الملخص
OBJECTIVE@#To investigate the effect of pachymic acid (PA) against TNBS-induced Crohn's disease (CD)-like colitis in mice and explore the possible mechanism.@*METHODS@#Twenty-four C57BL/6J mice were randomized equally into control group, TNBS-induced colitis model group and PA treatment group. PA treatment was administered via intraperitoneal injection at the daily dose of 5 mg/kg for 7 days, and the mice in the control and model groups were treated with saline. After the treatments, the mice were euthanized for examination of the disease activity index (DAI) of colitis, body weight changes, colon length, intestinal inflammation, intestinal barrier function and apoptosis of intestinal epithelial cells, and the expressions of TNF-α, IL-6 and IL-1β in the colonic mucosa were detected using ELISA. The possible treatment targets of PA in CD were predicted by network pharmacology. String platform and Cytoscape 3.7.2 software were used to construct the protein-protein interaction (PPI) network. David database was used to analyze the GO function and KEGG pathway; The phosphorylation of PI3K/AKT in the colonic mucosal was detected with Western blotting.@*RESULTS@#PA significantly alleviated colitis in TNBS-treated mice as shown by improvements in the DAI, body weight loss, colon length, and histological inflammation score and lowered levels of TNF-α, IL-6 and IL-1β. PA treatment also significantly improved FITC-dextran permeability, serum I-FABP level and colonic transepithelial electrical resistance, and inhibited apoptosis of the intestinal epithelial cells in TNBS-treated mice. A total of 248 intersection targets were identified between PA and CD, and the core targets included EGFR, HRAS, SRC, MMP9, STAT3, AKT1, CASP3, ALB, HSP90AA1 and HIF1A. GO and KEGG analysis showed that PA negatively regulated apoptosis in close relation with PI3K/AKT signaling. Molecular docking showed that PA had a strong binding ability with AKT1, ALB, EGFR, HSP90AA1, SRC and STAT3. In TNBS-treated mice, PA significantly decreased p-PI3K and p-AKT expressions in the colonic mucosa.@*CONCLUSION@#PA ameliorates TNBS-induced intestinal barrier injury in mice by antagonizing apoptosis of intestinal epithelial cells possibly by inhibiting PI3K/AKT signaling.
الموضوعات
Animals , Mice , Mice, Inbred C57BL , Crohn Disease , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Interleukin-6 , Molecular Docking Simulation , Tumor Necrosis Factor-alpha , Colitis/chemically induced , Inflammation , Apoptosis , ErbB Receptorsالملخص
BACKGROUND@#Spinal cord injury (SCI) is a worldwide medical concern. This study aimed to elucidate the mechanism underlying the protective effect of hyperbaric oxygen (HBO) against SCI-induced neurologic defects in rats via exploring the stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) axis and expression of brain-derived neurotrophic factor (BDNF).@*METHODS@#An acute SCI rat model was established in Sprague-Dawley rats using the Allen method. Sixty rats were divided into four groups (n = 15 in each group): sham-operated, SCI, SCI treated with HBO (SCI + HBO), and SCI treated with both HBO and AMD3100 (an antagonist of CXCR4; SCI + HBO + AMD) groups. The rats were treated with HBO twice a day for 3 days and thereafter once a day after the surgery for up to 28 days. Following the surgery, neurologic assessments were performed with the Basso-Bettie-Bresnahan (BBB) scoring system on postoperative day (POD) 7, 14, 21, and 28. Spinal cord tissues were harvested to assess the expression of SDF-1, CXCR4, and BDNF at mRNA and protein levels, using quantitative real-time polymerase chain reaction, Western blot analysis, and histopathologic analysis.@*RESULTS@#HBO treatment recovered SCI-induced descent of BBB scores on POD 14, (1.25 ± 0.75 vs. 1.03 ± 0.66, P < 0.05), 21 (5.27 ± 0.89 vs. 2.56 ± 1.24, P < 0.05), and 28 (11.35 ± 0.56 vs. 4.23 ± 1.20, P < 0.05) compared with the SCI group. Significant differences were found in the mRNA levels of SDF-1 (mRNA: day 21, SCI + HBO vs. SCI + HBO + AMD, 2.89 ± 1.60 vs. 1.56 ± 0.98, P < 0.05), CXCR4 (mRNA: day 7, SCI + HBO vs. SCI, 2.99 ± 1.60 vs.1.31 ± 0.98, P < 0.05; day 14, SCI + HBO vs. SCI + HBO + AMD, 4.18 ± 1.60 vs. 0.80 ± 0.34, P < 0.05; day 21, SCI + HBO vs. SCI, 2.10 ± 1.01 vs.1.15 ± 0.03, P < 0.05), and BDNF (mRNA: day 7, SCI + HBO vs. SCI, 3.04 ± 0.41 vs. 2.75 ± 0.31, P < 0.05; day 14, SCI + HBO vs. SCI, 3.88 ± 1.59 vs. 1.11 ± 0.40, P < 0.05), indicating the involvement of SDF-1/CXCR4 axis in the protective effect of HBO.@*CONCLUSIONS@#HBO might promote the recovery of neurologic function after SCI in rats via activating the SDF-1/CXCR4 axis and promoting BDNF expression.
