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Objective:To explore whether esketamine (ESK) can inhibit the proliferation and induce apoptosis of breast cancer cells, and explore the mechanism.Methods:CCK-8 assay was used to detect the inhibitory effect of ESK on the proliferation of breast cancer cells. Annexin V/PI staining was used to detect the morphological changes of cells; Apoptosis and reactive oxygen species were detected by flow cytometry. Western blot was used to detect apoptosis and pathway expression.Results:CCK-8 experiment results proved that ESK could inhibit the proliferation of breast cancer cells in a time-dependent manner. The survival rate of MDA-MB-468 cells treated with ESK at 20 μM was (35.47±2.61) %, which was statistically different from that treated with vinorelbine at the same concentration ( P<0.05). The IC50 value of ESK on MDA-MB-468 cells was (14.54±2.12) μM. After treatment with ESK, the mitochondrial membrane potential was significantly reduced. In the protein level, the expression of Cytochrome C, Bax and Caspase-3 was up-regulated, and the expression of Bcl-2 was down regulated, which induced the mitochondrial dependent apoptosis of MDA-MB-468 cells. ESK could up regulate the level of reactive oxygen species in MDA-MB-468 cells and regulate the expression of PI3K/AKT signaling pathway. Conclusions:ESK can inhibit the proliferation and migration of breast cancer cells and induce them to play a mitochondrial dependent apoptosis. Its mechanism is achieved by up regulating the level of ROS in breast cancer cells, thereby regulating the PI3K/AKT signaling pathway, which provides a theoretical basis for the development and utilization of Aln.
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Objective@#To determine the clinical problems and outcome indicators that need to be included in the expert consensus of 5-aminolevulinic acid (ALA) photodynamic therapy in the treatment of oral potential malignant diseases. @*Methods@# Based on the relevant literature, the clinical problems and outcome indicators were drafted during the meeting. The Delphi method was used for expert consultation and expert opinion collection. The average and standard deviation of the voting results were calculated to determine the importance of the indicators, and the positive coefficient, variation coefficient and coordination coefficient were calculated for quality control. @* Results@#In the first round of the Delphi method, 12 outcome indicators (the main reference elements include photon integral flux, power density, illumination time, and spot diameter were identified; the specific parameters are photon integral flux of 100 J/cm2 and power density of 100-600 mW/cm2. A diode laser of (630 ± 5) nm wavelength should be chosen. The analgesic regimen is local anesthesia supplemented by hypothermia and intermittent laser irradiation before treatment. Lesions with hyperkeratotic require pretreatment. The concentration of ALA administered was set at 20%. Eight clinical problems (main reference elements of photodynamic irradiation dose, specific parameters, choice of light source, evaluation criteria of efficacy, prevention of adverse effects, dosing concentration, whether oral potentially malignant diseases with hyperkeratosis should be pretreated, administration of photosensitizers) were included according to the literature and expert discussion. In the second round, 89 experts completed the questionnaire and gave very important evaluations of 9 outcome indicators (the main reference elements included photon integral flux, power density and illumination time; the specific parameters were a photon integral flux of 100 J/cm 2 and a power density of 100-600 mW/cm2). A diode laser of (630 ± 5)nm wavelength should be chosen. The concentration of ALA administered was set at 20%. Six clinical problems (main reference elements of photodynamic irradiation dose, specific parameters, choice of light source, evaluation criteria of efficacy, dosing concentration, administration of photosensitizers), and the remaining 3 were given important evaluations, with good consistency.@*Conclusion@# In this study, the irradiation dose, mode of administration and concentration, evaluation criteria of efficacy, prevention of adverse effects and pretreatment regimen of ALA photodynamic therapy for oral potentially malignant diseases determined by the Delphi method had good agreement among experts.
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@#Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia, often accompanied by bone metabolic disorders, microvascular diseases, etc. At present, it is still controversial whether diabetes will reduce the survival rate of implants, but studies have shown that diabetes can damage the bone tissue around the implants and interfere with the process of osseointegration by producing excessive reactive oxygen species(ROS). In this paper, combined with the literature published worldwide in recent years, the effect and mechanism of ROS on the osteointegration of implants of diabetic patients and the measures to improve the osteointegration under the condition of diabetes are reviewed. The results of literature review showed that excessive ROS induced by diabetes can damage osseointegration through adenosine 5′-monophosphate -activated protein kinase, Wnt/catenin, phosphatidylinositol 3-kinase-protein kinase B, mitogen activated protein kinase and other signaling pathways, as well as vascular injury. In animal models of diabetes, some drugs, such as insulin, curcumin, 1,25-dihydroxyvitamin D3, and metformin, have been shown to improve the osseointegration of implants to some extent by reducing ROS levels. These results suggest that ROS may be a key therapeutic target for improving success rate of dental implant treatment in diabetic patients.
