Throughout the globe,diabetes mellitus(DM) is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and af...Throughout the globe,diabetes mellitus(DM) is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin(m TOR) is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1(m TORC1) and m TOR Complex 2(m TORC2) and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase(PI 3-K),protein kinase B(Akt),AMP activated protein kinase(AMPK),silent mating type information regulation 2 homolog 1(Saccharomyces cerevisiae)(SIRT1),Wnt1 inducible signaling pathway protein 1(WISP1),and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.展开更多
放疗是肿瘤的重要治疗手段之一,仍有部分患者在接受放疗后存在复发或抗拒。哺乳动物雷帕霉素靶蛋白(mamma-lian target of rapamycin,mTOR)是PI3K/AKT信号通路的主要效应分子,分为mTORC1和mTORC2,对细胞生长及增殖、细胞周期进展及蛋白...放疗是肿瘤的重要治疗手段之一,仍有部分患者在接受放疗后存在复发或抗拒。哺乳动物雷帕霉素靶蛋白(mamma-lian target of rapamycin,mTOR)是PI3K/AKT信号通路的主要效应分子,分为mTORC1和mTORC2,对细胞生长及增殖、细胞周期进展及蛋白翻译等均有重要调节作用。mTOR异常表达与肿瘤发生及治疗反应密切相关。肿瘤的放疗敏感性与"4R"效应有关。mTOR抑制剂可通过影响细胞周期进展、DNA损伤修复及抗血管形成等多种途径发挥放疗增敏作用。初期研究证实依维莫司具有放疗增敏作用并且毒性可耐受。应用mTOR抑制剂后不同细胞及个体反应不同,可能与基因表达状态有关,需进一步研究证实。展开更多
Objective:To explore the protective mechanisms of nerve growth factor (NGF) on spinal cord injury (SCI) and provide theoretical basis for its clinical application. Methods: The SCI of Wistar rats was done by Allens w...Objective:To explore the protective mechanisms of nerve growth factor (NGF) on spinal cord injury (SCI) and provide theoretical basis for its clinical application. Methods: The SCI of Wistar rats was done by Allens weight dropping way by a 10 g×2.5 cm impact on the posterior of spinal cord T 8. NGF (3 g/L, 20 μl) or normal saline was injected through catheter into subarachnoid space 2, 4, 8, 12 and 24 h after SCI. The expression of N-methyl-D-asparate receptor 1 (NMDAR 1) and neuronal constitutive nitric oxide synthase (ncNOS) mRNA in rat spinal cord was detected by in situ hybridization. Results: Abnormal expression of NMDAR 1 and ncNOS mRNA appeared in spinal ventral horn motorneuron in injured rats, as compared with that in control group. The expression of NMDAR 1 and ncNOS mRNA in NGF group was significantly lower than that in saline group (P<0.01). Conclusion: NGF can protect spinal cord against injury in vivo. One of the mechanisms is that NGF can prohibit NMDAR 1 and nitric oxide (NO) production after spinal cord injury.展开更多
AIM: To investigate the anti-fibrosis effect of IκB kinase-beta inhibitor (IKK2 inhibitor IMD0354) in liver fibrosis. METHODS: Twenty male C57BL6 mice were divided into four groups. Five high-fat fed mice were inject...AIM: To investigate the anti-fibrosis effect of IκB kinase-beta inhibitor (IKK2 inhibitor IMD0354) in liver fibrosis. METHODS: Twenty male C57BL6 mice were divided into four groups. Five high-fat fed mice were injected with lipopolysaccharide (LPS, 10 mg/kg) intraperitoneally and five high-fat fed mice were without LPS injection to build models of liver injury, and the intervention group (five mice) was injected intraperitoneally with IKK2 inhibitor (IMD 30 mg/kg for 14 d), while the remaining five mice received a normal diet as controls. Hepatic function, pathological evaluation and liver interleukin-6 (IL-6) expression were examined. Western blotting and real-time polymerase chain reaction were used to detect the expressions of nuclear factor-κB (NF-κB), alpha-smooth muscle actin (α-SMA), tumor growth factor-beta1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), typeⅠand type Ⅲ collagen proteins and mRNA. RESULTS: A mouse model of liver injury was successfully established, and IMD decreased nuclear transloca-tion of NF-κB p65 in liver cells. In the IMD-treated group, the levels of