Metabolic syndrome(Met S), as a chronic inflammatory disorder has a potential role in the development of inflammatory and cancerous complications of the colonic tissue. The interaction of DNA damage and inflammation i...Metabolic syndrome(Met S), as a chronic inflammatory disorder has a potential role in the development of inflammatory and cancerous complications of the colonic tissue. The interaction of DNA damage and inflammation is affected by the insulin-like growth factor 1 receptor(IGF1 R) signaling pathway. The IGF1 R pathway has been reported to regulate autophagy, as well, but sometimes through a bidirectional context. Targeting the IGF1 R-autophagy crosstalk could represent a promising strategy for the development of new antiinflammatory and anticancer therapies, and may help for subjects suffering from Met S who are at increased risk of colorectal cancer. However, therapeutic responses to targeted therapies are often shortlived, since a signaling crosstalk of IGF1 R with other receptor tyrosine kinases or autophagy exists, leading to acquired cellular resistance to therapy. From a pharmacological point of view, it is attractive to speculate that synergistic benefits could be achieved by inhibition of one of the key effectors of the IGF1 R pathway, in parallel with the pharmacological stimulation of the autophagy machinery, but cautiousness is also required, because pharmacologic IGF1 R modulation can initiate additional, sometimes unfavorable biologic effects.展开更多
Embryo implantation in both humans and rodents is initiated by the attachment of a blastocyst to the uterine epithelium.For blastocyst attachment,the uterine epithelium needs to transform at both the structural and mo...Embryo implantation in both humans and rodents is initiated by the attachment of a blastocyst to the uterine epithelium.For blastocyst attachment,the uterine epithelium needs to transform at both the structural and molecular levels first,and then initiate the interaction with trophectoderm.Any perturbation during this process will result in implantation failure or long-term adverse pregnancy outcomes.Endocrine steroid hormones,which function through nuclear receptors,combine with the local molecules produced by the uteri or embryo to facilitate implantation.The insulin-like growth factor(IGF)signaling has been reported to play a vital role during pregnancy.However,its physiological function during implantation remains elusive.This study revealed that mice with conditional deletion of Igflr gene in uteri suffered from subfertility,mainly due to the disturbed uterine receptivity and abnormal embryo implantation.Mechanistically,we uncovered that in response to the nidatory estrogen on D4 of pregnancy,the epithelial IGF1R,stimulated by the stromal cell-produced IGF1,facilitated epithelial STAT3 activation to modulate the epithelial depolarity.Furthermore,embryonic derived IGF2 could activate both the epithelial ERK1/2 and STAT3 signaling through IGF1R,which was critical for the transcription of Cox2 and normal attachment reaction.In brief,our data revealed that epithelial IGF1R was sequentially activated by the uterine stromal IGF1 and embryonic IGF2 to guarantee normal epithelium differentiation during the implantation process.展开更多
The potential medicinal value of Ma bamboo(Dendrocalamus latiflorus), one of the most popular and economically important bamboo species in China, has been underestimated. In the present study, we found that D. latiflo...The potential medicinal value of Ma bamboo(Dendrocalamus latiflorus), one of the most popular and economically important bamboo species in China, has been underestimated. In the present study, we found that D. latiflorus leaf extract(DLE) reduced fasting blood glucose levels, body weight,and low-density lipoprotein cholesterol with low liver toxicity in db/db mice. In addition, gene expression profiling was performed and pathway enrichment analysis showed that DLE affected metabolic pathways.Importantly, DLE activated the AKT signaling pathway and reduced glucose production by downregulating glucose-6-phosphatase(G6 PC) and phosphoenolpyruvate carboxykinase 1(PCK1) expression. Moreover, network pharmacology analysis identified rutin as an active component in DLE through targeting insulin growth factor 1 receptor(IGF1 R), an upstream signaling transducer of AKT. Due to its hypoglycemic effects and low toxicity, DLE may be considered an adjuvant treatment option for type 2 diabetes patients.展开更多
基金Supported by the Hungarian Scientific Research Fund(No.OTKA-K111743)to Tulassay Z.The funders had no role in data collection,decision to publish,or preparation of the manuscript
文摘Metabolic syndrome(Met S), as a chronic inflammatory disorder has a potential role in the development of inflammatory and cancerous complications of the colonic tissue. The interaction of DNA damage and inflammation is affected by the insulin-like growth factor 1 receptor(IGF1 R) signaling pathway. The IGF1 R pathway has been reported to regulate autophagy, as well, but sometimes through a bidirectional context. Targeting the IGF1 R-autophagy crosstalk could represent a promising strategy for the development of new antiinflammatory and anticancer therapies, and may help for subjects suffering from Met S who are at increased risk of colorectal cancer. However, therapeutic responses to targeted therapies are often shortlived, since a signaling crosstalk of IGF1 R with other receptor tyrosine kinases or autophagy exists, leading to acquired cellular resistance to therapy. From a pharmacological point of view, it is attractive to speculate that synergistic benefits could be achieved by inhibition of one of the key effectors of the IGF1 R pathway, in parallel with the pharmacological stimulation of the autophagy machinery, but cautiousness is also required, because pharmacologic IGF1 R modulation can initiate additional, sometimes unfavorable biologic effects.
