AIM: To test whether oral L-81 treatment could im-prove the condition of mice with diabetes and to investigate how L-81 regulates microsomal triglyceride transfer protein (MTP) activity in the liver. METHODS: Genetica...AIM: To test whether oral L-81 treatment could im-prove the condition of mice with diabetes and to investigate how L-81 regulates microsomal triglyceride transfer protein (MTP) activity in the liver. METHODS: Genetically diabetic (db/db) mice were fed on chow supplemented with or without L-81 for 4 wk. The body weight, plasma glucose level, plasma lipid profile, and adipocyte volume of the db/db mice were assessed after treatment. Toxicity of L-81 was also evaluated. To understand the molecular mecha-nism, HepG2 cells were treated with L-81 and the effects on apolipoprotein B (apoB) secretion and mRNA level of the MTP gene were assessed.RESULTS: Treatment of db/db mice with L-81 sig-nificantly reduced and nearly normalized their body weight, hyperphagia and polydipsia. L-81 also markedly decreased the fasting plasma glucose level, improved glucose tolerance, and attenuated the elevated levels of plasma cholesterol and triglyceride. At the effective dosage, little toxicity was observed. Treatment of HepG2 cells with L-81 not only inhibited apoB secretion, but also signif icantly decreased the mRNA level of the MTP gene. Similar to the action of insulin, L-81 exerted its effect on the MTP promoter. CONCLUSION: L-81 represents a promising candidate in the development of a selective insulin-mimetic mol-ecule and an anti-diabetic agent.展开更多
Diabetes mellitus is the most common metabolic disease and its prevalence is increasing in many countries year by year.More than 90% of diabetes patients are type 2 diabetes,which is caused by insulin resistance and b...Diabetes mellitus is the most common metabolic disease and its prevalence is increasing in many countries year by year.More than 90% of diabetes patients are type 2 diabetes,which is caused by insulin resistance and beta-cell dysfunction.In this paper,the oligomannuronate-chromium(III)complex(OM2)was prepared and its effect and mechanism on attenuating insulin resistance in diabetic C57BL/KsJ-db/db mice were studied.The results indicated that oral intake of OM2(50 mg kg-1d-1)for 42 d decreased blood glucose and lipid concentration,which was associated with the reduced serum insulin concentration and insulin resistance.According to western blot assay,OM2 could activate AMPK pathway to regulate glycogen synthesis,gluconeogenesis and lipid metabolism in the liver,and attenuate the hyperglycemic symptom in db/db mice.The effects of OM2 on attenuating insulin resistance were com-parable to that of the established antidiabetic drug metformin,and OM2 showed less adverse effect than metformin in vivo.Based on the effectiveness and low toxicity,OM2 may potentially be used for prevention and treatment of type 2 diabetes mellitus.展开更多
In the present study,we utilized db/db mice to investigate the mechanisms of apoptosis in brain and retinal neurons.A total of 30 male db/db mice aged 8–9 weeks were randomly assigned to the model group,Dihuangyinzi ...In the present study,we utilized db/db mice to investigate the mechanisms of apoptosis in brain and retinal neurons.A total of 30 male db/db mice aged 8–9 weeks were randomly assigned to the model group,Dihuangyinzi decoction(DHYZ)group(30.03 g/kg),and metformin(MET)group(0.58 g/kg),with 10 mice in each group.The control group comprised 10 db/m mice of the same background and age.Paired-associate learning(PAL)tests were conducted to evaluate the learning and memory functions of the mice.Histological assessments,including Hematoxylin-Eosin(H&E)and Nissl staining,were employed to observe changes in nerve cells in the hippocampus and retina.Immunohistochemistry and real-time fluorescence quantitative PCR were employed to detect the positive expression of anti-apoptotic factor Bcl-2 and pro-apoptotic factor Bax at the