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OBJECTIVE To study the mechanism of interfering with long non-coding RNA nicotinamide nucleotide transhydrogenase-antisense RNA1 （LncRNA NNT-AS1） expressing to reduce paclitaxel （TAX） resistance in non-small cell lung cancer （NSCLC） cells. METHODS NSCLC TAX-resistant cell line （A549/TAX） was constructed， and the expressions of LncRNA NNT-AS1 in normal， parental， and drug-resistant cells were observed. The targeting relationship of microRNA-582-5p （miR-582- 5p） with LncRNA NNT-AS1 and high mobility group box2 （HMGB2） was verified. A549/TAX cells were cultured in vitro to observe the effects of interfering with LncRNA NNT-AS1 alone or interfering with LncRNA NNT-AS1 and miR-582-5p on the expressions of LncRNA NNT-AS1 and miR-582-5p， the mRNA and protein expressions of HMGB2， cell viability， clone formation and apoptosis. The effects of interfering with LncRNA NNT-AS1 on tumor growth and the expression of miR-582-5p and the mRNA and protein expressions of HMGB2 in tumor tissue were observed in nude mice. RESULTS Compared with normal cells， LncRNA NNT-AS1 was highly expressed in parental and drug-resistant cells （P＜0.05）， showing an increasing trend. It was validated that miR-582-5p had a targeting relationship with LncRNA NNT-AS1 and HMGB2. After interfering with the expression of LncRNA NNT-AS1， the expression of LncRNA NNT-AS1 and the mRNA and protein expressions of HMGB2， cell viability and the number of cloned cells in A549/TAX cell， decreased significantly， while the expression of miR-582-5p and the apoptotic rate increased significantly （P＜0.05）； simultaneously interfering with the expression of miR-582-5p could reverse above changes （P＜ 0.05）. Interfering with the expression of LncRNA NNT-AS1 in tumor cell could significantly reduce tumor volume and tumor weight of nude mice bearing tumors； at the same time， the expression of miR-582-5p was up-regulated significantly and the mRNA and protein expressions of HMGB2 were down-regulated significantly （P＜0.05）. CONCLUSIONS Interfering with the expression of LncRNA NNT-AS1 may alleviate TAX chemotherapy resistance in NSCLC through targeted up-regulation of miR-582-5p and down-regulation of HMGB2.
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In traditional Chinese medicine, Borneolum Syntheticum, a representative drug of aromatic orifice, is often widely used in the clinical treatment of neurotic diseases.In recent years, many scholars at home and abroad have studied and analyzed the effective components and pharmacological effects of Borneolum Syntheticum,and it is considered that Borneolum Syntheticum alone has a significant effect on brain diseases.In this paper, the mechanism of Borneolum Syntheticum on cerebral circulatory system and central nervous system is discussed.In inhibiting brain injury, Borneolum Syntheticum can reduce neuronal vascular endothelial injury, reduce brain edema and decrease the content of Ca2+ in ischemic brain tissue.In the aspect of anti-inflammation, Borneolum Syntheticum can reduce the expression of induced nitric oxide synthase(iNOS) and tumor necrosis factor-α(TNF-α), the number of leukocyte infiltration, the number of intercellular adhesion molecule-1(ICAM-1) positive vessels and the number of TNF-α positive cells.In regulating the blood-brain barrier, Borneolum Syntheticum can increase the expression of zonula occluden-1(ZO-1) and claudin-5 protein in microvascular endothelial cells.The strength of the transdermal absorption of the Borneolum Syntheticum may be related to its configuration, the ability to extract the lipid, and the hydrophilicity.The effect of Borneolum Syntheticum on improving the bioavailability of other drugs is widely used in clinic.Nasal administration of Borneolum Syntheticum can bypass blood-brain barrier (BBB), and reach the central nervous system of the brain. It has a good prospect in the treatment of cerebrovascular disease.In the treatment of brain diseases such as seizures and Alzheimer' s disease, the mechanism of Borneolum Syntheticum is closely related to its effect on various brain neurotransmitters such as γ-aminobutyric acid(GABA),glycine acid(GLY), D-aspartic acid(ASP), glutamic acid(GLU),β-endorphin(β-EP), norepinephrine(NE),epinephrine(E),5-hydroxytryptamine(5-HT),dopamine(DA). However, the experimental results are not the same. It may be related to the different dosage and time of Borneolum Syntheticum administration, which needs to be studied.
