Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related t...Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation.However,the effect of Spi1 on intracerebral hemorrhage remains unclear.In this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome.We showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained remyelination.Notably,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and coagulation.In conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage.This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.展开更多
Background:Inhibitor of NF-κB kinase-interacting protein(IKIP)is known to promote proliferation of glioblastoma(GBM)cells,but how it affects migration and invasion by those cells is unclear.Methods:We compared levels...Background:Inhibitor of NF-κB kinase-interacting protein(IKIP)is known to promote proliferation of glioblastoma(GBM)cells,but how it affects migration and invasion by those cells is unclear.Methods:We compared levels of IKIP between glioma tissues and normal brain tissue in clinical samples and public databases.We examined the effects of IKIP overexpression and knockdown on the migration and invasion of GBM using transwell and wound healing assays,and we compared the transcriptomes under these different conditions to identify the molecular mechanisms involved.Results:Based on data from our clinical samples and from public databases,IKIP was overexpressed in GBM tumors,and its expression level correlated inversely with survival.IKIP overexpression in GBM cells inhibited migration and invasion in transwell and wound healing assays,whereas IKIP knockdown exerted the opposite effects.IKIP overexpression in GBM cells that were injected into mouse brain promoted tumor growth but inhibited tumor invasion of surrounding tissue.The effects of IKIP were associated with downregulation of THBS1 mRNA and concomitant inhibition of THBS1/FAK signaling.Conclusions:IKIP inhibits THBS1/FAK signaling to suppress migration and invasion of GBM cells.展开更多
Objective:This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2(ROR2)in triple-negative breast cancer(TNBC).Methods:ROR2 expression in primary TNBC and metastatic TNBC tissues was...Objective:This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2(ROR2)in triple-negative breast cancer(TNBC).Methods:ROR2 expression in primary TNBC and metastatic TNBC tissues was analyzed by immunohistochemical staining and PCR.ROR2 expression in TNBC cell lines was detected by PCR and Western blot analysis.The migration,invasion and chemosensitivity of TNBC cells with overexpression or knockdown of ROR2 were examined.Results:ROR2 expression was high in metastatic TNBC tissues.ROR2 knockdown suppressed the migration,invasion and chemoresistance of TNBC cells.ROR2 overexpression in MDA-MB-435 cells promoted the migration,invasion,and chemoresistance.Moreover,ROR2 knockdown in HC1599 and MDA-MB-435 adriamycin-resistant cells enhanced chemosensitivity to adriamycin.ROR2 could activate PI3K/AKT/mTOR signaling in TNBC cells.Conclusion:ROR2 is upregulated and promotes metastatic phenotypes of TNBC by activating PI3K/AKT/mTOR signaling.展开更多
Alzheimer's disease(AD)is a degenerative disease of the central nervous system.The pathogenesis of AD is complex and diverse,and its occurrence and development is the result of the interaction of multiple factors....Alzheimer's disease(AD)is a degenerative disease of the central nervous system.The pathogenesis of AD is complex and diverse,and its occurrence and development is the result of the interaction of multiple factors.A number of studies have shown that mTOR signaling pathway is closely related to AD.In recent years,people in exploring relevant methods for the treatment of AD and the process of drugs,more and more studies have found that traditional Chinese medicine compound traditional Chinese medicine monomer,and can be applied to mTOR signaling pathway to improve symptoms in patients with AD.This paper will review the mechanism of action and treatment of TCM in Alzheimer's disease based on mTOR signaling pathway in recent years,so as to provide reference and expand thinking for the prevention and treatment of AD.展开更多
BACKGROUND Altered miR-188-3p expression has been observed in various human cancers.AIM To investigate the miR-188-3p expression,its roles,and underlying molecular events in gastric cancer.METHODS Fifty gastric cancer...BACKGROUND Altered miR-188-3p expression has been observed in various human cancers.AIM To investigate the miR-188-3p expression,its roles,and underlying molecular events in gastric cancer.METHODS Fifty gastric cancer and paired normal tissues were collected to analyze miR-188-3p and CBL expression.Normal and gastric cancer cells were used to manipulate miR-188-3p and CBL expression through different assays.The relationship between miR-188-3p and CBL was predicted bioinformatically and confirmed using a luciferase gene reporter assay.A Kaplan-Meier analysis was used to associate