MicroRNA(miR)-200b-3p has been associated with many tumors,but its involvement in pituitary adenoma is unclear.This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to...MicroRNA(miR)-200b-3p has been associated with many tumors,but its involvement in pituitary adenoma is unclear.This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to provide a theoretical basis for treatment.Bioinformatics was used to analyze pituitary adenoma-related genes and screen new targets related to RECK and miRNA.As well,the relationship between miR-200b-3p and RECK protein was verified using a double-luciferase reporter gene assay.The expression of miR-200b-3p in clinical samples was analyzed by in situ hybridization.Transfection of the miR-200b-3p inhibitor and small interfering-RECK(si-RECK)was verified by qPCR.GH3 cell viability and proliferation were detected using CCK8 and EdU assays.Apoptosis was detected by flow cytometry and western blotting.Wound healing and Transwell assays were used to detect cell migration and invasion.The effects of miR-200b-3p and RECK on GH3 cells were verified using salvage experiments.miR-200b-3p was highly expressed in pituitary tumor tissue.Inhibitors of miR-200b-3p inhibited cell proliferation promoted cell apoptosis,inhibited invasion and migration,and inhibited the expression of matrix metalloproteinases.Interestingly,miR-200b-3p negatively regulated RECK.The expression of RECK in pituitary adenoma tissues was lower than that in neighboring tissues.Si-RECK rescued the function of miR-200b-3p inhibitors in the above cellular behaviors,and miR-200b-3p accelerated the development of pituitary adenoma by negatively regulating RECK expression.In summary,this study investigated the molecular mechanism by which miR-200b-3p regulates the progression of pituitary adenoma through the negative regulation of RECK.The findings provide a new target for the treatment of pituitary adenoma.展开更多
Cigarette smoking is the top environmental risk factor for lung cancer. Nicotine, the addictive component of cigarettes, induces lung cancer cell proliferation, invasion and migration via the activation of nicotinic a...Cigarette smoking is the top environmental risk factor for lung cancer. Nicotine, the addictive component of cigarettes, induces lung cancer cell proliferation, invasion and migration via the activation of nicotinic acetylcholine receptors （nAChRs）. Genome-wide association studies （GWAS） show that CI4RNA5 gene encoding α5-nAChR is especially relevant to lung cancer. However, the mechanism of this subunit in lung cancer is not clear. In the present study, we demonstrate that the expression of α5-nAChR is correlated with phosphorylated STAT3 （pSTAT3） expression, smoking history and lower survival of non-small cell lung cancer （NSCLC） samples. Nicotine increased the levels of α5-nAChR mRNA and protein in NSCLC cell lines and activated the ]AK2/STAT3 signaling cascade. Nicotine-induced activation of JAK2/STAT3 signaling was inhibited by the silencing of α5-nAChR. Characterization of the CHRNA5 promoter revealed four STAT3-response elements. ChiP assays confirmed that the CHRNA5 promoter contains STAT3 binding sites. By silencing STAT3 expression, nicotine-induced upregulation of α5-nAChR was suppressed. Downregulation of α5-nAChR and/or STAT3 expression inhibited nicotine-induced lung cancer cell proliferation. These results suggest that there is a feedback loop between α5-nAChR and STAT3 that contributes to the nicotine-induced tumor cell proliferation, which indicates that α5-nAChR is an important therapeutic target involved in tobacco-associated lung carcinogenesis.展开更多
Gemcitabine is the first-line treatment for pancreatic ductual adenocarcinoma(PDAC)as well as acts against a wide range of other solid tumors.Patients usually have a good initial response to gemcitabine-based chemothe...Gemcitabine is the first-line treatment for pancreatic ductual adenocarcinoma(PDAC)as well as acts against a wide range of other solid tumors.Patients usually have a good initial response to gemcitabine-based chemotherapy but would eventually develop resistance.To improve survival and prognosis of cancer patients,better understanding of the mechanisms responsible for gemcitabine resistance and discovery of new therapeutic strategies are in great need.Amounting evidence indicate that the developmental pathways,such as Hedgehog(Hh),Wnt and Notch,become reactivated in gemcitabine-resistant cancer cells.Thus,the strategies for targeting these pathways may sensitize cancer cells to gemcitabine treatment.In this review,we will summarize recent development in this area of research and discuss strategies to overcome gemcitabine resistance.Given the cross-talk between these three developmental signaling pathways,designing clinical trials using a cocktail of inhibitory agents targeting all these pathways may be more effective.Ultimately,our hope is that targeting these developmental pathways may be an effective way to improve the gemcitabine treatment outcome in cancer patients.展开更多
