The liver is the most common site of metastases in patients with colorectal cancer.Colorectal liver metastases(CRLMs)are the result of molecular mechanisms that involve different cells of the liver microenvironment.Th...The liver is the most common site of metastases in patients with colorectal cancer.Colorectal liver metastases(CRLMs)are the result of molecular mechanisms that involve different cells of the liver microenvironment.The aberrant activation of Wingless/It(Wnt)/β-catenin signals downstream of Wnt ligands initially drives the oncogenic transformation of the colon epithelium,but also the progression of metastatization through the epithelial-mesenchymal transition/mesenchymalepithelial transition interactions.In liver microenvironment,metastatic cells can also survive and adapt through dormancy,which makes them less susceptible to pro-apoptotic signals and therapies.Treatment of CRLMs is challenging due to its variability and heterogeneity.Advances in surgery and oncology have been made in the last decade and a pivotal role for Wnt/β-catenin pathway has been recognized in chemoresistance.At the state of art,there is a lack of clear understanding of why and how this occurs and thus where exactly the opportunities for developing anti-CRLMs therapies may lie.In this review,current knowledge on the involvement of Wnt signaling in the development of CRLMs was considered.In addition,an overview of useful biomarkers with a revision of surgical and non-surgical therapies currently accepted in the clinical practice for colorectal liver metastasis patients were provided.展开更多
One new genus and three new species of wingless grasshoppers, i.e, Pseudozubovskia gen. nov., Pseudozubovskia xizangensis sp. nov., Eokingdonella gongbugyanda Sla. nov., Dysanema magna sp. nov. are described. The type...One new genus and three new species of wingless grasshoppers, i.e, Pseudozubovskia gen. nov., Pseudozubovskia xizangensis sp. nov., Eokingdonella gongbugyanda Sla. nov., Dysanema magna sp. nov. are described. The type specimens are deposited in the Institute of Zoology, Shaanxi Normal University.展开更多
A wing specific F 1 genetic screen was carried out using the powerful Drosophila genetic system, combined with yeast FRT/FLP and GAL4/UAS system. Form the wing phenotypes and germline clone embryonic cuticle phenotype...A wing specific F 1 genetic screen was carried out using the powerful Drosophila genetic system, combined with yeast FRT/FLP and GAL4/UAS system. Form the wing phenotypes and germline clone embryonic cuticle phenotypes observed in these mutant alleles, a number of mutant alleles of known or unknown genes were isolated. Among them, fifteen mutant alleles related to Wingless signal transduction were further isolated; the arm of these mutations located were determined, and their location in the chromosome were roughly mapped.展开更多