protein and mRNA levels in the hippocampus and retina.Western blotting analysis was adopted to assess protein expression levels of JNK,p-JNK,p38 MAPK,and p-p38 MAPK.Results revealed a significant decline in the correct rate of PAL test results in the model group(P<0.001),accompanied by increased reaction and delay times(P<0.001)and higher blood glucose levels(P<0.001).H&E and Nissl staining indicated a reduction in the number of nerve cells in the CA1 area of the hippocampus in the model group,with scattered arrangement and decreased Nissl corpuscles.Positive expression and mRNA expression of Bax in the hippocampus and retina increased significantly(P<0.001),while positive expression and mRNA expression of Bcl-2 decreased(P<0.001).Protein expression levels of p-JNK/JNK and p-p38 MAPK/p38 MAPK showed a significant increase(P<0.001).The DHYZ and MET groups exhibited enhanced accuracy in PAL experiments(P<0.05),decreased reaction time and delay time(P<0.05),and reduced blood glucose levels(P<0.05).The number of neurons in the CA1 region of the hippocampus increased,morphological structure improved,and the arrangement of the hippocampal structure became more orderly.Additionally,no obvious vacuolization was observed in the neuronal cell layer.The number of Nissl bodies increased,and the layers of the retina were closely arranged,with an increase in the number of Nissl bodies.Positive expressions of Bax in the hippocampus and retina,both at the protein and mRNA levels,decreased significantly(P<0.001),while positive expressions of Bcl-2 and its mRNA increased(P<0.01,P<0.001).Furthermore,the protein expressions of p-JNK/JNK and p-p38 MAPK/p38 MAPK decreased significantly(P<0.01).This study suggested that DHYZ decoction could inhibit the JNK/p38 MAPK signaling pathway,thereby increasing the anti-apoptotic factor Bcl-2 and reducing the expression of the pro-apoptotic factor Bax,consequently inhibiting apoptosis in the hippocampal CA1 region and retinal neurons of db/db mice.展开更多
针对强地物杂波背景下弹载雷达目标检测与识别的技术难题,提出将高分辨距离像(high resolution range profile,HRRP)技术和多普勒波束锐化技术联合对地面进行二维高分辨成像,提高雷达在杂波下目标检测与识别的性能。该方法以线性调频步...针对强地物杂波背景下弹载雷达目标检测与识别的技术难题,提出将高分辨距离像(high resolution range profile,HRRP)技术和多普勒波束锐化技术联合对地面进行二维高分辨成像,提高雷达在杂波下目标检测与识别的性能。该方法以线性调频步进频(linear frequency modulation stepped frequency,LFM-SF)信号为基本波形,首先对平台速度产生的多普勒效应等问题进行了详细讨论并校正;然后通过距离像抽取获得各帧对应的HRRP序列,并采用方位快速傅里叶变换(fast Fourier transform,FFT)实现方位高分辨;最后对实际飞行状态下平台造成的误差进行运动补偿,完成对波束内区域的二维分辨。实测数据的处理验证了所提算法的有效性与实用性。展开更多
基金Supported by The Area of Excellence scheme of University Grants Committeethe Research Grant Council Grant, HKU 7642/05M to MCL, from Hong Kong
文摘AIM: To test whether oral L-81 treatment could im-prove the condition of mice with diabetes and to investigate how L-81 regulates microsomal triglyceride transfer protein (MTP) activity in the liver. METHODS: Genetically diabetic (db/db) mice were fed on chow supplemented with or without L-81 for 4 wk. The body weight, plasma glucose level, plasma lipid profile, and adipocyte volume of the db/db mice were assessed after treatment. Toxicity of L-81 was also evaluated. To understand the molecular mecha-nism, HepG2 cells were treated with L-81 and the effects on apolipoprotein B (apoB) secretion and mRNA level of the MTP gene were assessed.RESULTS: Treatment of db/db mice with L-81 sig-nificantly reduced and nearly normalized their body weight, hyperphagia and polydipsia. L-81 also markedly decreased the fasting plasma glucose level, improved glucose tolerance, and attenuated the elevated levels of plasma cholesterol and triglyceride. At the effective dosage, little toxicity was observed. Treatment of HepG2 cells with L-81 not only inhibited apoB secretion, but also signif icantly decreased the mRNA level of the MTP gene. Similar to the action of insulin, L-81 exerted its effect on the MTP promoter. CONCLUSION: L-81 represents a promising candidate in the development of a selective insulin-mimetic mol-ecule and an anti-diabetic agent.
