Alzheimer’s disease is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathology. Recent preclinical and epidemiological studies proposed statins as a possible therapeutic drug...Alzheimer’s disease is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathology. Recent preclinical and epidemiological studies proposed statins as a possible therapeutic drug for Alzheimer’s disease, but the exact mechanisms of action are still unknown. Biliverdin reductase-A is a pleiotropic enzyme involved in cellular stress responses. It not only transforms biliverdin-IX alpha into the antioxidant bilirubin-IX alpha but its serine/threonine/ tyrosine kinase activity is able to modulate cell signaling networks. We previously reported the beneficial effects of atorvastatin treatment on biliverdin reductase-A and heme oxygenase-1 in the brains of a well characterized pre-clinical model of Alzheimer’s disease, aged beagles, together with observed improvement in cognition. Here we extend our knowledge of the effects of atorvastatin on inducible nitric oxide synthase in parietal cortex, cerebellum and liver of the same animals. We demonstrated that atorvastatin treatment （80 mg/day for 14.5 months） to aged beagles selectively increased inducible nitric oxide synthase in the parietal cortex but not in the cerebellum. In contrast, inducible nitric oxide synthase protein levels were significantly decreased in the liver. Significant positive correlations were found between biliverdin reductase-A and inducible nitric oxide synthase as well as heme oxygenase-1 protein levels in the parietal cortex. The opposite was observed in the liver. Inducible nitric oxide synthase up-regulation in the parietal cortex was positively associated with improved biliverdin reductase-A functions, whereas the oxidative-induced impairment of biliverdin reductase-A in the liver negatively affected inducible nitric oxide synthase expression, thus suggesting a role for biliverdin reductase-A in atorvastatin-dependent inducible nitric oxide synthase changes. Interestingly, increased inducible nitric oxide synthase levels in the parietal cortex were not associated with higher oxidative/nitrosativ展开更多
目的观察健脾滋阴消渴方联合西医常规疗法治疗2型糖尿病气阴两虚证患者临床疗效,及对患者胰岛素敏感性和胰岛β细胞功能的影响。方法采用随机数字表法将87例患者分为对照组(43例)和观察组(44例)。对照组予西医常规治疗;观察组在对照组...目的观察健脾滋阴消渴方联合西医常规疗法治疗2型糖尿病气阴两虚证患者临床疗效,及对患者胰岛素敏感性和胰岛β细胞功能的影响。方法采用随机数字表法将87例患者分为对照组(43例)和观察组(44例)。对照组予西医常规治疗;观察组在对照组基础上予健脾滋阴消渴方,每日1剂,每日2次,口服。2组均连续治疗2周。比较2组临床疗效,观察2组治疗前后餐后2 h血糖(2 h PBG)、空腹血糖(FBG)、胰岛素敏感指数(ISI)、胰岛β细胞功能指数(HOMA-β)、丙二醛(MDA)、超氧化物歧化酶(SOD)水平及中医症状积分。结果与本组治疗前比较,2组治疗后2hPBG、FBG、MDA水平明显降低,ISI、HOMA-β、SOD水平明显升高,差异有统计学意义(P<0.05);2组治疗后比较,观察组2hPBG、FBG、MDA水平低于对照组,ISI、HOMA-β、SOD水平高于对照组,差异有统计学意义(P<0.05)。与本组治疗前比较,2组治疗后乏力、多饮多食、五心烦热积分明显降低(P<0.05);2组治疗后比较,观察组上述症状积分明显低于对照组(P<0.05)。观察组总有效率为88.64%(39/44),对照组为69.77%(30/43),差异有统计学意义(P<0.05)。观察组低血糖发生率为6.82%(3/44),对照组为13.95%(6/43),差异无统计学意义(P>0.05)。结论健脾滋阴消渴方联合西医常规疗法治疗2型糖尿病气阴两虚证可提高临床疗效,有效减轻患者氧化应激反应,改善胰岛功能,增强胰岛素敏感性。展开更多
背景:骨质疏松症是一种全身性的代谢性疾病,其发病率逐年增加,严重危害中老年人的健康。褪黑素是人体分泌的一种内源性激素,可以调节生物昼夜节律。近年来研究发现,褪黑素可以调节骨吸收和骨形成的平衡,在维持骨代谢的稳定中发挥重要作...背景:骨质疏松症是一种全身性的代谢性疾病,其发病率逐年增加,严重危害中老年人的健康。褪黑素是人体分泌的一种内源性激素,可以调节生物昼夜节律。近年来研究发现,褪黑素可以调节骨吸收和骨形成的平衡,在维持骨代谢的稳定中发挥重要作用。目的:总结褪黑素治疗骨质疏松症的研究进展,为治疗骨质疏松症提供新的依据。方法:以“osteoporosis,melatonin,ovariectomized,pinealectomy,osteoblast,osteoclast,stem cells”为检索词,检索Pub Med和Web of Science数据库相关文献,最终共纳入62篇文献进行文献综述。结果与结论:(1)褪黑素的基因表达情况在机体不同年龄段之间存在差异,褪黑素可以维持间充质干细胞的自我更新和分化能力,并通过促进Sirt1,PRC1/2和细胞周期相关蛋白表达抑制细胞衰老。(2)褪黑素可以调控间充质干细胞的分化方向,促进干细胞向成骨细胞分化,抑制其向脂肪细胞和破骨细胞方向分化。(3)褪黑素可以有效减轻氧化应激和炎症反应诱导的细胞毒性损伤并抑制破骨细胞分化,维持线粒体的稳定,提高成骨细胞的分化和矿化能力。(4)褪黑素可以阻断RANKL和诱导型一氧化氮合酶引起的骨代谢紊乱,减少骨丢失,增加碱性磷酸酶和骨钙素的表达,在破骨细胞和成骨细胞平衡之间发挥相应的生物学效应。(5)褪黑素在骨质疏松方面取得了良好的治疗效果,但是其作用靶点过于复杂,同时涉及抗衰老、干细胞分化、抗炎和抗氧化多个方面,目前仍未能完全阐述清楚其作用机制,仍有待进一步的研究。展开更多
