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Aim To investigate the protective effects of ginkgolide K (GK) on neurovascular unit injured by ischemic stroke and the potential mechanism associated with hypoxia-inducible factor-1α (HIF-1α) pathway. Methods The BV-2 cells and EA. hy926 cells suffered from oxygen-glucose deprivation and reperfusion (OGD/R) were applied to mimic the injury of neurovascular unit induced by cerebral ischemia in vitro. After 4 h OGD insult, BV-2 cells and EA. hy926 cells received reperfusion and treated with GK. The levels of inflammatory cytokines in the supernatant of BV-2 cells were detected, while the protective effects of GK on EA. hy926 cells were also evaluated after GK administration for 24 h. The p-Akt and p-Erk expressions were examined by Western blot after 1 h of GK treatment, while HIF-1α was detected after 6 h of GK treatment. In addition, PI3K inhibitor LY294002 was applied to further verify the potential mechanisms underlying the beneficial effects of GK. The expressions of p-Akt after 1 h of GK treatment, and the protein levels of HIF-1α pathway after 6 h of GK treatment were also analyzed by Western blot. Results GK significantly inhibited the levels of TNF-α, IL-6 and IL-1β in supernatant of BV-2 cells injured by OGD/R, through increasing p-Akt and decreasing p-Erk expressions, and then affecting HIF-1α pathway. In addition, LY294002 reduced the regulatory effect of GK. Furthermore, GK significantly improved viability and inhibited the release of LDH in supernatant of EA. hy926 cells suffered from OGD/R, and up-regulated the expressions of p-Akt, HIF-1α, HO-1 and VEGF, while cleaved caspase-3/9 was inhibited. Conclusions GK exerts multi-effects on reducing neurovascular unit injury induced by ischemic stroke, and the potential mechanism might be associated with the different regulatory effects of HIF-1α in different cells.
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OBJECTIVE@#To investigate the relationship of PTEN/PI3K/AKT signaling pathway protein expression with apoptosis and drug-resistance of children's ALL primary cells treated with daunorubicin (DNR).@*METHODS@#The bone marrow mononuclear cells in newly diagnosed and untreated B-ALL children were collected and cultured. After the treatment of primary-cultured cells with DNR of final concentration 0.5 mg/L for 24 h, the cell apoptosis rate was detected by using cell apoptosis assay kit; the samples were collected at the on test of culture and after drug treatment, then expression levels of PTEN, PI3K and AKT proteins were detected by Western blot, moreover the interindex correlation was analyzed.@*RESULTS@#After DNR treatment, the apoptosis rate in PTEN low expression group was lower than that in PTEN high expression group (P<0.05), showing high positive correlation of the cell apoptosis rate with the expression of PTEN before DNR treatment; the cell apoptosis rate in PI3K and AKT low expression group was higher than that in PI3K and AKT high expression group (P<0.01); however, the expression of PI3K and AKT proteins was down-regulated after treatment with DNR (P<0.01).@*CONCLUSION@#The difference of PTEN expression is present in primary cells of B-ALL children, however the change of PTEN expression is not significant after DNR treatment, suggesting that the PTEN expression correlates with DNR-resistance. The DNR can induce the apoptosis of childrens B-ALL primary cells by down-regulating the expression of PI3K and AKT signaling pathway proteins.