基金the Program for Changjiang Scholars and Innovative Research Team in University (IRT0944)the National Natural Science Foundation of China (31070724, 30870506)+3 种基金the Special Fund for Marine Scientific Research in the Public Interest (201005024)the International Science and Technology Collaboration Program of China (2007DFA30980)the Open Research Fund of Key Laboratory of Marine Drugs of the Ministry of EducationOcean University of China (KLMD200802)
文摘Diabetes mellitus is the most common metabolic disease and its prevalence is increasing in many countries year by year.More than 90% of diabetes patients are type 2 diabetes,which is caused by insulin resistance and beta-cell dysfunction.In this paper,the oligomannuronate-chromium(III)complex(OM2)was prepared and its effect and mechanism on attenuating insulin resistance in diabetic C57BL/KsJ-db/db mice were studied.The results indicated that oral intake of OM2(50 mg kg-1d-1)for 42 d decreased blood glucose and lipid concentration,which was associated with the reduced serum insulin concentration and insulin resistance.According to western blot assay,OM2 could activate AMPK pathway to regulate glycogen synthesis,gluconeogenesis and lipid metabolism in the liver,and attenuate the hyperglycemic symptom in db/db mice.The effects of OM2 on attenuating insulin resistance were com-parable to that of the established antidiabetic drug metformin,and OM2 showed less adverse effect than metformin in vivo.Based on the effectiveness and low toxicity,OM2 may potentially be used for prevention and treatment of type 2 diabetes mellitus.
文摘In the present study,we utilized db/db mice to investigate the mechanisms of apoptosis in brain and retinal neurons.A total of 30 male db/db mice aged 8–9 weeks were randomly assigned to the model group,Dihuangyinzi decoction(DHYZ)group(30.03 g/kg),and metformin(MET)group(0.58 g/kg),with 10 mice in each group.The control group comprised 10 db/m mice of the same background and age.Paired-associate learning(PAL)tests were conducted to evaluate the learning and memory functions of the mice.Histological assessments,including Hematoxylin-Eosin(H&E)and Nissl staining,were employed to observe changes in nerve cells in the hippocampus and retina.Immunohistochemistry and real-time fluorescence quantitative PCR were employed to detect the positive expression of anti-apoptotic factor Bcl-2 and pro-apoptotic factor Bax at the protein and mRNA levels in the hippocampus and retina.Western blotting analysis was adopted to assess protein expression levels of JNK,p-JNK,p38 MAPK,and p-p38 MAPK.Results revealed a significant decline in the correct rate of PAL test results in the model group(P<0.001),accompanied by increased reaction and delay times(P<0.001)and higher blood glucose levels(P<0.001).H&E and Nissl staining indicated a reduction in the number of nerve cells in the CA1 area of the hippocampus in the model group,with scattered arrangement and decreased Nissl corpuscles.Positive expression and mRNA expression of Bax in the hippocampus and retina increased significantly(P<0.001),while positive expression and mRNA expression of Bcl-2 decreased(P<0.001).Protein expression levels of p-JNK/JNK and p-p38 MAPK/p38 MAPK showed a significant increase(P<0.001).The DHYZ and MET groups exhibited enhanced accuracy in PAL experiments(P<0.05),decreased reaction time and delay time(P<0.05),and reduced blood glucose levels(P<0.05).The number of neurons in the CA1 region of the hippocampus increased,morphological structure improved,and the arrangement of the hippocampal structure became more orderly.Additionally,no obvious vacuolization was observed in the neuronal cell layer.The number of Nissl bodies increased,and the layers of the retina were closely arranged,with an increase in the number of Nissl bodies.Positive expressions of Bax in the hippocampus and retina,both at the protein and mRNA levels,decreased significantly(P<0.001),while positive expressions of Bcl-2 and its mRNA increased(P<0.01,P<0.001).Furthermore,the protein expressions of p-JNK/JNK and p-p38 MAPK/p38 MAPK decreased significantly(P<0.01).This study suggested that DHYZ decoction could inhibit the JNK/p38 MAPK signaling pathway,thereby increasing the anti-apoptotic factor Bcl-2 and reducing the expression of the pro-apoptotic factor Bax,consequently inhibiting apoptosis in the hippocampal CA1 region and retinal neurons of db/db mice.
文摘针对强地物杂波背景下弹载雷达目标检测与识别的技术难题,提出将高分辨距离像(high resolution range profile,HRRP)技术和多普勒波束锐化技术联合对地面进行二维高分辨成像,提高雷达在杂波下目标检测与识别的性能。该方法以线性调频步进频(linear frequency modulation stepped frequency,LFM-SF)信号为基本波形,首先对平台速度产生的多普勒效应等问题进行了详细讨论并校正;然后通过距离像抽取获得各帧对应的HRRP序列,并采用方位快速傅里叶变换(fast Fourier transform,FFT)实现方位高分辨;最后对实际飞行状态下平台造成的误差进行运动补偿,完成对波束内区域的二维分辨。实测数据的处理验证了所提算法的有效性与实用性。