In this paper, we investigate the spatiotemporal dynamics of a reactio^diffusion epi- demic model with zero-flux boundary conditions. The value of our study lies in two aspects： mathematically, by using maximum princ...In this paper, we investigate the spatiotemporal dynamics of a reactio^diffusion epi- demic model with zero-flux boundary conditions. The value of our study lies in two aspects： mathematically, by using maximum principle and the linearized stability theory, a priori estimates of the steady state system and the local asymptotic stability of positive constant solution are given. By using the implicit function theorem, the exis- tence and nonexistence of nonconstant positive steady states are shown. Applying the bifurcation theory, the global bifurcation structure of nonconstant positive steady states is established. Epidemiologically, through numerical simulations, under the conditions of the existence of nonconstant positive steady states, we find that the smaller the space, the easier the pattern formation; the bigger the diffusion, the easier the pattern formation. These results are beneficial to disease control, that is, we must do our best to control the diffusion of the infectious to avoid disease outbreak.展开更多
Background:Nocardial brain abscesses are associated with significant morbidity and mortality rates.The optimal management remains unclear.Case presentation:We report a case of 49-year-old woman presented with dizzines...Background:Nocardial brain abscesses are associated with significant morbidity and mortality rates.The optimal management remains unclear.Case presentation:We report a case of 49-year-old woman presented with dizziness,progressive headache for 3 days,accompanied with left arm twitched for twice.The patient underwent a right parietal craniotomy for resection of the lesion.Gross total resection of the lesion was achieved.There were no new neurological deficits post-operatively,and no lesions was demonstrated on Gd-enhanced MRI images at six months follow-up.Conclusions:After review of the literature and experience learned from our case,we suggest that craniotomy and surgical resection of the lesions,instead of aspiration,is a safe,efficacious treatment for the patient with nocardial brain abscesses.Long-term chemotherapy and follow-up is mandatory in all cases.展开更多
基金supported by Correlation between RECK and GH-type pituitary adenomas(No.21JR11RE027).
文摘MicroRNA(miR)-200b-3p has been associated with many tumors,but its involvement in pituitary adenoma is unclear.This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to provide a theoretical basis for treatment.Bioinformatics was used to analyze pituitary adenoma-related genes and screen new targets related to RECK and miRNA.As well,the relationship between miR-200b-3p and RECK protein was verified using a double-luciferase reporter gene assay.The expression of miR-200b-3p in clinical samples was analyzed by in situ hybridization.Transfection of the miR-200b-3p inhibitor and small interfering-RECK(si-RECK)was verified by qPCR.GH3 cell viability and proliferation were detected using CCK8 and EdU assays.Apoptosis was detected by flow cytometry and western blotting.Wound healing and Transwell assays were used to detect cell migration and invasion.The effects of miR-200b-3p and RECK on GH3 cells were verified using salvage experiments.miR-200b-3p was highly expressed in pituitary tumor tissue.Inhibitors of miR-200b-3p inhibited cell proliferation promoted cell apoptosis,inhibited invasion and migration,and inhibited the expression of matrix metalloproteinases.Interestingly,miR-200b-3p negatively regulated RECK.The expression of RECK in pituitary adenoma tissues was lower than that in neighboring tissues.Si-RECK rescued the function of miR-200b-3p inhibitors in the above cellular behaviors,and miR-200b-3p accelerated the development of pituitary adenoma by negatively regulating RECK expression.In summary,this study investigated the molecular mechanism by which miR-200b-3p regulates the progression of pituitary adenoma through the negative regulation of RECK.The findings provide a new target for the treatment of pituitary adenoma.
