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This study aimed to investigate the effect of methyl eugenol(ME) on hypoxia/reoxygenation(H/R)-induced injury of human renal tubular epithelial HK-2 cells and its mechanism. The viability of HK-2 cells cultured with different concentrations of ME and exposed to H/R was detected by cell counting kit-8(CCK-8) assay. The effect of ME on the morphology of HK-2 cells was observed under an inverted microscope. The content of intracellular reactive oxygen species in different groups was detected after 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA) fluorescence staining. Cell apoptosis was determined by flow cytometry. Changes in mitochondrial membrane potential were monitored by JC-1 dye. The concentrations of nuclear factor erythroid 2 related factor 2(Nrf2), heme oxygenase-1(HO-1), and nicotinamide adenine dinucleotide phosphatase oxidase 4(Nox4) were measured by Western blot, followed by the assay of Nrf2 concentration changes in cytoplasm and nucleus by confocal fluorescence staining. The results showed that when the concentration of ME was 0-40 μmol·L~(-1), the activity of HK-2 cells was not affected. Compared with the model group, ME enhanced the activity of HK-2 cells and the cell morphology was normal. As revealed by further experiments, ME inhibited the release of reactive oxygen species and the decline in mitochondrial membrane potential of HK-2 cells after H/R injury, promoted Nrf2/HO-1 expression and Nrf2 translocation to the nucleus, and down-regulated the expression of Nox4, thereby significantly reducing apoptosis. This protective effect of ME could be reversed by the specific Nrf2 inhibitor ML385. These findings have preliminarily proved that ME effectively protected HK-2 cells against H/R injury, which might be related to its promotion of Nrf2/HO-1 signaling pathway and inhibition of Nox4. Such exploration on the possible mechanism of ME in the treatment of renal ischemia-reperfusion injury(IRI) and protection of organ function from the perspective of antioxidant stress has provided reference for related research on the treatment of acute kidney injury with traditional Chinese medicine.
Subject(s)
Humans , Apoptosis , Epithelial Cells/metabolism , Eugenol/pharmacology , Heme Oxygenase-1/metabolism , Hypoxia , NF-E2-Related Factor 2/metabolism , Oxidative Stress , Reactive Oxygen Species , Reperfusion Injury/drug therapyABSTRACT
Objective:Quantitative analysis of anti-inflammatory synergistic pharmacodynamics mechanism of baicalin and wogonoside by medium efficiency principle. Method:inflammatory cell model was constructed by stimulating RAW264.7 cells by lipopolysaccharide （LPS） 100 μg·L-1 in vitro. The experiment was performed in the normal group， the model group， the andrographolide group （10 μmol·L-1）， the baicalin group （2.06，4.13，8.25，16.5，33，66，132 μmol·L-1） and the wogonoside group （2.94，5.88，11.75，23.5，47，94，188 μmol·L-1） and the baicalin-wogonoside combination group ［（2.06+2.94）（4.13+5.88）（8.25+11.75）（16.5+23.5）（33+47）（66+94）（132+188） μmol·L-1］. The levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the cell culture supernatants after drug intervention for 50 min and 4 h were detected by enzyme-linked immunosorbent assay （ELISA） method. The level of nitric oxide （NO） in the cell culture supernatant after drug intervention for 24 h were detected by Griess method. Western blot was used to detect the activation levels of phosphorylation of nuclear factor-κB p65（p-NF-κB p65） and inducible nitric oxide synthase（iNOS） in cells after drug intervention for 2 h and 12 h. The fa/fu-dose profile of each indicator was drawn to observe the increase or decrease of effect. Result:Compared with normal group， the expression of p-NF-кB p65， iNOS and cytokines including TNF-α， IL-6 and NO （P<0.05，P<0.01） in the model group were significantly up-regulated. Compared with the model group， each group at high doses could inhibit the phosphorylation of NF-кB p65 protein（P<0.05），the baicalin group and the combined group could down-regulate the expression of iNOS protein in a concentration-dependent manner（P<0.01） and the baicalin group had no obvious inhibitory effect. each administration group at high dose could significantly inhibit the production of NO（P<0.05），but each group had no inhibitory effect on IL-6 production. The baicalin group and the combined group could significantly Inhibit the production of TNF-α（P<0.05） and there was no significant difference between the baicalin group and the model group. At the experimental dose， the fa/fu-dose table showed that the fa/fu value of p-NF-кB p65 and IL-6 in the combined group was not greater than the baicalin group and the wogonoside group. The fa/fu value of iNOS， TNF-α and NO in the combined group is higher than the baicalin group and the wogonoside group. Conclusion:The baicalin and wogonoside have different effects on different targets in the NF-κB pathway. The wogonoside is the main pharmacological substance in this combination and the combination shows different degrees of synergy or antagonism effects on different targets.