基金supported by the National Key R&D Program of China(2017YFC1001402 to H.W.2018YFC1004401 to S.K.)+1 种基金the National Natural Science Foundation of China(81830045 and 82030040 to H.W.,81971388 to S.K.)Institution of Higher Education Projects of Building First-class Discipline Construction in Ningxia Region(NXYLXK2017B05 to G.X.).
文摘Embryo implantation in both humans and rodents is initiated by the attachment of a blastocyst to the uterine epithelium.For blastocyst attachment,the uterine epithelium needs to transform at both the structural and molecular levels first,and then initiate the interaction with trophectoderm.Any perturbation during this process will result in implantation failure or long-term adverse pregnancy outcomes.Endocrine steroid hormones,which function through nuclear receptors,combine with the local molecules produced by the uteri or embryo to facilitate implantation.The insulin-like growth factor(IGF)signaling has been reported to play a vital role during pregnancy.However,its physiological function during implantation remains elusive.This study revealed that mice with conditional deletion of Igflr gene in uteri suffered from subfertility,mainly due to the disturbed uterine receptivity and abnormal embryo implantation.Mechanistically,we uncovered that in response to the nidatory estrogen on D4 of pregnancy,the epithelial IGF1R,stimulated by the stromal cell-produced IGF1,facilitated epithelial STAT3 activation to modulate the epithelial depolarity.Furthermore,embryonic derived IGF2 could activate both the epithelial ERK1/2 and STAT3 signaling through IGF1R,which was critical for the transcription of Cox2 and normal attachment reaction.In brief,our data revealed that epithelial IGF1R was sequentially activated by the uterine stromal IGF1 and embryonic IGF2 to guarantee normal epithelium differentiation during the implantation process.
基金supported by Beijing Talents Foundation (No.2017000021223ZK30,China)Consulting Research Project of the Chinese Academy of Engineering (No.2020-XZ-23,China)Beijing Lab Foundation (China)。
文摘The potential medicinal value of Ma bamboo(Dendrocalamus latiflorus), one of the most popular and economically important bamboo species in China, has been underestimated. In the present study, we found that D. latiflorus leaf extract(DLE) reduced fasting blood glucose levels, body weight,and low-density lipoprotein cholesterol with low liver toxicity in db/db mice. In addition, gene expression profiling was performed and pathway enrichment analysis showed that DLE affected metabolic pathways.Importantly, DLE activated the AKT signaling pathway and reduced glucose production by downregulating glucose-6-phosphatase(G6 PC) and phosphoenolpyruvate carboxykinase 1(PCK1) expression. Moreover, network pharmacology analysis identified rutin as an active component in DLE through targeting insulin growth factor 1 receptor(IGF1 R), an upstream signaling transducer of AKT. Due to its hypoglycemic effects and low toxicity, DLE may be considered an adjuvant treatment option for type 2 diabetes patients.