基金funded by grants from the National Natural Science Foundation of China(Nos.81272588,81602593,31671468 and 31672286)the Shandong Provincial Natural Science Foundation of China(No.ZR2012HM061)
文摘Cigarette smoking is the top environmental risk factor for lung cancer. Nicotine, the addictive component of cigarettes, induces lung cancer cell proliferation, invasion and migration via the activation of nicotinic acetylcholine receptors （nAChRs）. Genome-wide association studies （GWAS） show that CI4RNA5 gene encoding α5-nAChR is especially relevant to lung cancer. However, the mechanism of this subunit in lung cancer is not clear. In the present study, we demonstrate that the expression of α5-nAChR is correlated with phosphorylated STAT3 （pSTAT3） expression, smoking history and lower survival of non-small cell lung cancer （NSCLC） samples. Nicotine increased the levels of α5-nAChR mRNA and protein in NSCLC cell lines and activated the ]AK2/STAT3 signaling cascade. Nicotine-induced activation of JAK2/STAT3 signaling was inhibited by the silencing of α5-nAChR. Characterization of the CHRNA5 promoter revealed four STAT3-response elements. ChiP assays confirmed that the CHRNA5 promoter contains STAT3 binding sites. By silencing STAT3 expression, nicotine-induced upregulation of α5-nAChR was suppressed. Downregulation of α5-nAChR and/or STAT3 expression inhibited nicotine-induced lung cancer cell proliferation. These results suggest that there is a feedback loop between α5-nAChR and STAT3 that contributes to the nicotine-induced tumor cell proliferation, which indicates that α5-nAChR is an important therapeutic target involved in tobacco-associated lung carcinogenesis.
基金Current research in my laboratory is supported by grants from the National Cancer Institute CA155086Riley Children’s Foundation,Wells Center for Pediatric Research and Shandong Provincial Natural Science Foundation of China ZR2015HM018。
文摘Gemcitabine is the first-line treatment for pancreatic ductual adenocarcinoma(PDAC)as well as acts against a wide range of other solid tumors.Patients usually have a good initial response to gemcitabine-based chemotherapy but would eventually develop resistance.To improve survival and prognosis of cancer patients,better understanding of the mechanisms responsible for gemcitabine resistance and discovery of new therapeutic strategies are in great need.Amounting evidence indicate that the developmental pathways,such as Hedgehog(Hh),Wnt and Notch,become reactivated in gemcitabine-resistant cancer cells.Thus,the strategies for targeting these pathways may sensitize cancer cells to gemcitabine treatment.In this review,we will summarize recent development in this area of research and discuss strategies to overcome gemcitabine resistance.Given the cross-talk between these three developmental signaling pathways,designing clinical trials using a cocktail of inhibitory agents targeting all these pathways may be more effective.Ultimately,our hope is that targeting these developmental pathways may be an effective way to improve the gemcitabine treatment outcome in cancer patients.
文摘In this paper, we investigate the spatiotemporal dynamics of a reactio^diffusion epi- demic model with zero-flux boundary conditions. The value of our study lies in two aspects： mathematically, by using maximum principle and the linearized stability theory, a priori estimates of the steady state system and the local asymptotic stability of positive constant solution are given. By using the implicit function theorem, the exis- tence and nonexistence of nonconstant positive steady states are shown. Applying the bifurcation theory, the global bifurcation structure of nonconstant positive steady states is established. Epidemiologically, through numerical simulations, under the conditions of the existence of nonconstant positive steady states, we find that the smaller the space, the easier the pattern formation; the bigger the diffusion, the easier the pattern formation. These results are beneficial to disease control, that is, we must do our best to control the diffusion of the infectious to avoid disease outbreak.
基金This study was supported by National Natural Science Foundation of China，Gansu Province Science & Technology Program，Lanzhou City Science & Technology Program
文摘Background:Nocardial brain abscesses are associated with significant morbidity and mortality rates.The optimal management remains unclear.Case presentation:We report a case of 49-year-old woman presented with dizziness,progressive headache for 3 days,accompanied with left arm twitched for twice.The patient underwent a right parietal craniotomy for resection of the lesion.Gross total resection of the lesion was achieved.There were no new neurological deficits post-operatively,and no lesions was demonstrated on Gd-enhanced MRI images at six months follow-up.Conclusions:After review of the literature and experience learned from our case,we suggest that craniotomy and surgical resection of the lesions,instead of aspiration,is a safe,efficacious treatment for the patient with nocardial brain abscesses.Long-term chemotherapy and follow-up is mandatory in all cases.
