ABSTRACT
BACKGROUND: Primary hepatic lymphoma (PHL) is a lymphoproliferative disorder confined to the liver without peripheral lymph node involvement and bone marrow invasion. PHL is extremely rare in clinical practice. The etiology and pathogenesis of PHL are largely unknown. There are no common standard protocols or guidelines for the treatment of PHL. CASE SUMMARY: We report the case of a 66-year-old man who presented with fever and abdominal pain for three weeks. Computed tomography and magnetic resonance imaging scans showed a pyogenic liver abscess. The patient underwent a right posterior hepatectomy. The surgical pathology revealed aggressive B-cell lymphoma, with a primary consideration of diffuse large B-cell lymphoma of non-germinal center origin. CONCLUSION: This article reviews the characteristics, mechanism and treatment of PHL and provides insight into the diagnosis of PHL.
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Animal brains have discrete circadian neurons, but little is known about how they are coordinated to influence and maintain sleep. Here, through a systematic optogenetic screening, we identified a subtype of uncharacterized circadian DN3 neurons that is strongly sleep promoting in Drosophila. These anterior-projecting DN3s (APDN3s) receive signals from DN1 circadian neurons and then output to newly identified noncircadian "claw" neurons (CLs). CLs have a daily Ca2+ cycle, which peaks at night and correlates with DN1 and DN3 Ca2+ cycles. The CLs feedback onto a subset of DN1s to form a positive recurrent loop that maintains sleep. Using trans-synaptic photoactivatable green fluorescent protein (PA-GFP) tracing and functional in vivo imaging, we demonstrated that the CLs drive sleep by interacting with and releasing acetylcholine onto the mushroom body γ lobe. Taken together, the data identify a novel self-reinforcing loop within the circadian network and a new sleep-promoting neuropile that are both essential for maintaining normal sleep.
Subject(s)
Drosophila Proteins , Drosophila melanogaster , Animals , Brain/physiology , Circadian Rhythm/physiology , Drosophila/metabolism , Drosophila Proteins/metabolism , Drosophila melanogaster/physiology , Sleep/physiologyABSTRACT
BACKGROUND: Inflammatory bowel disease (IBD) is a prevalent worldwide health problem featured by relapsing, chronic gastrointestinal inflammation. Enhancer of zeste homolog 2 (EZH2) is a critical epigenetic regulator in different pathological models, such as cancer and inflammation. However, the role of EZH2 in the IBD development is still obscure. AIM: To explore the effect of EZH2 on IBD progression and the underlying mechanism. METHODS: The IBD mouse model was conducted by adding dextran sodium sulfate (DSS), and the effect of EZH2 on DSS-induced colitis was assessed in the model. The function of EZH2 in regulating apoptosis and permeability was evaluated by Annexin V-FITC Apoptosis Detection Kit, transepithelial electrical resistance analysis, and Western blot analysis of related markers, including Zona occludens 1, claudin-5, and occludin, in NCM460 and fetal human colon (FHC) cells. The mechanical investigation was performed by quantitative reverse transcription-polymerase chain reaction, Western blot analysis, and chromatin immunoprecipitation assays. RESULTS: The colon length was inhibited in the DSS-treated mice and was enhanced by the EZH2 depletion in the system. DSS treatment caused a decreased histological score in the mice, which was reversed by EZH2 depletion. The inflammatory cytokines, such as tumor necrosis factor-α, interleukin-6, and interleukin-1ß, were induced in the DSS-treated mice, in which the depletion of EZH2 could reverse this effect. Moreover, the tumor necrosis factor-α treatment induced the apoptosis of NCM460 and FHC cells, in which EZH2 depletion could reverse this effect in the cells. Moreover, the depletion of EZH2 attenuated permeability of colonic epithelial cells. Mechanically, the depletion of EZH2 or EZH2 inhibitor GSK343 was able to enhance the expression and the phosphorylation of janus kinase 2 (JK2) and signal transducer and activator of transcription in the NCM460 and FHC cells. Specifically, EZH2 inactivated JAK2 expression by regulating histone H3K27me3. JAK2 inhibitor TG101348 was able to reverse EZH2 knockdown-mediated colonic epithelial cell permeability and apoptosis. CONCLUSION: Thus, we concluded that EZH2 contributed to apoptosis and inflammatory response by inactivating JAK2/ signal transducer and activator of transcription signaling in IBD. EZH2 may be applied as a potential target for IBD therapy.
