BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression result...BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression results in a loss of this capacity to facilitate cyclin E degradation.The ubiquitination and degradation of cyclin E1 may be associated with phosphorylation at specific sites on the protein,with Cx43 potentially enhancing this process by facilitating the phosphorylation of these critical residues.AIM To investigate the correlation between expression of Cx43,SKP1/Cullin1/F-box(SCF)FBXW7,p-cyclin E1(ser73,thr77,thr395)and clinicopathological indexes in colon cancer.METHODS Expression levels of Cx43,SCFFBXW7,p-cyclin E1(ser73,thr77,thr395)in 38 clinical colon cancer samples were detected by immunohistochemistry and were analyzed by statistical methods to discuss their correlations.RESULTS Positive rate of Cx43,SCFFBXW7,p-cyclin E1(Ser73),p-cyclin E1(Thr77)and p-cyclin E1(Thr395)in detected samples were 76.32%,76.32%,65.79%,5.26%and 55.26%respectively.Positive expressions of these proteins were not related to the tissue type,degree of tissue differentiation or lymph node metastasis.Cx43 and SCFFBXW7(r=0.749),p-cyclin E1(Ser73)(r=0.667)and p-cyclin E1(Thr395)(r=0.457),SCFFBXW7 and p-cyclin E1(Ser73)(r=0.703)and p-cyclin E1(Thr395)(0.415)were correlated in colon cancer(P<0.05),and expressions of the above proteins were positively correlated in colon cancer.CONCLUSION Cx43 may facilitate the phosphorylation of cyclin E1 at the Ser73 and Thr195 sites through its interaction with SCFFBXW7,thereby influencing the ubiquitination and degradation of cyclin E1.展开更多
目的骨髓间充质干细胞(BMSCs)具有力学敏感性,对周围力学微环境高度敏感。连接蛋白43(connexin 43,Cx43)作为骨组织细胞中组成半通道和间隙连接的主要蛋白,在力学信号传导中发挥重要作用。然而关于Cx43是否参与基质刚度对BMSCs分化的调...目的骨髓间充质干细胞(BMSCs)具有力学敏感性,对周围力学微环境高度敏感。连接蛋白43(connexin 43,Cx43)作为骨组织细胞中组成半通道和间隙连接的主要蛋白,在力学信号传导中发挥重要作用。然而关于Cx43是否参与基质刚度对BMSCs分化的调节仍有待研究。方法本实验制备了模拟骨髓力学微环境不同位置处基质刚度(1、10、34 k Pa)的聚丙烯酰胺水凝胶培养基底;培养间充质干细胞细胞系C3H10T1/2,利用18α-GA抑制C3H10T1/2中Cx43功能;提取BMSCs条件性敲除(c KO)Cx43小鼠(Prx1-Cre;Cx43 flox/flox)和同窝对照flox小鼠(Cx43 flox/flox)原代BMSCs进一步验证。结果抑制Cx43均会导致BMSCs在10、34 k Pa基质刚度上的成脂能力显著下降,而对1 k Pa上BMSCs成脂能力无影响。相比于1 k Pa和34 k Pa,在10 k Pa基质刚度上抑制Cx43导致了BMSCs成骨能力显著下降。在不同基质刚度上抑制BMSCs上Cx43均会导致糖酵解和线粒体融合裂变相关基因表达显著变化,以及成脂和成骨分化过程中ATP的生成。结论BMSCs响应骨髓力学微环境,较软的基质刚度可能对成脂能力有一定程度的恢复作用,而Cx43可能通过代谢途径参与了基质刚度对BMSCs分化的调节。展开更多
Magnesium(Mg)alloys are considered to be a new generation of revolutionary medical metals.Laser-beam powder bed fusion(PBF-LB)is suitable for fabricating metal implants withpersonalized and complicated structures.Howe...Magnesium(Mg)alloys are considered to be a new generation of revolutionary medical metals.Laser-beam powder bed fusion(PBF-LB)is suitable for fabricating metal implants withpersonalized and complicated structures.However,the as-built part usually exhibits undesirable microstructure and unsatisfactory performance.In this work,WE43 parts were firstly fabricated by PBF-LB and then subjected to heat treatment.Although a high densification rate of 99.91%was achieved using suitable processes,the as-built parts exhibited anisotropic and layeredmicrostructure with heterogeneously precipitated Nd-rich intermetallic.After heat treatment,fine and nano-scaled Mg24Y5particles were precipitated.Meanwhile,theα-Mg grainsunderwent recrystallization and turned coarsened slightly,which effectively weakened thetexture intensity and reduced the anisotropy.As a consequence,the yield strength and ultimate tensile strength were significantly improved to(250.2±3.5)MPa and(312±3.7)MPa,respectively,while the elongation was still maintained at a high level of 15.2%.Furthermore,the homogenized microstructure reduced the tendency of localized corrosion and favoredthe development of uniform passivation film.Thus,the degradation rate of WE43 parts was decreased by an order of magnitude.Besides,in-vitro cell experiments proved their favorable biocompatibility.展开更多
基金Supported by Innovative Practice Platform for Undergraduate Students,School of Public Health Xiamen University,No.2021001.
