Chronic spinal cord compression associated with intervertebral disc degeneration in SPARC-null mice

Chronic spinal cord compression(CSCC)is induced by disc herniation and other reasons,leading to movement and sensation dysfunction,with a serious impact on quality of life.Spontaneous disc herniation rarely occurs in rodents,and therefore establishing a chronic spinal cord compression(CSCC)animal model is of crucial importance to explore the pathogenesis and treatment of CSCC.The absence of secreted protein,acidic,and rich in cysteine(SPARC)leads to spontaneous intervertebral disc degeneration in mice,which resembles human disc degeneration.In this study,we evaluated whether SPARC-null mice may serve as an animal model for CSCC.We performed rod rotation test,pain threshold test,gait analysis,and Basso Mouse Scale score.Our results showed that the motor function of SPARC-null mice was weakened,and magnetic resonance images revealed compression at different spinal cord levels,particularly in the lumbar segments.Immunofluorescence staining and western blot assay showed that the absence of SPARC induced apoptosis of neurons and oligodendrocytes,activation of microglia/macrophages with M1/M2 phenotype and astrocytes with A1/A2 phenotype;it also activated the expression of the NOD-like receptor protein 3 inflammasome and inhibited brain-derived neurotrophic factor/tyrosine kinase B signaling pathway.Notably,these findings are characteristics of CSCC.Therefore,we propose that SPARC-null mice may be an animal model for studying CSCC caused by disc herniation.

Effect of Galla chinensis on the remineralization of two bovine root lesions morphous in vitro

The present study aims to evaluate the effect of Galla chinensis compounds on the remineralization of two artificial root lesions morphous in vitro. Sixty bovine dentine blocks were divided into two groups and individually treated with two levels of demineralization solutions to form erosive and subsurface artificial carious lesions in vitro. Each group was then divided into three subgroups, each of which were treated with a remineralization solution （positive control）, deionized water （negative control）, or 4 000 mg-L-1 aqueous solutions of Galla chinensis extract. The dentine blocks were then subjected to a pH-cycling regime for 7 days. During the first 4 days, the daily cycle included 21-h deal and 3-h demineralization applications. The dentine blocks were dealt with the entire day during the remaining 3 days. Two specimens from each of the treatment groups were selected and observed under a polarized light microscope. Data collected using a laser scanning confocal microscope were computerized and analyzed. Galla chinensis extract clearly enhanced the remineralization of both erosive lesion and subsurface lesion patterns in the specimens （P〈0.05）. The level of remineralization of the erosive lesion by Galla chinensis extract was lower than that of the subsurface lesion （P〈0.05）. In addition, the remineralization of the subsurface lesion by Galla chinensis extract was higher than that of the remineralization solution （P〈0.05）. No significant difference between the remineralization of erosive lesions by Galla chinensis extract and the remineralization solution was observed （P〉0.05）. So Galla chinensis extract has the potential to improve the remineralization of artificial root lesions under dynamic pH-cyclic conditions, indicating its potential use as a natural remineralization medicine.

Mechanism of resveratrol on the promotion of induced pluripotent stem cells

OBJECTIVE： To investigate the effects of resveratrol （RV） in reprogramming mouse embryonic fibroblasts （MEFs） into induced pluripotent stem cells （iPSCs） and the related mechanism. METHODS： Primary MEFs were isolated from E13.5 embryos and used within three passages. Retroviruses expressing Sox2 and Oct4 were produced by transfecting GP2-293t cells with recombinant plasmids murine stern cell virus （MSCV）-Sox2 and MSCV-Oct4. Supernatants containing retroviruses were obtained after 48-hour transfection and MEFs were then infected. Different concentrations （0, 5, 10 and 20 IJmol/L） of RV were added to embryonic stem cell （ESC） medium to culture MEFs 48 h post-infection, iPSC clones emerged and were further cultured. Expression of pluripotent markers of iPSCs was identified by cell immunofluorescence and reverse transcription-polymerase chain reaction. Both cytotoxicity and cell proliferation were assayed by Western blot analysis after RV was added into ESC medium. The ultrastructure change of mitochondria was observed by electron microscopy. RESULTS： More than 2.9-fold and 1.3-fold increases in colony number were observed by treatment with RV at 5 and 10 pmol/L, respectively. The reprogramming efficiency was significantly decreased by treatment with 20 pmol/L RV. The proliferation effect on MEFs or MEFs infected by two factors Sox2/Oct4 （2 factors-MEFs, 2F-MEFs） was investigated after RV treatment. At 20 pmol/L RV, induced cell apoptosis and proliferation inhibition were more obvious than those of 5 and 10 IJmol/L treatments. Clones were selected from the 10 pmol/L RV-treated group and cultured. Green fluorescent protein expression from one typical clone was silenced one month later which expressed ESC-associated marker genes Gdf3, Nanog, Ecatl, Fgf4 and Foxd3. Electron transmission microscope showed obvious cavitations in mitochondria. The expression of hypoxia-inducible factor-la was up-regulated when 2F-MEFs were treated with RV compared to the control group. CONCLUSION： RV improved the efficiency of reprogramming 2F-MEFs into iPSCs at low and moderate concentrations （5 and 10 pmol/L）. The effect of 10 pmol/L RV on reprogramming was much greater than that of 5 pmol/L RV. However, high concentration of RV （20 pmol/L） led to more severe cavitations in mitochondria and caused cytotoxic effects. Taken together, these findinqs suqclest that RV mimics hypoxia in cells and promotes reprogramming at a low concentration.