Subject(s)
Colitis , Enhancer of Zeste Homolog 2 Protein , Inflammatory Bowel Diseases , Janus Kinase 2 , STAT Transcription Factors , Animals , Apoptosis , Colitis/chemically induced , Colitis/pathology , Dextran Sulfate , Disease Models, Animal , Enhancer of Zeste Homolog 2 Protein/genetics , Humans , Inflammatory Bowel Diseases/drug therapy , MiceSubject(s)
Carbapenem-Resistant Enterobacteriaceae , Cross Infection , Enterobacteriaceae Infections , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Carbapenems , Child , Cross Infection/drug therapy , Cross Infection/epidemiology , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/epidemiology , Humans , Microbial Sensitivity Tests , Risk Factors , beta-LactamasesABSTRACT
OBJECTIVE: To find out the prevalence of respiratory syncytial virus (RSV) genotypes in southern Zhejiang Province, China, and to study the genetic characteristics of G protein from subtype A of RSV. METHODS: The lower respiratory tract secretions of children under 5 years of age who were hospitalized for pneumonia and bronchiolitis in three hospitals in southern Zhejiang Province from July 2009 to June 2014 were collected. Direct immunofluorescence assay was used to detect RSV antigens from the collected secretions. A total of 200 samples were randomly selected from RSV-positive specimens in each prevailing year (from July of a specific year to June of the next year). RT-PCR was used to determine RSV subtypes, and the near-full length gene sequence of G protein from subtype A was amplified and sequenced to identify the genotype. RESULTS: A total of 25 449 samples of lower respiratory tract secretions were collected from 2009 to 2014, among which 6 416 (25.21%) samples were RSV-positive. Among the 1 000 RSV-positive specimens randomly sampled, 462 strains (46.2%) were subtype A, and 538 strains (53.8%) were subtype B. Subtype A accounted for 22.5%, 74.5%, 84.5%, 19.0%, and 30.5% of the total strains in each year from 2009 to 2014. A total of 25 RSV subtype A strains were randomly sampled and sent out for bidirectional sequencing in each year, which confirmed 52 positive subtype A strains. Four genotypes of subtype A strains were obtained from the above strains, including NA1 (39 strains), NA4 (1 strain), ON1 (10 strains), and GA2 (2 strains). NA1 was the dominant genotype between 2009 and 2012, and ON1 was the only genotype of subtype A during 2013-2014. The nucleotide homology and amino acid homology between the G protein of subtype A and the prototype strain A2 were 80.7%-89.3% and 74.4%-82.6%, respectively. The nucleotide homology and amino acid homology between the isolates of subtype A were 81.5%-100% and 80.2%-100%, respectively. CONCLUSIONS: In southern Zhejiang Province from 2009 to 2014, there was a co-circulation of RSV subtypes A and B, as well as a co-circulation of several different genotypes of RSV subtype A, which had highly variable G protein genes.
Subject(s)
Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Child, Preschool , China , Epidemiologic Studies , Genotype , Humans , Infant , Infant, Newborn , Phylogeny , Respiratory Syncytial Virus Infections/epidemiologyABSTRACT
BACKGROUND: To identify asthma clinical phenotypes using cluster analysis and improve our understanding of heterogeneity in asthma. METHODS: Clustering approaches were applied to 203 patients who were diagnosed with asthma in XinHua Hospital (January 2012 to December 2015). One hundred and twenty patients underwent multi-slice spiral computed tomography (MSCT) examination and 30 underwent bronchial mucosal biopsy for evaluation of airway remodeling and airway inflammation among the phenotypes. RESULTS: Four groups were identified. Patients in cluster 1 (n=52) had early onset atopic asthma and patients in cluster 2 (n=65) had small airway obstruction and atopic asthma. Cluster 3 (n=52) was a unique group of patients with late-onset and non-atopic asthma. Patients in cluster 4 (n=34) had severe airflow obstruction and obvious airway remodeling as observed on MSCT (P<0.05). According to the immunohistochemistry of IL-5 and IL-17 (P<0.05), the results of clusters 1 and 2 may be attributable to the Th2 immune response, whereas those of clusters 3 and 4 to the Th17 immune response. CONCLUSIONS: Four distinct clinical phenotypes of asthma were identified by cluster analysis. The results of the MSCT and pathological examinations may suggest specific pathogeneses among the phenotypes.