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<p><b>OBJECTIVE</b>To investigate the expression of long non coding RNA RP11-69I8.3 in acute leukemia and its clinical significance.</p><p><b>METHODS</b>lncRNA RP11-69I8.3 expression was detected by RT-PCR in bone marrow samples from 17 healthy controls, 32 newly diagnosed AML patients and 32 newly diagnosed ALL patients, and 25 ALL patients of complete remission after chemotherapy. Meanwhile, the clinical data were collected and the relation of lncRNA RP11-6918.3 expression with the clinical characteristics was analyzed.</p><p><b>RESULTS</b>Compared with the control group, there was no significant difference in the expression of lncRNA RP11-69I8.3 in AML group(P>0.05). lncRNA RP11-69I8.3 lowly expressed in untreated ALL group(P=0.001). Compared with the de novo ALL group, lncRNA RP11-69I8.3 was highly expressed in complete remission ALL group (P<0.013). In 32 de novo ALL patients,the expression of lncRNA RP11-69I8.3 in children was significantly lower than that in adult(P=0.017). There was no correlation of the expression of lncRNA RP11-69I8.3 with the sex, WBC count, HB level, Plt count, LDH level, T or B type, ratio of bone marrow blast cell, BCR/ABL and WT1 fusion gene expression, chromosome karyotype, extramedullary infiltration, whether complete remission after one chemotherapy, whether relapse. In 26 B-ALL patients, there was no correlation between lncRNA RP11-69I8.3 and the immunophenotype.</p><p><b>CONCLUSION</b>The expression of lncRNA RP11-69I8.3 in the untreated AML is not significantly different from the control group. lncRNA RP11-69I8.3 is low expressed in ALL group, highly expressed in ALL group with complete remission. In untreated ALL, the expression of lncRNA RP11-69I8.3 in children is significantly lower than that in adult. In B-ALL patients, the lncRNA RP11-69I8.3 is not relevant with the immunophenotype.</p>
Subject(s)
Humans , Acute Disease , Fusion Proteins, bcr-abl , Leukemia , RNA, Long NoncodingABSTRACT
Objective: To explore GRACE (global registry of acute coronary events)score on short term prognosis of ST-segment elevation myocardial infarction (STEMI)in patients elder than 75 years with primary percutaneous coronary intervention(PCI). Methods: A total of 104 STEMI patients elder than 75 years with primary PCI in our hospital from 2011-11 to 2014-01 were studied. Based on GRACEscore at admission, the patients were divided into 2 groups: Lower/mid risk group, n=72 patients with GRACEscore at 112-154 (136.5±10.6) and High risk group, n=32 patients with GRACE score at 155-202(167.8±12.3). The baseline condition and outcomes were compared between 2 groups and the primary endpoint was 1 year mortality. Predictive value of GRACEscore on 1 year mortality was evaluated by ROC curve, the relationships between Lower/mid risk group, High risk group and clinical outcomes were assessed by log-ranksurvive curve andunivariate Cox regression analysis. Results: The area under ROC curve for GRACEscore predicting 1 year mortality was 0.788 with the sensitivity at 70.0%and specificity at 84.0 %.Univariate Cox regression analysis indicated that compared with Lower/mid risk group, High risk group had the higher risk of 1-year death (HR=5.75, 95% CI 1.486-22.256, P=0.0113); log-rank survive curve presented that High risk group had the higher 1 year mortality (21.9% vs 4.2%, P=0.0039). Conclusion: GRACE score may further distinguish the lower/mid risk and high risk populations in elder STEMI patients; it may also predict 1 year clinical prognosis.
