Implantation of human urine stem cells promotes neural repair in spinal cord injury rats associated cadeharin-1 and integrin subunit beta 1 expression.

BACKGROUND: The aim of this study was to determine the effect of human urine-derived stem cells (HUSCs) for the treatment of spinal cord injury (SCI) and investigate associated the molecular network mechanism by using bioinformatics combined with experimental validation. METHODS: After the contusive SCI model was established, the HUSC-expressed specific antigen marker was implanted into the injury site immediately, and the Basso, Beattie and Bresnahan locomotor rating scale (BBB scale) was utilized to evaluate motor function so as to determine the effect of HUSCs for the neural repair after SCI. Then, the geneCards database was used to collect related gene targets for both HUSCs and SCI, and cross genes were merged with the findings of PubMed screen. Subsequently, protein-protein interaction (PPI) network, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment, as well as core network construction, were performed using Cytoscape software. Lastly, real-time quantitative polymerase chain reaction (PCR) and immunofluorescence were employed to validate the mRNA expression and localization of 10 hub genes, and two of the most important, designated as cadherin 1 (CDH1) and integrin subunit beta 1 (ITGB1), were identified successfully. RESULTS: The immunophenotypes of HUSCs were marked by CD90+ and CD44+ but not CD45, and flow cytometry confirmed their character. The expression rates of CD90, CD73, CD44 and CD105 in HUSCs were 99.49, 99.77, 99.82 and 99.51%, respectively, while the expression rates of CD43, CD45, CD11b and HLA-DR were 0.08, 0.30, 1.34 and 0.02%, respectively. After SCI, all rats appeared to have severe motor dysfunction, but the BBB score was increased in HUSC-transplanted rats compared with control rats at 28 days. By using bioinformatics, we obtained 6668 targets for SCI and 1095 targets for HUSCs and identified a total of 645 cross targets between HUSCs and SCI. Based on the PPI and Cytoscape analysis, CD44, ACTB, FN1, ITGB1, HSPA8, CDH1, ALB, HSP90AA1 and GAPDH were identified as possible therapeutic targets. Enrichment analysis revealed that the involved signal pathways included complement and coagulation cascades, lysosome, systemic lupus erythematosus, etc. Lastly, quantificational real-time (qRT)-PCR confirmed the mRNA differential expression of CDH1/ITGB1 after HUSC therapy, and glial fibrillary acidic protein (GFAP) immunofluorescence staining showed that the astrocyte proliferation at the injured site could be reduced significantly after HUSC treatment. CONCLUSIONS: We validated that HUSC implantation is effective for the treatment of SCI, and the underlying mechanisms associated with the multiple molecular network. Of these, CDH1 and ITGB1 may be considered as important candidate targets. Those findings therefore provided the crucial evidence for the potential use of HUSCs in SCI treatment in future clinic trials.

Electroacupuncture promotes nerve regeneration and functional recovery in rats with spinal cord contusion through the coordinate interaction of CD4 and BDNF.

To explore the effect of electroacupuncture on spinal cord injury (SCI) involving immune-related factors and regeneration-related factors in rats. The model of spinal cord contusion was established by PCI 3000 instrument. Two types of acupuncture points were selected for electroacupuncture treatment on rats. The rats were tested once a week, and the fiber remodeling was detected by magnetic resonance imaging. Transcriptome sequencing was performed on spinal scar samples. Using Python to write code, statistical analysis and bioinformatics analysis of the correlation between transcriptome sequencing data and fiber reconstruction results are carried out. Lastly, the expression of CD4 and brain-derived neurotrophic factor (BDNF) in spinal cord scar was verified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Electroacupuncture exhibited a positive effect on the recovery of motor function in rats after SCI. Bioinformatics analysis found a direct interaction between CD4 and BDNF. Transcriptome sequencing and PCR results verified that electroacupuncture significantly reduced the expression of CD4, and increased significantly the expression of BDNF, simultaneously corresponding to nerve regeneration in rats with SCI. Our results showed that electroacupuncture intervention in SCI rats improves neural behavior via inhibiting the expression of CD4 and increasing the expression of BDNF.

Low serum albumin may predict poor efficacy in patients with perforated peptic ulcer treated nonoperatively.

BACKGROUND: Nonoperative management (NOM) is a promising therapeutic modality for patients with perforated peptic ulcer (PPU). However, the risk factors for poor efficacy and adverse events of NOM are a concern. AIM: To investigate the factors predictive of poor efficacy and adverse events in patients with PPU treated by NOM. METHODS: This retrospective case-control study enrolled 272 patients who were diagnosed with PPU and initially managed nonoperatively from January 2014 to December 2018. Of these 272 patients, 50 converted to emergency surgery due to a lack of improvement (surgical group) and 222 patients were included in the NOM group. The clinical data of these patients were collected. Baseline patient characteristics and adverse outcomes were compared between the two groups. Logistic regression analysis and receiver operating characteristic curve analyses were conducted to investigate the factors predictive of poor efficacy of NOM and adverse outcomes in patients with PPU. RESULTS: Adverse outcomes were observed in 71 patients (32.0%). Multivariate analyses revealed that low serum albumin level was an independent predictor for poor efficacy of NOM and adverse outcomes in patients with PPU. CONCLUSION: Low serum albumin level may be used as an indicator to help predict the poor efficacy of NOM and adverse outcomes, and can be used for risk stratification in patients with PPU.

Bioinformatics analysis of the wheel treadmill test on motor function recovery after spinal cord injury.

