Background:Glioma is the most common tumor of the central nervous system with a poor prognosis.This study aims to explore the role of calcium/calmodulin-dependent protein kinase IIβ(CAMK2B)in regulating the malignant...Background:Glioma is the most common tumor of the central nervous system with a poor prognosis.This study aims to explore the role of calcium/calmodulin-dependent protein kinase IIβ(CAMK2B)in regulating the malignant progression of glioma cells,as well as the molecular mechanisms underlying these malignant behaviors.Methods:The correlation between CAMK2B expression in gliomas and patient prognosis was analyzed using immunohistochemistry,quantitative reverse transcription polymerase chain reaction(qRT-PCR),and western blot.Furthermore,the study explored the role of CAMK2B in glioma cell proliferation,invasion,and migration using cell counting kit-8(CCK-8),5-Ethynyl-2′-deoxyuridine(EdU),wound healing,transwell,and in vivo tumor xenograft assays.Result:Patients with high CAMK2B expression exhibited significantly better prognostic outcomes compared to those with low expression levels.Furthermore,CAMK2B expression was significantly lower in glioma tissues and cells compared to both normal brain tissue and human astrocyte cell lines.Notably,overexpression of CAMK2B in glioma cells led to an approximate 40%reduction in proliferative capacity and a 60–70%decrease in invasive and migratory abilities,compared to control glioma cells.These differences were statistically significant at p<0.05.Conversely,knockdown of CAMK2B using siRNA-CAMK2B significantly enhanced the proliferative,invasive,and migratory capabilities of glioma cells in both in vitro and in vivo settings,enhancing these abilities by 1.5 to 3 times.Notably,these effects were reversed through the application of the Rat Sarcoma viral oncogene homolog(Ras)pathway inhibitor,Salirasib.Western blot analysis revealed that knockdown of CAMK2B led to activation of the Ras/Rapidly Accelerated Fibrosarcoma(Raf)/Mitogen-activated protein kinase kinase(MEK)/Extracellular signal-regulated kinase(ERK)signaling pathway in glioma cell lines,whereas overexpression of CAMK2B resulted in the suppression of this pathway.Conclusion:CAMK2B inhibits glioma proliferation,invasion,andmigration through the Ras/Raf/MEK/ERK signaling pathway.展开更多
目的探讨微小核糖核苷酸-219（microRNA-219，miR-219）及其靶基因钙离子／钙调蛋白依赖性蛋白激酶Ⅱγ（Ca2＋／calmodulin-dependent protein kinaseⅡ gamma，CAMK2G）多态性与精神分裂症的关系。方法采用TaqMan探针基因分型技术在...目的探讨微小核糖核苷酸-219（microRNA-219，miR-219）及其靶基因钙离子／钙调蛋白依赖性蛋白激酶Ⅱγ（Ca2＋／calmodulin-dependent protein kinaseⅡ gamma，CAMK2G）多态性与精神分裂症的关系。方法采用TaqMan探针基因分型技术在中国汉族人群中对1041例精神分裂症患者和953例正常对照者进行miR-219基因rs107822和CAMK2G基因rs2306327的分型。利用二级结构预测软件CentroidFold预测rsl07822对miR．219二级结构影响。结果miR-219基因rs107822多态的等位基因分布在患者组与正常对照组之间差异有统计学意义（X2=7．33，P=0．007）；在非条件Logistic回归分析中，rs107822基因型分布最符合加性遗传模式（P=0．0072），携带C等位基因可降低精神分裂症的发生风险（OR=O．84，95％CI=O．74～0．95）；软件预测发现rs107822T等位基因突变成C等位基因后，miR-219基因的初级转录产物的二级结构发生了改变。CAMK2G基因多态性rs2306327的等位基因和基因型分布在病例组与对照组间的差异均无统计学意义（均P〉0．05）。结论在中国汉族人群中，miR-219基因rs107822多态可能与精神分裂症有关。展开更多
Background:Oral squamous cell carcinoma(OSCC)is a prevalent type of cancer with a high mortality rate in its late stages.One of the major challenges in OSCC treatment is the resistance to epidermal growth factor recep...Background:Oral squamous cell carcinoma(OSCC)is a prevalent type of cancer with a high mortality rate in its late stages.One of the major challenges in OSCC treatment is the resistance to epidermal growth factor receptor(EGFR)inhibitors.Therefore,it is imperative to elucidate the mechanism underlying drug resistance and develop appropriate precision therapy strategies to enhance clinical efficacy.Methods:To evaluate the efficacy of the combination of the Ca^(2+)/calmodulin-dependent protein kinase II(CAMK2)inhibitor KN93 and EGFR inhibitors,we performed in vitro and in vivo experiments using two FAT atypical cadherin 1(FAT1)-deficient(SCC9 and SCC25)and two FAT1 wild-type(SCC47 and HN12)OSCC cell lines.We assessed the effects of EGFR inhibitors(afatinib or cetuximab),KN93,or their combination on the malignant phenotype of OSCC in vivo and in vitro.The alterations in protein expression levels of members of the EGFR signaling pathway and SRY-box