Craniometaphyseal dysplasia(CMD),a rare craniotubular disorder,occurs in an autosomal dominant(AD)or autosomal recessive(AR)form.CMD is characterized by hyperostosis of craniofacial bones and metaphyseal flaring of lo...Craniometaphyseal dysplasia(CMD),a rare craniotubular disorder,occurs in an autosomal dominant(AD)or autosomal recessive(AR)form.CMD is characterized by hyperostosis of craniofacial bones and metaphyseal flaring of long bones.Many patients with CMD suffer from neurological symptoms.The pathogenesis of CMD is not fully understood.展开更多
BACKGROUND Colonic motility dysfunction is a common symptom of ulcerative colitis(UC),significantly affecting patients’quality of life.Evidence suggests that glial cell line-derived neurotrophic factor(GDNF)plays a r...BACKGROUND Colonic motility dysfunction is a common symptom of ulcerative colitis(UC),significantly affecting patients’quality of life.Evidence suggests that glial cell line-derived neurotrophic factor(GDNF)plays a role in restoring colonic function.AIM To investigate whether GDNF enhances aberrant colonic motility in mice with experimental colitis via connexin 43(Cx43).METHODS An experimental colitis model was induced in male C57BL/6 mice using dextran sodium sulfate(DSS).The measurement of colonic transit time was conducted,and colon tissues were evaluated through transmission electron microscopy and hematoxylin and eosin staining.The mice were treated with exogenous GDNF and Gap 19,a selective Cx43 inhibitor.The Cx43 and GDNF levels were detected via immunofluorescence,immunohistochemistry,and real-time polymerase chain reaction.The levels of inflammatory markers,including interleukin-1β,tumor necrosis factor-α,interleukin-6,and C-reactive protein,were quantified using enzyme-linked immunosorbent assay.RESULTS Experimental colitis was successfully induced using DSS,and the findings exhibited that the colonic transit time was significantly delayed in colitis mice relative to the UC group(P<0.01).GDNF treatment improved colonic transit time and alleviated intestinal inflammation in DSS-induced colitis mice(P<0.05).In the UC+Gap19+GDNF group,colitis symptoms,colonic transit time,and inflammatory marker levels remained comparable to those in the UC group,indicating that the therapeutic effects of GDNF in UC mice were blocked by Gap 19.CONCLUSION GDNF improves colonic motility in mice with experimental colitis through a partially Cx43-mediated mechanism.GDNF holds promise as a therapeutic option for improving colonic motility in patients with colitis.展开更多
目的:研究细胞间隙连接蛋白connexin43基因(Cx43)在膀胱移行细胞癌(transitional cell carcinoma of the bladder,BTCC)组织中的表达,及其与凋亡相关基因bcl-2、bax表达的相关性。方法:分别采用逆转录聚合酶链反应(RT-PCR)和免疫组织化...目的:研究细胞间隙连接蛋白connexin43基因(Cx43)在膀胱移行细胞癌(transitional cell carcinoma of the bladder,BTCC)组织中的表达,及其与凋亡相关基因bcl-2、bax表达的相关性。方法:分别采用逆转录聚合酶链反应(RT-PCR)和免疫组织化学法检测60例BTCC中Cx43 mRNA和bcl-2、bax蛋白的表达,并与癌旁组织、正常膀胱组织各15例进行对照。结果:60例BTCC组织中Cx43 mRNA的表达率为43.33%,显著低于癌旁组织和正常膀胱组织的表达率73.33%及100%(χ2=17.58,P<0.01)。Cx43的表达与肿瘤的病理分级和淋巴转移均呈显著负相关(χ2=9.33和9.74,P均<0.01),而与患者性别、年龄、临床分期、肿瘤直径和肿瘤生长方式等均无相关性(P均>0.05)。相关性检验表明Cx43与bcl-2蛋白表达呈显著负相关(r=-0.63,P<0.01),而与bax蛋白表达则呈正相关(r=0.52,P<0.01)。结论:Cx43在BTCC组织中的表达下调提示其与膀胱癌的发生发展和侵袭转移密切相关,可作为判断其预后的重要参考指标。Cx43基因可能与凋亡相关基因bcl-2、bax在膀胱移行细胞癌的发生发展中分别起拮抗和协同作用。展开更多
基金supported by NIH/NIDCR grant R01DE025664 to IPC.