Тема - темы
Child , Humans , Apoptosis , Daunorubicin , PTEN Phosphohydrolase , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal TransductionРеферат
Four children (two boys and two girls), aged from 3 years and 7 months to 5 years, had mild or moderate anemia, mild hepatosplenomegaly, jaundice (mainly an increase in indirect bilirubin), an increase in the percentages of reticulocytes and spherical erythrocytes in peripheral blood smear and an increase in erythrocyte osmotic brittleness. High-throughput sequencing found two novel mutations in the SLC4A1 gene, c.37G>A and c.340T>C, in case 1 and case 2 respectively, and these two mutations were predicted to be pathogenic by Mutation Taster. The Polyphen2 scores of these two mutations were 0.87 and 0.83 respectively, which suggested that these mutations were probably damaging. The SIFT scores of these two mutations were 0.008 and 0.09 respectively, suggesting that these mutations were probably damaging. No abnormality in this gene was found in their parents. Two reported heterozygous mutations in the ANK1 gene, c.830A>G and c.985G>C, were found in case 3 and case 4 respectively. Gene detection was not performed for the parents of case 3. The mother of case 4 was diagnosed with hereditary spherocytosis and had a heterozygous mutation of c.985G>C in the ANK1 gene. All four children were diagnosed with hereditary spherocytosis. Case 3 had a hemoglobin level of 105 g/L. Hereditary spherocytosis is a hereditary hemolytic disease caused by abnormality in erythrocyte membrane protein, and gene detection helps to make a confirmed diagnosis.
Тема - темы
Child , Child, Preschool , Female , Humans , Male , Ankyrins , Erythrocytes , Heterozygote , Mutation , Spherocytosis, HereditaryРеферат
<p><b>OBJECTIVE</b>To investigate the effect of high-fat diet on the expression of transient receptor potential vanilloid 1 (TRPV1) in the respiratory system and the dorsal root ganglion (DRG) of mice, as well as its effect on the excitability of sensory neurons.</p><p><b>METHODS</b>A total of 20 C57BL/6 mice were randomly divided into normal-diet (ND) group and high-fat diet (HFD) group, with 10 mice in each group. The mice were given corresponding diets and body weights were monitored. After 7 weeks of feeding, lung tissue, bronchial tissue, and DRG at thoracic segments 3-4 were collected and immunohistochemical staining was performed. A patch clamp was used to measure the number of action potentials and TRPV1 current intensity in the DRG.</p><p><b>RESULTS</b>After 7 weeks of feeding, the HFD group had significantly greater mean weight gain than the ND group (6.4±2.6 g vs 2.3±0.5 g; P<0.001). The HFD group had significantly higher expression of TRPV1 in the bronchus, pulmonary alveoli, and DRG than the ND group (P<0.05). Compared with the ND group, the HFD group had significant increases in the TRPV1 current intensity and number of action potentials in the DRG (P<0.05).</p><p><b>CONCLUSIONS</b>High-fat diet induces a significant increase in body weight and leads to high expression of TRPV1 and high excitability in the respiratory system and the peripheral sensory neurons. This suggests that TRPV1 may be an important factor in the physiopathological mechanisms of bronchial hyperresponsiveness.</p>
Тема - темы
Animals , Male , Mice , Action Potentials , Body Weight , Diet, High-Fat , Ganglia, Spinal , Chemistry , Mice, Inbred C57BL , Respiratory System , Chemistry , TRPV Cation Channels , PhysiologyРеферат
<p><b>OBJECTIVE</b>To investigate the clinical features of Diamond-Blackfan anemia (DBA) and related pathogenic genes.</p><p><b>METHODS</b>A retrospective analysis was performed for the clinical data of two children with DBA, and related literature was reviewed.</p><p><b>RESULTS</b>The two children with DBA (2-3 months old) manifested with severe normochromic normocytic anemia, decreased reticulocyte count, and increased serum iron and serum ferritin. Normal white blood cell and platelet counts were noted in the two patients. Bone marrow examination showed a decreased percentage of erythrocytes and rare normoblasts in the two patients. Gene screening showed a reported pathogenic heterozygous mutation in RPS19 gene, c.212G>A (p. Gly71Glu), in one patient, and there were no mutations in his parents. In the other patient, gene screening showed a heterozygous mutation in RPL5 gene, c.740T>C (p. I247L), which had not been reported in literature, and there were no mutations in her parents. A bioinformatic analysis showed that this might be a pathogenic mutation.</p><p><b>CONCLUSIONS</b>The onset age of DBA is early infancy in most children, with a manifestation of erythroid deficiency. RPS19 and RPL5 gene mutations are common causes of this disease. Molecular detection helps with the early diagnosis of DBA.</p>
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Humans , Infant , Male , Anemia, Diamond-Blackfan , Genetics , Computational Biology , Mutation , Ribosomal Proteins , GeneticsРеферат
This review article introduces the research advances in the pathophysiological mechanism of obesity in inducing pediatric bronchial asthma, including the role of leptin in obesity and asthma, the association of plasminogen activator inhibitor-1 with obesity and asthma, the association of adiponectin and interleukins with obesity and asthma, and the influence of neurotransmitter on asthma. In particular, this article introduces the latest research on the inhibition of allergic asthma through targeting at the nociceptor of dorsal root ganglion and blocking the signaling pathway of the nociceptor.