transcription factor 2(SOX2)were analyzed.Changes in the yes-associated protein 1(YAP1)protein were characterized.Moreover,we analyzed mitochondrial dysfunction.Besides,the effects of combination therapy on mitochondrial dynamics were also evaluated.Results:OSCC with FAT1 mutations exhibited resistance to EGFR inhibitors treatment.The combination of KN93 and EGFR inhibitors significantly inhibited the proliferation,survival,and migration of FAT1-mutated OSCC cells and suppressed tumor growth in vivo.Mechanistically,combination therapy enhanced the therapeutic sensitivity of FAT1-mutated OSCC cells to EGFR inhibitors by modulating the EGFR pathway and downregulated tumor stemness-related proteins.Furthermore,combination therapy induced reactive oxygen species(ROS)-mediated mitochondrial dysfunction and disrupted mitochondrial dynamics,ultimately resulting in tumor suppression.Conclusion:Combination therapy with EGFR inhibitors and KN93 could be a novel precision therapeutic strategy and a potential clinical solution for EGFR-resistant OSCC patients with FAT1 mutations.展开更多
Objective: To explore the mechanism of Ningshenling Granule in the treatment of depression. Methods: The rat model of depression was established, and Ningshenling Granule was given orally. The morphological changes of...Objective: To explore the mechanism of Ningshenling Granule in the treatment of depression. Methods: The rat model of depression was established, and Ningshenling Granule was given orally. The morphological changes of hippocampus were observed by HE staining, and the changes of dopamine receptor D2 and CAMK2a mRNA were observed by RT-pcr. Result:Ningshenling group could significantly improve the morphological changes of pyramidal cells in hippocampus and the expressions of D2 and CAMK2a in brain tissue. Conclusion:Ningshenling can treat depression, and its mechanism is related to regulating the expression of related factors in the brain.展开更多
Objective:To explore the mechanism of Ningshenling Granule in the treatment of depression.Methods:The rat model of depression was established,and Ningshenling Granule was given orally.The morphological changes of hipp...Objective:To explore the mechanism of Ningshenling Granule in the treatment of depression.Methods:The rat model of depression was established,and Ningshenling Granule was given orally.The morphological changes of hippocampus were observed by HE staining,and the changes of dopamine receptor D2 and CAMK2a mRNA were observed by RT-pcr.Result:Ningshenling group could significantly improve the morphological changes of pyramidal cells in hippocampus and the expressions of D2 and CAMK2a in brain tissue.Conclusions:Ningshenling can treat depression,and its mechanism is related to regulating the expression of related factors in the brain.展开更多
Many of the effects of Ca^2＋ signaling are mediated through the Ca^2＋/calmodulin complex and its acceptors, the Ca^2＋/calmodulin-dependent protein kinases, including PSKHI. Studies of the proteins involved in the c...Many of the effects of Ca^2＋ signaling are mediated through the Ca^2＋/calmodulin complex and its acceptors, the Ca^2＋/calmodulin-dependent protein kinases, including PSKHI. Studies of the proteins involved in the calcium metabolism in oysters will help elucidate the pearl formation mechanism. This paper describes a full-length PSKH1 cDNA isolated from pearl oyster Pinctada fucata. Oyster PSKH1 shares 65% homology with human PSKH1 and 48% similarity with rat CaM kinase I in the amino acid sequence, and contains a calmodulin-binding domain. The results of semi-quantitative reverse transcription-polymerase chain reaction and in situ hybridization revealed that oyster PSKH1 mRNA is highly expressed in the outer epithelial cells of the mantle pallial and in the gill epithelial cells. These studies provide important information describing the complex Ca^2＋ signaling mechanism in oyster calcium metabolism.展开更多
基金supported by the Natural Science Foundation of Hebei Province(H2021206037)the Government-funded Project on Training of Outstanding Clinical Medical Personnel of Hebei Province in the year 2021(303-16-20-06)the Medical Research Project of Hebei Provincial Health Commission(20230031).