miR-188-3p or CBL expression with patient survival.A nude mouse tumor cell xenograft assay was used to confirm the in vitro data.RESULTS MiR-188-3p was found to be lower in the plasma of gastric cancer patients,tissues,and cell lines compared to their healthy counterparts.It was associated with overall survival of gastric cancer patients(P<0.001),tumor differentiation(P<0.001),lymph node metastasis(P=0.033),tumor node metastasis stage(I/II vs III/IV,P=0.024),and American Joint Committee on Cancer stage(I/II vs III/IV,P=0.03).Transfection with miR-188-3p mimics reduced tumor cell growth and invasion while inducing apoptosis and autophagy.CBL was identified as a direct target of miR-188-3p,with its expression antagonizing the effects of miR-188-3p on gastric cancer(GC)cell proliferation by inducing tumor cell apoptosis and autophagy through the inactivation of the Akt/mTOR signaling pathway.The in vivo data confirmed antitumor activity via CBL downregulation in gastric cancer.CONCLUSION The current data provides ex vivo,in vitro,and in vivo evidence that miR-188-3p acts as a tumor suppressor gene or possesses antitumor activity in GC.展开更多
Objective:This study aimed to elucidate the differences in effects and mechanisms of action of electric-needle therapy at Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)and Shang Ju Xu(ST37)acupoints on chronic expe...Objective:This study aimed to elucidate the differences in effects and mechanisms of action of electric-needle therapy at Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)and Shang Ju Xu(ST37)acupoints on chronic experimental colitis in rats through the PI3K/AKT/mTOR signaling pathway.Methods:Sixty pathogen-free SD rats were randomly assigned to six groups:the normal,model,Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)and Shang Ju Xu(ST37)groups,each with 10 rats.Chronic colitis was induced in rats by combining immunization and local stimulation.After model establishment,electrical needle intervention combined with dispersing wave of 2 Hz/50 Hz with a current intensity of 2 mA once daily for 20 min was applied on acupoints of each group.Subsequently,the inflammation of colonic mucosa and serum levels of inflammatory factors(IL-23,IL-17,IL-10)were observed;ELISA was used to detect mRNA expressions of PI3K,Akt and mTOR in colitic tissues by RT-PCR as well as protein content of p-PI3k/PI3K,p-Akt/Akt,and p-mTOR/mTOR in colitic tissues by Western blotting.Result:Compared with the normal group,the model rats showed a poor general condition,serious damage to the colonic mucosa with a large number of inflammatory cells infiltration.The serum IL-23 and IL-17 expressions were significantly increased(P<0.01),while the serum IL-10 expression was significantly decreased(P<0.01);the mRNA and protein expressions of PI3K,Akt,mTOR and p-PI3K,p-Akt and p-mTOR were significantly increased(P<0.05,P<0.01).Compared with the model group,the pathological slices of rats in each acupoints intervention group showed obvious improvement of colitis inflammatory reaction and tissue damage;the serological levels of IL-23 and IL-17 were significantly reduced(P<0.01),while the serology level of IL-10 was significantly increased(P<0.01);the expressions of PI3K,Akt,mTOR mRNA and p-PI3K,p-Akt,p-mTOR proteins were significantly decreased(P<0.05,P<0.01).Compared with Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)groups,the recovery degree of mucosa layers in Shang Ju Xu(ST37)group was closer to that of normal group,and the curative effect was relatively the best;in terms of serological levels of IL-23 and IL-17,the Shang Ju Xu(ST37)group was significantly lower(P<0.05),while the level of IL-10 was significantly higher(P<0.01);the expressions of PI3K,Akt,mTOR mRNA and p-PI3K,p-Akt,p-mTOR proteins were significantly decreased(P<0.05,P<0.01).Conclusion:Results indicate that electrical acupuncture at Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)and Shang Ju Xu(ST37)show similar effects in relieving the colitis-induced damage in the mucosa of chronic colitis rats,as well as inflammatory response.Among them,Shang Ju Xu(ST25)has a superior overall effect in treating chronic colitis compared to Tian Shu(ST25),Da Chang Shu(BL25)and Zu San Li(ST36).The mechanism may be related to inhibition of PI3K/Akt/mTOR signaling pathway.展开更多
基金supported by the National Natural Science Foundation of China,No.81971097(to JY)。
文摘Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral hemorrhage.The E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and maturation.However,the effect of Spi1 on intracerebral hemorrhage remains unclear.In this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage transcriptome.We showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained remyelination.Notably,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and coagulation.In conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral hemorrhage.This new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.