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Bladder cancer ( BC) is a fatal malignancy with considerable mortality, and can cause a serious threat to human health. The successful treatment of bladder cancer relies mainly on early detection. Biomarkers are vital to early diagnosis of bladder cancer, and metabonomics play an important role in biomarkers finding. In this study, we used 69 polar metabolites to select the appropriate separation system and develop the zwitterionic hydrophilic chromatography/mass spectrometry ( ZIC-HILIC/MS ) method. In this method, 50 representative compounds had broad linear ranges between 2-6 orders of magnitude. Moreover the limit of detection of the method was below ng/mL levels. The analysis for six serum samples prepared in parallel showed that this method had good reproducibility, and the RSDs of more than 85% metabolites were less than 30%. Based on this method, it was found that 35 metabolites had significant differences in BC group and healthy control. After screening and validation, the combination of chenodeoxycholic acid, eicosenoic acid, GPC, dodecenoic acid and cystine was a potential biomarker to distinguish BC and normal group. These results indicated that the ZIC-HILIC/MS method could detect diverse metabolites for metabolomic analysis purpose with good reproducibility and stability.
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Cerebrovascular disease has become the first cause of death in China, which brings heavy social economy burden and psychological pressure to the patients and their families. Recent years have witnessed rapid development in cerebrovascular disease research, which promotes the rapid development of its prevention and treatment. This review summarized several focuses in studies of cerebrovascular diseases, including focuses of basic research, diagnoses and therapies of acute ischemic stroke and endovascular treatments, cerebral hemorrhage, prevention and rehabilitation of cerebral stroke, evidence-based medicine, translational medicine and precision medicine, hoping to provide insights for all those who involved in the field.
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<p><b>OBJECTIVE</b>To analyze the reason of biochemical suboptimal response in CHB patients with complete virological response after more than 2 years standard treatment with Nucleos(t)-ide analogs (NUCs).To evaluate the efficacy and safety profiles of bicyclol tablets plus on the basis of the original treatment and lifestyle intervention. in CHB patients complicated with fatty liver.</p><p><b>METHODS</b>In 40 patients with chronic hepatitis B meeting the inclusion criteria,the liver biopsy was conducted.And patients complicated with fatty liver were treated with bicyclol tablets (25 mg, t.i.d) additional consecutive 48 weeks. The changes of serum biochemistry indexes and liver fibrosis index were observed before and after treatment.</p><p><b>RESULTS</b>Among 40 patients, 27 were complicated with fatty liver(69.23%), fatty degree in liver cell and liver inflammatory were closely related to the advanced fibrosis (x² =4.746, P=0.029; x² =5.072, P=0.024). The expression of HBsAg in serum and liver tissue showed no correlation with the advanced fibrosis (x² = 0.273, P=0.601; x² = 0.020, P =0.887) After bicyclol tablets treatment, serum biochemistry of patients complicated with fatty liver significantly decreased (F=58.045, P =0.000), plasma GST-PX significantly increased (t=15.109, P =0.000), plasma MDA significantly decreased (t=-10.786, P=0.000); LSM significantly decreased (t=2.255, P=0.036; t =5.376, P =0.002).</p><p><b>CONCLUSION</b>For the antiviral purpose of guide treatment, CHB patients treated with Nucleos(t)-ide analogs (NUCs) with biochemical suboptimal response, other risk factors should be considered as early as possible. Bicyclol plus lifestyle intervention was effective for chronic hepatitis B combined fatty liver patients with poor biochemical responses.</p>
