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Ischemic stroke is a severe disorder resulting from acute cerebral thrombosis. Here we demonstrated that post-ischemic treatment with ciclopirox olamine (CPX), a potent antifungal clinical drug, alleviated brain infarction, neurological deficits and brain edema in a classic rat model of ischemic stroke. Single dose post-ischemic administration of CPX provided a long-lasting neuroprotective effect, which can be further enhanced by multiple doses administration of CPX. CPX also effectively reversed ischemia-induced neuronal loss, glial activation as well as blood-brain barrier (BBB) damage. Employing quantitative phosphoproteomic analysis, 130 phosphosites in 122 proteins were identified to be significantly regulated by CPX treatment in oxygen glucose deprivation (OGD)-exposed SH-SY5Y cells, which revealed that phosphokinases and cell cycle-related phosphoproteins were largely influenced. Subsequently, we demonstrated that CPX markedly enhanced the AKT (protein kinase B, PKB/AKT) and GSK3 (glycogen synthase kinase 3) phosphorylation in OGD-exposed SH-SY5Y cells, and regulated the cell cycle progression and nitric oxide (NO) release in lipopolysaccharide (LPS)-induced BV-2 cells, which may contribute to its ameliorative effects against ischemia-associated neuronal death and microglial inflammation. Our study suggests that CPX could be a promising compound to reduce multiple ischemic injuries; however, further studies will be needed to clarify the molecular mechanisms involved.
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Objective To investigate the associated factors and trends of prehospital delay in elderly patients with acute ischemic stroke (AIS).Methods Elderly patients with AIS admitted to the First People's Hospital of Qujing from 2007 to 2017 were enrolled retrospectively.The data of patients was collected from the medical records.Onset-to-door time ＞ 2 h was defined as prehospital delay.The demographic and baseline data were compared between the delay group and the non-delay group.Multivariate logistic regression analysis was used to determine the associated factors for prehospital delay.In addition,the trends of prehospital delay time at the different stages of the study were also analyzed.Results A total of 1 566 patients with AIS aged ≥65 years were enrolled.Their mean age was 75.61 ±6.06 years.The mean time of prehospital delay was 10.83 ± 7.47 h (median time 8.27 h).Multivariatelogistic regression analysis showed that advanced age (odds ratio [OR] 1.271,95％ confidence interval [CI] 1.029-2.896;P =0.039),nocturnal onset (OR 1.413,95％ CI 1.067-3.859;P=0.013),and atypical symptom onset (OR 2.345,95％ CI 1.184-8.126;P=0.029) were independently positively correlated with prehospital delay,while the emergency medical service transport (OR 0.743,95％ CI 0.261-0.998;P =0.010),having medical insurance (OR 0.219,95％ CI 0.015-0.799;P =0.042),and having a bystander at the time of onset (OR 0.618,95％ CI 0.149-0.814;P=0.003) were independently negatively correlated with prehospital delay.At the different stages of the study,January 2007 to October 2010,November 2010 to April 2015,and May 2015 to December 2017,the mean time of prehospital delay was 12.59 ± 7.06 h,10.57 ±7.78 h,and 8.47 ±7.07 h,respectively.They showed a decrease trend,but the difference was not statistically significant.Conclusion Advanced age,nocturnal onset,and atypical symptom onset were the independent risk factors for prehospital delay,while emergency medical service transport,having medical insurance,and having a bystander at the time of onset were the independent protective factors for prehospital delay.The delay time of the elderly patients with AIS is declining year by year,but the improvement is not significant.The delay in seeking timely medical intervention remains an important public health problem.
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Objective To investigate the effects of c?myc promoter binding protein 1(MBP?1)gene on the proliferation of human Saos?2 osteo?sarcoma cells in vitro. Methods Saos?2 cells were divided into three groups:blank control group(untransfected cells),negative group(cells transfected with missense sequence)and experimental group(cells transfected with MBP?1 shRNA). Two MBP?1 shRNA sequences and one neg?ative control shRNA sequence were designed ,synthesized and cloned into pSIREN?retroQ plasma. Then the recombinant plasmids were construct?ed and transfected into human Saos?2 osteosarcoma cells by Lipofectamine 2000. The expressions of MBP?1 mRNA and protein in Saos?2 cells were detected by real?time PCR and Western blot ,respectively. The effects of altered expression of MBP?1 on cell proliferation were measured by CCK?8 cell proliferation assay. The expressions of cyclin D1 and cyclin E in Saos?2 were determined by Western blot. Results PCR and sequenc?ing results indicated that the recombinant plasmids pSIREN?retroQ was constructed. The relative expression level of MBP?1 mRNA in the MBP?1 siRNA transfection group was significantly decreased than that in blank control group(P<0.05). Compared with the blank control group,the ex?pression levels of MBP?1 protein in the experimental group also significantly decreased. The proliferation abilities of Saos?2 cells at 48,72,and 96 hours after MBP?1 siRNA transfection were significantly increased than those in the blank control group(P<0.05). Compared with the blank con?trol group,the expression levels of cyclin D1 and cyclin E protein in the experimental group also significantly increased(P<0.05). Conclusion Knockdown of the expression of MBP?1 gene promotes the proliferation of human Saos?2 osteosarcoma cells. MBP?1 gene may become the new tar?get of gene therapy for osteosarcoma.
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Objective To investigate the advantages of emergent ureteroscopy for the treatment of acute obstructive renal failure resulted from upper ureteral calculi.Methods A total of 123 cases of acute renal failure caused by bilateral upper ureteral calculi was treated with ureteroscopic exploration,ballistic lithotripsy,catheter indwelling,and percutaneous nephrolithotomy.Results The serum BUN(blood urea nitrogen) and Cr(creatinine) were decreased to normal levels 2～10 days after operation in 100 cases(81.3%);the levels of Cr were maintained at 188.6～232.3 ?mol/L 10～15 days after operation in 22 cases.In 1 case of congenital solitary kidney(renal failure caused by chronic contralateral ureteral calculous obstruction),a hemodialysis was needed on the 3rd day after operation,and the serum Cr was 810 ?mol/L on the 15th day after operation and was dropped to normal after 2 months postoperatively.In 4 cases of previous unilateral nephrectomy or congenital solitary kidney,azotaemia remained at 3 months after operation.Conclusions Emergent ureteroscopy for acute renal failure caused by calculous obstruction possesses advantages of immediate obstruction relief,effective renal function protection,little trauma,low complication rate,and simple performance.