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Silver-containing preparations are widely used in the management of skin wounds, but the effects of silver ions on skin wound healing remain poorly understood. This study investigated the effects of silver ions (Ag) on the proliferation of human skin keratinocytes (HaCaT) and the production of intracellular reactive oxygen species (ROS). After treating HaCaT cells with Ag and/or the active oxygen scavenger N-acetyl cysteine (NAC), cell proliferation and intracellular ROS generation were assessed using CCK-8 reagent and DCFH-DA fluorescent probe, respectively. In addition, 5-bromo-2-deoxyUridine (BrdU) incorporation assays, cell cycle flow cytometry, and proliferating cell nuclear antigen (PCNA) immunocytochemistry were conducted to further evaluate the effects of sub-cytotoxic Ag concentrations on HaCaT cells. The proliferation of HaCaT cells was promoted in the presence of 10 and 10 mol/L Ag at 24, 48, and 72 h. Intracellular ROS generation also significantly increased for 5-60 min after exposure to Ag. The number of BrdU-positive cells and the presence of PCNA in HaCaT cells increased 48 h after the addition of 10 and 10 mol/L Ag, with 10 mol/L Ag markedly increasing the cell proliferation index. These effects of sub-cytotoxic Ag concentrations were repressed by 5 mmol/L NAC. Our results suggest that sub-cytotoxic Ag concentrations promote the proliferation of human keratinocytes and might be associated with a moderate increase in intracellular ROS levels. This study provides important experimental evidence for developing novel silver-based wound agents or dressings with few or no cytotoxicity.
Subject(s)
Humans , Apoptosis , Cell Line , Cell Proliferation , Fluorescent Antibody Technique , Keratinocytes , Cell Biology , Proliferating Cell Nuclear Antigen , Metabolism , Reactive Oxygen Species , Metabolism , Silver , PharmacologyABSTRACT
Objective To explore the mechanism of Shuilu erxiandan against male′s infertility and asthenoospermia .Methods Human sperm with normal physiological function were collected ,and then sperm suspension were divided into the normal group ,the model group ,Vitamin C group and the groups of large ,medium and small dose of Shuilu erxiandan .The reactive of species was made from hypoxanthine-xanthine oxidase .In the oxygen environment ,Vitamin C(0 .25 g/L) and different content (1 .0 ,0 .5 ,0 .25 g/mL) of extract from Shuilu erxiandan were hatched with sperm .Then the function of sperm membrane in every group was evalu-ated using hypoosmoticswelling .Meanwhile the content of MDA and SOD were detected .Results Expansion of sperm and sperm motility in all the groups of vitamin C and large ,medium and small dose of Shuilu erxiandan′s extract were significantly higher than that in the model group at time point of 1 ,3 and 6 h (P< 0 .05) .Also ,medium dose of Shuilu erxiandan (0 .5 g/mL) displayed more effective on expansion of sperm and sperm motility compared with that in the vitamin group C (P< 0 .05) .All the groups of vitamin C and large ,medium and small dose of Shuilu erxiandan′s extract significantly indicated descreased MDA content and improved SOD activity compared with that in the model group (P< 0 .05) .Also ,this effect of medium dose of Shuilu erxiandan (0 .5 g/mL ) on MDA and SOD activity were superior to that in vitamin C group ,which showed significant difference (P< 0 .05) .Conclusion Ex-tract from Shuilu erxiandan could significantly protect structure and function of sperm membrane ,which is correlated with interve-ning its lipin peroxidation .