基金supported by the National Natural Science Foundation of China(82002638)the National Natural Science Foundation of Sichuan Province(2023NSFSC0734).
文摘Background:Inhibitor of NF-κB kinase-interacting protein(IKIP)is known to promote proliferation of glioblastoma(GBM)cells,but how it affects migration and invasion by those cells is unclear.Methods:We compared levels of IKIP between glioma tissues and normal brain tissue in clinical samples and public databases.We examined the effects of IKIP overexpression and knockdown on the migration and invasion of GBM using transwell and wound healing assays,and we compared the transcriptomes under these different conditions to identify the molecular mechanisms involved.Results:Based on data from our clinical samples and from public databases,IKIP was overexpressed in GBM tumors,and its expression level correlated inversely with survival.IKIP overexpression in GBM cells inhibited migration and invasion in transwell and wound healing assays,whereas IKIP knockdown exerted the opposite effects.IKIP overexpression in GBM cells that were injected into mouse brain promoted tumor growth but inhibited tumor invasion of surrounding tissue.The effects of IKIP were associated with downregulation of THBS1 mRNA and concomitant inhibition of THBS1/FAK signaling.Conclusions:IKIP inhibits THBS1/FAK signaling to suppress migration and invasion of GBM cells.
基金supported by Medical and Health Research Project of Nanjing Health Science and Technology Development Special Fund(ZKX21040).
文摘Objective:This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2(ROR2)in triple-negative breast cancer(TNBC).Methods:ROR2 expression in primary TNBC and metastatic TNBC tissues was analyzed by immunohistochemical staining and PCR.ROR2 expression in TNBC cell lines was detected by PCR and Western blot analysis.The migration,invasion and chemosensitivity of TNBC cells with overexpression or knockdown of ROR2 were examined.Results:ROR2 expression was high in metastatic TNBC tissues.ROR2 knockdown suppressed the migration,invasion and chemoresistance of TNBC cells.ROR2 overexpression in MDA-MB-435 cells promoted the migration,invasion,and chemoresistance.Moreover,ROR2 knockdown in HC1599 and MDA-MB-435 adriamycin-resistant cells enhanced chemosensitivity to adriamycin.ROR2 could activate PI3K/AKT/mTOR signaling in TNBC cells.Conclusion:ROR2 is upregulated and promotes metastatic phenotypes of TNBC by activating PI3K/AKT/mTOR signaling.
基金Youth Foundation of National Natural Science Foundation of China(No.81303028)Shandong Province Science and Technology Development Plan(No.2014GSF119038)+2 种基金Jinan Science and Technology Innovation Development Plan(No.202019027、201805083)TCM Science and Technology Development Plan of Shandong Province(No.2017‑040,2019‑0107,2019‑0094,2017‑037)First Batch of Youth Scientific Research Innovation Team Project of Shandong University of Traditional Chinese Medicine Affiliated Hospital。
文摘Alzheimer's disease(AD)is a degenerative disease of the central nervous system.The pathogenesis of AD is complex and diverse,and its occurrence and development is the result of the interaction of multiple factors.A number of studies have shown that mTOR signaling pathway is closely related to AD.In recent years,people in exploring relevant methods for the treatment of AD and the process of drugs,more and more studies have found that traditional Chinese medicine compound traditional Chinese medicine monomer,and can be applied to mTOR signaling pathway to improve symptoms in patients with AD.This paper will review the mechanism of action and treatment of TCM in Alzheimer's disease based on mTOR signaling pathway in recent years,so as to provide reference and expand thinking for the prevention and treatment of AD.
基金Supported by the National Natural Science Funds of China,No.81974448Guangdong Medical Research Foundation,No.B2019126Shenzhen Science and Technology Innovation Commission,No.JCYJ20210324135005013.