الموضوعات
Animals , Male , Rats , Blotting, Western , Brain-Derived Neurotrophic Factor , Metabolism , Disease Models, Animal , Hyperbaric Oxygenation , Methods , Rats, Sprague-Dawley , Receptors, CXCR4 , Metabolism , Receptors, Interleukin-8A , Metabolism , Spinal Cord Injuries , Metabolism , Therapeuticsالملخص
Objective To investigate the prevalence of primary teeth caries and oral hygiene status of preschool children in Kunming.Methods 6958 children aged 3-5 years from 30 kindergartens in Kunming were randomly selected for this study.The reserch of caries prevalence rate and soft dirt were investigated.Results The caries prevalence rate and the mean decayed,missing and filled teeth (XDMFT) values in primary teeth were 58.68%and 2.61 respectively.We can see the difference of significant between Dental caries prevalence and mean debris index simplified ( DI - S) scores between age groups, and there was no statistical significance of the same index between sex. There was no correlation between the investigation of dental caries and oral hygiene status. Conclusion The caries prevalence rate in 3-5 year-old children in the downtown area of Kunming city is very high,pointing out that preventive treatment against primary teeth caries should be strengthened.
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<p><b>BACKGROUND</b>The administration of immunosuppressive agents is always an important factor affecting the long-term survival of organ transplantation recipients. The best therapeutic regimen which either decreases the side effects of immune inhibitors or enhances the immunosuppressive efficacy is the goal of transplantation surgeons continue to search. This study investigated the effects of Bailing (Cordyceps sinensis) capsules on renal function and other systems of the body after renal transplantation.</p><p><b>METHODS</b>Clinical data of 80 renal transplant recipients who were administered Bailing capsules and 100 renal transplant recipients in the control group were retrospectively analyzed to compare the incidences of graft rejection and infection after transplantation. The results of routine blood and urine tests, liver and kidney functions, uric acid (UA), 24-hour urine protein (24 h-Upro), as well as 1- and 5-year patient renal allograft survival rates were compared between the two groups.</p><p><b>RESULTS</b>The follow-up was 3 - 5 years. The two groups were not shown to have statistically significant differences in age, gender, cold ischemia time, donor-recipient human leukocyte antigen typing, panel reactive antibodies, lymphocytotoxicity tests, and the application of immunosuppressive agents at the baseline. The two groups were also not significantly different in the incidence of acute injection after transplantation, recovery of renal function, and blood glucose level. The Bailing group was significantly lower than the control in the incidence of infection, serum aspartate aminotransferase/alanine aminotransferase, total bilirubin, UA, and 24-hour Upro, but significantly higher than the control group in peripheral red blood cell count and white blood cell count (P < 0.05). One-year and 5-year patient survival rates were 98.7% and 98.0%, respectively in the Bailing group, 95.0% and 93.0%, respectively, in the control group. One-year and 5-year renal allograft survival rates were 97.5% and 95.0%, respectively, in the Bailing group, and 92.5% and 84.0%, respectively, in the control group. The comparison of patient and renal allograft survival rates between the two groups using Kaplan-Meier survival curves and log-rank test showed that only the differences in renal allograft survival rates were statistically significant (Log-rank: 5 years: patient survival P = 0.420; renal allograft survival P = 0.049).</p><p><b>CONCLUSION</b>Bailing capsules were effective in preventing allograft rejection, protecting liver and kidney functions, stimulating hematopoiesis, and reducing the incidence of infection and thus are ideal immunoregulators.</p>