The main task of cancer vaccines is to deliver tumorspecifc antigens to antigen-presenting cells for immune recognition that can lead to potent and durable immune response against treated tumor. Using photodynamic the...The main task of cancer vaccines is to deliver tumorspecifc antigens to antigen-presenting cells for immune recognition that can lead to potent and durable immune response against treated tumor. Using photodynamic therapy （PDT）-generated vaccines as an example of autologous whole-cell cancer vaccines, the importance is discussed of the expression of death-associated molecules on cancer vaccine cells. This aspect appears critical for the optimal capture of vaccine cells by host’s sentinel phagocytes in order that the tumor antigenic material is processed and presented for immune recognition and elimination of targeted malignancy. It is shown that changing death pattern of vaccine cells by agents modulating apoptosis, autophagy or necrosis can significantly alter the therapeutic impact of PDT-generated vaccines. Improved therapeutic effect was observed with inhibitors of necrosis/necroptosis using IM-54, necrostatin-1 or necrostatin-7, as well as with lethal autophagy inducer STF62247. In contrast, reduced vaccine potency was found in case of treating vaccine cells with apoptosis inhibitors or lethal autophagy inhibitor spautin-1. Therefore, PDT-generated cancer vaccine cells undergoing apoptosis or lethal autophagy are much more likely to produce therapeutic benefit than vaccine cells that are necrotic. These fndings warrant further detailed examination of the strategy using cell death modulating agents for the enhancement of the efficacy of cancer vaccines.展开更多
基金Funding for the canine atorvastatin study was through the Alzheimer's Association IIRG-03-5673 to Elizabeth Head
文摘Alzheimer’s disease is a neurodegenerative disorder characterized by progressive cognitive impairment and neuropathology. Recent preclinical and epidemiological studies proposed statins as a possible therapeutic drug for Alzheimer’s disease, but the exact mechanisms of action are still unknown. Biliverdin reductase-A is a pleiotropic enzyme involved in cellular stress responses. It not only transforms biliverdin-IX alpha into the antioxidant bilirubin-IX alpha but its serine/threonine/ tyrosine kinase activity is able to modulate cell signaling networks. We previously reported the beneficial effects of atorvastatin treatment on biliverdin reductase-A and heme oxygenase-1 in the brains of a well characterized pre-clinical model of Alzheimer’s disease, aged beagles, together with observed improvement in cognition. Here we extend our knowledge of the effects of atorvastatin on inducible nitric oxide synthase in parietal cortex, cerebellum and liver of the same animals. We demonstrated that atorvastatin treatment （80 mg/day for 14.5 months） to aged beagles selectively increased inducible nitric oxide synthase in the parietal cortex but not in the cerebellum. In contrast, inducible nitric oxide synthase protein levels were significantly decreased in the liver. Significant positive correlations were found between biliverdin reductase-A and inducible nitric oxide synthase as well as heme oxygenase-1 