Male sterility induced by a chemical hybridization agent （CHA） is an important tool for utilizing crop heterosis. Leaves, especially the flag leaves, as CHA initial recipients play a decisive role in inducing male s...Male sterility induced by a chemical hybridization agent （CHA） is an important tool for utilizing crop heterosis. Leaves, especially the flag leaves, as CHA initial recipients play a decisive role in inducing male sterility. To investigate effects of different treatment times of CHA-SQ-1 used, morphological, biochemical and physiological responses of wheat flag leaves were detected in thistudy. CHA induced programmed cell death （PCD） as shown in terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling （TUNEL） and DNA laddering analysis. In the early phase, CHA-SQ-1 trig- gered organelle changes arid PCD in wheat leaves accompanied by excess production of reactive oxygen species （O2- and H202） and down-regulation of the activities of superoxide dismutase （SOD）, catalase （CAT） and guaiacol peroxidase （POD）. Meanwhile, leaf cell DNAs showed ladder-like patterns on agarose gel, indicating that CHA-SQ-1 led to the activation of the responsible endonuclease. The oxidative stress assays showed that lipid peroxidation was strongly activated and photosynthesis was obviously inhibited in SQ-l-induced leaves. However, CHA contents in wheat leaves gradually reduced along with the time CHA-SQ-1 applied. Young flags returned to an oxidative/antioxidative balance and ultimately developed into mature green leaves. These results provide explanation of the relations between PCD and anther abortion and practical application of CHA for hybrid breeding.展开更多
AIM: To elucidate the mechanism(s) by which S-adenosyl-L-methionine(SAM) decreases hepatitis C virus(HCV) expression.METHODS: We examined the effects of SAM on viral expression using an HCV subgenomic replicon cell cu...AIM: To elucidate the mechanism(s) by which S-adenosyl-L-methionine(SAM) decreases hepatitis C virus(HCV) expression.METHODS: We examined the effects of SAM on viral expression using an HCV subgenomic replicon cell culture system. Huh7 HCV-replicon cells were treated with 1 mmol/L SAM for different times(24-72 h), then total RNA and proteins were isolated. c DNA was synthesized and real time-PCR was achieved to quantify HCV-RNA, superoxide dismutase 1 and 2(SOD-1, SOD-2) catalase, thioredoxin 1, methionine adenosyltransferase 1A and 2A(MAT1A, MAT2A) expression, and GAPDH and RPS18 as endogenous genes. Expression of cellular and viral protein was evaluated by western-blot analysis using antibodies vs HCV-NS5 A, SOD-1, SOD-2, catalase, thioredoxin-1, MAT1 A, MAT2 A, GAPDH and actin. Total glutathione levels were measured at different times by Ellman's recycling method(0-24 h). Reactive oxidative species(ROS) levels were quantified by the dichlorofluorescein assay(0-48 h); Pyrrolidin dithiocarbamate(PDTC) was tested as an antioxidant control and H2O2 as a positive oxidant agent.RESULTS: SAM exposition decreased HCV-RNA levels 50%-70% compared to non-treated controls(24-72 h). SAM induced a synergic antiviral effect with standard IFN treatment but it was independent of IFN signaling. In addition, 1 mmol/L SAM exposition did not modify viral RNA stability, but it needs cellular translation machinery in order to decrease HCV expression. Total glutathione levels increased upon SAM treatment in HCV-replicon cells. Transcriptional antioxidant enzyme expression(SOD-1, SOD-2 and thioredoxin-1) was increased at different times but interestingly, there was no significant change in ROS levels upon SAM treatment, contrary to what was detected with PDTC treatment, where an average 40% reduction was observed in exposed cells. There was a turnover from MAT1A/MAT2 A, since MAT1 A expression was increased(2.5 fold-times at 48 h) and MAT2 A was diminished(from 24 h) upon SAM treatment at both the transcriptional and translational level. CONCLUSION: A likely mechanism(s) by which SAM diminish HCV expression could involve modulating antioxidant enzymes, restoring biosynthesis of glutathione and switching MAT1/MAT2 turnover in HCV expressing cells.展开更多
