TNFAIP3 alleviates pain in lumbar disc herniation rats by inhibiting the NF-κB pathway.

Background: It's been reported that the tumor necrosis factor alpha inducible protein 3 (TNFAIP3) gene played an important role in the pathogenesis of autoimmune and chronic inflammation diseases. Moreover, in degenerative diseases of the lumbar spine the nuclear factor-κB (NF-κB) pathway is significantly activated. This study aimed to explore the role of the tumor necrosis protein-induced zinc finger protein A20 (A20) protein in degenerative diseases of the lumbar spine on the NF-κBp65 pathway. Methods: A total of 96 rats were randomly divided into 4 groups. Lumbar disc herniation (DH) was set as a sham operation group (Sham group), DH + A20 group and DH + control group (Control group); measured changes in rat paw withdrawal threshold (PWT) and paw withdrawal latency (PWL); detected the proportion of apoptotic cells in a single nucleus pulposus cell suspension, analyzed the correlation between tumor necrosis factor-α (TNF-α) content and pain in DH rats, and the expression changes of NF-κB pathway in nucleus pulposus tissue. Results: compared with the DH + Control group, the PWT and PWL of the DH + A20 group increased significantly (P<0.05); apoptosis in the DH + A20 group was significantly reduced (P<0.01); the nucleus pulposus tissue and serum levels of TNF-α and interleukin-6 (IL-6) in the DH + A20 rat group were significantly lower than those in the DH + Control group (P<0.05); the protein expression of rats in the DH + A20 group (p-p65) was significantly lower than that in the DH + Control group (P<0.05). Conclusions: The pain of lumbar disc herniation rats is related to TNF-α, and overexpression of A20 protein can reduce the pain of lumbar disc herniation by inhibiting the NF-κB pathway. Keywords: Lumbar disc herniation (lumbar DH); tumor necrosis factor-α (TNF-α); interleukin-6 (IL-6); tumor necrosis factor alpha inducible protein 3 (TNFAIP3).

The Expression Levels and Significance of GSH, MDA, SOD, and 8-OHdG in Osteochondral Defects of Rabbit Knee Joints.

OBJECTIVE: To observe the dynamic changes in oxidative stress and the expression levels of antioxidant and oxidative parameters in the blood and synovial fluid in the osteochondral defects of the rabbit knee joints and to explore the significance. METHODS: Thirty New Zealand white rabbits were randomly selected and divided into a blank control group (n = 10), a model control group (n = 10), and an osteochondral defect group (n = 10). The osteochondral defect model of rabbit knee joint was constructed by medial parapatellar arthrotomy. The expression levels of glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and 8-hydroxydeoxyguanosine (8-OHdG) in peripheral venous blood and knee synovial fluid of the three groups were measured at the end of the 4th, 8th, and 12th weeks after treatment. RESULTS: The expression levels of GSH and SOD in the blood and synovial fluid in the osteochondral defect group at the end of the 8th and 12th weeks were observably lower than those of the other two groups (P < 0.05); higher expression levels of MDA and 8-OHdG in the blood and synovial fluid of the osteochondral defect group compared with those of the other two groups were obtained (P < 0.05). At the end of the 4th, 8th, and 12th weeks, the expression levels of MDA and 8-OHdG in the blood and synovial fluid of the osteochondral defect group presented an upward trend (P < 0.05). CONCLUSION: The osteochondral defects initiate the oxidative stress in the body, which is presented as the decrease of GSH and SOD expression, and the upregulation of MDA and 8-OHdG expression.

Targeting NLRP3 inflammasome improved the neurogenesis and post-stroke cognition in a mouse model of photothrombotic stroke.