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Objective In the present study, we investigated the effects of advanced oxidation protein products(AOPP) on reactive oxygen species(ROS) production in murine osteoblastic MC3T3-E1 cells by NADPH oxidase enzymes pathway. Methods Experiments were divided into three groups, including control group, rats albumin(RSA) group, and AOPP group. Different concentrations of AOPP were added to the osteoblastic MC3T3-E1 cells culture medium. The production of ROS in MC3T3-E1 cells was measured by the fluorescence intensity of intracellular fluoroprobe ( DCFD ) . In order to verify the effect of enzyme of the production of ROS, the specific inhibitors of corresponding enzymes were added in the MC3T3-E1 cells which were cultured in the medium with AOPP. Finally, western blot and immunofluorescence were used to observe the changes of NADPH oxidase enzymes subunits. Results Different concentrations of AOPP (50,100,200μg/ml) induced MC3T3-E1 cells to produce different amount of ROS. The higher concentrations of AOPP were added, the more ROS were produced. Furthermore,200μg/ml AOPP induced the maximum amount of ROS production(P<0. 05). Meanwhile, AOPP induced MC3T3-E1 cells to produce different amount of ROS with a time-dependent manner. The peak amount of ROS production in MC3T3-E1 cells was observed in 3h when AOPP were added (P<0. 05). In addition, when specific inhibitors of corresponding enzymes were added in the MC3T3-E1 cells, the production of ROS were significantly suppressed by C-SOD, DPI, and apocynin(P<0. 05). On the other hand, AOPP can up-regulate the expression of Nox4 protein of the MC3T3-E1 cells, which is one of the subunits of NADPH oxidase enzymes. Meanwhile, AOPP can also induce the membrane migration of p47phox subunit. Conclusion AOPP induces osteoblastic MC3T3-E1 cells to produce ROS by NADPH oxidase enzymes pathway, and which may be one of the pathogenesis of AOPP involved in osteoporosis.
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Many things are unknown about the radioactive hot springs. We have not yet obtained the conclusive evidence of whether the low dose of radiation by radon in the hot springs is healthful or harmful for us. Thus, to grasp the present conditions of the radioactive hot springs scientifically, I reviewed them from the many-sided viewpoints in the following order. At first, some basic information on the radioactive hot springs was summarized to look around them all over. Next, based on the hot spring analysis tables obtained from three representative hot spring resorts in our country, the effective ingredients such as radon, metals, and several kinds of ions presented in the spring waters were evaluated for each hot spring. Then, radon as an element, the radon exposure, and the active oxygen species generated by the radiation of radon were explained to understand the fundamental action of radon. Furthermore, some reports related to the lung cancer risk by inhaling radon were introduced to take the cancer risk in the radioactive hot springs into consideration. Since the oxidative DNA damage induced by hydroxyl radical is considered to be a cause for cancers, it was discussed that the urinary concentrations of 8-hydroxy-2’-deoxyguanosine (8-OHdG), a marker of the DNA damage, could be used as an index for evaluating the effects of the radioactive hot springs on human health.
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Many things are unknown about the radioactive hot springs. We have not yet obtained the conclusive evidence of whether the low dose of radiation by radon in the hot springs is healthful or harmful for us. Thus, to grasp the present conditions of the radioactive hot springs scientifically, I reviewed them from the many-sided viewpoints in the following order. At first, some basic information on the radioactive hot springs was summarized to look around them all over. Next, based on the hot spring analysis tables obtained from three representative hot spring resorts in our country, the effective ingredients such as radon, metals, and several kinds of ions presented in the spring waters were evaluated for each hot spring. Then, radon as an element, the radon exposure, and the active oxygen species generated by the radiation of radon were explained to understand the fundamental action of radon. Furthermore, some reports related to the lung cancer risk by inhaling radon were introduced to take the cancer risk in the radioactive hot springs into consideration. Since the oxidative DNA damage induced by hydroxyl radical is considered to be a cause for cancers, it was discussed that the urinary concentrations of 8-hydroxy-2’-deoxyguanosine (8-OHdG), a marker of the DNA damage, could be used as an index for evaluating the effects of the radioactive hot springs on human health.