目的评价褪黑素对神经病理性疼痛夜间加重的影响,并通过特异性沉默信息调节因子1(SIRT1)-脑和肌肉ARNT样蛋白1(BMAL1)通路探讨其机制。方法96只SPF级雄性C57/B6小鼠,随机分为3组:假手术(S)组、神经病理性疼痛模型(NP)组和NP模型+褪黑素...目的评价褪黑素对神经病理性疼痛夜间加重的影响,并通过特异性沉默信息调节因子1(SIRT1)-脑和肌肉ARNT样蛋白1(BMAL1)通路探讨其机制。方法96只SPF级雄性C57/B6小鼠,随机分为3组:假手术(S)组、神经病理性疼痛模型(NP)组和NP模型+褪黑素治疗(NP+M)组;术前试验小鼠置于指定光照模式环境中;采用12 h光照与12 h黑暗交替环境,持续至少两周,将自然时间转换为授时时间(ZT),光照起点定为ZT0;S组小鼠仅分离坐骨神经,NP组和NP+M组采用坐骨神经慢性缩窄性损伤制备小鼠NP模型,NP+M组术后注射10 mg/kg褪黑素;Western blot法检测术后14 d各时点脊髓的SIRT1、BMAL1和谷胱甘肽过氧化酶1(Gpx1)表达量的变化;术后通过免疫荧光技术对脊髓背角SIRT1和脊髓神经元标志物神经元特异性核蛋白(NeuN)、小胶质细胞激活标记物离子钙结合适配器分子1(iba-1)、星形胶质细胞标记物胶质纤维酸性蛋白(GFAP)进行共染色,并检测各时点iba-1以确定小胶质细胞激活状态。结果与NP组ZT10时点相比,NP组小鼠术后14 d ZT22时点SIRT1、BMAL1和Gpx1降低(P<0.05);与NP组ZT14时点相比,NP+M组ZT14时点SIRT1与BMAL1升高(P<0.05),而Gpx1于ZT18时点升高(P<0.05)。SIRT1在脊髓背角与小胶质细胞共表达;与ZT10时点相比,NP组小鼠术后14 d ZT22时点小胶质细胞表达降低(P<0.05);与ZT10时点相比,NP+M组小鼠术后14 d ZT22时点小胶质细胞表达差异无统计学意义。结论褪黑素可以减轻神经病理性疼痛夜间加重,其机制可能与激活小胶质细胞SIRT1-BMAL1通路蛋白表达有关。展开更多
Cells have intrinsic mechanisms for cleaning harmful oxidants represented mainly by reactive oxygen species (ROS). Despite the antioxidant defense, ROS can cause serious damage to the retina that with age leads to var...Cells have intrinsic mechanisms for cleaning harmful oxidants represented mainly by reactive oxygen species (ROS). Despite the antioxidant defense, ROS can cause serious damage to the retina that with age leads to various eye diseases and even blindness. Among numerous cell sites of ROS generation, mitochondrial electron transport is of crucial importance. Recently, for the purpose of cleaning ROS in the mitochondrial matrix, powerful mitochondria- targeted antioxidant “SkQ1” has been invented. We studied SkQ1 effects upon tissues of rat posterior eye cup that consisted: retinal pigment epithelium (RPE) ? choroidal coat ? scleral coat. The eye cups were isolated from the eyes of adult albino rats and cultivated in rotary tissue culture system in the presence of 20 nM SkQ1 or without this compound. After 7 days - 1 month in vitro eye cup samples were studied by immunohistochemistry, routine histology, morphometry, and digital image analysis. We have found that under chosen, “in vitro like in vivo” conditions 20 nM SkQ1 effectively reduced cell death in RPE and choroid, protected RPE from disintegration caused by cell phenotypic transformation and withdrawal from the layer, suppressed transmigration of choroidal coat cells. In the ex vivo model we used degenerative processes were more pronounced in the eye cup center where SkQ1 effect was most vivid. All this give us hopes for effectiveness of SkQ1 treatment of retinal central part that is very susceptible to light-induced over-oxidation injury and mostly suffering in many age-related diseases, AMD, in particular.展开更多
Liver diseases with the central pathogenetic mechanism of oxidative stress are one of the main causes of mortality worldwide.Therefore,dihydroquinoline derivatives,which are precursors of hepatoprotectors and have ant...Liver diseases with the central pathogenetic mechanism of oxidative stress are one of the main causes of mortality worldwide.Therefore,dihydroquinoline derivatives,which are precursors of hepatoprotectors and have antioxidant activity,are of interest.We have previously found that some compounds in this class have the ability to normalize redox homeostasis under experimental conditions.Here,we initially analyzed the hepatoprotective potential of the dihydroquinoline derivative 1-benzoyl-6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline(BHDQ)for carbon tetrachloride(CCl4)-induced liver injury in rats.Results suggested that BHDQ normalized the alanine aminotransferase,aspartate aminotransferase,and gamma-glutamyl transpeptidase in serum.We also observed an improvement in liver tissue morphology related to BHDQ.Animals with CCl4-induced liver injuries treated with BHDQ had less oxidative stress compared to animals with CCl4-induced liver injury.BHDQ promoted activation changes in superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase,and glutathione transferase on control values in animals with CCl4-induced liver injury.BHDQ also activated gene transcription in Sod1 and Gpx1 via nuclear factor erythroid 2-related factor 2 and forkhead box protein O1 factors.Therefore,the compound of concern has a hepatoprotective effect by inhibiting the development of necrotic processes in the liver tissue,through antioxidation.展开更多