ABSTRACT
Acrossocheilus jishouensis is an endemic south China stream-dwelling cyprinid species. Its complete mitochondrial genome is 16,587 bp in length, consisting of 13 protein-coding genes, 22 tRNA genes (ranging from 67 bp in tRNACys to 76 bp in tRNALeu and tRNALys ), two rRNA genes (956 bp in 12S rRNA and 1673 bp in 16S rRNA), and one control region (942 bp). Its overall base composition is A: 31.2%, C: 27.6%, G: 16.2%, and T: 25.1%. The complete mitogenome of the Chinese barred species of Cpynidae could provide a basic data for further phylogenetics analysis.
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AIMS: Asiaticoside (AS) is a saponin monomer extracted from the medicinal plant Centella asiatica, which has a variety of biological effects. We intended to investigate the effects of asiaticoside on a hypoxia-induced pulmonary hypertension (HPH) rat model and examine the possible effects of asiaticoside on TGF-ß1/Smad signaling in vivo and in vitro. MAIN METHODS: The rat HPH model was established by hypoxic exposure and asiaticoside was administered for four weeks. Parameters including the mean pulmonary artery pressure (mPAP), the right ventricular hypertrophy (RVH) and the percentage of medial wall thickness were used to evaluate the development of HPH. TGF-ß1, TGF-ß receptor, Smad2/3 and phospho-Smad2/3 expressions were detected and the proliferation, migration and apoptosis of pulmonary arterial smooth muscle cells (PASMCs) adjusted by asiaticoside under the hypoxic condition were evaluated. KEY FINDINGS: Our data indicate that asiaticoside attenuated pulmonary hypertension, pulmonary vascular remodeling and RV hypertrophy in HPH rats, which was probably mediated by restraining the hypoxia-induced overactive TGF-ß1/Smad2/3 signaling and inhibiting the proliferation by inducing apoptosis of the PASMCs. SIGNIFICANCE: Given the preventative potential in animal models and in vitro, we propose asiaticoside as a promising protective treatment in HPH.
Subject(s)
Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/prevention & control , Hypoxia/drug therapy , Signal Transduction/drug effects , Smad3 Protein/metabolism , Transforming Growth Factor beta1/metabolism , Triterpenes/pharmacology , Triterpenes/therapeutic use , Animals , Apoptosis/drug effects , Blood Pressure/drug effects , Blood Pressure/physiology , Caspase 3/metabolism , Cell Movement/drug effects , Cell Proliferation/drug effects , Disease Progression , Heart Ventricles/drug effects , Heart Ventricles/pathology , Hypertension, Pulmonary/complications , Hypertension, Pulmonary/physiopathology , Hypertrophy/drug therapy , Hypoxia/complications , Hypoxia/pathology , Hypoxia/physiopathology , Male , Phosphorylation/drug effects , Pulmonary Artery/drug effects , Pulmonary Artery/metabolism , Rats , Receptors, Transforming Growth Factor beta/biosynthesis , Smad2 Protein/biosynthesis , Vascular Remodeling/drug effects , Vascular Remodeling/physiologyABSTRACT
Fanconi syndrome results from a generalized abnormality of the proximal tubules of the kidney and owing to phosphate depletion can cause hypophosphatemic osteomalacia. Adefovir dipivoxyl (ADV) effectively suppresses hepatitis B virus replication but exhibits nephrotoxicity when administered at a low dosage. We report two cases of Fanconi syndrome induced by ADV at 10 mg/day to call for regular screening for evidence of proximal tubular dysfunction and detailed bone metabolic investigations for prompt detection of ADV nephrotoxicity is critically important to ensure timely drug withdrawal before the development of irreversible tubulointerstitial injury.