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Recently, new hot springs are born in Tokyo one after another. Most of these are artificial hot springs by digging deep under the ground on the bowling, and pumping up the deep water warmed by the heat source of geothermal gradient. Maeda et al. have investigated the ingredients in these hot springs of Tokyo 23 wards, and concluded that they are medically effective to promote health. It is unclear, however, how much these hot springs are medically effective compared to the well-known volcanic hot springs. Thus, sodium-chloride type hot springs (Tokyo-A & Atami) and sodium-hydrogen carbonate type hot springs (Tokyo-B & Naruko) were chosen, and their analytical tables of chemical compositions were obtained from each hot spring resort through the Internet. Comparisons of the ingredients shown in the analytical tables were carried out to clarify difference between the artificial hot springs and the volcanic hot springs. Since Tokyo-A and Tokyo-B do not belong to volcanic hot springs, their source temperatures are lower than the source temperatures of Atami and Naruko, and they do not contain various pharmacologically effective chemicals, such as sulfur compounds, free carbonate, etc. Furthermore, the modulation effects by the environmental factors such as hot spring location, climate, landscape etc. cannot be expected for the hot springs in Tokyo. However, the physical effects of hydrostatic pressure and buoyancy are expected in Tokyo-A containing large amounts of seawater components. The most important medical effects of hot springs are considered to be suppressing active oxygen species and their activities, and repairing the cells damaged by the active oxygen species. From these points, although Tokyo hot springs have some healing effects, the medical effects as observed in the volcanic hot springs cannot be expected in Tokyo hot springs. For the establishment of balneology, the evaluations of each hot spring based on scientifically accurate information are required.
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Recently, new hot springs are born in Tokyo one after another. Most of these are artificial hot springs by digging deep under the ground on the bowling, and pumping up the deep water warmed by the heat source of geothermal gradient. Maeda et al. have investigated the ingredients in these hot springs of Tokyo 23 wards, and concluded that they are medically effective to promote health. It is unclear, however, how much these hot springs are medically effective compared to the well-known volcanic hot springs.<BR> Thus, sodium-chloride type hot springs (Tokyo-A & Atami) and sodium-hydrogen carbonate type hot springs (Tokyo-B & Naruko) were chosen, and their analytical tables of chemical compositions were obtained from each hot spring resort through the Internet. Comparisons of the ingredients shown in the analytical tables were carried out to clarify difference between the artificial hot springs and the volcanic hot springs.<BR> Since Tokyo-A and Tokyo-B do not belong to volcanic hot springs, their source temperatures are lower than the source temperatures of Atami and Naruko, and they do not contain various pharmacologically effective chemicals, such as sulfur compounds, free carbonate, etc. Furthermore, the modulation effects by the environmental factors such as hot spring location, climate, landscape etc. cannot be expected for the hot springs in Tokyo. However, the physical effects of hydrostatic pressure and buoyancy are expected in Tokyo-A containing large amounts of seawater components.<BR> The most important medical effects of hot springs are considered to be suppressing active oxygen species and their activities, and repairing the cells damaged by the active oxygen species. From these points, although Tokyo hot springs have some healing effects, the medical effects as observed in the volcanic hot springs cannot be expected in Tokyo hot springs. For the establishment of balneology, the evaluations of each hot spring based on scientifically accurate information are required.
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BACKGROUND:The viability of human umbilical cord-derived mesenchymal stem cel s is often declined with the commonly used transplantation storage solution in clinics, which may influence the therapeutic effects of cel ular transplantation. However, reasons for this are stil unknown. OBJECTIVE:To investigate the role of oxidative stress in the reduction of human umbilical cord-derived mesenchymal stem cel s viability in the storage process during clinical transplantation and to observe the effects of radical scavenger on the results. METHODS:Human umbilical cord-derived mesenchymal stem cel s were harvested and cultured in normal saline for 0, 2, 4 and 6 hours at room temperature. Intracel ular reactive oxygen levels were detected at those time points. Antioxidant enzyme activities and levels of malondialdehyde were measured to determine the intracel ular oxidative stress levels after storage. Cel adhesion rate changes were retested after adding N-acetyl cysteine to the storage solution. RESULTS AND CONCLUSION:The reactive oxygen levels in human umbilical cord-derived mesenchymal stem cel s were increased significantly after normal saline storage and levels of malondialdehyde were increased in a time-dependent manner. Activities of superoxide dismutase, catalase and glutathione peroxidase were al reduced. Addition of N-acetyl cysteine into the storage medium decreased the reactive oxygen levels and improved the human umbilical cord-derived mesenchymal stem cel s viabilities. Experimental findings indicate that, increased reactive oxygen species in human umbilical cord-derived mesenchymal stem cel s is one of the reasons for reduced cel viability. Adding the radical scavenger N-acetyl cysteine can improve the storage effects of human umbilical cord-derived mesenchymal stem cel s.