From (2,3-dihydro-1<i>H</i>-perimidin-2-yl)-phenyl, the substitution of OH group in <i>ortho</i> or <i>para</i> position on the phenyl ring, allows us to synthesize the studied comp...From (2,3-dihydro-1<i>H</i>-perimidin-2-yl)-phenyl, the substitution of OH group in <i>ortho</i> or <i>para</i> position on the phenyl ring, allows us to synthesize the studied compounds. These three compounds have been characterized by conventional spectroscopic methods (NMR and MS). The interest of this work is to review the antioxidant activity of our compounds. The antioxidant activity screening carried out according to FRAP and DPPH methods revealed significant anti-free radical properties for compounds 1 and 2 even at low concentrations. In contrast to the compound 2, compound 3 for which the OH group is substituted in <i>para</i> position has the lowest activity in both cases. Therefore the <i>para</i> position seems to be the least sensitive position to increase the antioxidant activity of this pharmacophore.展开更多
Novel fluorine substituted α-amino phosphonic acids containing 1,2,4-triazin- 5-one (6a-f) have been obtained from fluoroacylation of 6-(2′-amino-5′-nitrophenyl)-3-thioxo-1,2,4-triazin-5(4H)-one (...Novel fluorine substituted α-amino phosphonic acids containing 1,2,4-triazin- 5-one (6a-f) have been obtained from fluoroacylation of 6-(2′-amino-5′-nitrophenyl)-3-thioxo-1,2,4-triazin-5(4H)-one (1) followed by ammonilysis to give the corresponding 3-amino-derivative 3. Condensation of compound 3 with nitro/halogenated aromatic aldehydes yielded the Schiff bases 4. The simple addition of diethyl phosphonate to compound 4 produced the α-amino phosphonates 5. Acidic hydrolysis of compound 5 produced the fluorine substituted α-amino acids derivatives 6. Structures of the new compounds have been established with the help of elemental analysis and spectral measurements. Also, the products evaluated as antioxidants, where the fluorinated α-amino phosphonic acids 6 are more active than the other synthesized systems.展开更多
During life human eye is constantly exposed to sunlight and artificial light, the sources of reactive oxygen species (ROS)—the main cause of age-related eye pathology. A novel mitochondria-targeted antioxidant SkQ1 h...During life human eye is constantly exposed to sunlight and artificial light, the sources of reactive oxygen species (ROS)—the main cause of age-related eye pathology. A novel mitochondria-targeted antioxidant SkQ1 has recently been invented to reduce mitochondrial ROS by cleaning the mitochondria matrix, “the dirtiest place in the cell” in respect of ROS production and accumulation. Earlier we studied SkQ1 effects upon retinal pigment epithelium and choroid in the rat eye posterior cups exposed to long-term 3D organotypic culturing. It was found that under in vitro conditions 20 nM SkQ1 effectively reduced cell death in retinal pigment epithelium and choroid and protected the tissues from disintegration and cell withdrawal. In the present study we used same ex vivo conditions to examine the effect of SkQ1 upon the rat neural retina kept in the content of the posterior eye cup. Eye cups were isolated and cultured in vitro during 7, 14, and 30 days under rotation in the presence and absence of 20 nM SkQ1 in the culture medium. Serial sections of cultivated eye cups were subjected to histology, computer morphometry and immunohistochemistry. Obtained results show that SkQ1 operates as a strong protective agent, preventing neuronal cell death and other degenerative processes in the neural retina. Cell rescue by SkQ1 was more vivid in the central part of the retina than at the periphery. That, in turn, suggests SkQ1 effectiveness in treatment of some age-related eye diseases when central part of the retina, including macula, is most susceptible to degeneration.展开更多
