ2＝11.62、16.34，P均〈0.01）；也高于单纯EPS组的78.4%（58/74）和90.5%（67/74），差异均有统计学意义（χ2＝6.10、6.67，P均〈0.05）。PDS重叠EPS组的躯体焦虑评分和精神焦虑评分分别为（16.34±3.70）和（14.18±2.99）分，高于单纯PDS组的（11.26±3.42）和（10.70±2.94）分，也高于单纯EPS组的（12.30±4.29）和（10.36±2.63）分，差异均有统计学意义（t＝8.33、5.97，6.85、8.06，P均〈0.01）。3组生活事件发生频率居于前两位的都是睡眠习惯改变[67.6%（142/210）]和严重疾病外伤[26.7%（56/210）]。单纯PDS组睡眠习惯改变发生率为53.6%（37/69），低于单纯EPS组的77.0%（57/74）和PDS重叠EPS组的71.6%（48/67），差异均有统计学意义（χ2＝8.68、4.71，P均〈0.05）。单纯PDS组、单纯EPS组和PDS重叠EPS组的P量表评分均以正常居多，E和L量表评分均以偏低居多；单纯PDS组的N量表评分以偏低居多，单纯EPS组和PDS重叠EPS组以正常居多。结论PDS重叠EPS患者抑郁和焦虑的发生率最高。PDS重叠EPS和单纯EPS患者的躯体焦虑比精神焦虑更明显，都有较多的睡眠事件；单纯PDS患者以情绪反应慢最多见。

关键词：功能性消化不良亚型社会心理特征比较

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气体放电镀染料膜装置的研制

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华东化工学院学报 1986年第5期 589-592页

作者：潘孝仁包于诗刘宝坤滕湘君华东化工学院物理系华东化工学院物理系

本文描述了装有充气部件的利用气体放电的镀膜装置。它适用于镀染料薄膜。在特殊的放电结构下,放电电压取2 kV,内充氩气压力7—8 Pa,能得到理想的染料薄膜。与真空蒸发法比较,用此法制成的薄膜致密、均匀和牢固。此外还讨论了镀膜的原... 详细信息

本文描述了装有充气部件的利用气体放电的镀膜装置。它适用于镀染料薄膜。在特殊的放电结构下,放电电压取2 kV,内充氩气压力7—8 Pa,能得到理想的染料薄膜。与真空蒸发法比较,用此法制成的薄膜致密、均匀和牢固。此外还讨论了镀膜的原理及一些特殊现象。

关键词：薄膜气体放电染料离子镀溅射

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NF-κB Signaling Pathway, Inflammation and Colorectal Cancer

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Cellular & Molecular Immunology 2009年第5期6卷 327-334页

作者： Soly Wang Zhanjie liu Lunshan Wang xiaoren Zhang Key Laboratory of Stem Cell Biology Institute of Health Sciences Shanghai Institutes for Biological Sciences Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine Shanghai 200025 China Department of Pathology Soochow University School of Medicine Suzhou215123 China Key Laboratory of Stem Cell Biology Laboratory of Immunoregulation and Tolerance Institute of Health Sciences Shanghai Institutes for Biological Sciences Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine Shanghai 200025 China

There is growing evidence for a connection between inflammation and tumor development, and the nuclear factor kappa B （NF-κB）, a proinflammatory transcription factor, is hypothesized to promote tumorigenesis. Although the genetic evidence for the hypothesis has been lacking, recent papers have lent credence to this hypothesis. It has been reported that constitutive NF-κB activation in inflammatory bowel diseases （IBDs） increases risk of colorectal cancer （CRC） in the patients with the number of years of active disease. NF-κB activation might induce cellular transformation, mediate cellular proliferation, prevent the elimination of pre-neoplastic and fully malignant cells by up-regulating the anti-apoptosis proteins. Furthermore, NF-κB may contribute to the progression of CRC by regulating the expression of diverse target genes that are involved in cell proliferation （Cyclin D1）, angiogenesis （VEGF, IL-8, COX2）, and metastasis （MMP9）. These findings implicate NF-κB inhibition as an important therapeutic target in CRC. However, due to lack of knowledge about the specific roles of different NF-r,B subunits in different stage of carcinogenesis, and compounds to block specific subunits of NF-κB family, it will be a long time before the coming of targeting NF-κB in CRC therapy.