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Objective To explore effects of dizocilpine (MK-801) preconditioning on excitatory amino acids and inflammatory response in rats induced by cardiac arrest-cardiopulmonary resuscitation (CACPR).Methods 18 male Sprague Dawley (SD) rats were randomly divided into three groups:control group,CA group and CA + MK-801 group.To establish rat models of CA-CPR and keep samples of serum and specimens of brain tissues for following detection.The injury of neurons was observed by HE staining and expression of N-methyl-D-aspartic acid receptor (NMDAR) in brain tissues was detected by Western blot.The concentrations of interleukin 1 beta (IL-1 β) and tumor necrosis factor (TNF)-α in serum were detected by enzyme linked immunosorbent assay (ELISA).Results Neurons in CA group were disorganized,cells shrank,nuclei pyknosis,and cytoplasmic eosinophilia,accompanied by inflammatory cell infiltration.Preconditioning with MK-801 reduced the pathological damage of neuron and degree of macrophage infiltration.The relative expression of NMDAR protein in CA group were significantly higher than that in control group (907.9 ±24.9 vs 321.6 ± 18.4,P ＜0.001).Preconditioning with MK-801 significantly decreased the expression of NMDAR in CA + MK-801 group compared with that in CA group (512.4 ± 21.1 vs 907.9 ± 24.9).The CA group showed significantly increased concentrations of IL-1 β and TNF-α than that in control group (P ＜ 0.001),and this effect was abolished by preconditioning with MK-801.CA rats treated with MK-801 showed higher concentrations of IL-1 β and TNF-α than the control group.Conclusions Cardiac arrest causes pathological injury of neurons,up-regulates expression of NMDAR and aggravates inflammatory response.These results induce the apoptosis of nerve cells.Blocking glutamate receptor with MK-801 can inhibit expression of NMDAR,decrease level of cytokines,down-regulate inflammatory reaction degree therefore to protect the brain.
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BACKGROUND: Combined use of multiple interventions for different targets play superimposed or synergistic effects,which has become the current idea for spinal cord injury treatment.OBJECTIVE: To investigate the synergistic effects of low doses of 17-β estradiol combined with bone marrow mesenchymal stem cells (BMSCs) transplantation on the recovery of motor function and inflammatory reactions after spinal cord injury in rats.METHODS: The 10 of 70 male Sprague-Dawley rats served as sham group in which the spinal cord was only exposed but with no treatment, and the rest 60 rats were used to make animal models of spinal cord injury using modified Allen's method and then randomized into four groups (n=15 per group): model, estrogen, stem cell and combined treatment groups. Rats in the stem cell and combined treatment groups were given BMSCs transplantation at injured side; rats in the estrogen and combined treatment groups were given intramuscular injection of 17-β estradiol at 1 and 24 hours after modeling. At 1, 3, 5 and 7 days after modeling, rat functional recovery was evaluated by the Basso, Beatlie, Bresnahan score. The expressions of interleukin-1β and tumor necrosis factor-α in the injured spinal cord were detected by ELISA at 6, 12, 24, and 72 hours after modeling. Apoptosis in nerve cells was observed using TUNEL staining. RESULTS AND CONCLUSION: The Basso, Beatlie, Bresnahan scores were declined significantly after modeling,increased at 5 and 7 days after stem cell transplantation, estrogen treatment or their combined treatment (P < 0.05),especially in the combined treatment group (P < 0.05). The levels of interleukin-1β and tumor necrosis factor-α were elevated gradually after spinal cord injury (P < 0.05), but the levels decreased significantly at 12 and 24 hours in stem cell,estrogen and combined treatment groups (P < 0.05), and this decrease trend was more significant in the combined treatment group compared with the stem cell and estrogen groups (P < 0.05). At 72 hours after modeling, the rate of TUNEL positive cells was highest in the model group (P < 0.05) and lowest in the combined treatment group (P < 0.05).To conclude, the combined use of low doses of 17-β estradiol and BMSCs transplantation can facilitate the recovery of motor function after spinal cord injury by effectively inhibiting apoptosis in nerve cells.