文摘BACKGROUND Altered miR-188-3p expression has been observed in various human cancers.AIM To investigate the miR-188-3p expression,its roles,and underlying molecular events in gastric cancer.METHODS Fifty gastric cancer and paired normal tissues were collected to analyze miR-188-3p and CBL expression.Normal and gastric cancer cells were used to manipulate miR-188-3p and CBL expression through different assays.The relationship between miR-188-3p and CBL was predicted bioinformatically and confirmed using a luciferase gene reporter assay.A Kaplan-Meier analysis was used to associate miR-188-3p or CBL expression with patient survival.A nude mouse tumor cell xenograft assay was used to confirm the in vitro data.RESULTS MiR-188-3p was found to be lower in the plasma of gastric cancer patients,tissues,and cell lines compared to their healthy counterparts.It was associated with overall survival of gastric cancer patients(P<0.001),tumor differentiation(P<0.001),lymph node metastasis(P=0.033),tumor node metastasis stage(I/II vs III/IV,P=0.024),and American Joint Committee on Cancer stage(I/II vs III/IV,P=0.03).Transfection with miR-188-3p mimics reduced tumor cell growth and invasion while inducing apoptosis and autophagy.CBL was identified as a direct target of miR-188-3p,with its expression antagonizing the effects of miR-188-3p on gastric cancer(GC)cell proliferation by inducing tumor cell apoptosis and autophagy through the inactivation of the Akt/mTOR signaling pathway.The in vivo data confirmed antitumor activity via CBL downregulation in gastric cancer.CONCLUSION The current data provides ex vivo,in vitro,and in vivo evidence that miR-188-3p acts as a tumor suppressor gene or possesses antitumor activity in GC.
基金Shanxi Province Applied Basic Research Project(No.201801D121358)。
文摘Objective:This study aimed to elucidate the differences in effects and mechanisms of action of electric-needle therapy at Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)and Shang Ju Xu(ST37)acupoints on chronic experimental colitis in rats through the PI3K/AKT/mTOR signaling pathway.Methods:Sixty pathogen-free SD rats were randomly assigned to six groups:the normal,model,Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)and Shang Ju Xu(ST37)groups,each with 10 rats.Chronic colitis was induced in rats by combining immunization and local stimulation.After model establishment,electrical needle intervention combined with dispersing wave of 2 Hz/50 Hz with a current intensity of 2 mA once daily for 20 min was applied on acupoints of each group.Subsequently,the inflammation of colonic mucosa and serum levels of inflammatory factors(IL-23,IL-17,IL-10)were observed;ELISA was used to detect mRNA expressions of PI3K,Akt and mTOR in colitic tissues by RT-PCR as well as protein content of p-PI3k/PI3K,p-Akt/Akt,and p-mTOR/mTOR in colitic tissues by Western blotting.Result:Compared with the normal group,the model rats showed a poor general condition,serious damage to the colonic mucosa with a large number of inflammatory cells infiltration.The serum IL-23 and IL-17 expressions were significantly increased(P<0.01),while the serum IL-10 expression was significantly decreased(P<0.01);the mRNA and protein expressions of PI3K,Akt,mTOR and p-PI3K,p-Akt and p-mTOR were significantly increased(P<0.05,P<0.01).Compared with the model group,the pathological slices of rats in each acupoints intervention group showed obvious improvement of colitis inflammatory reaction and tissue damage;the serological levels of IL-23 and IL-17 were significantly reduced(P<0.01),while the serology level of IL-10 was significantly increased(P<0.01);the expressions of PI3K,Akt,mTOR mRNA and p-PI3K,p-Akt,p-mTOR proteins were significantly decreased(P<0.05,P<0.01).Compared with Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)groups,the recovery degree of mucosa layers in Shang Ju Xu(ST37)group was closer to that of normal group,and the curative effect was relatively the best;in terms of serological levels of IL-23 and IL-17,the Shang Ju Xu(ST37)group was significantly lower(P<0.05),while the level of IL-10 was significantly higher(P<0.01);the expressions of PI3K,Akt,mTOR mRNA and p-PI3K,p-Akt,p-mTOR proteins were significantly decreased(P<0.05,P<0.01).Conclusion:Results indicate that electrical acupuncture at Tian Shu(ST25),Da Chang Shu(BL25),Zu San Li(ST36)and Shang Ju Xu(ST37)show similar effects in relieving the colitis-induced damage in the mucosa of chronic colitis rats,as well as inflammatory response.Among them,Shang Ju Xu(ST25)has a superior overall effect in treating chronic colitis compared to Tian Shu(ST25),Da Chang Shu(BL25)and Zu San Li(ST36).The mechanism may be related to inhibition of PI3K/Akt/mTOR signaling pathway.