Тема - темы
Humans , Asthma , Leptin , Physiology , Nerve Growth Factor , Physiology , Neurotransmitter Agents , Physiology , Obesity , Plasminogen Activator Inhibitor 1 , PhysiologyРеферат
<p><b>OBJECTIVE</b>To study the role of Helicobacter pylori (H. pylori) infection in newly diagnosed childhood immune thrombocytopenia (ITP).</p><p><b>METHODS</b>A total of 495 children with newly diagnosed ITP who were hospitalized for the first time between January 2011 and December 2013 were included as the case group. A total of 123 children with common respiratory tract infection (not ITP or other diseases of blood system) were randomly selected as the control group. All patients were divided into four groups by age: <1 year group, 1-3 years group, 3-7 years group, and 7-14 years group. The incidence of H. pylori infection in all age groups and the clinical outcomes of ITP children with or without H. pylori infection were retrospectively analyzed.</p><p><b>RESULTS</b>The incidence rate of H. pylori infection in the case group increased with increasing age. There was no significant difference in the incidence rate of H. pylori infection between the case and the control groups among subjects of the same age (P>0.05). All the ITP patients were not given anti-H. pylori treatment and only received the treatment (glucocorticoid and/or immunoglobulin) for ITP, and their remission rate declined with increasing age. There was no significant difference in the remission rate between the ITP children with H. pylori infection and those without H. pylori infection in the same age group (P>0.05).</p><p><b>CONCLUSIONS</b>H. pylori infection may not be a major cause of ITP in children, and the clinical outcomes of children with acute ITP are not affected by receiving anti-H. pylori treatment or not.</p>
Тема - темы
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Age Factors , Helicobacter Infections , Epidemiology , Helicobacter pylori , Incidence , Purpura, Thrombocytopenic, IdiopathicРеферат
This paper summarized the recent 30 years research progress of the chemical constituents from Notopterygii Rhizoma et Radix. The chemical constituents from Notopterygii Rhizoma et Radix mainly consist of coumarins, polyene-polyacetylenes, sesquiterpenes, phenolic acids, while steroids and flavonoids were less reported. All constituents were confirmed and corrected through SciFinder. We also checked the Chinese name and English name and listed the CAS number of each compound. It can provide some guidelines for the research, development and utilization of Notopterygii Rhizoma et Radix in the future. Whether there is columbianin in the Notopterygii Rhizoma et Radix need to be further researched.