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OBJECTIVE: To explore the association between CYP11B2 gene polymorphism and essential hypertension, blood pressure level in Chinese Han population by meta-analysis. METHODS: After searching database, the research quality was quantified according to NOS. Genetic model, heterogeneity, publication bias, overall OR/standardized mean difference (SMD) and 95%CI were explored by Stata, 19 studies including 9249 subjects were included in this meta-analysis. RESULTS: Compared to control group, OR(95%CI) of CC vs. TT, CT vs. TT, CC vs. CT in essential hypertensive patients were 1.022(95%CI: 0.879-1.190), 1.108 (95%CI: 0.951-1.291), 1.050(95%CI:0.995-1.109), respectively; SMD (95%CI) was 0.315 (0.066-0.565, P < 0.05) for systolic pressure derived CC vs. TT, and 0.088 (0.014-0.162, P < 0.05) for CT vs. TT CONCLUSION: Individuals with -344C CYP11B2 allele are at higher risk of increased systolic blood pressure, but there is no evidence showing association between CYP11B2 polymorphism and susceptibility of essential hypertension in Chinese Han population.
Subject(s)
Cytochrome P-450 CYP11B2/genetics , Hypertension/genetics , Asian People/genetics , Essential Hypertension , Genetic Predisposition to Disease , Genotype , Humans , Polymorphism, Single NucleotideABSTRACT
AIM: To clone human interleukin-32(hIL-32) gene and express it in E.coli efficiently. METHODS: The gene of hIL-32 was amplified by RT-PCR from human peripheral blood mononuclear cells (PBMC) which stimulated with Con A for 60 h. The PCR product was inserted into the pMD18-T vector. The hIL-32 cDNA confirmed by sequencing was inserted into expression vector pET-30a(+) and expressed in E.coli BL21(DE3) strain. The hIL-32 protein expression was induced by IPTG and assayed by SDS-PAGE and coomassie blue stain. The recombination protein was identified by Western blot and its biological activity was analyzed. RESULTS: DNA sequencing confirmed that the cloned cDNA was identical to the published sequence of hIL-32 that the nucleotide sequence of this gene was 567 bp. The recombinant plasmid pET30a-hIL32 was transformed into E.coli BL21(DE3) strain for expression. An expected 28 kDa protein of hIL-32 was found mainly in the induced host strains by SDS-PAGE and coomassie blue stain. The 28 kDa protein was recognized by anti-IL-32 antibody in western blot. The purified recombination protein could induce the producing of IL-6 in the human PBMC. CONCLUSION: We have successfully cloned the gene and expressed the protein of hIL-32 and the expressed protein has specific bioactivity.
Subject(s)
Interleukins/genetics , Recombinant Proteins/biosynthesis , Cloning, Molecular , Escherichia coli/genetics , Humans , Interleukins/isolation & purification , Interleukins/pharmacology , Recombinant Proteins/isolation & purification , Recombinant Proteins/pharmacologyABSTRACT
OBJECTIVE: This study was to explore the cytotoxic effect and the related injury mechanism of deoxynivalenol (DON) on articular chondrocytes in human embryo. METHODS: Articular cartilage cells were isolated from knees of human embryo and cultured in DMEM/F12 medium. The cells of the 4th generation were divided into five groups and incubated with varying concentrations of DON as the followings: control group and group with DON of 0.1, 0.2, 0.4, 1.0 µg/ml. The effects of DON were observed 72 hours after incubation. Cell apoptosis was assayed by flow cytometry (FCM) with Annexin V-FITC/PI staining; MMP-13 and PGE2 were detected by ELISA kits; NO was measured by Griess assay with spectrophotometer. Inducible nitric oxide synthase (iNOS) and collagen II in cells were detected by FCM. The expression levels of iNOS, mRNA and collagen II mRNA were measured with RT-PCR. RESULTS: The rates of cell apoptosis in DON groups were 6.78% - 19.05%, which were significantly higher than that in control (1.20%, F = 174.761, P < 0.05). The levels of NO in DON groups were 20.8 - 40.7 µmol/L, which were significantly higher than that in control (10.2 µmol/L, F = 91.966, P < 0.05). The levels of MMP-13 in DON groups were 0.25 - 0.56 µmol/L, which were significantly higher than that in control (0 µmol/L, F = 78.420, P < 0.05). The levels of PGE2 in DON groups were 3.2-20.6 µmol/L, which were significantly higher than that in control (11.6 µmol/L, F = 276.453, P < 0.05). The proportions of cells with positive iNOS in DON groups were 14.8% - 56.8% which were significantly higher than that in controls (7.1%, F = 214.614, P < 0.05). The proportions of cells with positive collagen II in groups with DON of 0.4 µg/ml and 1.0 µg/ml were 56.7% and 52.7%, which were significantly lower than that in control (62.2%, F = 5.134, P < 0.05). The relative absorbance values of iNOS mRNA in DON groups were 1.07 - 1.33, which were significantly higher than that in control (0.62, F = 8.358, P < 0.05). The levels of collagen II mRNA in groups with DON of 0.4 µg/ml and 1.0 µg/ml were 0.83 and 0.82, which were significantly lower than that in control (1.14, F = 7.887, P < 0.05). CONCLUSION: DON could promote anabolism of NO in articular cartilage cells by which up-regulated the expression of PGE2 and MMP-13, which both promoted resolution of articular cartilage matrix such as collagen II. DON induced apoptosis in articular cartilage cells.