Subject(s)
Humans , Antiviral Agents , Fatty Liver , Hepatitis B Surface Antigens , Hepatitis B, Chronic , Liver CirrhosisABSTRACT
<p><b>OBJECTIVE</b>To compared outcomes of robotic mitral valve repair with those of standard sternotomy, and right anterolateral thoracotomy.</p><p><b>METHOD</b>From August 2010 to July 2011, 70 patients with degenerative mitral valve disease and posterior leaflet prolapsed scheduled for elective isolated mitral valve repair were prospectively nonrandomized to undergo mitral valve operation by standard sternotomy (n = 30), right anterolateral thoracotomy (n = 30), or a robotic approach (n = 10). There were 49 male and 21 female patients, aging from 16 to 70 years with a mean of 53.4 years. Outcomes of the three groups were compared.</p><p><b>RESULTS</b>Mitral valve repair was achieved in all patients except 1 patient in the standard group. There were no in-hospital deaths. The median operation time [(300 ± 41) min, (184 ± 20) min and (169 ± 22) min, F = 112.5, P < 0.01], cardiopulmonary bypass time [(139 ± 26) min, (82 ± 20) min and (69 ± 23) min, F = 36.8, P < 0.01], aortic cross-clamping time [(93 ± 23) min, (47 ± 10) min and (38 ± 8) min, F = 75.0, P < 0.01] were longer for robotic than standard sternotomy and right anterolateral thoracotomy. The robotic group had shortest time of mechanical ventilation time [(4.9 ± 2.1) h, (5.3 ± 4.5) h and (14.1 ± 10.2) h, F = 13.2, P < 0.01], ICU time [(15.1 ± 2.1) h, (16.4 ± 5.4) h and (28.7 ± 16.1) h, F = 11.6, P < 0.01], postoperative hospital stay time [(4.6 ± 1.0) d, (5.7 ± 1.7) d and (8.8 ± 5.1) d, F = 8.0, P < 0.01] with the lowest of drainage [(192 ± 200) ml, (215 ± 163) ml and (405 ± 239) ml, F = 7.1, P < 0.01] and ratio of the patients needed blood transfusion (0, 20.0% and 66.7%, χ(2) = 22.7, P < 0.01). Patients were followed up 6 to 17 months, with 100% completed. No patients died during follow-ups, and no moderate or more mitral regurgitation was observed. The robotic group had the shortest time of return to normal activities compared with the other two groups [(2.4 ± 0.7) weeks, (4.2 ± 1.2) weeks and (8.2 ± 1.8) weeks, F = 83.0, P < 0.01].</p><p><b>CONCLUSION</b>This study shows mitral valve repair via the right anterolateral thoracotomy and a robotic approach is safe and feasible, with good cosmetic results and rapid postoperative recovery, and is worthy of clinical selective application.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Mitral Valve , General Surgery , Mitral Valve Prolapse , General Surgery , Prospective Studies , Robotics , Thoracic Surgical Procedures , Methods , Treatment OutcomeABSTRACT
OBJECTIVE@#To explore the effects of Tongxinluo on adenosine triphosphatase (ATPase), anti-oxidant enzymes activities, and lipid peroxidation of mitochondria or brain homogenate in focal brain ischemia-reperfusion rats.@*METHODS@#The models of the focal brain ischemia-reperfusion rats were made by the middle cerebral artery occlusion (MCAO). Activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and ATPase and malonaldehyde (MDA) levels of mitochondria or brain homogenate were measured by biochemical methods.@*RESULTS@#Tongxinluo significantly inhibited the decrease of activities of SOD and the increase of MDA levels, but had no difference in GSH-Px in brain homogenate. It also inhibited the decrease of activities of SOD, GSH-Px, ATPase, and the increase of MDA levels in mitochondria.@*CONCLUSION@#The protective mechanisms of Tongxinluo against mitochondrial injuries in focal ischemia-reperfusion rats may be derived from reducing lipid peroxides, scavenging free radicals and improving the energy metabolism.