In this article,we comment on the article by Huang et al.The urgent development of new therapeutic strategies targeting macrophage polarization is critical in the fight against liver cancer.Tumor-associated macrophage...In this article,we comment on the article by Huang et al.The urgent development of new therapeutic strategies targeting macrophage polarization is critical in the fight against liver cancer.Tumor-associated macrophages(TAMs),primarily of the M2 subtype,are instrumental in cellular communication within the tumor microenvironment and are influenced by various signaling pathways,including the wingless/integrated(Wnt)pathway.Activation of the Wnt signaling pathway is pivotal in promoting M2 TAMs polarization,which in turn can exacerbate hepatocarcinoma cell proliferation and migration.This manuscript emphasizes the burgeoning significance of the Wnt signaling pathway and M2 TAMs polarization in the pathogenesis and progression of liver cancer,highlighting the potential therapeutic benefits of inhibiting the Wnt pathway.Lastly,we point out areas in Huang et al’s study that require further research,providing guidance and new directions for similar studies.展开更多
目的探讨心外膜脂肪厚度(epicardial fat thickness,EFT)、血清分泌型卷曲相关蛋白5(secreted frizzled-related protein 5,SFRP5)、无翅型MMTV整合位点家族成员5a(winglesstype MMTV integration site family member 5a,Wnt5a)与急性S...目的探讨心外膜脂肪厚度(epicardial fat thickness,EFT)、血清分泌型卷曲相关蛋白5(secreted frizzled-related protein 5,SFRP5)、无翅型MMTV整合位点家族成员5a(winglesstype MMTV integration site family member 5a,Wnt5a)与急性ST段抬高型心肌梗死(ST-segment elevation myocardial infarction,STEMI)患者经皮冠状动脉介入(percutaneous coronary intervention,PCI)治疗后支架内再狭窄(in-stent restenosis,ISR)的关系。方法纳入128例接受急诊PCI的STEMI患者,随访12个月后根据冠状动脉造影结果分为非ISR组(80例)和ISR组(48例)。比较两组的一般资料,出院前及术后1个月EFT,术前及术后1个月血清SFRP5、Wnt5a水平,以及不同冠状动脉病变程度患者指标水平的差异。采用Pearson相关性分析,评估术后1个月EFT和血清SFRP5、Wnt5a水平的相关性。采用多因素Logistic回归分析,确定STEMI患者PCI术后发生ISR的危险因素。采用ROC曲线分析,评估EFT和血清SFRP5、Wnt5a水平对ISR的预测价值。结果ISR组出院前及术后1个月EFT均大于非ISR组;术后1个月血清SFRP5低于非ISR组,血清Wnt5a高于非ISR组(均P<0.01)。非ISR组术后1个月血清SFRP5较术前显著升高,而ISR组则显著降低;非ISR组术后1个月血清Wnt5a较术前轻度升高,ISR组则显著升高(均P<0.05)。3支病变组术后1个月血清SFRP5显著低于单支或2支病变组(P<0.05)。术后1个月EFT与SFRP5呈负相关,与Wnt5a呈正相关。单因素Logistic回归分析及校正年龄、BMI等因素后的Logistic回归分析均显示,术后1个月EFT、血清SFRP5和Wnt5a是ISR的独立影响因素。ROC曲线分析显示,三者联合检测的AUC值(0.906)高于单一指标检测。结论STEMI患者术后1个月EFT增大、血清SFRP5降低及Wnt5a升高与PCI术后ISR密切相关,早期检查有助于预测ISR,联合检测的预测价值更高。展开更多
目的观察腓肠肌钝挫伤白兔的腓肠肌中的无翅型MMTV整合位点家族成员5a(wingless-type MMTV integration site family member 5a,Wnt5a)、糖原合成酶激酶3(glycogen synthase kinase 3,GSK3)/β-联蛋白(β-catenin)的mRNA和蛋白表达,以...目的观察腓肠肌钝挫伤白兔的腓肠肌中的无翅型MMTV整合位点家族成员5a(wingless-type MMTV integration site family member 5a,Wnt5a)、糖原合成酶激酶3(glycogen synthase kinase 3,GSK3)/β-联蛋白(β-catenin)的mRNA和蛋白表达,以及病理染色中呈现的肌肉纤维、脂肪组织的情况,为揭示按揉法治疗骨骼肌损伤的修复机制提供依据。方法选择健康新西兰白兔42只,雌雄各半。采用随机数字表法将其分为空白组、模型3 d组、模型7 d组、模型14 d组、按揉3 d组、按揉7 d组、按揉14 d组,每组6只。各模型组、按揉组在操作后第4、8、15天取材。采用实时定量聚合酶链反应和蛋白质印迹法检测Wnt5a、GSK3、β-catenin的mRNA和蛋白表达情况;采用苏木精-伊红(hematoxylin and eosin,HE)染色和油红O染色观察肌肉组织肌纤维及脂肪组织的情况。结果HE染色显示,模型7 d组发生显著纤维组织增生和炎性细胞浸润;模型14 d组可见部分肌纤维变性坏死、再生伴纤维组织增生及轻微炎性细胞浸润,轻微钙化;各按揉组可见明显肌纤维变性坏死、再生,炎性细胞浸润伴随显著纤维组织增生。油红O染色显示,各模型组可见脂肪细胞沉积,其中模型7 d组最重;各按揉组肌肉纤维及序列未见明显破坏,间隙可见少量脂肪细胞浸润。各组腓肠肌Wnt5a、GSK3、β-catenin的mRNA表达与蛋白表达比较,差异均有统计学意义(P<0.001)。结论腓肠肌损伤组织病理变化随着时间推移会逐渐恢复,按揉法刺激了Wnt5a、GSK3、β-catenin的mRNA的表达活性,从而可能减缓支架蛋白复合物(GSK3为其重要的组成部分)对β-catenin蛋白的降解,使β-catenin的蛋白水平始终维持在稳定范围,使得按揉法干预后的腓肠肌中脂肪变性减少,促进了损伤骨骼肌功能修复。展开更多