This study aimed to explore the possible target and mechanism of the wheel treadmill (WTM) test for motor function recovery of spinal cord injury (SCI). Rats were divided into sham, control and WTM groups to establish an SCI mode. Rats in the WTM group were trained on the WTM test, and Basso-Beattie-Bresnahan (BBB) scores were determined. The samples were collected, and mRNA sequencing was conducted to determine the changes in gene expression. The coexpressed genes were screened to construct a protein-protein interaction (PPI), followed by the Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology function enrichment analysis, and the differentially expressed genes (DEGs) volcano map and hub gene expression heat map were constructed using R language. The BBB scores in the control and WTM groups increased with time, with the WTM group scoring higher than the control group. The results of rat spinal cord tissue sequencing showed that a total of 1679 DEGs were screened in the sham and control groups; 928 DEGs and 731 overlapping genes were screened in the WTM and control groups. The key genes were identified by PPI analysis. One hundred and thirty-three genes were found to be overlapping by combined analysis of spinal cord sequencing data and BBB scores of rats at Week 7. The top 10 DEGs from high to low were Tyrobp, Rac2, Cd68, C1qb, Aif1, Cd74, Spi1, Fcer1g, RT1-DA, and Ccl4. The terms with the highest enrichment scores were microglia-mediated positive regulation of cytotoxicity and major histocompatibility complex class II protein complexes. Treatment with the WTM test promotes recovery of motor function after SCI in rats by modulating intercellular communication and immune function.

Vof-16 knockout improves the recovery from hypoxic-ischemic brain damage of neonatal rats.

Hypoxic-ischemic encephalopathy (HIE) results in high neonatal mortality and severe neurological impairments, and its underlying molecular mechanism underwent extensive investigations. Long non-coding RNA (lncRNA) is considered to be an important regulator on brain development and many neurological diseases. Currently, little is known about the role of Vof-16 (lncRNA) in HIE. We detected the relative expression level of Vof-16 in the cortex and hippocampus of hypoxic-ischemic (HI) models whose successful establishment was verified by TTC staining. Then, Vof-16 knockout rats were generated using the CRISPR/Cas engineering technology to search the specific function of the Vof-16 through a series of behavioral evaluations including Neurological severity scores (NSS), Y-maze test, Morris water maze (MWW) test, open field test, and Rotarod test. The results demonstrated the expression of Vof-16 was substantially up-regulated in the cortex and hippocampus of rats with HI injury. Importantly, Vof-16 knockout facilitated the recovery from long-term HI induced nerve damage and neurobehavioral dysfunctions. In conclusion, this study suggests Vof-16 knockout is a promising treatment target for neonatal HIE.

Source apportionment of nitrogen and phosphorus from non-point source pollution in Nansi Lake Basin, China.

Nitrogen (N) and phosphorus (P) from non-point source (NPS) pollution in Nansi Lake Basin greatly influenced the water quality of Nansi Lake, which is the determinant factor for the success of East Route of South-North Water Transfer Project in China. This research improved Johnes export coefficient model (ECM) by developing a method to determine the export coefficients of different land use types based on the hydrological and water quality data. Taking NPS total nitrogen (TN) and total phosphorus (TP) as the study objects, this study estimated the contributions of different pollution sources and analyzed their spatial distributions based on the improved ECM. The results underlined that the method for obtaining output coefficients of land use types using hydrology and water quality data is feasible and accurate, and is suitable for the study of NPS pollution at large-scale basins. The average output structure of NPS TN from land use, rural breeding and rural life is 33.6, 25.9, and 40.5%, and the NPS TP is 31.6, 43.7, and 24.7%, respectively. Especially, dry land was the main land use source for both NPS TN and TP pollution, with the contributed proportions of 81.3 and 81.8% respectively. The counties of Zaozhuang, Tengzhou, Caoxian, Yuncheng, and Shanxian had higher contribution rates and the counties of Dingtao, Juancheng, and Caoxian had the higher load intensities for both NPS TN and TP pollution. The results of this study allowed for an improvement in the understanding of the pollution source contribution and enabled researchers and planners to focus on the most important sources and regions of NPS pollution.

Effects of environmental hypothermia on hemodynamics and oxygen dynamics in a conscious swine model of hemorrhagic shock.

BACKGROUND: Hypothermia is associated with poor outcome in trauma patients; however, hemorrhagic shock (HS) model with anesthetized swine was different from that of clinical reality. To identify the effects of environmental hypothermia on HS, we investigated hemodynamics and oxygen dynamics in an unanesthetized swine model of HS under simulating hypothermia environment. METHODS: Totally 16 Bama pigs were randomly divided into ambient temperature group (group A) and low temperature group (group B), 8 pigs in each group. Venous blood (30 mL/kg) was continuously withdrawn for more than 15 minutes in conscious swine to establish a hemorrhagic shock model. Pulmonary arterial temperature (Tp), heart rate (HR), mean arterial pressure (MAP), pulmonary arterial pressure (PAP), pulmonary arterial wedge pressure (PAWP), central venous pressure (CVP), cardiac output (CO), hemoglobin (Hb), saturation of mixed venous blood (SvO2) and blood gas analysis were recorded at the baseline and different hemorrhagic shock time (HST). The whole body oxygen delivery indices, DO2I and VO2I, and the O2 extraction ratio (O2ER) were calculated. RESULTS: Core body temperature in group A decreased slightly after the hemorrhagic shock model was established, and environmental hypothermia decreased in core body temperature. The mortality rate was significantly higher in group B (50%) than in group A (0%). DO2I and VO2I decreased significantly after hemorrhage. No difference was found in hemodynamics, DO2I and VO2I between group A and group B, but the difference in pH, lactic acid and O2ER was significant between the two groups. CONCLUSION: Environmental hypothermia aggravated the disorder of oxygen metabolism after hemorrhagic shock, which was associated with poor prognosis.