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Objective To investigate the role of zinc finger protein 36,C3H type-like 1 (ZFP36L1) mediating astrocytes activation in the degeneration of motor neurons in amyotrophic lateral sclerosis (ALS). Methods Superoxide dismutase 1 (S0D1)-G93A transgenic mice were used as animal models, the wild-type littermates as the control (13 mice were taken from mutant and wild-type mice at each time point) . The ZFP36L1 mRNA and protein levels of the spinal cord in the early, middle and late stage were detected by Real-time PGR and Western blotting. The expression and distribution of ZFP36L1 in the spinal cord were detected by immunofluorescence. Primary astrocyte model was established from 15 postnatal 1-2 day mice. The ZFP36L1 mRNA and protein levels in astrocytes were detected by Real-time PCR and Western blotting. Si-ZFP36L1 was transfected into SOD1-G93A mutant primary astrocytes. The transfection efficiency was detected by Western blotting. Tumor necrosis factor a (TNF-a) and interleukin-18 (IL-18) secreted from astrocytes after transfection were assessed by Western blotting and ELISA. After silencing ZFP36L1 in SOD1-G93A mutant primary astrocytes, it was cocultured with SOD1-G93A mutant NSC34 cells. 5 ' -ethynyl-2' deoxyuridine (EdU) test and the level of proliferating cell nuclear antigen (PCNA) were used to determine the effect of ZFP36L1 on NSC34 cell proliferation. TUNEL test and the level of cleaved-Caspase-3 were used to determine the effect of ZFP36L1 on NSC34 cell apoptosis. Blank small interfering RNA(siRNA) was transfected as the control group. Results Compared with the wild-type mice, the mRNA and protein levels of ZFP36L1 were downregulated in the spinal cord of SOD1-G93A transgenic mice. In wild type mice, ZFP36L1 positive cells were mainly [
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Objective To investigate the relationship between changes in protein tyrosine kinase 7 (PTK7) and receptor tyrosine kinase-like orphan receptor 2 ( ROR2) expression in the brainstem and the pathogenesis of amyotrophic lateral sclerosis (ALS). Methods Forty-four human superoxide dismutase 1( hSODl)-G93A mutant ALS transgenic mice were selected, and an equal number of wild-type littermates was used as control. The brainstems were isolated at da)' 70, day 95, day 108 and da)' 122 after birth, and the morphology of frypoglossal nucleus (12N) and nucleus of facial nerve(7N) neurons in the brainstem of the model mice were observed by Nissl staining. The mRNA and protein expression of PTK7 and ROR2 were detected by RT-PCR and Western blotting respectively, and the cellular localization and distribution of PTK7 and ROR2 in 12N and 7N were observed by immunofluorescence double-labeling technique. Results The result of Nissl staining showed that Nissl bodies in the neurons reduced distinctly with vacuolar degeneration of neurons, cell body atrophy and nuclear volume reduction in the 12N and 7N brainstems of ALS transgenic mice. RT-PCR result indicated that ROR2 and PTK7 mRNA level in the brainstem of ALS transgenic mice were up-regulated at da)' 70, da)' 95, day 108 and day 122 compared with wild-type littermates. Western blotting result showed that PTK7 protein was up-regulated at day 70, day 95, day 108 and day 122, ROR2 protein was up-regulated at day 70, day 95, day 108, and down-regulated at day 122 in the brainstem of ALS transgenic mice compared with wild-type littermates. Immunofluorescence result showed that ROR2/neuronal nuclei (NeuN)and PTK7/NeuN double positive cells, ROR2/glial fibrillary acidic protein (GFAP) and PTK7/GFAP double positive cells were observed in the 12N and 7N of the brainstem of ALS transgenic mice and wild-type mice, suggesting that ROR2 and PTK7 were expressed both in neurons and astrocytes. Conclusion PTK7 and ROR2 are abnormally expressed in the brainstem of ALS transgenic mice, which is closely related to the pathogenesis of ALS.
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Objective:To validate the revised BMI-MNA-SF and CC-MNA-SF with regard to association and agreement with the full MNA(R),considered as gold standard,in geriatric internal medicine patients.Methods:105 cases of hospitalized elderly patients in internal medicine were recruited for the study.The nutritional status correlation and coherence were evaluated with the revised BMI-MNA-SF、CC-MNA-SF and the full MNA(R),respectively.Results:The BMI-MNA-SF and CC-MNA-SF all correlated strongly with the full MNA(R) (Pearson's correlation coefficient r=0.9080,0.8381 respectively;P ＜ 0.001).High values of sensitivity,specificity and predictive values were observed for the BMI-MNA-SF and CC-MNA-SF against the full MNA(R) as the dichotomized categorizations "malnourished-at risk of malnutrition" vs "well nourished" and "malnourished" vs "at risk of malnutrition-well nourished" were considered.Most of values of those for CC-MNA-SF are lower slightly than BMI-MNA-SF.Areas under the ROC curves also reached high values (BMI-MNA-SF:0.951 and CC-MNA-SF:0.938 for the first categorization;BMI-MNA-SF:1.000 and CC-MNA-SF:0.985 for the second one) showing both tests excellent accuracy with the full-MNA.The agreement between the MNA-SFs and the ful1-MNA was quantified as the percentage of correct classifications.The BMI-MNA-SF classified 83.81％,correctly and the CC-MNA-SF classified 68.57％ correctly.Malnutrition proportions of subjects were not underestimated by both MNA-SFs.Conclusion:The revised BMI-MNA-SF and CC-MNA-SF are rapid、easy and reliable tools are capable to identify malnourished individuals in internal medicine and those who are at risk of malnutrition.Due to the special characteristics of elderly patients,the CC-MNA-SF is a good option to replace the BMI-MNA-SF when BMI is not available.