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BACKGROUND: Oxidative injury is considered to be one of the important factors of cerebral ischemia-reperfusion injury. Superoxide dismutase 2 (SOD2) is a key mitochondrial antioxidant molecule, and fenofibrate can regulate the expression of SOD2 by activating peroxisome proliferator-activated receptor α.OBJECTIVE: To explore whether the mechanism of fenofibrate in the treatment of cerebral ischemia-reperfusion injury depends on the expression of SOD2. METHODS: The TALENs system was used to construct SOD2 transgenic mice. The transgenic mice were genotyped by PCR and DNA sequencing techniques. The expression of SOD2 protein in transgenic mice was detected by western blot assay. Wild-type and SOD2 transgenic mice were randomly divided into four groups: wild-type control group (n=6), wild-type fenofibrate group (n=6), SOD2 transgenic control group (n=5) and SOD2 transgenic fenofibrate group (n=5). A mouse model of middle cerebral artery occlusion was prepared using the suture-occlusion method. After 90 minutes of ischemia, the thread was removed to reperfuse cerebral blood flow for 30 minutes. A cerebral blood flow monitor was used to monitor local cerebral blood flow. Brain tissue slices were taken for 2,3,5-triphenyltetrazolium chloride staining to analyze the situation of cerebral infarction in each group. RESULTS AND CONCLUSION: After PCR and DNA sequencing analysis, nine SOD2+/+ transgenic mice were successfully constructed. After cerebral ischemiareperfusion, the wild-type fenofibrate group showed partial recovery of cerebral blood flow and significantly reduced cerebral infarction volume compared with the wild-type control group (P < 0.001). There was no significant difference in cerebral blood flow and cerebral infarction volume between the SOD2 transgenic fenofibrate group and the SOD2 transgenic control group. The SOD2 transgenic control was superior to the wild-type control group in terms of improving cerebral blood flow and cerebral infarction (P < 0.001). There were also no significant differences in cerebral blood flow and cerebral infarction volume between the wild-type fenofibrate group and the SOD2 transgenic control group and between the wild-type fenofibrate group and the SOD2 transgenic fenofibrate group. To conclude, the expression of SOD2 is one of the mechanisms of fenofibrate in the treatment of cerebral ischemia-reperfusion injury. [ABSTRACT FROM AUTHOR]

BACKGROUND: Intervertebral disc degeneration is a condition caused by the combined effects of various factors, such as cellular apoptosis, oxidative stress, and inflammatory responses. Currently, it is believed that the core of this condition lies in the degeneration and apoptosis of nucleus pulposus cells (NPCs). However, the specific pathological mechanisms remain unclear. OBJECTIVE: By investigating the expression of the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt)/hypoxia-inducible factor 1-alpha (HIF-1α) signaling pathway and the apoptosis of NPCs under different oxygen concentrations, to clarify the biological characteristics of NPCs under varying oxygen levels, and to explore the mechanisms of intervertebral disc degeneration. METHODS: Normal and degenerated NPCs were collected. The second-generation cells were used for imaging identification. The third-generation cells were cultured in the following conditions: 37°C, air, 100% humidity. Leibovitz’s medium containing 100 μmol/L CoCl2 and 10% fetal bovine serum medium containing 100 μmol/L H2O2 were used to create distinct oxygen concentration environments for the third-generation cells, allowing for the investigation of cellular responses and behaviors under normal, low oxygen, and oxidative stress conditions. The third-generation cells were divided into six groups: normal NPCs+hypoxia, normal NPCs+normoxia, normal NPCs+oxidative stress, degenerated NPCs+hypoxia, degenerated NPCs+normoxia, and degenerated NPCs+oxidative stress groups. Cell viability and proliferation were assessed using the cell counting kit-8 method. Cell apoptosis was detected using flow cytometry. RT-PCR and western blot assay were utilized to examine the protein and mRNA expression levels of PI3K, AKT, and HIF-1α. RESULTS AND CONCLUSION: At different oxygen concentrations, the cell proliferation rate of both normal and degenerated NPCs decreased as the oxygen concentration increased. Conversely, the apoptosis rate increased as the oxygen concentration rose (P < 0.05). With the normal NPCs+hypoxia group as the control group, the effect of degenerated NPCs on the apoptosis rate was highly significant (P < 0.001). Oxygen concentration had a highly significant impact on both NPC proliferation rate and apoptosis rate (P < 0.001). The interaction between cell degeneration and oxygen concentration significantly affected both NPC proliferation and apoptosis rates (P < 0.05). At different oxygen concentrations, the protein and mRNA expression levels of PI3K, AKT, and HIF-1α in normal NPCs were highest under low oxygen concentration, followed by oxidative stress environment, and lowest under normoxia. In degenerated NPCs, the protein and mRNA expression levels of PI3K, AKT, and HIF-1α decreasd as the oxygen concentration increased. The protein and mRNA expression levels of PI3K and Akt in normal NPCs were significantly higher than those in degenerated NPCs (P < 0.05). With the normal NPCs+hypoxia group as the control group, the effects of normal or degenerated NPCs, as well as oxygen concentration, on the protein and mRNA expression of PI3K, AKT, and HIF-1α were highly significant. The interaction between cell degeneration and oxygen concentration also had an extremely significant effect on the protein and mRNA expression of PI3K, AKT, and HIF-1α (P < 0.001). To conclude, there is a close correlation between the proliferation and apoptosis of NPCs and both oxygen concentration and the cellular functional state. The PI3K/Akt/HIF-1α signaling pathway exhibits antagonistic regulatory effects under various cellular functional states and different oxygen concentration environments. The mechanism may be associated with the activation of the PI3K/Akt signaling pathway, which consequently transcribes HIF-1α, thus maintaining the balance of reactive oxygen species metabolism. This pathway plays a significant role in inhibiting oxidative stress, antagonizing NPCs apoptosis, and consequently delaying intervertebral disc degeneration. [ABSTRACT FROM AUTHOR]