alanine aminotransferase (103 ± 9.77 μ/L vs 62.4 ± 7.90 μ/L, P < 0.05) and aminotransferase (295.8 ± 38.56 μ/L vs 212 ± 25.10 μ/L, P < 0.05) were significantly decreased when compared with the model groups. The histological changes were significantly ameliorated. After treatment, the expressions of IL-6 (681 ± 45.96 vs 77 ± 7.79, P < 0.05), TGF-β1 (Western blotting 5.65% ± 0.017% vs 2.73% ± 0.005%, P < 0.05), TNF-α (11.58% ± 0.0063% vs 8.86% ± 0.0050%, P < 0.05), typeⅠcollagen (4.49% ± 0.014% vs 1.90% ± 0.0006%, P < 0.05) and type Ⅲ collagen (3.46% ± 0.008% vs 2.29% ± 0.0035%, P < 0.05) as well as α-SMA (6.19 ± 0.0036 μ/L vs 2.16 ± 0.0023 μ/L, P < 0.05) protein and mRNA were downregulated in the IMD group compared to the fibrosis control groups (P < 0.05). CONCLUSION: IKK2 inhibitor IMD markedly improved non-alcoholic fatty liver disease in mice by lowering NF-κB activation, which could become a remedial target for liver fibrosis.展开更多
Recently, Popa and Rata [27, 28] have shown the (in)stability of some classical operators defined on [0, 1] and found best constant when the positive linear operators are stable in the sense of Hyers-Ularn. In this ...Recently, Popa and Rata [27, 28] have shown the (in)stability of some classical operators defined on [0, 1] and found best constant when the positive linear operators are stable in the sense of Hyers-Ularn. In this paper we show Hyers-Ulam (in)stability of complex Bernstein-Schurer operators, complex Kantrovich-Schurer operators and Lorentz operators on compact disk. In the case when the operator is stable in the sense of Hyers and Ulam, we find the infimum of Hyers-Ulam stability constants for respective operators.展开更多
基金supported by American Diabetes Association,American Heart Association,NIH NIEHS,NIH NIA,NIH NINDS,and NIH ARRA
文摘Throughout the globe,diabetes mellitus(DM) is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin(m TOR) is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1(m TORC1) and m TOR Complex 2(m TORC2) and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase(PI 3-K),protein kinase B(Akt),AMP activated protein kinase(AMPK),silent mating type information regulation 2 homolog 1(Saccharomyces cerevisiae)(SIRT1),Wnt1 inducible signaling pathway protein 1(WISP1),and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.
文摘放疗是肿瘤的重要治疗手段之一,仍有部分患者在接受放疗后存在复发或抗拒。哺乳动物雷帕霉素靶蛋白(mamma-lian target of rapamycin,mTOR)是PI3K/AKT信号通路的主要效应分子,分为mTORC1和mTORC2,对细胞生长及增殖、细胞周期进展及蛋白翻译等均有重要调节作用。mTOR异常表达与肿瘤发生及治疗反应密切相关。肿瘤的放疗敏感性与"4R"效应有关。mTOR抑制剂可通过影响细胞周期进展、DNA损伤修复及抗血管形成等多种途径发挥放疗增敏作用。初期研究证实依维莫司具有放疗增敏作用并且毒性可耐受。应用mTOR抑制剂后不同细胞及个体反应不同,可能与基因表达状态有关,需进一步研究证实。
文摘Objective:To explore the protective mechanisms of nerve growth factor (NGF) on spinal cord injury (SCI) and provide theoretical basis for its clinical application. Methods: The SCI of Wistar rats was done by Allens weight dropping way by a 10 g×2.5 cm impact on the posterior of spinal cord T 8. NGF (3 g/L, 20 μl) or normal saline was injected through catheter into subarachnoid space 2, 4, 8, 12 and 24 h after SCI. The expression of N-methyl-D-asparate receptor 1 (NMDAR 1) and neuronal constitutive nitric oxide synthase (ncNOS) mRNA in rat spinal cord was detected by in situ hybridization. Results: Abnormal expression of NMDAR 1 and ncNOS mRNA appeared in spinal ventral horn motorneuron in injured rats, as compared with that in control group. The expression of NMDAR 1 and ncNOS mRNA in NGF group was significantly lower than that in saline group (P<0.01). Conclusion: NGF can protect spinal cord against injury in vivo. One of the mechanisms is that NGF can prohibit NMDAR 1 and nitric oxide (NO) production after spinal cord injury.