Objective: To investigate the correlation of serum β-amyloid 1-42 (Aβ1-42) content with inflammatory factors and receptors as well as antioxidant enzymes in patients with Parkinson's Disease. Methods: A total of...Objective: To investigate the correlation of serum β-amyloid 1-42 (Aβ1-42) content with inflammatory factors and receptors as well as antioxidant enzymes in patients with Parkinson's Disease. Methods: A total of 48 patients with Parkinson's disease who were treated in this hospital between December 2014 and October 2017 were selected as Parkinson's disease group, and 50 healthy volunteers who received physical examination in this hospital during the same period were selected as normal control group. The differences in serum contents of Aβ1-42, inflammatory factors and receptors as well as antioxidant enzymes were compared between the two groups, and Pearson test was used to assess the correlation between serum Aβ1-42 content and illness in patients with Parkinson's disease. Results: Serum Aβ1-42 content of Parkinson's disease group was lower than that of normal control group;serum inflammatory factors and receptors IL-2, sIL-2R, IL-6 and sIL-6R contents were higher than those of normal control group;serum antioxidant enzymes SOD, GSH-Px, CAT and TPX contents were lower than those of control group. Pearson test showed that serum Aβ1-42 content of patients with Parkinson's disease was directly correlated with the contents of inflammatory factors and receptors as well as antioxidant enzymes. Conclusions: Serum Aβ1-42 content decreases in patient with Parkinson's disease, and the specific content is directly correlated with the condition of Parkinson's disease, and can be used as an important auxiliary indicator for diagnosis and judgment of Parkinson's disease.展开更多
目的对比胰高血糖素样肽-1(GLP-1)受体激动剂和二肽基肽酶-4(DPP-4)抑制剂分别联合二甲双胍治疗2型糖尿病(T2DM)的疗效及对其血清抗氧因子、炎症因子的影响。方法将2020年5月至2022年5月中国中医科学院广安门医院南区收治的120例T2DM患...目的对比胰高血糖素样肽-1(GLP-1)受体激动剂和二肽基肽酶-4(DPP-4)抑制剂分别联合二甲双胍治疗2型糖尿病(T2DM)的疗效及对其血清抗氧因子、炎症因子的影响。方法将2020年5月至2022年5月中国中医科学院广安门医院南区收治的120例T2DM患者纳入本次前瞻性研究,采用随机数字表法分成GLP-1联合组(n=40)、DPP-4联合组(n=40)和对照组(n=40)。GLP-1联合组患者治疗方案为二甲双胍治疗+利拉鲁肽,DPP-4联合组患者治疗方案为二甲双胍+沙格列汀,对照组患者仅口服二甲双胍治疗。治疗为期6个月。比较3组患者治疗前后的血糖相关指标[空腹血糖、餐后2 h血糖(2 h PPG)、糖化血红蛋白(HbA1c)]及胰岛素抵抗指数(HOMA-IR)、氧化应激指标[超氧化物歧化酶(SOD)和6-酮-前列环素F1α(6-Keto-PGF1α)]和炎症因子[肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和超敏C反应蛋白(hs-CRP)]表达情况。结果GLP-1联合组治疗后的空腹血糖、2 hPPG、HbA1c和HOMA-IR分别为(5.05±0.69)mmol/L、(7.42±0.98)mmol/L、(6.11±0.70)%和(3.20±0.45),DPP-4联合组分别为(5.58±0.61)mmol/L、(8.09±1.04)mmol/L、(6.65±0.76)%和(3.78±0.50),对照组分别为(6.50±0.75)mmol/L、(10.14±1.22)mmol/L、(7.80±0.81)%和(4.61±0.59),GLP-1联合组与DPP-4联合组治疗后的上述血糖相关指标及HOMA-IR均较对照组显著下降,且GLP-1联合组显著低于DPP-4联合组,差异均有统计学意义(P<0.05)。GLP-1联合组治疗后的SOD和6-Keto-PGF1α分别为(95.09±9.97)U/mL、(76.19±6.80)ng/L,DPP-4联合组分别为(85.17±10.18)U/mL、(67.32±6.39)ng/L,对照组分别为(76.89±9.06)U/mL、(60.46±6.02)ng/L,GLP-1联合组与DPP-4联合组治疗后的血清SOD、6-Keto-PGF1α均较对照组显著上升,且GLP-1联合组血清SOD、6-Keto-PGF1α均较DPP-4联合组显著上升,差异均有统计学意义(P<0.05)。GLP-1联合组TNF-α、IL-6和hs-CRP分别为(7.05±1.16)ng/L、(5.01±1.35)pg/mL、(4.04±0.51)mg/L,DPP-4联合组为(7.93±1.29)ng/L、(5.97±1.40)pg/mL、(4.99±0.59)mg/L,对照组为(10.34±1.58)ng/L、(7.58±1.49)pg/mL、(5.94±0.64)mg/L,GLP-1联合组与DPP-4联合组治疗后的上述血清炎症因子均较对照组显著下降,且GLP-1联合组显著低于DPP-4联合组,差异均有统计学意义(P<0.05)。结论GLP-1受体激动剂联合二甲双胍治疗T2DM的降糖效果优于DPP-4受体抑制剂联合二甲双胍,在改善胰岛素抵抗和氧化应激,降低炎症反应方面同样优于DPP-4受体抑制剂联合二甲双胍治疗。展开更多
基金supported by the National High Technology Research and Development Program of China (2011AA10A106)the National Natural Science Foundation of China (31171611, 31371697)+1 种基金the Technological Innovation and Over Planning Projects of Shaanxi Province, China (2014KTZB02-01-02, 2011KTZB02-01-01)the Projects Opening Up New Function of Precision Instrument of Northwest A&F University, China (dysb130210)