Background:Lung cancer remains a major factor causing cancer-associated mortality globally.While there have been advancements in treatment options,advanced lung cancer patients still have poor outcomes.This study aims...Background:Lung cancer remains a major factor causing cancer-associated mortality globally.While there have been advancements in treatment options,advanced lung cancer patients still have poor outcomes.This study aims to investigate the potential role of Transmembrane protein 33(TMEM33)in the development of lung adenocarcinoma.Methods:We leveraged The Cancer Genome Atlas(TCGA)database to analyze the connection between TMEM33 expression to the prognosis of lung adenocarcinoma(LUAD).Cell proliferation,invasiveness,and sphere formation were analyzed by various experiments.The association of miR-214-3p with TMEM33 was explored using luciferase reporter assay,immunoblotting,and real-time quantitative PCR(RT-qPCR).Additionally,TMEM33’s biological role was confirmed in the mouse xenograft model through lung cancer transplantation and metastasis studies.Results:TMEM33 showed high expression within both LUAD tissues and cells,with its expression correlating with poor patient survival outcomes.Silencing TMEM33 resulted in significant reductions in cell proliferation,invasiveness,and stem-like properties.Further investigation suggested that miR-214-3p negatively regulated TMEM33.In both cellular and animal models,we further demonstrated that TMEM33 knockdown could effectively suppress the aggressiveness of lung cancer cells,impeding tumor growth and inhibiting metastasis in the mouse model.Moreover,reducing TMEM33 expression reduced key signaling molecules within the Wnt/β-catenin pathway,providing insights into TMEM33’s mechanistic role in LUAD.Conclusion:TMEM33 functions as an oncogene,which is under the negative regulation of miR-214-3p,to promote the LUAD malignant characteristics by engaging the Wnt/β-catenin cascade.展开更多
目的探讨补骨脂素通过调控无翅型MMTV整合位点家族(wingless type MMTV integration site family,Wnt)信号通路对绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)大鼠的骨保护作用机制。方法将60只SPF级SD雌性大鼠随机分为空白组...目的探讨补骨脂素通过调控无翅型MMTV整合位点家族(wingless type MMTV integration site family,Wnt)信号通路对绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)大鼠的骨保护作用机制。方法将60只SPF级SD雌性大鼠随机分为空白组、模型组、雌二醇片组(0.09mg/kg,每日1次)和补骨脂素低、中、高剂量组(分别为11、22、44mg/kg,每日3次),每组10只。除空白组外,其余组以去卵巢方法构建PMOP大鼠模型。药物干预6周后麻醉取材,行股骨骨密度测定;苏木精-伊红(hematoxylin-eosin,HE)染色观察股骨组织病理形态;逆转录聚合酶链式反应(reverse transcription polymerase chain reaction,RT-PCR)检测大鼠股骨组织Dickkopf相关蛋白1(dickkopf-related protein 1,DKK1)、β-连环蛋白(β-catenin)、Runt相关转录因子2(runt-related transcription factor 2,Runx2)mRNA表达。结果①股骨骨密度方面,与空白组比较,模型组大鼠的双侧股骨骨密度明显降低(P均<0.05);与模型组比较,雌二醇片组、补骨脂素高剂量组大鼠的双侧股骨骨密度及补骨脂素低、中剂量组大鼠的左侧股骨骨密度均明显升高(P均<0.05);与雌二醇片组比较,补骨脂素低剂量组大鼠的双侧股骨骨密度较低(P<0.05)。②股骨组织病理形态方面,与空白组比较,模型组大鼠的股骨骨小梁结构破坏明显且排列紊乱,骨吸收孔增多,骨质疏松特征明显;与模型组比较,雌二醇片组和补骨脂素低、中、高剂量组大鼠的股骨骨小梁结构有所改善,其中,雌二醇片组与补骨脂素高剂量组的骨小梁连续性明显增加,骨陷窝缩小,骨吸收孔减少。③mRNA表达方面,与空白组比较,模型组大鼠股骨组织的DKK1mRNA表达水平明显升高,而β-catenin、Runx2mRNA表达水平明显降低(P均<0.05);与模型组比较,雌二醇片组以及补骨脂素中、高剂量组大鼠股骨组织的DKK1mRNA表达水平明显降低(P<0.05),而β-catenin、Runx2mRNA表达水平明显升高(P均<0.05);与雌二醇片组比较,补骨脂素低剂量组β-catenin、Runx2mRNA表达水平降低(P均<0.05),补骨脂素中、高剂量组大鼠股骨组织的DKK1、β-catenin、Runx2mRNA表达水平差异无统计学意义(P均>0.05)。结论补骨脂素可能通过抑制DKK1表达,进而激活Wnt/β-catenin信号通路,上调Runx2水平,增强骨形成,最终对PMOP大鼠发挥骨保护作用。展开更多
基金Supported by National Natural Science Foundation of China(No.31040018 and No.31172146)Shanxi Scholarship Council of China(2010-2012)International Cooperation Projects of Shanxi Province~~