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AIM: To discuss the protective effects and possible mechanisms of 17β-estradiol on human retinal pigment epithelial ( RPE) cells induced by high glucose. ·METHODS: RPE cells were cultured and divided into four groups according to randomized controlled method:blank control group:the cells were treated with 5. 5mmol/L routine glucose medium for processing; high glucose group: cells were treated with 100mmol/L glucose for 12h;17β-estradiol low concentration group: after treated with 10 μmol/L 17β-estradiol, cells were treated with 100mmol/L glucose for 12h; 17β-estradiol high concentration group: after treated with 100 μmol/L 17β-estradiol, cells were treated with 100mmol/L glucose for 12h. Cell viability were tested by MTT colorimetric detection. Cells apoptosis were detected by Hochest33258 staining. Intracellular reactive oxygen species( ROS) level were detected by H2 DCFDA staining. Expression of CAT, SOD and MDA were tested by colorimetric detection. · RESULTS: RPE cell activity decreased with the concentration of glucose increased; 17β-estradiol inhibited high glucose-induced cell viability decrease in RPE cells, decreased the apoptosis rate of RPE cells and intracellular ROS generation; besides, 17β-estradiol significantly increased the expression of CAT, SOD and decreased the expression of MDA in RPE cells. ·CONCLUSION: The 17β-estradiol effectively inhibited high glucose -induced RPE cells damage, which provide reliable experimental basis for the treatment of injuries in RPE cells.
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Objective To discuss MRI diagnositic value and evaluation of the treatment of cervical Brucella spondylitis(BS).Meth-ods MRI data of 39 cases with cervical BS in our hospital were collected.Non-operative treatment,minimal invasive surgery and the open surgery were selected according to the MRI manifestations.The correlation was analyzed by consistensy check,imaging score and clinical effect evaluation.The data were analyzed by SPSS15.0.Results 39 cases of patients were examined by MRI before the treatment.37 cases were reviewed after 6 months treatment and 33 cases were reviewed after 12 months treatment.All of the Kappa values were more than 0.75 by imaging consistency check.MRI of cervical BS possessed characteristic expressions.The treatment effect according to MRI classification before the treatment:(1)drug therapy was performed in 14 cases (Group A);(2)minimal inva-sive surgery was performed in 7 cases (Group B);(3)focus clearance and bone graft were performed in 18 cases (Group C);(4)the clinical effects showed the healing rate in every group at different time point was different and the difference had statistical signifi-cance(P0.05). Conclusion MRI classification for cervical BS has important value and guiding significance in the selection of clinical conservative treatment,minimal invasive surgery or the open surgery.
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Objective To explore clinical curative effects of superficial temporal artery-middle cer-ebral artery bypass combining with encephalo-duroarterio-synangiosis( STA-MCA+EDMS) in the treatment of moyamoya disease. Methods Thirteen cases were confirmed to be moyamoya disease by digital subtrac-tion angiography ( DSA) , and treated with STA-MCA+EDMS methods. Four cases were ischemic, and the others were hemorrhagic in this group. Results The follow-up was 6-12 months. The clinical symptoms were improved significantly, without cerebral ischemic attack in 4 ischemic cases. Seven hemorrhagic cases got blood from the external carotid artery by means of vascular bypass or temporal muscle, and established effective collateral circulation half a year after operation. Two hemorrhagic cases bleed again in July after operation. However, the family gave up treatment. Ten cases were good, one case was moderate, while two cases got bad. The total effective rate was 76. 9％. Conclusions STA-MCA+EDMS can improve cerebral hemodynamics of moyamoya disease, improve quality of life, and reduce incidence of stroke.