文摘Male sterility induced by a chemical hybridization agent （CHA） is an important tool for utilizing crop heterosis. Leaves, especially the flag leaves, as CHA initial recipients play a decisive role in inducing male sterility. To investigate effects of different treatment times of CHA-SQ-1 used, morphological, biochemical and physiological responses of wheat flag leaves were detected in thistudy. CHA induced programmed cell death （PCD） as shown in terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling （TUNEL） and DNA laddering analysis. In the early phase, CHA-SQ-1 trig- gered organelle changes arid PCD in wheat leaves accompanied by excess production of reactive oxygen species （O2- and H202） and down-regulation of the activities of superoxide dismutase （SOD）, catalase （CAT） and guaiacol peroxidase （POD）. Meanwhile, leaf cell DNAs showed ladder-like patterns on agarose gel, indicating that CHA-SQ-1 led to the activation of the responsible endonuclease. The oxidative stress assays showed that lipid peroxidation was strongly activated and photosynthesis was obviously inhibited in SQ-l-induced leaves. However, CHA contents in wheat leaves gradually reduced along with the time CHA-SQ-1 applied. Young flags returned to an oxidative/antioxidative balance and ultimately developed into mature green leaves. These results provide explanation of the relations between PCD and anther abortion and practical application of CHA for hybrid breeding.
基金Supported by CONACYT-Mexico,grant register CB2010-01-155082 to Rivas-Estilla AM
文摘AIM: To elucidate the mechanism(s) by which S-adenosyl-L-methionine(SAM) decreases hepatitis C virus(HCV) expression.METHODS: We examined the effects of SAM on viral expression using an HCV subgenomic replicon cell culture system. Huh7 HCV-replicon cells were treated with 1 mmol/L SAM for different times(24-72 h), then total RNA and proteins were isolated. c DNA was synthesized and real time-PCR was achieved to quantify HCV-RNA, superoxide dismutase 1 and 2(SOD-1, SOD-2) catalase, thioredoxin 1, methionine adenosyltransferase 1A and 2A(MAT1A, MAT2A) expression, and GAPDH and RPS18 as endogenous genes. Expression of cellular and viral protein was evaluated by western-blot analysis using antibodies vs HCV-NS5 A, SOD-1, SOD-2, catalase, thioredoxin-1, MAT1 A, MAT2 A, GAPDH and actin. Total glutathione levels were measured at different times by Ellman's recycling method(0-24 h). Reactive oxidative species(ROS) levels were quantified by the dichlorofluorescein assay(0-48 h); Pyrrolidin dithiocarbamate(PDTC) was tested as an antioxidant control and H2O2 as a positive oxidant agent.RESULTS: SAM exposition decreased HCV-RNA levels 50%-70% compared to non-treated controls(24-72 h). SAM induced a synergic antiviral effect with standard IFN treatment but it was independent of IFN signaling. In addition, 1 mmol/L SAM exposition did not modify viral RNA stability, but it needs cellular translation machinery in order to decrease HCV expression. Total glutathione levels increased upon SAM treatment in HCV-replicon cells. Transcriptional antioxidant enzyme expression(SOD-1, SOD-2 and thioredoxin-1) was increased at different times but interestingly, there was no significant change in ROS levels upon SAM treatment, contrary to what was detected with PDTC treatment, where an average 40% reduction was observed in exposed cells. There was a turnover from MAT1A/MAT2 A, since MAT1 A expression was increased(2.5 fold-times at 48 h) and MAT2 A was diminished(from 24 h) upon SAM treatment at both the transcriptional and translational level. CONCLUSION: A likely mechanism(s) by which SAM diminish HCV expression could involve modulating antioxidant enzymes, restoring biosynthesis of glutathione and switching MAT1/MAT2 turnover in HCV expressing cells.
