Obesity is a chronic,complex disease,which is associated with several comorbidities,including diabetes mellitus,hypertension,and cardiovascular diseases.It is estimated that the prevalence of obesity among both adults...Obesity is a chronic,complex disease,which is associated with several comorbidities,including diabetes mellitus,hypertension,and cardiovascular diseases.It is estimated that the prevalence of obesity among both adults and children nearly tripled between 1975 and 2016,highlighting a huge unmet treatment need.However,the currently available antiobesity drugs have serious side effects,which limit their long-term use.The finding that the newly-identified brain GDF15-GFRAL-RET receptor signaling complex is involved in stress/disease-induced anorexia will certainly impact our knowledge of body weight homeostasis under healthy and disease conditions.Based on this breakthrough,a new class of GFRAL/RETbased drugs is highly anticipated for the treatment of obesity,as well as cancer-induced cachexia.展开更多
为检测正常胃粘膜及胃癌组织和正常结肠及结肠癌组织中GFRa1 m RNA表达量,以及两种剪接体GFRa1a和GFRa1b的m RNA含量。初步明确胃及结肠组织中GFRa1剪接体存在形式以及与胃癌、结肠癌发生的相关性。采用收集23例正常胃粘膜/胃炎组织、2...为检测正常胃粘膜及胃癌组织和正常结肠及结肠癌组织中GFRa1 m RNA表达量,以及两种剪接体GFRa1a和GFRa1b的m RNA含量。初步明确胃及结肠组织中GFRa1剪接体存在形式以及与胃癌、结肠癌发生的相关性。采用收集23例正常胃粘膜/胃炎组织、20对胃癌及其切缘组织和6例非癌患者正常结肠活检组织、20对结肠癌及其切缘组织的方法。选择并提取结肠癌细胞系RKO,正常人胃粘膜上皮细胞系GES-1和人胃癌细胞SGC-7901这3种细胞系的RNA。以Alu m RNA为内参照,用定量RT-PCR的方法对胃组织、结肠组织以及所选的细胞系中GFRa1总m RNA含量进行分析。运用DHPLC技术区分GFRa1不同的剪接体,定量测定两种转录本剪接体的比值。结果显示,胃及结肠组织中,与正常及癌组织相比,切缘组织GFRa1总m RNA、剪接体a及剪接体b的m RNA相对拷贝数均显著增加(P<0.05)。所有组织中GFRa1剪接体b的m RNA相对拷贝数均高于剪接体a。细胞系RKO、GES-1和SGC-7901均检测到GFRa1剪接体b的表达,而未检测到剪接体a。由此可知,胃和结肠组织以及相应的细胞系中GFRa1主要以剪接体b的形式存在;GFRa1剪接体b的高表达可能在胃及结肠组织癌变过程发挥作用。展开更多
基金Work in Dr.Xiong-Zhong Ruan’s laboratory is supported by Moorhead Trust Research Grant and National Natural Science Foundation of China(Key Program No 81390354).
文摘Obesity is a chronic,complex disease,which is associated with several comorbidities,including diabetes mellitus,hypertension,and cardiovascular diseases.It is estimated that the prevalence of obesity among both adults and children nearly tripled between 1975 and 2016,highlighting a huge unmet treatment need.However,the currently available antiobesity drugs have serious side effects,which limit their long-term use.The finding that the newly-identified brain GDF15-GFRAL-RET receptor signaling complex is involved in stress/disease-induced anorexia will certainly impact our knowledge of body weight homeostasis under healthy and disease conditions.Based on this breakthrough,a new class of GFRAL/RETbased drugs is highly anticipated for the treatment of obesity,as well as cancer-induced cachexia.
文摘为检测正常胃粘膜及胃癌组织和正常结肠及结肠癌组织中GFRa1 m RNA表达量,以及两种剪接体GFRa1a和GFRa1b的m RNA含量。初步明确胃及结肠组织中GFRa1剪接体存在形式以及与胃癌、结肠癌发生的相关性。采用收集23例正常胃粘膜/胃炎组织、20对胃癌及其切缘组织和6例非癌患者正常结肠活检组织、20对结肠癌及其切缘组织的方法。选择并提取结肠癌细胞系RKO,正常人胃粘膜上皮细胞系GES-1和人胃癌细胞SGC-7901这3种细胞系的RNA。以Alu m RNA为内参照,用定量RT-PCR的方法对胃组织、结肠组织以及所选的细胞系中GFRa1总m RNA含量进行分析。运用DHPLC技术区分GFRa1不同的剪接体,定量测定两种转录本剪接体的比值。结果显示,胃及结肠组织中,与正常及癌组织相比,切缘组织GFRa1总m RNA、剪接体a及剪接体b的m RNA相对拷贝数均显著增加(P<0.05)。所有组织中GFRa1剪接体b的m RNA相对拷贝数均高于剪接体a。细胞系RKO、GES-1和SGC-7901均检测到GFRa1剪接体b的表达,而未检测到剪接体a。由此可知,胃和结肠组织以及相应的细胞系中GFRa1主要以剪接体b的形式存在;GFRa1剪接体b的高表达可能在胃及结肠组织癌变过程发挥作用。