Post-stroke cognitive impairment (PSCI) severely affects the quality of a survivor's life, but its neurophysiological basis remains unknown. Neuroinflammation has been considered as an important contributor to PSCI, which could be induced or exacerbated by system inflammation. NACHT-LRR- and pyrin-domain-containing protein 3 (NLRP3) inflammasome is the most widely studied in the initiation of inflammation. Here, using a mouse model of photothrombotic stroke, we demonstrated that NLRP3 activation plays a critical role in PSCI. Intraperitoneal injection of the lipopolysaccharide-activated NLRP3 inflammasome, exacerbated the microglial activation and decreased the number of neurons, impaired the hippocampal neurogenesis, eventually aggravated PSCI. Intraperitoneal injection of MCC950 inhibited the NLRP3 activation, decreased the number of microglia, increased the number of neurons and promoted the hippocampal neurogenesis, eventually improved PSCI. Our results identified NLRP3 inflammasome as an important modifier of neuropathology in PSCI, which could be a could be a potential therapeutic target for PSCI treatment.

Highly sensitive determination of reduced glutathione based on a cobalt nanoparticle implanted-modified indium tin oxide electrode.

Cobalt nanoparticle modified indium tin oxide (CoNP/ITO) electrodes fabricated by ion implantation were applied for the detection of reduced glutathione (GSH). The CoNP/ITO electrode was characterized by scanning electron microscopy (SEM), energy dispersive X-ray (EDX) detector and X-ray photoelectron spectroscopy (XPS). The assay performance with regard to GSH were evaluated by cyclic voltammetry (CV) and chronoamperometry (I-t). The proposed sensor exhibited a much higher electrocatalytic activity toward the oxidation of GSH than the bare ITO electrode, with a detection limit of 5 nM. The CoNP/ITO electrode showed enhanced electrocatalytic properties, high sensitivity, good long-term stability and reproducibility as well as a rapid response to detect GSH. In addition, the CoNP/ITO electrode was also used to analyse the GSH concentration in eye drop samples, and the results were in good agreement with the labelled values.

Venlafaxine modulates depression-induced behaviour and the expression of Bax mRNA and Bcl-xl mRNA in both hippocampus and myocardium.

OBJECTIVES: Major depressive disorder is associated with progressive brain changes and is frequently comorbid with cardiovascular disease. There may be shared pathophysiological pathways between cerebral and myocardial dysfunction that impact on apoptosis related proteins. Our aim was to examine behaviour changes of rats with chronic mild stress (CMS), explore the expression of Bax and Bcl-xl in the hippocampus and myocardium, and additionally evaluate the effects of venlafaxine on these molecular mechanisms. METHODS: Rats were randomly divided into three groups. The behaviour was assessed using the open field and sucrose consumption tests. Gene expression was measured by RT-PCR. RESULTS: In CMS, there was a significant reduction of movements and sucrose consumption, an increased Bax level and a decreased Bcl-xl level in both the hippocampus and myocardium. The venlafaxine group showed an increase in movements and sucrose consumption, as well as upregulated expression of Bcl-xl and downregulated expression of Bax in both the hippocampus and myocardium. CONCLUSIONS: These results demonstrate that in CMS, there is an increase in pro-apoptotic pathways that is reversed by venlafaxine. This suggests that there are shared active biochemical pathways that may play a role in the process of neuroprogression that is seen in depression and cardiovascular disorders.

Involvement of dimethylarginine dimethylaminohydrolase-2 in visfatin-enhanced angiogenic function of endothelial cells.

BACKGROUND: Visfatin, a new adipocytokine, was reported to promote angiogenesis. Dimethylarginine dimethylaminohydrolase (DDAH), which could regulate vascular endothelial growth factor (VEGF) expression in endothelial cells, is thought as a novel modulator of angiogenesis. The aim of the study was to investigate the role of DDAH2 in visfatin-induced angiogenesis in human umbilical vein endothelial cells (HUVECs). METHODS AND RESULTS: Visfatin could concentration- and time-dependently enhance cell migration and tube formation reflecting angiogenic capability of HUVECs. Moreover, visfatin upregulated both mRNA and protein expressions of DDAH2 and VEGF. Angiogenic effects of visfatin were attenuated by DDAH2 small interfering RNA. Visfatin-induced protein kinase B (Akt) phosphorylation and phosphoinositide 3 kinase (PI3K) inhibitors could suppress visfatin-induced upregulation of DDAH2 and VEGF expressions. CONCLUSIONS: Taken together, our results demonstrate that PI3K/Akt-mediated upregulation of DDAH2 expression plays a critical role in visfatin-promoted angiogenesis via regulating VEGF-dependent pathway.