文摘目的评价褪黑素对神经病理性疼痛夜间加重的影响,并通过特异性沉默信息调节因子1(SIRT1)-脑和肌肉ARNT样蛋白1(BMAL1)通路探讨其机制。方法96只SPF级雄性C57/B6小鼠,随机分为3组:假手术(S)组、神经病理性疼痛模型(NP)组和NP模型+褪黑素治疗(NP+M)组;术前试验小鼠置于指定光照模式环境中;采用12 h光照与12 h黑暗交替环境,持续至少两周,将自然时间转换为授时时间(ZT),光照起点定为ZT0;S组小鼠仅分离坐骨神经,NP组和NP+M组采用坐骨神经慢性缩窄性损伤制备小鼠NP模型,NP+M组术后注射10 mg/kg褪黑素;Western blot法检测术后14 d各时点脊髓的SIRT1、BMAL1和谷胱甘肽过氧化酶1(Gpx1)表达量的变化;术后通过免疫荧光技术对脊髓背角SIRT1和脊髓神经元标志物神经元特异性核蛋白(NeuN)、小胶质细胞激活标记物离子钙结合适配器分子1(iba-1)、星形胶质细胞标记物胶质纤维酸性蛋白(GFAP)进行共染色,并检测各时点iba-1以确定小胶质细胞激活状态。结果与NP组ZT10时点相比,NP组小鼠术后14 d ZT22时点SIRT1、BMAL1和Gpx1降低(P<0.05);与NP组ZT14时点相比,NP+M组ZT14时点SIRT1与BMAL1升高(P<0.05),而Gpx1于ZT18时点升高(P<0.05)。SIRT1在脊髓背角与小胶质细胞共表达;与ZT10时点相比,NP组小鼠术后14 d ZT22时点小胶质细胞表达降低(P<0.05);与ZT10时点相比,NP+M组小鼠术后14 d ZT22时点小胶质细胞表达差异无统计学意义。结论褪黑素可以减轻神经病理性疼痛夜间加重,其机制可能与激活小胶质细胞SIRT1-BMAL1通路蛋白表达有关。
文摘Cells have intrinsic mechanisms for cleaning harmful oxidants represented mainly by reactive oxygen species (ROS). Despite the antioxidant defense, ROS can cause serious damage to the retina that with age leads to various eye diseases and even blindness. Among numerous cell sites of ROS generation, mitochondrial electron transport is of crucial importance. Recently, for the purpose of cleaning ROS in the mitochondrial matrix, powerful mitochondria- targeted antioxidant “SkQ1” has been invented. We studied SkQ1 effects upon tissues of rat posterior eye cup that consisted: retinal pigment epithelium (RPE) ? choroidal coat ? scleral coat. The eye cups were isolated from the eyes of adult albino rats and cultivated in rotary tissue culture system in the presence of 20 nM SkQ1 or without this compound. After 7 days - 1 month in vitro eye cup samples were studied by immunohistochemistry, routine histology, morphometry, and digital image analysis. We have found that under chosen, “in vitro like in vivo” conditions 20 nM SkQ1 effectively reduced cell death in RPE and choroid, protected RPE from disintegration caused by cell phenotypic transformation and withdrawal from the layer, suppressed transmigration of choroidal coat cells. In the ex vivo model we used degenerative processes were more pronounced in the eye cup center where SkQ1 effect was most vivid. All this give us hopes for effectiveness of SkQ1 treatment of retinal central part that is very susceptible to light-induced over-oxidation injury and mostly suffering in many age-related diseases, AMD, in particular.