protein levels in the parietal cortex. The opposite was observed in the liver. Inducible nitric oxide synthase up-regulation in the parietal cortex was positively associated with improved biliverdin reductase-A functions, whereas the oxidative-induced impairment of biliverdin reductase-A in the liver negatively affected inducible nitric oxide synthase expression, thus suggesting a role for biliverdin reductase-A in atorvastatin-dependent inducible nitric oxide synthase changes. Interestingly, increased inducible nitric oxide synthase levels in the parietal cortex were not associated with higher oxidative/nitrosativ
文摘目的观察健脾滋阴消渴方联合西医常规疗法治疗2型糖尿病气阴两虚证患者临床疗效,及对患者胰岛素敏感性和胰岛β细胞功能的影响。方法采用随机数字表法将87例患者分为对照组(43例)和观察组(44例)。对照组予西医常规治疗;观察组在对照组基础上予健脾滋阴消渴方,每日1剂,每日2次,口服。2组均连续治疗2周。比较2组临床疗效,观察2组治疗前后餐后2 h血糖(2 h PBG)、空腹血糖(FBG)、胰岛素敏感指数(ISI)、胰岛β细胞功能指数(HOMA-β)、丙二醛(MDA)、超氧化物歧化酶(SOD)水平及中医症状积分。结果与本组治疗前比较,2组治疗后2hPBG、FBG、MDA水平明显降低,ISI、HOMA-β、SOD水平明显升高,差异有统计学意义(P<0.05);2组治疗后比较,观察组2hPBG、FBG、MDA水平低于对照组,ISI、HOMA-β、SOD水平高于对照组,差异有统计学意义(P<0.05)。与本组治疗前比较,2组治疗后乏力、多饮多食、五心烦热积分明显降低(P<0.05);2组治疗后比较,观察组上述症状积分明显低于对照组(P<0.05)。观察组总有效率为88.64%(39/44),对照组为69.77%(30/43),差异有统计学意义(P<0.05)。观察组低血糖发生率为6.82%(3/44),对照组为13.95%(6/43),差异无统计学意义(P>0.05)。结论健脾滋阴消渴方联合西医常规疗法治疗2型糖尿病气阴两虚证可提高临床疗效,有效减轻患者氧化应激反应,改善胰岛功能,增强胰岛素敏感性。
文摘背景:骨质疏松症是一种全身性的代谢性疾病,其发病率逐年增加,严重危害中老年人的健康。褪黑素是人体分泌的一种内源性激素,可以调节生物昼夜节律。近年来研究发现,褪黑素可以调节骨吸收和骨形成的平衡,在维持骨代谢的稳定中发挥重要作用。目的:总结褪黑素治疗骨质疏松症的研究进展,为治疗骨质疏松症提供新的依据。方法:以“osteoporosis,melatonin,ovariectomized,pinealectomy,osteoblast,osteoclast,stem cells”为检索词,检索Pub Med和Web of Science数据库相关文献,最终共纳入62篇文献进行文献综述。结果与结论:(1)褪黑素的基因表达情况在机体不同年龄段之间存在差异,褪黑素可以维持间充质干细胞的自我更新和分化能力,并通过促进Sirt1,PRC1/2和细胞周期相关蛋白表达抑制细胞衰老。(2)褪黑素可以调控间充质干细胞的分化方向,促进干细胞向成骨细胞分化,抑制其向脂肪细胞和破骨细胞方向分化。(3)褪黑素可以有效减轻氧化应激和炎症反应诱导的细胞毒性损伤并抑制破骨细胞分化,维持线粒体的稳定,提高成骨细胞的分化和矿化能力。(4)褪黑素可以阻断RANKL和诱导型一氧化氮合酶引起的骨代谢紊乱,减少骨丢失,增加碱性磷酸酶和骨钙素的表达,在破骨细胞和成骨细胞平衡之间发挥相应的生物学效应。(5)褪黑素在骨质疏松方面取得了良好的治疗效果,但是其作用靶点过于复杂,同时涉及抗衰老、干细胞分化、抗炎和抗氧化多个方面,目前仍未能完全阐述清楚其作用机制,仍有待进一步的研究。
基金Supported by The Canadian Cancer SocietyNo.#701132
文摘The main task of cancer vaccines is to deliver tumorspecifc antigens to antigen-presenting cells for immune recognition that can lead to potent and durable immune response against treated tumor. Using photodynamic therapy （PDT）-generated vaccines as an example of autologous whole-cell cancer vaccines, the importance is discussed of the expression of death-associated molecules on cancer vaccine cells. This aspect appears critical for the optimal capture of vaccine cells by host’s sentinel phagocytes in order that the tumor antigenic material is processed and presented for immune recognition and elimination of targeted malignancy. It is shown that changing death pattern of vaccine cells by agents modulating apoptosis, autophagy or necrosis can significantly alter the therapeutic impact of PDT-generated vaccines. Improved therapeutic effect was observed with inhibitors of necrosis/necroptosis using IM-54, necrostatin-1 or necrostatin-7, as well as with lethal autophagy inducer STF62247. In contrast, reduced vaccine potency was found in case of treating vaccine cells with apoptosis inhibitors or lethal autophagy inhibitor spautin-1. Therefore, PDT-generated cancer vaccine cells undergoing apoptosis or lethal autophagy are much more likely to produce therapeutic benefit than vaccine cells that are necrotic. These fndings warrant further detailed examination of the strategy using cell death modulating agents for the enhancement of the efficacy of cancer vaccines.