文摘Craniometaphyseal dysplasia(CMD),a rare craniotubular disorder,occurs in an autosomal dominant(AD)or autosomal recessive(AR)form.CMD is characterized by hyperostosis of craniofacial bones and metaphyseal flaring of long bones.Many patients with CMD suffer from neurological symptoms.The pathogenesis of CMD is not fully understood.
文摘BACKGROUND Colonic motility dysfunction is a common symptom of ulcerative colitis(UC),significantly affecting patients’quality of life.Evidence suggests that glial cell line-derived neurotrophic factor(GDNF)plays a role in restoring colonic function.AIM To investigate whether GDNF enhances aberrant colonic motility in mice with experimental colitis via connexin 43(Cx43).METHODS An experimental colitis model was induced in male C57BL/6 mice using dextran sodium sulfate(DSS).The measurement of colonic transit time was conducted,and colon tissues were evaluated through transmission electron microscopy and hematoxylin and eosin staining.The mice were treated with exogenous GDNF and Gap 19,a selective Cx43 inhibitor.The Cx43 and GDNF levels were detected via immunofluorescence,immunohistochemistry,and real-time polymerase chain reaction.The levels of inflammatory markers,including interleukin-1β,tumor necrosis factor-α,interleukin-6,and C-reactive protein,were quantified using enzyme-linked immunosorbent assay.RESULTS Experimental colitis was successfully induced using DSS,and the findings exhibited that the colonic transit time was significantly delayed in colitis mice relative to the UC group(P<0.01).GDNF treatment improved colonic transit time and alleviated intestinal inflammation in DSS-induced colitis mice(P<0.05).In the UC+Gap19+GDNF group,colitis symptoms,colonic transit time,and inflammatory marker levels remained comparable to those in the UC group,indicating that the therapeutic effects of GDNF in UC mice were blocked by Gap 19.CONCLUSION GDNF improves colonic motility in mice with experimental colitis through a partially Cx43-mediated mechanism.GDNF holds promise as a therapeutic option for improving colonic motility in patients with colitis.
文摘目的:研究细胞间隙连接蛋白connexin43基因(Cx43)在膀胱移行细胞癌(transitional cell carcinoma of the bladder,BTCC)组织中的表达,及其与凋亡相关基因bcl-2、bax表达的相关性。方法:分别采用逆转录聚合酶链反应(RT-PCR)和免疫组织化学法检测60例BTCC中Cx43 mRNA和bcl-2、bax蛋白的表达,并与癌旁组织、正常膀胱组织各15例进行对照。结果:60例BTCC组织中Cx43 mRNA的表达率为43.33%,显著低于癌旁组织和正常膀胱组织的表达率73.33%及100%(χ2=17.58,P<0.01)。Cx43的表达与肿瘤的病理分级和淋巴转移均呈显著负相关(χ2=9.33和9.74,P均<0.01),而与患者性别、年龄、临床分期、肿瘤直径和肿瘤生长方式等均无相关性(P均>0.05)。相关性检验表明Cx43与bcl-2蛋白表达呈显著负相关(r=-0.63,P<0.01),而与bax蛋白表达则呈正相关(r=0.52,P<0.01)。结论:Cx43在BTCC组织中的表达下调提示其与膀胱癌的发生发展和侵袭转移密切相关,可作为判断其预后的重要参考指标。Cx43基因可能与凋亡相关基因bcl-2、bax在膀胱移行细胞癌的发生发展中分别起拮抗和协同作用。