Objective To explore the effect of zinc deficiency on oxidative stress and methylation of human normal esophageal epithelial cells (HEEC) induced by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) .Methods The cells were divided into the normal control group, the zinc-rich group, the positive control group and the zinc-deficient group, and intervened for 12,24 and 48 hours respectively. The levels of malondialdehyde (MDA),superoxide dismutase (SOD),glutathione peroxidase (GSH-Px),methylation status of O6-methylguanine-DNA methyltransferase (MGMT) and MLH1 genes and expression level of MGMT protein were compared in each group. Results The median inhibitory concentration of TPEN on HEEC was 1.0 μmol/L. The levels of MDA and GSH-Px in the four groups at different time points were significantly different (P<0.05) .The level of SOD in the four groups at 12 hours was significantly different (P<0.05) .MGMT and MLH1 genes in the four groups showed partial methylation. The expression level of MGMT protein in the four groups was significantly different at 24 hours (P<0.05),but there was no significant difference at 12 and 48 hours (P>0.05) .Conclusion Zinc deficiency can lead to oxidative stress, methylation of MGMT and MLH1 genes and abnormal expression of MGMT protein in HEEC induced by MNNG. [ABSTRACT FROM AUTHOR]

Copyright of Progress in Modern Biomedicine is the property of Publishing House of Progress in Modern Biomedicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

BACKGROUND: More and more evidences show that ROCK signaling pathway is involved in inflammation and oxidative stress. Fasudil is an effective Rho kinase inhibitor. Our previous series of studies have proved that fasudil has neuroprotective effects. However, it is still unclear that whether fasudil has protective effect on oxidative damage to astrocytes and its possible mechanisms. OBJECTIVE: To explore the protective effect and mechanism of fasudil on lipopolysaccharide-induced oxidative injury in astrocytes. METHODS: Primary C57BL/6 mouse astrocytes were cultured and divided into PBS control group, lipopolysaccharide stimulation group (1 mg/L), lipopolysaccharide (1 mg/L) combined with fasudil (15 mg/L) treatment group. After 24 hours of treatment, MTT assay was used to detect the viability of astrocytes. The content of malondialdehyde and the activity of superoxide dismutase in astrocytes were measured using the kit to evaluate the level of oxidative stress. Immunofluorescence staining was used to detect the expression of cleaved-caspase-3, the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1) in astrocytes. Western blot assay was used to detect the total Nrf2, nuclear Nrf2 and HO-1 protein levels. RESULTS AND CONCLUSION: (1) Compared with the PBS control group, the astrocyte viability in the lipopolysaccharide stimulation group was reduced, and fasudil treatment improved the cell damage induced by lipopolysaccharide. (2) Compared with the PBS control group, lipopolysaccharide resulted in a significant decrease in the activity of superoxide dismutase and a significant increase in the level of malondialdehyde in astrocytes (P < 0.01). Fasudil significantly increased the activity of superoxide dismutase (P < 0.01) and reduced the level of malondialdehyde (P < 0.01). (3) Compared with the PBS control group, the expression of cleaved-caspase-3 was significantly increased in the lipopolysaccharide stimulation group. Compared with the lipopolysaccharide stimulation group, the expression of cleaved-caspase-3 was decreased in the lipopolysaccharide combined with fasudil treatment group. (4) Fasudil could promote the nuclear translocation of Nrf2 and significantly increase the expression of total Nrf2, nucleus Nrf2 and HO-1 after lipopolysaccharide stimulation. (5) The results indicate that fasudil can inhibit lipopolysaccharide-induced astrocytic injury by regulating the Nrf2/HO-1 signaling pathway. [ABSTRACT FROM AUTHOR]

Copyright of Chinese Journal of Tissue Engineering Research / Zhongguo Zuzhi Gongcheng Yanjiu is the property of Chinese Journal of Tissue Engineering Research and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Diabetic mellitus is a kind of chronic disease threatening people’s health. Microvascular lesions is the specificity of diabetes disease, the complications including nephropathy, retinopathy and neuropathy. The occurrence of diabetic microvascular lesion development is influenced by many factors, the mechanism of research has formed a variety of theories, such as the enzyme glycosylated chemical, polyol pathway, oxidative stress and hexose amine path theory, etc. In recent years, lipoic acid for the treatment of diabetic microvascular complications is the hot spot in home and abroad. Lipoic acid is powerful antioxidant. Their functions include: scavenging free radicals and reactive oxygen species, and regeneration of exogenous and endogenous antioxidants such as glutathione in the body.They are attenuate the oxidative stress reaction. Lipoic acid also decrease causative factor resulting in complication of diabetic microangiopathy, and intervene in the polyol pathway and hexose amine pathway and exert protective effect on target organ. In this paper, lipoic acid in diabetic microangiopathy application to do a brief overview. [ABSTRACT FROM AUTHOR]