文摘The liver is the most common site of metastases in patients with colorectal cancer.Colorectal liver metastases(CRLMs)are the result of molecular mechanisms that involve different cells of the liver microenvironment.The aberrant activation of Wingless/It(Wnt)/β-catenin signals downstream of Wnt ligands initially drives the oncogenic transformation of the colon epithelium,but also the progression of metastatization through the epithelial-mesenchymal transition/mesenchymalepithelial transition interactions.In liver microenvironment,metastatic cells can also survive and adapt through dormancy,which makes them less susceptible to pro-apoptotic signals and therapies.Treatment of CRLMs is challenging due to its variability and heterogeneity.Advances in surgery and oncology have been made in the last decade and a pivotal role for Wnt/β-catenin pathway has been recognized in chemoresistance.At the state of art,there is a lack of clear understanding of why and how this occurs and thus where exactly the opportunities for developing anti-CRLMs therapies may lie.In this review,current knowledge on the involvement of Wnt signaling in the development of CRLMs was considered.In addition,an overview of useful biomarkers with a revision of surgical and non-surgical therapies currently accepted in the clinical practice for colorectal liver metastasis patients were provided.
文摘One new genus and three new species of wingless grasshoppers, i.e, Pseudozubovskia gen. nov., Pseudozubovskia xizangensis sp. nov., Eokingdonella gongbugyanda Sla. nov., Dysanema magna sp. nov. are described. The type specimens are deposited in the Institute of Zoology, Shaanxi Normal University.
基金Project (No.30230070) supported partially by the National Natural Science Foundation of China
文摘A wing specific F 1 genetic screen was carried out using the powerful Drosophila genetic system, combined with yeast FRT/FLP and GAL4/UAS system. Form the wing phenotypes and germline clone embryonic cuticle phenotypes observed in these mutant alleles, a number of mutant alleles of known or unknown genes were isolated. Among them, fifteen mutant alleles related to Wingless signal transduction were further isolated; the arm of these mutations located were determined, and their location in the chromosome were roughly mapped.
基金Supported by Macao Science and Technology Development Fund,No.0086/2022/A and No.0097/2022/A2.
文摘In this article,we comment on the article by Huang et al.The urgent development of new therapeutic strategies targeting macrophage polarization is critical in the fight against liver cancer.Tumor-associated macrophages(TAMs),primarily of the M2 subtype,are instrumental in cellular communication within the tumor microenvironment and are influenced by various signaling pathways,including the wingless/integrated(Wnt)pathway.Activation of the Wnt signaling pathway is pivotal in promoting M2 TAMs polarization,which in turn can exacerbate hepatocarcinoma cell proliferation and migration.This manuscript emphasizes the burgeoning significance of the Wnt signaling pathway and M2 TAMs polarization in the pathogenesis and progression of liver cancer,highlighting the potential therapeutic benefits of inhibiting the Wnt pathway.Lastly,we point out areas in Huang et al’s study that require further research,providing guidance and new directions for similar studies.