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Objective To investigate the role of methylprednisolone (MP) in treatment of spinal cord injured (SCI) with bone marrow mesenchymal stem cells (BMSCs) transplantation in rats and its effect on the expressions of tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β) at the local tissues.Methods Forty male Sprague-Dawley(SD) rats were used to establish the models of SCI according to the modified Allen's contusion method and then divided into four groups (n=10 in each group) by using random numbers table:MP group,BMSCs group,BMSCs+MP group,and control group.MP was intravenously administrated immediately after SCI.BMSCs labeled by 5-bromo-2-deoxyuridine(BrdU)were transplanted into the injured sites of spinal cord after two hours of SCI.On the 1 st,7 th,and 14th days after SCI,when functional outcome measurements were evaluated by the Basso-Beattie-Bresnahan (BBB) score.On the 14th day after treatment,the spine cord tissues were harvested for the TNF-α/IL-1β immunohistochemistry,and Tunel staining method was used to detect cell apoptosis rate.BrdU-positive BMSCs were examined in BMSCs group and BMSCs+MP group.Results Functional recovery of hind limb in MP+BMSCs group was the best among the four group.On the 1 st day after injury,the BBB scores showed no significant difference among four group(χ=1.0756,P=0.7829).On the 7th and 14th day,the BBB score of MP+BMSCs group was significantly higher than MP group (χ=17.7186,P=0.0002;χ= 24.7259,P<0.0001) and BMSCs group (χ=15.8110,P=0.0024;χ=25.6014,P<0.0001),respectively.The BBB score of the control group was significantly lower than MP group (χ=8.3265,P=0.0325;χ=13.5060,P=0.0062) and BMSCs group (χ=14.1166,P=0.0036;χ=8.9613,P=0.0299),respectively.On the 14th day,immunohistochemical staining presented that the TNF-α and IL-1β-positive cells in MP+BMSCs group were significantly lower than MP group (q=5.573,P=0.0004;q=4.596,P=0.0025) and BMSCs group (q=13.780,P<0.0001;q=8.456,P<0.0001),and control group was significantly higher than MP group (q=14.710,P<0.0001;q=6.710,P<0.0001) and BMSCs group (q=6.502,P=0.0001;q=2.849,P=0.0514).Tunel staining showed the apoptotic rate of spinal cord cells in four group were (48.47±5.70)%,(31.95±3.58)%,(41.39±2.33)%,and (23.48±2.69)%.The number of apoptotic cells in MP+BMSCs group was least in four groups;compared with the control group,the apoptotic rate significantly decreased in MP group (q=14.840,P<0.0001) and BMSCs group (q=6.716,P=0.0002);compared with the MP+BMSCs group,the apoptotic rate was significantly increased in the MP group (q=7.332,P=0.0001) and BMSCs group (q=15.460,P<0.0001). BrdU staining revealed BrdU-positive rate in MP+BMSCs group [(9.3000±0.5175)%] was significantly higher than that in BMSCs group [(6.6000±0.3399)%](t=4.361,P=0.0004).Conclusion MP can improve the function of the hind limbs of SCI rats treated with BMSCs transplantation and lower the expressions of TNF-α and IL-1β in injured tissue.
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Previous studies have reported the association of prodynorphin (PDYN) promoter polymorphism with temporal lobe epilepsy (TLE) susceptibility, but the results remain inconclusive. To further precisely evaluate this association, we performed a meta-analysis. Published studies of TLE and PDYN polymorphism up to February 2015 were identified. Subgroup analysis by TLE subtype was performed. Moreover, sensitivity, heterogeneity, and publication bias were also analyzed. Seven case-control studies were finally included in this meta-analysis with 875 TLE cases and 1426 controls. We did not find synthetic evidence of association between PDYN promoter polymorphism and TLE susceptibility (OR=1.184, 95% CI: 0.873-1.606, P=0.277). Similar results were also obtained in non-familial-risk TLE subgroup. However, in the familial-risk TLE subgroup analysis, a significant association was observed (OR=1.739, 95% CI: 1.154-2.619, P=0.008). In summary, this meta-analysis suggests that PDYN gene promoter polymorphism might contribute to familial-risk TLE.