基金Supported by Shanghai Municipal Health Bureau Youth Grant, No. 2008Y032
文摘AIM: To investigate the anti-fibrosis effect of IκB kinase-beta inhibitor (IKK2 inhibitor IMD0354) in liver fibrosis. METHODS: Twenty male C57BL6 mice were divided into four groups. Five high-fat fed mice were injected with lipopolysaccharide (LPS, 10 mg/kg) intraperitoneally and five high-fat fed mice were without LPS injection to build models of liver injury, and the intervention group (five mice) was injected intraperitoneally with IKK2 inhibitor (IMD 30 mg/kg for 14 d), while the remaining five mice received a normal diet as controls. Hepatic function, pathological evaluation and liver interleukin-6 (IL-6) expression were examined. Western blotting and real-time polymerase chain reaction were used to detect the expressions of nuclear factor-κB (NF-κB), alpha-smooth muscle actin (α-SMA), tumor growth factor-beta1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), typeⅠand type Ⅲ collagen proteins and mRNA. RESULTS: A mouse model of liver injury was successfully established, and IMD decreased nuclear transloca-tion of NF-κB p65 in liver cells. In the IMD-treated group, the levels of alanine aminotransferase (103 ± 9.77 μ/L vs 62.4 ± 7.90 μ/L, P < 0.05) and aminotransferase (295.8 ± 38.56 μ/L vs 212 ± 25.10 μ/L, P < 0.05) were significantly decreased when compared with the model groups. The histological changes were significantly ameliorated. After treatment, the expressions of IL-6 (681 ± 45.96 vs 77 ± 7.79, P < 0.05), TGF-β1 (Western blotting 5.65% ± 0.017% vs 2.73% ± 0.005%, P < 0.05), TNF-α (11.58% ± 0.0063% vs 8.86% ± 0.0050%, P < 0.05), typeⅠcollagen (4.49% ± 0.014% vs 1.90% ± 0.0006%, P < 0.05) and type Ⅲ collagen (3.46% ± 0.008% vs 2.29% ± 0.0035%, P < 0.05) as well as α-SMA (6.19 ± 0.0036 μ/L vs 2.16 ± 0.0023 μ/L, P < 0.05) protein and mRNA were downregulated in the IMD group compared to the fibrosis control groups (P < 0.05). CONCLUSION: IKK2 inhibitor IMD markedly improved non-alcoholic fatty liver disease in mice by lowering NF-κB activation, which could become a remedial target for liver fibrosis.
文摘Recently, Popa and Rata [27, 28] have shown the (in)stability of some classical operators defined on [0, 1] and found best constant when the positive linear operators are stable in the sense of Hyers-Ularn. In this paper we show Hyers-Ulam (in)stability of complex Bernstein-Schurer operators, complex Kantrovich-Schurer operators and Lorentz operators on compact disk. In the case when the operator is stable in the sense of Hyers and Ulam, we find the infimum of Hyers-Ulam stability constants for respective operators.