关键词： NF-κB inflammation colorectal cancer

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CT血管造影数字化三维重建技术设计股前外侧穿支皮瓣在下肢大面积软组织缺损患者中的应用效果

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广西医学 2023年第5期45卷 511-515页

作者：何雨生刘俊陈耀武郭双飞赵鑫刘小仁李承杰王新平郴州市第一人民医院肢体手足显微外科湖南省郴州市423000

目的分析CT血管造影数字化三维重建技术设计股前外侧穿支皮瓣在下肢大面积软组织缺损患者中的应用效果。方法将80例下肢大面积软组织缺损患者分为观察组和对照组,各40例。观察组术前采用CT血管造影数字化三维重建技术进行皮瓣设计并指... 详细信息

目的分析CT血管造影数字化三维重建技术设计股前外侧穿支皮瓣在下肢大面积软组织缺损患者中的应用效果。方法将80例下肢大面积软组织缺损患者分为观察组和对照组,各40例。观察组术前采用CT血管造影数字化三维重建技术进行皮瓣设计并指导手术操作,对照组术中采用多普勒超声辅助设计皮瓣后进行皮瓣移植。比较观察组穿支血管的术前CT血管造影数字化三维重建技术测量结果与术中实际测量值。比较两组患者术后4周的皮瓣成活率、皮瓣并发症发生率、供区并发症发生率及移植皮瓣区的感觉功能。结果观察组术前CT血管造影数字化三维重建技术测量的穿支起始点直径、穿支起始点至髌骨上缘直线距离、穿支起始点至大腿外侧缘直线距离与术中实际测量值的差异均无统计学意义(均P>0.05)。术后4周,观察组患者皮瓣并发症发生率低于对照组,移植皮瓣区的感觉功能优于对照组(均P0.05)。结论术前采用CT血管造影数字化三维重建技术可以准确了解旋股外侧动脉分支及穿支血管的解剖学特点,以此设计穿支皮瓣进行逆行股前外侧穿支皮瓣移植可维持皮瓣良好血运,降低术后皮瓣并发症发生率,利于移植皮瓣区感觉功能的恢复。

关键词：下肢大面积软组织缺损穿支皮瓣逆行股前外侧穿支皮瓣移植 CT血管造影数字化三维重建

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Elevating H3K27me3 level sensitizes colorectal cancer to oxaliplatin

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Journal of Molecular Cell Biology 2020年第2期12卷 125-137页

作者： Qi Wang Xi Chen Yuhang Jiang Sanhong liu Hanshao liu Xiaohua Sun Haohao Zhang Zhi liu Yu Tao Cuifeng Li Yiming Hu Dandan liu Deji Ye Yongzhong liu Mingliang Wang xiaoren Zhang The Key Laboratory of Stem Cell Biology Shanghai Jiao Tong University School of Medicine&Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200025227 Chongqing South RoadShanghaiChina Affiliated Cancer Hospital&Institute Guangzhou Medical UniversityGuangzhou 510000195 Dongfeng West RoadGuangzhouChina Shanghai Institute for Advanced Immunochemical Studies ShanghaiTech UniversityShanghai 201210393 Huaxia Middle RoadShanghaiChina State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteRenji HospitalShanghai Jiao Tong University School of MedicineShanghai 200032Ruijin 2nd RoadShanghaiChin Department of General Surgery Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025Ruijin 2nd RoadShanghaiChina

Histone methylation is a context-dependent modification that regulates gene expression,and the trimethylation of histone H3 lysine 27(H3K27me3)usually induces gene *** colorectal cancer(CRC)chemoresistance is currently a huge challenge,but the relationship between H3K27me3 modification and chemoresistance remains largely ***,we found that H3K27me3 levels positively correlated with the metastasis-free survival of CRC patients and a low H3K27me3 level predicted a poor outcome upon chemotherapeutic drug *** stimulation significantly induced the expression of H3K27 lysine demethylase 6A/6B(KDM6A/6B),thus decreasing the level of H3K27me3 in CRC *** of H3K27me3 level through KDM6A/6B depletion or GSK-J4(a KDM6A/6B inhibitor)treatment significantly enhanced oxaliplatin-induced ***,when inhibiting the expression of H3K27me3 by EPZ-6438,an inhibitor of the histone methyltransferase EZH2,the proportion of apoptotic cells remarkably *** addition,the combination of GSK-J4 and oxaliplatin significantly inhibited tumor growth in an oxaliplatin-resistant patient-derived xenograft ***,we revealed that oxaliplatin treatment dramatically induced NOTCH2 expression,which was caused by downregulation of H3K27me3 level on the NOTCH2 transcription initiation ***,the activated NOTCH signaling promoted the expression of stemness-related genes,which resulted in oxaliplatin ***,oxaliplatin-induced NOTCH signaling could be interrupted by GSK-J4 ***,our findings suggest that elevating H3K27me3 level can improve drug sensitivity in CRC patients.