Тема - темы
Apiaceae , Chemistry , Drugs, Chinese Herbal , Rhizome , ChemistryРеферат
<p><b>OBJECTIVE</b>To investigate the association between single nucleotide polymorphism (SNP) (rs17166050) in RAD50 gene and acute lymphoid leukemia (ALL) in children.</p><p><b>METHODS</b>A total of 177 ALL children from Wuhan and surrounding areas and 232 healthy children were selected. The numbers of standard-risk, medium-risk, and high-risk children were 66, 69, and 42, respectively. The genotypes of SNP in RAD50 gene were determined using PCR-RFLP, and the relationship of the RAD50 polymorphism with ALL susceptibility and clinical risk was analyzed.</p><p><b>RESULTS</b>The genotype (AA, GA, and GG) distribution of SNP in RAD50 gene showed significant differences between the ALL and control groups (P=0.038), and G allele was significantly associated with ALL susceptibility (OR=1.459, 95% CI: 1.034-2.057, P=0.031). However, the SNP was not associated with the risk stratification of ALL.</p><p><b>CONCLUSIONS</b>The SNP (rs17166050) in RAD50 gene is associated with the susceptibility to ALL in children, but is not associated with the risk stratification of ALL.</p>
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Child , Child, Preschool , Female , Humans , Infant , Male , DNA Repair Enzymes , Genetics , DNA-Binding Proteins , Genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Genetics , RiskРеферат
<p><b>OBJECTIVE</b>To explore the clinical curative effect and safety of Jiedu Tongluo Lishi decoction on treating active rheumatoid arthritis (RA).</p><p><b>METHOD</b>106 cases of RA in active period were randomly divided into the integrated Chinese and western medicine group (n=54) and western medicine contrast group (n=52). The former group were treated by Jiedu Tongluo Lishi decoction combined with SASP, the latter by MTX combined with SASP. The arthritis morning stiffness time, ache indexes, tumidness indexes, function indexes, hands grip, 20-m walking time and experimental indexes including ESR, RF, CRP, C3, immune globin of both groups were observed and compared.</p><p><b>RESULT</b>The obviously clinical effective ratio and the total clinical effective ratio in the former group were 77.78% and 90.74% respectively, which are better than those in the latter group (59.62% and 71.15% respectively) (P < 0.01). The arthritis morning stiffness time, ache indexes, tumidness indexes, function indexes, hands grip and 20-m walking time in both groups were obviously released after treatment (P < 0.01). The clinical release in the former group was better than that in the latter group (P < 0.05). ESR, RF and CRP in both groups were markedly improved (P < 0.05). The improvement of ESR, RF, CRP, C3 and IgA in the former group were better than those in the latter group (P < 0.05). The side effect includes gastroenteric tract reaction, decrease of leucocyte, abnormity of liver function, tetter and catamenia maladjustment. The occurent ratio in the former group was 7.41%, which was obviously lower than that in the latter group (15.38%) (P < 0.01).</p><p><b>CONCLUSION</b>The compositively clinical curative effect of Jiedu Tongluo Lishi decoction combined with MTX on treating RA is obviously better than that of western medicine only such as MTX and SASP, with less side effect and higher safety, which is worth applying in clinics extensively.</p>
Тема - темы
Animals , Female , Male , Mice , Rats , Antirheumatic Agents , Therapeutic Uses , Arthritis, Experimental , Blood , Drug Therapy , Dinoprostone , Blood , Drug Combinations , Drugs, Chinese Herbal , Therapeutic Uses , Freund's Adjuvant , Interleukin-1beta , Blood , Materia Medica , Therapeutic Uses , Medicine, Chinese Traditional , Pain Threshold , Plants, Medicinal , Chemistry , Random Allocation , Rats, Wistar , Scorpions , Chemistry , Tumor Necrosis Factor-alpha , BloodРеферат