Subject(s)
Animals , Male , Rats , Adenosine Triphosphatases , Metabolism , Antioxidants , Pharmacology , Brain Ischemia , Drugs, Chinese Herbal , Pharmacology , Glutathione Peroxidase , Metabolism , Malondialdehyde , Metabolism , Rats, Sprague-Dawley , Reperfusion Injury , Superoxide Dismutase , MetabolismABSTRACT
The objective was designed to assess the clinical efficiency of preventing febrile nonhemolytic transfusion reactions (FNHTR) with transfusion of leukocyte-depleted RBC and platelet concentrates. One hundred patients with cirrhosis of liver, gastric ulcer and cancer were selected to receive RBC concentrates with leukocyte filtration. Another group of 50 patients with liver necrosis, gastric ulcer and cancer were selected to receive non-filtered RBC concentrates. Two hundred and forty patients with acute or chronic leukemia, aplastic anemia, multiple myeloma, thrombocytopenia purpura, diabetes mellitus, cirrhosis of liver, upper gastrointestinal hemorrhage, severe hepatitis, burn and cancer post radioactive or chemical treatment were divided into two group with 120 patients in each one and selected randomly to receive platelet concentrates. The incidence rates of FNHTR in all patients were investigated. Results showed that there was no FNHTR in 100 transfusions with leukocyte-depleted RBC concentrates. Eight out of 50 patients with non-filtrated RBC concentrates showed FNHTR. The incidence of FNHTR was sixteen (16%) in non-filtrated transfusion. Twenty-five and 7 patients manifested FNHTR respectively in non-filtrated or filtrated platelets transfusions. The incidence of FNHTR was 20.83% and 5.83% respectively in non-filtrated or filtrated platelet transfusion. It is concluded that leukocyte-depleted RBC and platelet concentrates reduces FNH TR in blood transfusion.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Blood Component Removal , Fever , Filtration , Leukocytes , Transfusion ReactionABSTRACT
Objective To study the effects of irradiation and W11-a12，a kind of repair-promoting drug，on anion-selective channel in membranes of mouse peritoneal macrophage. Methods The activity of anion-selective channel was recorded from cell-attached patches with patch clamp techniques． Results The effects of irradiation on anion-selective channel in membranes of peritoneal macrophage included：①decreasing the mean number of activated channels by the presence of zymosan; ②prolonging the mean time from stimulus to the opening of channels; ③depressing the opening of channels by decreasing open-state probability，shortening open-time and prolonging close-time． The effects of irradiation could partly be depressed by W11-a12. Conclusion Irradiation will depress the anion-selective channel of peritoneal macrophage, which may be an important way to depress the function of macrophage．
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Objective To study the effects of irradiation and W11-a12，a kind of repair-promoting drug，on anion-selective channel in membranes of mouse peritoneal macrophage. Methods The activity of anion-selective channel was recorded from cell-attached patches with patch clamp techniques． Results The effects of irradiation on anion-selective channel in membranes of peritoneal macrophage included：①decreasing the mean number of activated channels by the presence of zymosan; ②prolonging the mean time from stimulus to the opening of channels; ③depressing the opening of channels by decreasing open-state probability，shortening open-time and prolonging close-time． The effects of irradiation could partly be depressed by W11-a12. Conclusion Irradiation will depress the anion-selective channel of peritoneal macrophage, which may be an important way to depress the function of macrophage．
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Objective To investigate the effect of brain-derived neurotrophic factor (BDNF) gene modified neural stem cells (NSCs)transplantation on cerebral ischemic injury in rats.Methods NSCs from newborn rat hippocampus were isolated,cultured in a medium containing fibroblast factor (FGF) in vitro. Their proliferation and differentiation were detected by immunohistochemistry.Virus vectors pLXSN-BDNF were built and BDNF were transfected into NSCs.Biological activity were detected to obtained engineering stem cells of BDNF protein with secretary activity.Middle cerebral artery occlusion (MCAO) models were made and transplanted with NSCs-BDNF by stereotaxic technique.The effect of transplantation on MCAO models was evaluated histologically and behaviorally.Results Statistical analysis showed that the behavioral performance of the animals improved after transplantation (Longa mark being 1.343?0.293 four weeks after stem cell transplantation).The number of hippocampal dentate gyrus neurons increased to 87.5%?6.6% , four weeks after stem cell transplantation on Nissle stained hippocampal sections,which was significantly different from that of controls.Positively BrdU stained neural stem cells revealed by immunohistochemistry in the cultured cells and in the transplanted brain sections,indicated that the engineering cells transplanted had survived in the host brain and began to proliferate.Conclusion Transplantation of BDNF genetically modified NSCs can effectively promote the recovery from cerebral ischemic injury.