文摘Background:Glioma is the most common tumor of the central nervous system with a poor prognosis.This study aims to explore the role of calcium/calmodulin-dependent protein kinase IIβ(CAMK2B)in regulating the malignant progression of glioma cells,as well as the molecular mechanisms underlying these malignant behaviors.Methods:The correlation between CAMK2B expression in gliomas and patient prognosis was analyzed using immunohistochemistry,quantitative reverse transcription polymerase chain reaction(qRT-PCR),and western blot.Furthermore,the study explored the role of CAMK2B in glioma cell proliferation,invasion,and migration using cell counting kit-8(CCK-8),5-Ethynyl-2′-deoxyuridine(EdU),wound healing,transwell,and in vivo tumor xenograft assays.Result:Patients with high CAMK2B expression exhibited significantly better prognostic outcomes compared to those with low expression levels.Furthermore,CAMK2B expression was significantly lower in glioma tissues and cells compared to both normal brain tissue and human astrocyte cell lines.Notably,overexpression of CAMK2B in glioma cells led to an approximate 40%reduction in proliferative capacity and a 60–70%decrease in invasive and migratory abilities,compared to control glioma cells.These differences were statistically significant at p<0.05.Conversely,knockdown of CAMK2B using siRNA-CAMK2B significantly enhanced the proliferative,invasive,and migratory capabilities of glioma cells in both in vitro and in vivo settings,enhancing these abilities by 1.5 to 3 times.Notably,these effects were reversed through the application of the Rat Sarcoma viral oncogene homolog(Ras)pathway inhibitor,Salirasib.Western blot analysis revealed that knockdown of CAMK2B led to activation of the Ras/Rapidly Accelerated Fibrosarcoma(Raf)/Mitogen-activated protein kinase kinase(MEK)/Extracellular signal-regulated kinase(ERK)signaling pathway in glioma cell lines,whereas overexpression of CAMK2B resulted in the suppression of this pathway.Conclusion:CAMK2B inhibits glioma proliferation,invasion,andmigration through the Ras/Raf/MEK/ERK signaling pathway.
文摘目的探讨微小核糖核苷酸-219（microRNA-219，miR-219）及其靶基因钙离子／钙调蛋白依赖性蛋白激酶Ⅱγ（Ca2＋／calmodulin-dependent protein kinaseⅡ gamma，CAMK2G）多态性与精神分裂症的关系。方法采用TaqMan探针基因分型技术在中国汉族人群中对1041例精神分裂症患者和953例正常对照者进行miR-219基因rs107822和CAMK2G基因rs2306327的分型。利用二级结构预测软件CentroidFold预测rsl07822对miR．219二级结构影响。结果miR-219基因rs107822多态的等位基因分布在患者组与正常对照组之间差异有统计学意义（X2=7．33，P=0．007）；在非条件Logistic回归分析中，rs107822基因型分布最符合加性遗传模式（P=0．0072），携带C等位基因可降低精神分裂症的发生风险（OR=O．84，95％CI=O．74～0．95）；软件预测发现rs107822T等位基因突变成C等位基因后，miR-219基因的初级转录产物的二级结构发生了改变。CAMK2G基因多态性rs2306327的等位基因和基因型分布在病例组与对照组间的差异均无统计学意义（均P〉0．05）。结论在中国汉族人群中，miR-219基因rs107822多态可能与精神分裂症有关。
基金This study was supported by grants from National Natural Science Foundation of China(Nos.81902784,82273320,and 81771086)the CAMS Innovation Fund for Medical Sciences(No.2019-I2M-5-004)+1 种基金the Fund of Sichuan Provincial Department of Science and Technology(Nos.2022YFSY0058,2022YFS0039,and 2022YFS0003)the Research and Develop Program,West China Hospital of Stomatology,Sichuan University(Nos.LCYJ2023-DL-2 and RCDWJS2020-20).