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Objective To study the anti-oxidative stress effects of benazepril and candesartan.Methods SHRs of 12 weeks old were given benazepril(10 mg/kg?d,n=9)or candesartan(4 mg/kg?d,n=9)or combina- tion(Ben:10 mg/kg?d+Can:4 mg/kg?d)for 12 weeks.The tail arterial pressure was measured every two weeks.At end of study,pathological changes in the thoracic aorta,activity of SOD,serum contents of NO and hydroxy radicals,plasma Ang Ⅱ and cGMP,eNOS and P22~(phox)protein expressions in aortic tunica intima were de- termined.Results The thoracic aorta wall was thickened markedly in SHRs,and blood pressure,hydroxy radi- cal,Ang Ⅱ and P22~(phox)protein expression were increased significantly,while the serum NO,level of cGMP and eNOS expression were decreased.Benazepril(Ben)or Candesartan(Can)inhibit the thickening of vessel wall, enhance the activity of SOD(Ben:68.7?2.1,Can:65.6?4.2 vs SHR:48.8?3.2 U/mL,P
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It has been suggested that various neurological diseases (particularly those accompanying aging, the cranial nerves, etc.) involve oxidative stress. Some of these diseases have been successfully controlled with traditional herbal medicine. In the present study, Ougi-keishi-gomotsu-to, reported to be effective against subacute myelo-opticoneuropathy (SMON), showed an inhibitory effect on lipid peroxidation of homogenate by hydroxy radical, a type of active oxygen derived from the interaction of Fe<sup>3+</sup> and 8-hydroxyquinoline. 8-hydroxyquinoline is a homologue of chinoform, which is causally related to the pathogenic process of SMON. It has also been indicated that Ougi-keishi-gomotsu-to has a hydroxy radical scavenger with radical-quenching effects. It is, therefore concluded that Ougi-keishi-gomotsu-to has an inhibitory effect on oxidative stress.
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The changes of active oxygen species and some enzymes in Grifola umbellata induced by Armillaria mellea elicitor were studied.The results showed that active oxygen species appeared in both mycelia and sclerotia of G.umbellata after treated with A.mellea.There were two phases of active oxygen production upon addition of A.mellea elicitor.Phase I occured at 10 minute after addition of A.mellea elicitor.Phase Ⅱ occurred about 90 minute.The changes of some enzyme activity were also studied in this paper.Compared with control,the A.mellea elicitor could reduce the activity of superoxide dismutase and peroxidase.The catalase activity changed only little.The phenylanine ammonia lyase activity declined in the early stages and then increased in the late stages.
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By the method of chemiluminescence, it was showed that BW-755C strongly inhibited the generation of active oxygen in PMNs stimulated by f-MLP, A23187 or opsonized zymosan A, while the inhibitory effect of indomethacin was quite weaker, Nifidipine, diltiazem and verapamil inhibited the generation of active oxygen in PMNs stimulated by A23187 at low concentration, but they did not block intracel-lular calcium ion increase stimulated by A23187. PGE1 was shown in to be a selective inhibitor of f-MLP-induced active oxygen production PMNs.
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The scavenging effects of Total Flavonoids of Hippophae ( TFH ) were studied by using ESR-spin trapping technique in different systems, and the inhibitery effects on chemiluminescence ( CL ) of poly-morphonuclear leukocytes ( PMN) were measured by using luminol-de-pendent CL. TFH ( 1.7mg/L ) significantly reduced the active oxygen radicals level of PMA-stimulated PMN; TFH ( 0.03-3mg/L ) could remarkably scavenged O2 in xanthine/xanthine oxidase (Xan/XO)system and the effect was concentration-dependent. The scavenging effect of TFH on O2 in irradiation riboflavin system was not so strong as in Xan/XO system. TFH ( 3 mg/L ) could scavenged OH produced in Fenton's reaction; TFH ( 1 mg/L ) effectively inhibited PMN CL stimulated by PMA.The effects of TFH on active oxygen radicals produced by PMN and O2 in Xan/XO system were stronger than Vit E.
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Aim To investigate the effects of Curcumin on Heme oxygenase isozymes in SH-SY5Y cells and explore a new mechanism of Curcumin in neuroprotection. Methods The human SH-SY5Y cells were cultured in vitro and treated with Curcumin at 0,1.25,5.0,20 ?mol?L-1 for 24 h,or with Curcumin at 5.0 ?mol?L-1 for 0,12,24,and 48 h. The active oxygen was detected by fluorescent probe DCFH-DA and fluorospectro-photometer. RT-PCR was used to detect the expression of HO-1 and HO-2 mRNA. Western blot was performed to detect the levels of HO-1 and HO-2 protein.Results The results showed that Curcumin could inhibit the levels of active oxygen(P