文摘目的探讨心外膜脂肪厚度(epicardial fat thickness,EFT)、血清分泌型卷曲相关蛋白5(secreted frizzled-related protein 5,SFRP5)、无翅型MMTV整合位点家族成员5a(winglesstype MMTV integration site family member 5a,Wnt5a)与急性ST段抬高型心肌梗死(ST-segment elevation myocardial infarction,STEMI)患者经皮冠状动脉介入(percutaneous coronary intervention,PCI)治疗后支架内再狭窄(in-stent restenosis,ISR)的关系。方法纳入128例接受急诊PCI的STEMI患者,随访12个月后根据冠状动脉造影结果分为非ISR组(80例)和ISR组(48例)。比较两组的一般资料,出院前及术后1个月EFT,术前及术后1个月血清SFRP5、Wnt5a水平,以及不同冠状动脉病变程度患者指标水平的差异。采用Pearson相关性分析,评估术后1个月EFT和血清SFRP5、Wnt5a水平的相关性。采用多因素Logistic回归分析,确定STEMI患者PCI术后发生ISR的危险因素。采用ROC曲线分析,评估EFT和血清SFRP5、Wnt5a水平对ISR的预测价值。结果ISR组出院前及术后1个月EFT均大于非ISR组;术后1个月血清SFRP5低于非ISR组,血清Wnt5a高于非ISR组(均P<0.01)。非ISR组术后1个月血清SFRP5较术前显著升高,而ISR组则显著降低;非ISR组术后1个月血清Wnt5a较术前轻度升高,ISR组则显著升高(均P<0.05)。3支病变组术后1个月血清SFRP5显著低于单支或2支病变组(P<0.05)。术后1个月EFT与SFRP5呈负相关,与Wnt5a呈正相关。单因素Logistic回归分析及校正年龄、BMI等因素后的Logistic回归分析均显示,术后1个月EFT、血清SFRP5和Wnt5a是ISR的独立影响因素。ROC曲线分析显示,三者联合检测的AUC值(0.906)高于单一指标检测。结论STEMI患者术后1个月EFT增大、血清SFRP5降低及Wnt5a升高与PCI术后ISR密切相关,早期检查有助于预测ISR,联合检测的预测价值更高。
文摘Background:Lung cancer remains a major factor causing cancer-associated mortality globally.While there have been advancements in treatment options,advanced lung cancer patients still have poor outcomes.This study aims to investigate the potential role of Transmembrane protein 33(TMEM33)in the development of lung adenocarcinoma.Methods:We leveraged The Cancer Genome Atlas(TCGA)database to analyze the connection between TMEM33 expression to the prognosis of lung adenocarcinoma(LUAD).Cell proliferation,invasiveness,and sphere formation were analyzed by various experiments.The association of miR-214-3p with TMEM33 was explored using luciferase reporter assay,immunoblotting,and real-time quantitative PCR(RT-qPCR).Additionally,TMEM33’s biological role was confirmed in the mouse xenograft model through lung cancer transplantation and metastasis studies.Results:TMEM33 showed high expression within both LUAD tissues and cells,with its expression correlating with poor patient survival outcomes.Silencing TMEM33 resulted in significant reductions in cell proliferation,invasiveness,and stem-like properties.Further investigation suggested that miR-214-3p negatively regulated TMEM33.In both cellular and animal models,we further demonstrated that TMEM33 knockdown could effectively suppress the aggressiveness of lung cancer cells,impeding tumor growth and inhibiting metastasis in the mouse model.Moreover,reducing TMEM33 expression reduced key signaling molecules within the Wnt/β-catenin pathway,providing insights into TMEM33’s mechanistic role in LUAD.Conclusion:TMEM33 functions as an oncogene,which is under the negative regulation of miR-214-3p,to promote the LUAD malignant characteristics by engaging the Wnt/β-catenin cascade.