文摘Background:Oral squamous cell carcinoma(OSCC)is a prevalent type of cancer with a high mortality rate in its late stages.One of the major challenges in OSCC treatment is the resistance to epidermal growth factor receptor(EGFR)inhibitors.Therefore,it is imperative to elucidate the mechanism underlying drug resistance and develop appropriate precision therapy strategies to enhance clinical efficacy.Methods:To evaluate the efficacy of the combination of the Ca^(2+)/calmodulin-dependent protein kinase II(CAMK2)inhibitor KN93 and EGFR inhibitors,we performed in vitro and in vivo experiments using two FAT atypical cadherin 1(FAT1)-deficient(SCC9 and SCC25)and two FAT1 wild-type(SCC47 and HN12)OSCC cell lines.We assessed the effects of EGFR inhibitors(afatinib or cetuximab),KN93,or their combination on the malignant phenotype of OSCC in vivo and in vitro.The alterations in protein expression levels of members of the EGFR signaling pathway and SRY-box transcription factor 2(SOX2)were analyzed.Changes in the yes-associated protein 1(YAP1)protein were characterized.Moreover,we analyzed mitochondrial dysfunction.Besides,the effects of combination therapy on mitochondrial dynamics were also evaluated.Results:OSCC with FAT1 mutations exhibited resistance to EGFR inhibitors treatment.The combination of KN93 and EGFR inhibitors significantly inhibited the proliferation,survival,and migration of FAT1-mutated OSCC cells and suppressed tumor growth in vivo.Mechanistically,combination therapy enhanced the therapeutic sensitivity of FAT1-mutated OSCC cells to EGFR inhibitors by modulating the EGFR pathway and downregulated tumor stemness-related proteins.Furthermore,combination therapy induced reactive oxygen species(ROS)-mediated mitochondrial dysfunction and disrupted mitochondrial dynamics,ultimately resulting in tumor suppression.Conclusion:Combination therapy with EGFR inhibitors and KN93 could be a novel precision therapeutic strategy and a potential clinical solution for EGFR-resistant OSCC patients with FAT1 mutations.
文摘Objective: To explore the mechanism of Ningshenling Granule in the treatment of depression. Methods: The rat model of depression was established, and Ningshenling Granule was given orally. The morphological changes of hippocampus were observed by HE staining, and the changes of dopamine receptor D2 and CAMK2a mRNA were observed by RT-pcr. Result:Ningshenling group could significantly improve the morphological changes of pyramidal cells in hippocampus and the expressions of D2 and CAMK2a in brain tissue. Conclusion:Ningshenling can treat depression, and its mechanism is related to regulating the expression of related factors in the brain.
基金Natural science foundation of heilongjiang province(No.H2017043)Harbin applied technology and development project excellent academic leader program(No.2017RAXQJ069).
文摘Objective:To explore the mechanism of Ningshenling Granule in the treatment of depression.Methods:The rat model of depression was established,and Ningshenling Granule was given orally.The morphological changes of hippocampus were observed by HE staining,and the changes of dopamine receptor D2 and CAMK2a mRNA were observed by RT-pcr.Result:Ningshenling group could significantly improve the morphological changes of pyramidal cells in hippocampus and the expressions of D2 and CAMK2a in brain tissue.Conclusions:Ningshenling can treat depression,and its mechanism is related to regulating the expression of related factors in the brain.
基金Supported by the National High-Tech Research and Development (863) Program of China (No. 2003AA603430) and the National Natural Science Foundation of China (No. 30371092)
文摘Many of the effects of Ca^2＋ signaling are mediated through the Ca^2＋/calmodulin complex and its acceptors, the Ca^2＋/calmodulin-dependent protein kinases, including PSKHI. Studies of the proteins involved in the calcium metabolism in oysters will help elucidate the pearl formation mechanism. This paper describes a full-length PSKH1 cDNA isolated from pearl oyster Pinctada fucata. Oyster PSKH1 shares 65% homology with human PSKH1 and 48% similarity with rat CaM kinase I in the amino acid sequence, and contains a calmodulin-binding domain. The results of semi-quantitative reverse transcription-polymerase chain reaction and in situ hybridization revealed that oyster PSKH1 mRNA is highly expressed in the outer epithelial cells of the mantle pallial and in the gill epithelial cells. These studies provide important information describing the complex Ca^2＋ signaling mechanism in oyster calcium metabolism.