基金supported by the Russian Foundation for Basic Research (Grant No. 20-04-00526А)
文摘Liver diseases with the central pathogenetic mechanism of oxidative stress are one of the main causes of mortality worldwide.Therefore,dihydroquinoline derivatives,which are precursors of hepatoprotectors and have antioxidant activity,are of interest.We have previously found that some compounds in this class have the ability to normalize redox homeostasis under experimental conditions.Here,we initially analyzed the hepatoprotective potential of the dihydroquinoline derivative 1-benzoyl-6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline(BHDQ)for carbon tetrachloride(CCl4)-induced liver injury in rats.Results suggested that BHDQ normalized the alanine aminotransferase,aspartate aminotransferase,and gamma-glutamyl transpeptidase in serum.We also observed an improvement in liver tissue morphology related to BHDQ.Animals with CCl4-induced liver injuries treated with BHDQ had less oxidative stress compared to animals with CCl4-induced liver injury.BHDQ promoted activation changes in superoxide dismutase,catalase,glutathione peroxidase,glutathione reductase,and glutathione transferase on control values in animals with CCl4-induced liver injury.BHDQ also activated gene transcription in Sod1 and Gpx1 via nuclear factor erythroid 2-related factor 2 and forkhead box protein O1 factors.Therefore,the compound of concern has a hepatoprotective effect by inhibiting the development of necrotic processes in the liver tissue,through antioxidation.
文摘From (2,3-dihydro-1<i>H</i>-perimidin-2-yl)-phenyl, the substitution of OH group in <i>ortho</i> or <i>para</i> position on the phenyl ring, allows us to synthesize the studied compounds. These three compounds have been characterized by conventional spectroscopic methods (NMR and MS). The interest of this work is to review the antioxidant activity of our compounds. The antioxidant activity screening carried out according to FRAP and DPPH methods revealed significant anti-free radical properties for compounds 1 and 2 even at low concentrations. In contrast to the compound 2, compound 3 for which the OH group is substituted in <i>para</i> position has the lowest activity in both cases. Therefore the <i>para</i> position seems to be the least sensitive position to increase the antioxidant activity of this pharmacophore.
文摘Novel fluorine substituted α-amino phosphonic acids containing 1,2,4-triazin- 5-one (6a-f) have been obtained from fluoroacylation of 6-(2′-amino-5′-nitrophenyl)-3-thioxo-1,2,4-triazin-5(4H)-one (1) followed by ammonilysis to give the corresponding 3-amino-derivative 3. Condensation of compound 3 with nitro/halogenated aromatic aldehydes yielded the Schiff bases 4. The simple addition of diethyl phosphonate to compound 4 produced the α-amino phosphonates 5. Acidic hydrolysis of compound 5 produced the fluorine substituted α-amino acids derivatives 6. Structures of the new compounds have been established with the help of elemental analysis and spectral measurements. Also, the products evaluated as antioxidants, where the fluorinated α-amino phosphonic acids 6 are more active than the other synthesized systems.
文摘During life human eye is constantly exposed to sunlight and artificial light, the sources of reactive oxygen species (ROS)—the main cause of age-related eye pathology. A novel mitochondria-targeted antioxidant SkQ1 has recently been invented to reduce mitochondrial ROS by cleaning the mitochondria matrix, “the dirtiest place in the cell” in respect of ROS production and accumulation. Earlier we studied SkQ1 effects upon retinal pigment epithelium and choroid in the rat eye posterior cups exposed to long-term 3D organotypic culturing. It was found that under in vitro conditions 20 nM SkQ1 effectively reduced cell death in retinal pigment epithelium and choroid and protected the tissues from disintegration and cell withdrawal. In the present study we used same ex vivo conditions to examine the effect of SkQ1 upon the rat neural retina kept in the content of the posterior eye cup. Eye cups were isolated and cultured in vitro during 7, 14, and 30 days under rotation in the presence and absence of 20 nM SkQ1 in the culture medium. Serial sections of cultivated eye cups were subjected to histology, computer morphometry and immunohistochemistry. Obtained results show that SkQ1 operates as a strong protective agent, preventing neuronal cell death and other degenerative processes in the neural retina. Cell rescue by SkQ1 was more vivid in the central part of the retina than at the periphery. That, in turn, suggests SkQ1 effectiveness in treatment of some age-related eye diseases when central part of the retina, including macula, is most susceptible to degeneration.