文摘BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression results in a loss of this capacity to facilitate cyclin E degradation.The ubiquitination and degradation of cyclin E1 may be associated with phosphorylation at specific sites on the protein,with Cx43 potentially enhancing this process by facilitating the phosphorylation of these critical residues.AIM To investigate the correlation between expression of Cx43,SKP1/Cullin1/F-box(SCF)FBXW7,p-cyclin E1(ser73,thr77,thr395)and clinicopathological indexes in colon cancer.METHODS Expression levels of Cx43,SCFFBXW7,p-cyclin E1(ser73,thr77,thr395)in 38 clinical colon cancer samples were detected by immunohistochemistry and were analyzed by statistical methods to discuss their correlations.RESULTS Positive rate of Cx43,SCFFBXW7,p-cyclin E1(Ser73),p-cyclin E1(Thr77)and p-cyclin E1(Thr395)in detected samples were 76.32%,76.32%,65.79%,5.26%and 55.26%respectively.Positive expressions of these proteins were not related to the tissue type,degree of tissue differentiation or lymph node metastasis.Cx43 and SCFFBXW7(r=0.749),p-cyclin E1(Ser73)(r=0.667)and p-cyclin E1(Thr395)(r=0.457),SCFFBXW7 and p-cyclin E1(Ser73)(r=0.703)and p-cyclin E1(Thr395)(0.415)were correlated in colon cancer(P<0.05),and expressions of the above proteins were positively correlated in colon cancer.CONCLUSION Cx43 may facilitate the phosphorylation of cyclin E1 at the Ser73 and Thr195 sites through its interaction with SCFFBXW7,thereby influencing the ubiquitination and degradation of cyclin E1.
文摘目的骨髓间充质干细胞(BMSCs)具有力学敏感性,对周围力学微环境高度敏感。连接蛋白43(connexin 43,Cx43)作为骨组织细胞中组成半通道和间隙连接的主要蛋白,在力学信号传导中发挥重要作用。然而关于Cx43是否参与基质刚度对BMSCs分化的调节仍有待研究。方法本实验制备了模拟骨髓力学微环境不同位置处基质刚度(1、10、34 k Pa)的聚丙烯酰胺水凝胶培养基底;培养间充质干细胞细胞系C3H10T1/2,利用18α-GA抑制C3H10T1/2中Cx43功能;提取BMSCs条件性敲除(c KO)Cx43小鼠(Prx1-Cre;Cx43 flox/flox)和同窝对照flox小鼠(Cx43 flox/flox)原代BMSCs进一步验证。结果抑制Cx43均会导致BMSCs在10、34 k Pa基质刚度上的成脂能力显著下降,而对1 k Pa上BMSCs成脂能力无影响。相比于1 k Pa和34 k Pa,在10 k Pa基质刚度上抑制Cx43导致了BMSCs成骨能力显著下降。在不同基质刚度上抑制BMSCs上Cx43均会导致糖酵解和线粒体融合裂变相关基因表达显著变化,以及成脂和成骨分化过程中ATP的生成。结论BMSCs响应骨髓力学微环境,较软的基质刚度可能对成脂能力有一定程度的恢复作用,而Cx43可能通过代谢途径参与了基质刚度对BMSCs分化的调节。
基金supported by the following funds:National Natural Science Foundation of China(51935014,52165043)Jiangxi Provincial Cultivation Program for Academic and Technical Leaders of Major Subjects(20225BCJ23008)+1 种基金Jiangxi Provincial Natural Science Foundation(20224ACB204013,20224ACB214008)Scientific Research Project of Anhui Universities(KJ2021A1106)。
文摘Magnesium(Mg)alloys are considered to be a new generation of revolutionary medical metals.Laser-beam powder bed fusion(PBF-LB)is suitable for fabricating metal implants withpersonalized and complicated structures.However,the as-built part usually exhibits undesirable microstructure and unsatisfactory performance.In this work,WE43 parts were firstly fabricated by PBF-LB and then subjected to heat treatment.Although a high densification rate of 99.91%was achieved using suitable processes,the as-built parts exhibited anisotropic and layeredmicrostructure with heterogeneously precipitated Nd-rich intermetallic.After heat treatment,fine and nano-scaled Mg24Y5particles were precipitated.Meanwhile,theα-Mg grainsunderwent recrystallization and turned coarsened slightly,which effectively weakened thetexture intensity and reduced the anisotropy.As a consequence,the yield strength and ultimate tensile strength were significantly improved to(250.2±3.5)MPa and(312±3.7)MPa,respectively,while the elongation was still maintained at a high level of 15.2%.Furthermore,the homogenized microstructure reduced the tendency of localized corrosion and favoredthe development of uniform passivation film.Thus,the degradation rate of WE43 parts was decreased by an order of magnitude.Besides,in-vitro cell experiments proved their favorable biocompatibility.