Subject(s)
Cartilage, Articular/cytology , Chondrocytes/drug effects , Trichothecenes/toxicity , Cartilage, Articular/embryology , Cells, Cultured , Chondrocytes/metabolism , Dinoprostone/metabolism , Humans , Matrix Metalloproteinase 13/metabolism , Nitric Oxide/biosynthesisABSTRACT
OBJECTIVE: To reveal the possible role of combined therapy with Chinese drug and narrow broad ultraviolet B (NB-UVB) on keratinocytes apoptosis in skin lesion of psoriasis vulgaris (PV). METHODS: Skin samples were taken from 20 healthy subjects and 30 PV patients before and after they received the combined therapy for 8 weeks. SP immunohistochemical method was used to detect the expressions of Bcl-2, Caspase-3 and survivin in the samples. RESULTS: As compared with those in the normal skin, expression of Bcl-2 in PV skin was significantly lower (7.50 +/- 2.01 vs. 12.65 +/- 2.83), while expression of Caspase-3 (21.73 +/- 3.70 vs. 8.55 +/- 2.16), and survivin (23.90 +/- 2.82 vs. 7.06 +/- 1.96) were higher (all P < 0.01). After treatment, in skin of PV, Bcl-2 expression increased to 13.63 +/- 2.14, Caspase-3 and survivin decreased to 11.70 +/- 2.44 and 12.46 +/- 1.80, respectively (all P < 0.01), showing a normalizing trend. Moreover, patients' psoriasis area and severity index (PASI) score decreased from 14.24 +/- 3.42 before treatment to 3.52 +/- 1.07 after treatment (P < 0.01). CONCLUSION: The curing effect of the combined therapy with Chinese drug and NB-UVB in treating PV is possibly realized by way of regulating Bcl-2, Caspase-3 and survivin expressions to adjust keratinocyte apoptosis.
Subject(s)
Phytotherapy , Psoriasis/therapy , Skin/metabolism , Ultraviolet Therapy , Adult , Case-Control Studies , Caspase 3/metabolism , Combined Modality Therapy , Drugs, Chinese Herbal/therapeutic use , Female , Humans , Inhibitor of Apoptosis Proteins/metabolism , Male , Middle Aged , Proto-Oncogene Proteins c-bcl-2/metabolism , Psoriasis/metabolism , Survivin , Young AdultABSTRACT
OBJECTIVE: To investigate the correlationship between congenital heart disease and 5, 10-methylenetetra hydrofolate reductase (MTHFR)'s C677T or folacin intakes, and to study the interaction of them in the occurring of congenital heart disease. METHODS: We used case-control study (case = 104, control = 208) method. Cases and controls were chosen by age, sex and other conditions. The MTHFR C677T genotype distribution was analyzed by using polymerase chain reaction restricted fragment length polymorphism (PCR-RFLP), and non-conditional and multi-conditional logistic regression analysis were also used to analyze the correlationship and interaction of the factors. RESULTS: In case group, the number of people in low folacin intake level was 38 (36.54%), which in control group was 21(10.10%). The intake level of folacin during pregnancy was related to congenital heart disease (chi(2) = 31.614, nu = 1, P < 0.0001). The value of OR was 1.417 with 95%CI 1.216 - 1.651, indicating that the low level of folacin intakes was a risk factor to the congenital heart disease. In case group, the number of TT genotype was 46 (44.24%), the number of CT genotype was 42 (40.38%), the number of CC genotype was 16 (15.38%). In control group, the number of TT genotype was 39 (18.75%), the number of CT genotype was 114 (54.81%), the number of CC genotype was 55 (26.44%). A significant genotype distribution difference was identified between case and control group (chi(2) = 23.13, nu = 2, P < 0.0001). Genotype MTHFR 677TT was a risk factor of congenital heart disease and the OR value was 3.437 (95%CI: 2.042 - 5.784). The interaction analysis suggested that the low level of folacin intakes and the MTHFR 677TT genotype had a positive adding effect in the occurring of congenital heart disease. After adjusted some factors such as the ages of parents, fetus age and sex, the effect values of interaction were 13.343 and 15.911 respectively, and the percentages of attributable interaction effects were 0.619 and 0.612. The percentages of effect values of interaction between pure factors were 0.649 and 0.637 and the population attributable risks were 25.26% and 27.82% according to the estimated exposure rate of population risk factors. CONCLUSION: The low level of folacin intakes during pregancy should be a risk factor to congenital heart disease and the MTHFR 677TT genotype be correlated to congenital heart disease. There is interaction between folacin intakes and the MTHFR 677TT genotype. Increasing the intakes of folacin among MTHFR 677TT genotype people might decrease the incidence rate of congenital heart disease.