Subject(s)
Humans , Case-Control Studies , Enkephalins , Genetics , Epilepsy, Temporal Lobe , Diagnosis , Genetics , Pathology , Family , Gene Expression , Genetic Association Studies , Genetic Predisposition to Disease , Inheritance Patterns , Odds Ratio , Polymorphism, Genetic , Prognosis , Promoter Regions, Genetic , Protein Precursors , GeneticsABSTRACT
The study aimed to investigate the impact of intraclot recombinant tissue-type plasminogen activator (rt-PA) on perihematomal edema (PHE) development in patients with intracerebral hemorrhage (ICH) treated with minimally invasive surgery (MIS) and the effects of intraclot rt-PA on the 30-day survival. We reviewed the medical records of ICH patients undergoing MIS between October 2011 and July 2013. A volumetric analysis was done to assess the change in PHE and ICH volumes at pre-MIS (T1), post-MIS (T2) and day 10-16 (T3) following diagnostic computed tomographic scans (T0). Forty-three patients aged 52.8±11.1 years with (n=30) or without rt-PA (n=13) were enrolled from our institutional ICH database. The median rt-PA dose was 1.5 (1) mg, with a maximum dose of 4.0 mg. The ratio of clot evacuation was significantly increased by intraclot rt-PA as compared with controls (77.9%±20.4% vs. 64%±15%; P=0.046). From T1 to T2, reduction in PHE volume was strongly associated with the percentage of clot evacuation (ρ=0.34; P=0.027). In addition, PHE volume was positively correlated with residual ICH volume at the same day (ρ ranging from 0.39-0.56, P<0.01). There was no correlation between the cumulative dose of rt-PA and early (T2) PHE volume (ρ=0.24; P=0.12) or delayed (T3) PHE volume (ρ=0.19; P=0.16). The 30-day mortality was zero in this cohort. In the selected cohort of ICH patients treated with MIS, intraclot rt-PA accelerated clot removal and had no effects on PHE formation. MIS aspiration and low dose of rt-PA seemed to be feasible to reduce the 30-day mortality in patients with severe ICH. A large, randomized study addressing dose titration and long-term outcome is needed.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Brain Edema , Drug Therapy , Mortality , Pathology , General Surgery , Cerebral Hemorrhage , Drug Therapy , Mortality , Pathology , General Surgery , Minimally Invasive Surgical Procedures , Tissue Plasminogen Activator , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
The study aimed to investigate the impact of intraclot recombinant tissue-type plasminogen activator (rt-PA) on perihematomal edema (PHE) development in patients with intracerebral hemorrhage (ICH) treated with minimally invasive surgery (MIS) and the effects of intraclot rt-PA on the 30-day survival. We reviewed the medical records of ICH patients undergoing MIS between October 2011 and July 2013. A volumetric analysis was done to assess the change in PHE and ICH volumes at pre-MIS (T1), post-MIS (T2) and day 10-16 (T3) following diagnostic computed tomographic scans (T0). Forty-three patients aged 52.8±11.1 years with (n=30) or without rt-PA (n=13) were enrolled from our institutional ICH database. The median rt-PA dose was 1.5 (1) mg, with a maximum dose of 4.0 mg. The ratio of clot evacuation was significantly increased by intraclot rt-PA as compared with controls (77.9%±20.4% vs. 64%±15%; P=0.046). From T1 to T2, reduction in PHE volume was strongly associated with the percentage of clot evacuation (ρ=0.34; P=0.027). In addition, PHE volume was positively correlated with residual ICH volume at the same day (ρ ranging from 0.39-0.56, P<0.01). There was no correlation between the cumulative dose of rt-PA and early (T2) PHE volume (ρ=0.24; P=0.12) or delayed (T3) PHE volume (ρ=0.19; P=0.16). The 30-day mortality was zero in this cohort. In the selected cohort of ICH patients treated with MIS, intraclot rt-PA accelerated clot removal and had no effects on PHE formation. MIS aspiration and low dose of rt-PA seemed to be feasible to reduce the 30-day mortality in patients with severe ICH. A large, randomized study addressing dose titration and long-term outcome is needed.