文摘Objective: To investigate the correlation of serum β-amyloid 1-42 (Aβ1-42) content with inflammatory factors and receptors as well as antioxidant enzymes in patients with Parkinson's Disease. Methods: A total of 48 patients with Parkinson's disease who were treated in this hospital between December 2014 and October 2017 were selected as Parkinson's disease group, and 50 healthy volunteers who received physical examination in this hospital during the same period were selected as normal control group. The differences in serum contents of Aβ1-42, inflammatory factors and receptors as well as antioxidant enzymes were compared between the two groups, and Pearson test was used to assess the correlation between serum Aβ1-42 content and illness in patients with Parkinson's disease. Results: Serum Aβ1-42 content of Parkinson's disease group was lower than that of normal control group;serum inflammatory factors and receptors IL-2, sIL-2R, IL-6 and sIL-6R contents were higher than those of normal control group;serum antioxidant enzymes SOD, GSH-Px, CAT and TPX contents were lower than those of control group. Pearson test showed that serum Aβ1-42 content of patients with Parkinson's disease was directly correlated with the contents of inflammatory factors and receptors as well as antioxidant enzymes. Conclusions: Serum Aβ1-42 content decreases in patient with Parkinson's disease, and the specific content is directly correlated with the condition of Parkinson's disease, and can be used as an important auxiliary indicator for diagnosis and judgment of Parkinson's disease.
文摘目的对比胰高血糖素样肽-1(GLP-1)受体激动剂和二肽基肽酶-4(DPP-4)抑制剂分别联合二甲双胍治疗2型糖尿病(T2DM)的疗效及对其血清抗氧因子、炎症因子的影响。方法将2020年5月至2022年5月中国中医科学院广安门医院南区收治的120例T2DM患者纳入本次前瞻性研究,采用随机数字表法分成GLP-1联合组(n=40)、DPP-4联合组(n=40)和对照组(n=40)。GLP-1联合组患者治疗方案为二甲双胍治疗+利拉鲁肽,DPP-4联合组患者治疗方案为二甲双胍+沙格列汀,对照组患者仅口服二甲双胍治疗。治疗为期6个月。比较3组患者治疗前后的血糖相关指标[空腹血糖、餐后2 h血糖(2 h PPG)、糖化血红蛋白(HbA1c)]及胰岛素抵抗指数(HOMA-IR)、氧化应激指标[超氧化物歧化酶(SOD)和6-酮-前列环素F1α(6-Keto-PGF1α)]和炎症因子[肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和超敏C反应蛋白(hs-CRP)]表达情况。结果GLP-1联合组治疗后的空腹血糖、2 hPPG、HbA1c和HOMA-IR分别为(5.05±0.69)mmol/L、(7.42±0.98)mmol/L、(6.11±0.70)%和(3.20±0.45),DPP-4联合组分别为(5.58±0.61)mmol/L、(8.09±1.04)mmol/L、(6.65±0.76)%和(3.78±0.50),对照组分别为(6.50±0.75)mmol/L、(10.14±1.22)mmol/L、(7.80±0.81)%和(4.61±0.59),GLP-1联合组与DPP-4联合组治疗后的上述血糖相关指标及HOMA-IR均较对照组显著下降,且GLP-1联合组显著低于DPP-4联合组,差异均有统计学意义(P<0.05)。GLP-1联合组治疗后的SOD和6-Keto-PGF1α分别为(95.09±9.97)U/mL、(76.19±6.80)ng/L,DPP-4联合组分别为(85.17±10.18)U/mL、(67.32±6.39)ng/L,对照组分别为(76.89±9.06)U/mL、(60.46±6.02)ng/L,GLP-1联合组与DPP-4联合组治疗后的血清SOD、6-Keto-PGF1α均较对照组显著上升,且GLP-1联合组血清SOD、6-Keto-PGF1α均较DPP-4联合组显著上升,差异均有统计学意义(P<0.05)。GLP-1联合组TNF-α、IL-6和hs-CRP分别为(7.05±1.16)ng/L、(5.01±1.35)pg/mL、(4.04±0.51)mg/L,DPP-4联合组为(7.93±1.29)ng/L、(5.97±1.40)pg/mL、(4.99±0.59)mg/L,对照组为(10.34±1.58)ng/L、(7.58±1.49)pg/mL、(5.94±0.64)mg/L,GLP-1联合组与DPP-4联合组治疗后的上述血清炎症因子均较对照组显著下降,且GLP-1联合组显著低于DPP-4联合组,差异均有统计学意义(P<0.05)。结论GLP-1受体激动剂联合二甲双胍治疗T2DM的降糖效果优于DPP-4受体抑制剂联合二甲双胍,在改善胰岛素抵抗和氧化应激,降低炎症反应方面同样优于DPP-4受体抑制剂联合二甲双胍治疗。