<p><b>OBJECTIVE</b>The study was designed to explore the influence of transfected bone marrow mononuclear cells (BMMNC) transplantation on the hematopoietic cells activity and the recipient mice hematopoietic reconstitution.</p><p><b>METHODS</b>The exogenous mFasL-cDNA gene was transferred to Balb/C mouse BMMNC by liposomes. Then the transferred BMMNC was co-cultured with BMMNC from BAC mouse (H-2d x b, male) at a ratio of 0.625 to 1 for 6 days. In the experimental group (the 3rd group), 1 x 10(7) (0.5 ml) mixed viable cells were injected into whole bodily irradiated ((60)Co-r) mice (6 to 8 week old female Balb/C) via the tail vein. The following grafted mice were simultaneously used in the study, the mice transplanted with 0.5 ml of culture medium, the mice transplanted with the mixture of untransferred Balb/C mouse BMMNC and BAC mouse BMMNC, the mice transplanted with the mixture of transferred Balb/C mouse BMMNC and BAC mouse BMMNC and the mice transplanted with Balb/C mouse BMMNC. The hematopoietic reconstitution, the origin of bone marrow cells responsible for the reconstitution, the graft versus host disease (GVHD), the survival rate for the recipient mice were observed after bone marrow transplantation (BMT).</p><p><b>RESULTS</b>The counts of leukocytes and platelets in recipient blood of group four on +10 d and +20 d after BMT were higher than those in group three and group two (P < 0.01), but on +30 d after BMT the counts of leukocytes and platelets in recipient blood of group two, group three and group four were at their normal levels. The Y chromosome from donor mice was discovered in BMMNC of recipient mice having survived for over two months after BMT in group two and group three. The survival rate of the recipient mice two mouths after BMT in all groups were 0% for group one, 30% for group two, 80% for group three, and 100% for group four, respectively. The total survival rate of recipient mice in the experimental group was obviously higher than that of group two (P < 0.01). Grade II to III GVHD signs were found on the histology from dead mice after BMT in group three and group two, and the mice having survived for over two months in the group two. Grade I GVHD signs were found on histology from 7 out of 8 mice which survived for over two months after BMT in group three.</p><p><b>CONCLUSIONS</b>The transplantation of mixed cells into recipient mice made the recipient mice achieve hematopoietic reconstitution from donor BMMNC.</p>
Тема - темы
Animals , Female , Male , Mice , Fas Ligand Protein , Genetics , Physiology , Graft vs Host Disease , Epidemiology , Hematopoiesis , Hematopoietic Stem Cell Transplantation , Leukocyte Count , Mice, Inbred BALB C , Mice, Inbred C57BL , TransfectionРеферат
To explore the new approach to prevent graft versus host disease (GVHD) by purging ex vivo T lymphocytes of bone marrow graft through Fas-FasL way, FasL-cDNA was transfected into BALB/c mouse bon e marrow cells by liposome ex vivo. The transfected cells were cultured together with BAC (BALB/c x C57BL/6) mouse bone marrow graft. The mixing bone marrow graft was infused into BALB/c mouse recipients after 60Co-gamma irradiation. The mortality, manifestation and pathologic change of GVHD in recipient mice were observed. The CFU-S and Y chromosome from donor mice were detected. The results showed that compared with control group, the mortality in 60 days of the recipients in the experimental group decreased (20% vs 70%, P < 0.01) and the morbidity of GVHD lowered (40% vs 100%, P < 0.01). The CFU-S counts for all groups were at normal level on 20 days after transplantation. The Y chromosome from donor mice was discovered in 70% bone marrow nucleated cells of recipient mice survived over 2 months in the experimental group. It is concluded that mFasL-cDNA transfected mouse bone marrow cells prevent GVHD after culturing together with bone marrow graft, and accelerate hematopoietic reconstitution in recipient mice.
Тема - темы
Animals , Female , Male , Mice , Bone Marrow Cells , Metabolism , Bone Marrow Purging , Bone Marrow Transplantation , Fas Ligand Protein , Genetic Therapy , Graft vs Host Disease , Membrane Glycoproteins , Genetics , Mice, Inbred BALB C , TransfectionРеферат
Objective To investigate the influence of angelica sinenisis injection on bone marrow histology and ultrastructure in immune-induced aplastic anemia(AA) mice.Methods Female Balb/c mice were divided into normal group,model group,therapy group and contrast group.All mice were killed by cutting neck on the 12 th day, ulnas and femur were taken out. The bone marrow histology section and ultrastructure of mice ulnas were observed. The quantities of hematopoietic cells were counted. The number of femur bone marrow mononucleate cells (MNC) were measured.Results The quantities of hematopoietic cells in model group were lower than those in normal group (P