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The neuroimaging results of drug-resistant epilepsy patients play an important role in the surgery decision and prognosis. The aim of this study was to evaluate the impact of these results on the efficacy of epilepay surgery, and then to explore surgical benefit for epilepsy patients with negative magnetic resonance (MR) images. Twenty-four subgroups describing the outcomes of 1475 epilepsy patients with positive-neuroimaging results and 696 patients with negative-neuroimaging results were involved in the meta-analysis. Overall, the odds of postoperational seizure-free rate were 2.03 times higher in magnetic resonance imaging-positive (MRI-positive) patients than in MRI-negative patients [odds ratio (OR)=2.03, 95% CI (1.67, 2.47), P<0.00001]. For patients with temporal lobe epilepsy (TLE), the odds were 1.76 times higher in those with MRI-positive results than in those with MRI-negative results [OR=1.76, 95% CI (1.34, 2.32), P<0.0001]. For patients with extra-temporal lobe epilepsy (extra-TLE), the odds were 2.88 times higher in MRI-positive patients than in MRI-negative patients [OR=2.88, 95% CI (1.53, 5.43), P=0.001]. It was concluded that the seizure-free rate of MRI-positive patients after surgery was higher than that of MRI-negative patients. For patients with negative results, an appropriate surgery should be concerned for TLE.
Subject(s)
Humans , China , Epidemiology , Epilepsy , Diagnosis , Epidemiology , General Surgery , Magnetic Resonance Imaging , Neurosurgical Procedures , Prevalence , Prognosis , Reproducibility of Results , Sensitivity and Specificity , Surgery, Computer-Assisted , Treatment OutcomeABSTRACT
The neuroimaging results of drug-resistant epilepsy patients play an important role in the surgery decision and prognosis. The aim of this study was to evaluate the impact of these results on the efficacy of epilepay surgery, and then to explore surgical benefit for epilepsy patients with negative magnetic resonance (MR) images. Twenty-four subgroups describing the outcomes of 1475 epilepsy patients with positive-neuroimaging results and 696 patients with negative-neuroimaging results were involved in the meta-analysis. Overall, the odds of postoperational seizure-free rate were 2.03 times higher in magnetic resonance imaging-positive (MRI-positive) patients than in MRI-negative patients [odds ratio (OR)=2.03, 95% CI (1.67, 2.47), P<0.00001]. For patients with temporal lobe epilepsy (TLE), the odds were 1.76 times higher in those with MRI-positive results than in those with MRI-negative results [OR=1.76, 95% CI (1.34, 2.32), P<0.0001]. For patients with extra-temporal lobe epilepsy (extra-TLE), the odds were 2.88 times higher in MRI-positive patients than in MRI-negative patients [OR=2.88, 95% CI (1.53, 5.43), P=0.001]. It was concluded that the seizure-free rate of MRI-positive patients after surgery was higher than that of MRI-negative patients. For patients with negative results, an appropriate surgery should be concerned for TLE.
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<p><b>BACKGROUND</b>Recently, new anti-epileptic drugs (AEDs) have been more frequently selected to treat epilepsy. In the present study, we evaluated the dynamic changes of efficacy and safety of three newer AEDs for treating partial epilepsy in China.</p><p><b>METHODS</b>Patients were collected sequentially and were divided into three groups which accepted oxcarbazepine (OXC), lamotrigine (LTG) or topiramate (TPM) therapy. Each group included monotherapy and add-on therapy subgroups. We followed all patients for one year and recorded the indexes of efficacy and safety in detail.</p><p><b>RESULTS</b>A total of 909 patients finished the follow-up observation. No significant difference was found in proportion of patients with > or = 50% reduction, > or = 75% reduction and 100% seizure reduction in the LTG and OXC groups between the first and the second six months. In the TPM group there was a statistical difference between the first and the second six months in proportion of patients with > or = 50% reduction (P = 0.002), > or = 75% reduction (P < 0.0001) and 100% seizure reduction (P = 0.009) in the monotherapy subgroup, and about > or = 75% reduction and 100% seizure reduction in the add-on therapy subgroup (P < 0.0001). The efficacy between the add-on and monotherapy subgroups showed a statistical difference. The safety of the three newer AEDs was good.</p><p><b>CONCLUSIONS</b>The three newer AEDs all showed good efficacy and tolerability for partial epilepsy. And the efficacy can be maintained for at least one year.</p>