MK-801 attenuates lesion expansion following acute brain injury in rats: a meta-analysis

OBJECTIVE: To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury.DATA SOURCES: Key terms were "stroke","brain diseases","brain injuries","brain hemorrhage, traumatic","acute brain injury","dizocilpine maleate","dizocilpine","MK-801","MK801","rat","rats","rattus" and "murine". PubMed, Cochrane library, EMBASE, the China National Knowledge Infrastructure, WanFang database, the VIP Journal Integration Platform(VJIP) and SinoMed databases were searched from their inception dates to March 2018.DATA SELECTION: Studies were selected if they reported the effects of MK-801 in experimental acute brain injury. Two investigators independently conducted literature screening, data extraction, and methodological quality assessments.OUTCOME MEASURES: The primary outcomes included lesion volume and brain edema. The secondary outcomes included behavioral assessments with the Bederson neurological grading system and the water maze test 24 hours after brain injury.RESULTS: A total of 52 studies with 2530 samples were included in the systematic review. Seventeen of these studies had a high methodological quality. Overall, the lesion volume(34 studies, n = 966, MD =-58.31, 95% CI:-66.55 to-50.07;P < 0.00001) and degree of cerebral edema(5 studies, n = 75, MD =-1.21, 95% CI:-1.50 to-0.91;P < 0.00001) were significantly decreased in the MK-801 group compared with the control group. MK-801 improved spatial cognition assessed with the water maze test(2 studies, n = 60, MD =-10.88, 95% CI:-20.75 to-1.00;P = 0.03) and neurological function 24 hours after brain injury(11 studies, n = 335, MD =-1.04, 95% CI:-1.47 to-0.60;P < 0.00001). Subgroup analysis suggested an association of reduction in lesion volume with various injury models(34 studies, n = 966, MD =-58.31, 95% CI:-66.55 to-50.07;P = 0.004). Further network analysis showed that 0–1 mg/kg MK-801 may be the optimal dose for treatment in the middle cerebral artery occlusion animal model.CONCLUSION: MK-801 effectively reduces brain lesion volume and the degree of cerebral edema in rat models of experimental acute brain injury, providing a good neuroprotective effect. Additionally, MK-801 has a good safety profile, and its mechanism of action is well known. Thus, MK-801 may be suitable for future clinical trials and applications.

Study on the therapeutic effect of external application of Shounian powder combined with acupuncture at Zhitong acupoint on intercostobrachial nerve syndrome after breast cancer operation

Background:To explore the clinical effect of external application of ShouNian Powder combined with acupuncture at Zhitong acupoint in the treatment of intercostobrachial nerve syndrome(ICBNs)after breast cancer operation.Methods:A total of 80 patients with ICBNs who underwent modified radical mastectomy in our hospital from July 2014 to July 2016 were collected and divided into control group and study group according to the different treatment methods of ICBNs.40 patients in the control group were treated with symptomatic analgesia and 40 patients in the study group were treated with external application of ShouNian Powder combined with acupuncture at Zhitong acupoint to compare and analyze the pain relief,quality of life and analgesic recurrence rate of ICBNs between the two groups.Results:Compared with the control group,the pain relief rate of ICBNs in the study group was higher.The patient satisfaction and long-term quality of life in the study group were better than those in the control group.However,there was no significant difference in postoperative pain recurrence rate.Conclusion:External application of ShouNian Powder combined with acupuncture at Zhitong acupoint can effectively relieve pain and improve quality of life for patients with ICBNs after breast cancer operation,which has a certain popularizing significance in clinical practice.