关键词： H3K27 trim ethylation colorectal cancer chem oresistance NOTCH signaling

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B-cell-derived IL-10 promotes allergic sensitization in asthma regulated by Bcl-3

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Cellular & Molecular Immunology 2023年第11期20卷 1313-1327页

作者： Guojun Qian Wenxia Jiang Donglin Sun Zhun Sun Anning Chen Hongwei Fang Jingyao Wang Yongzhong liu Zhinan Yin Haiming Wei Hao Fang xiaoren Zhan Affiliated Cancer Hospital/Institute and GMU-GIBH Joint School of Life Sciences of Guangzhou Medical University The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and DiseasesState Key Laboratory of Respiratory Disease511436GuangzhouChina Shanghai Institute of Nutrition and Health Chinese Academy of Sciences200031ShanghaiChina Department of Anesthesiology Zhongshan HospitalFudan University200032ShanghaiChina Shanghai Cancer Institute Renji HospitalShanghai Jiao Tong University School of Medicine200032ShanghaiChina Zhuhai People’s Hospital Biomedical Translational Research InstituteJinan University510632GuangzhouChina Institute of Immunology University of Science and Technology of China230000HefeiChina Department of Anesthesiology Minhang HospitalFudan University201100ShanghaiChina Key Laboratory of Anesthesiology(Shanghai Jiao Tong University) Ministry of Education200001ShanghaiChina

Aeroallergen sensitization,mainly mediated by lung epithelium and dendritic cells(DCs),is integral to allergic asthma pathogenesis and ***-10 has a dual role in immune responses,as it inhibits myeloid cell activation but promotes B-cell responses and epithelial cell ***,we report a proinflammatory function of B-cell-derived IL-10 modulated by Bcl-3 in allergic ***,Bcl-3^(−/−)mice showed elevated IL-10 levels and were found to be highly vulnerable to allergic asthma induced by house dust mites(HDMs).IL-10 had a positive correlation with the levels of the DC chemoattractant CCL-20 in HDM-sensitized mice and in patients with asthma and induced a selective increase in CCL-20 production by mouse lung epithelial *** of IL-10 or IL-10 receptors during sensitization dampened both HDM-induced sensitization and asthma ***-10 levels peaked 4 h post sensitization with HDM and IL-10 was primarily produced by B cells under Bcl-3–Blimp-1–Bcl-6 *** lacking B-cell-derived IL-10 displayed decreased lung epithelial CCL-20 production and diminished DC recruitment to the lungs upon HDM sensitization,thereby demonstrating resistance to HDM-induced ***,responses to HDM stimulation in Bcl-3^(−/−)mice lacking B-cell-derived IL-10 were comparable to those in Bcl-3^(+/+)*** results revealed an unexpected role of B-cell-derived IL-10 in promoting allergic sensitization and demonstrated that Bcl-3 prevents HDM-induced asthma by inhibiting B-cell-derived IL-10 ***,targeting the Bcl-3/IL-10 axis to inhibit allergic sensitization is a promising approach for treating allergic asthma.

关键词： Bcl-3 Plasma cell IL-10 Allergic sensitization Airway inflammation Asthma

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Bcl-3 promotes Wnt signaling by maintaining the acetylation ofβ-catenin at lysine 49 in colorectal cancer

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1913-1924页

作者： Xi Chen Chen Wang Yuhang Jiang Qi Wang Yu Tao Haohao Zhang Yongxu Zhao Yiming Hu Cuifeng Li Deji Ye Dandan liu Wenxia Jiang Eugene Y.Chin Sheng Chen Yongzhong liu Mingliang Wang Sanhong liu xiaoren Zhang CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and HealthShanghai Institutes for Biological SciencesUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200025China Shanghai Institute for Advanced Immunochemical Studies ShanghaiTech UniversityShanghai 201210China Affiliated Cancer Hospital&Institute of Guangzhou Medical University Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and DegradationState Key Laboratory of Respiratory DiseaseGuangzhou 510000China Renji Hospital Shanghai Jiao Tong University School of MedicineShanghai 200025China State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteRenji HospitalShanghai Jiao Tong University School of MedicineShanghai 200032China Department of General Surgery Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

Wnt/β-catenin signaling plays a critical role in colorectal cancer(CRC)tumorigenesis and the homeostasis of colorectal cancer stem cells(CSCs),but its molecular mechanism remains unclear.B-cell lymphoma 3(Bcl-3),a member of the IκB family,is overexpressed in CRC and promotes ***,we report a novel function of Bcl-3 in maintaining colorectal CSC homeostasis by activating Wnt/β-catenin *** Bcl-3 suppresses the self-renewal capacity of colorectal CSCs and sensitizes CRC cells to chemotherapeutic drugs through a decrease in Wnt/β-catenin ***,our data show that Bcl-3 is a crucial component of Wnt/β-catenin signaling and is essential forβ-catenin transcriptional activity in CRC ***,Wnt3a increases the level and nuclear translocation of Bcl-3,which binds directly toβ-catenin and enhances the acetylation ofβ-catenin at lysine 49(Ac-K49-β-catenin)and transcriptional ***-3 depletion decreases the Ac-K49-β-catenin level by increasing the level of histone deacetylase 1 to remove acetyl groups fromβ-catenin,thus interrupting Wnt/β-catenin *** CRC clinical specimens,Bcl-3 expression negatively correlates with the overall survival of CRC patients.A significantly positive correlation was found between the expression of Bcl-3 and Ac-K49-β-***,our data reveal that Bcl-3 plays a crucial role in CRC chemoresistance and colorectal CSC maintenance via its modulation of the Ac-K49-β-catenin,which serves as a promising therapeutic target for CRC.

关键词： colorectal homeostasis cancer

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