RESUMEN
OBJECTIVE@#To investigate the regulatory roles of Shexiang Baoxin Pill (SXBXW) in neointimal formation and vascular smooth muscle cells (VSMCs) invasion and apoptosis as well as the potential molecular mechanisms using cultured VSMCs model of vascular injury (platelet-derived growth factor (PDGF)-BB-stimulated) in vitro.@*METHODS@#VSMCs were randomly assigned to 5 groups: blank, PDGF-BB (20 ng/mL+ 0.1% DMSO), SXBXW-L (PDGF-BB 20 ng/mL + SXBXW low dose 0.625 g/L), SXBXW-M (PDGF-BB 20 ng/mL + SXBXW medium dose 1.25 g/L) and SXBXW-H (PDGF-BB 20 ng/mL+ SXBXW high dose 2.5 g/L) group. Cell proliferation was assessed using cell counting kit-8 (CCK-8) assay and bromodeoxyuridine (BrdU) incorporation assay, the migration effects were detected by Transwell assay, cell apoptosis rate was measured by the Annexin V/propidium iodide (PI) apoptosis kit. The markers of contractile phenotype of VSMCs were detected with immunofluorescent staining. To validate the effects of miR-451 in regulating proliferation, migration and apoptosis treated with SXBXW, miR-451 overexpression experiments were performed, the VSMCs were exposed to PDGF-BB 20 ng/mL + 0.1% DMSO and later divided into 4 groups: mimic-NC (multiplicity of infection, MOI=50), SXBXW (1.25 g/L) + mimic-NC, mimic-miR451 (MOI=50), and SXBXW (1.25 g/L) + mimic-miR451, and alterations of proteins related to the miR-451 pathway were analyzed using Western blot.@*RESULTS@#PDGF-BB induced VSMCs injury causes acceleration of proliferation and migration. SXBXW inhibited phenotypic switching, proliferation and migration and promoted cell apoptosis in PDGF-BB-induced VSMCs. In addition, miR-451 was shown to be down-regulated in the VSMCs following PDGF-BB stimulation. SXBXW treatment enhanced the expression of miR-451 in PDGF-BB-induced VSMCs (P<0.05). Compared with SXBXW + mimic-NC and mimic-miR451 groups, the expression of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (Ywhaz) and p53 was further reduced in SXBXW + mimic-miR451 group, while activating transcription factor 2 (ATF2) was increased in VSMCs (P<0.05).@*CONCLUSION@#SXBXW regulated proliferation, migration and apoptosis via activation of miR-451 through ATF2, p53 and Ywhaz in PDGF-BB-stimulated VSMCs.
Asunto(s)
Humanos , Apoptosis , Becaplermina/farmacología , Movimiento Celular , Proliferación Celular , Células Cultivadas , Dimetilsulfóxido/farmacología , Medicamentos Herbarios Chinos , Hiperplasia/metabolismo , MicroARNs/metabolismo , Músculo Liso Vascular , Miocitos del Músculo Liso , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
<p><b>BACKGROUND</b>Pediatric infectious endophthalmitis is a serious sight-threatening disease for children. The purpose of this study was to investigate the etiology, microbiological spectrum, and visual outcomes of infectious endophthalmitis in children at a single institution in China.</p><p><b>METHODS</b>It is a retrospective study of the medical records of all patients under 14 years of age with histories of infectious endophthalmitis, treated at a single institution from January 1, 2009 to January 1, 2015. The clinical characteristics, etiology, microbiological spectrum, and management, as well as the visual outcomes, were analyzed. The Kappa test and Chi-square test were used in the statistical evaluation.</p><p><b>RESULTS</b>A total of 271 children were identified, with a mean age of 5.61 ± 2.93 years (range 5 months to 14 years). Ocular trauma (94.8%) and previous ocular surgery (3.0%) were the most common etiologies. Overall, 147 (54.2%) cases had positive cultures, and 176 organisms were isolated from these patients. A single species was isolated in 120 (81.6%) cases, with multiple organisms in 27 (18.4%) cases, and the most commonly identified organisms were coagulase-negative Staphylococcus and Streptococcus species, comprising 29.5% and 26.8% of the isolates, respectively. Moreover, of 176 isolates, 142 (80.8%) were Gram-positive organisms, 23 (13.0%) were Gram-negative organisms, and 11 (6.2%) were fungi. The final visual outcomes were 20/200 or better in 66 (24.4%) eyes, counting fingers to 20/200 in 34 (12.5%), hand motions in 30 (11.1%), light perception in 33 (12.2%), no light perception in 32 (11.8%), and 9 (3.3%) eyes were enucleated or eviscerated. The visual outcomes were not available in 67 (24.7%) patients.</p><p><b>CONCLUSIONS</b>Penetrating ocular trauma is the most frequent cause of pediatric endophthalmitis in China. Streptococcus and Staphylococcus species are the most commonly identified organisms in exogenous pediatric endophthalmitis whereas Fusarium species are commonly seen in endogenous endophthalmitis. In this research, in spite of aggressive management with antibiotics and vitrectomy, the visual prognosis was found to be generally poor.</p>