Subject(s)
Folic Acid/metabolism , Heart Defects, Congenital/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Polymorphism, Single Nucleotide , Case-Control Studies , Child, Preschool , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Heart Defects, Congenital/metabolism , Humans , Infant , Male , Pregnancy , Risk FactorsABSTRACT
The study aimed to investigate the effect of extract of Ginkgo biloba (EGb) on the expression of vascular endothelial growth factor (VEGF) after subarachnoid hemorrhage (SAH). Wistar rats were divided into non-SAH, SAH, vehicle, EGb1 (low-dose), and EGb2 (high-dose) groups. VEGF mRNA and VEGF protein were measured from brain tissues. The expressions of VEGF mRNA in SAH and vehicle groups were enhanced 24 and 72 hr after the establishment of SAH. Increased VEGF positive cells were found in the brain tissues in SAH and vehicle groups. The expressions of VEGF mRNA and VEGF protein were further increased by the pretreatment of EGb. We concluded that EGb exerts protective effects on secondary cerebral ischemic injury after SAH via the promotion of the expression of VEGF.
Subject(s)
Angiogenesis Inducing Agents/therapeutic use , Ginkgo biloba/chemistry , Phytotherapy , Plant Extracts/therapeutic use , Subarachnoid Hemorrhage/drug therapy , Vascular Endothelial Growth Factor A/biosynthesis , Angiogenesis Inducing Agents/pharmacology , Animals , Brain Ischemia/drug therapy , Brain Ischemia/etiology , Drug Evaluation, Preclinical , Female , Gene Expression Regulation/drug effects , Male , Plant Extracts/pharmacology , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Rats , Rats, Wistar , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/genetics , Vascular Endothelial Growth Factor A/geneticsABSTRACT
The study was aimed to investigate the alterations of vascular endothelial growth factor (VEGF) receptors and the influence of extract of Ginkgo biloba (EGb) after subarachnoid hemorrhage (SAH). Wistar rats were divided into non-SAH, SAH, vehicle, EGb1 (lower dose), and EGb2 (higher dose) groups. Autologus arterial hemolysate was injected into cisterna magna to induce SAH. The non-SAH rats received cisternal injection of saline instead. Rats underwent RT-PCR determination of one of the VEGF receptors flt-1mRNA, and immunohistochemistry for VEGF receptors Flt-1 and Flk-1. The results revealed that there was only slight expression of flt-1mRNA in the brain tissue in non-SAH rats. The expression in SAH group was enhanced 24 hours and 72 hours after cisternal injection. No Flt-1 and Flk-1 positive cell was observed in the brain in non-SAH group. A good few Flt-1 and Flk-1 positive cells were found in cortex and other regions of the brain in SAH group. The expression of flt-1mRNA, Flt-1 and Flk-1 proteins were increased by the use of two doses of EGb. It was concluded that the up-regulated expression of the two kinds of VEGF receptors may be an intrinsic protective mechanism in the process of SAH, which can be enhanced by EGb.
Subject(s)
Ginkgo biloba/chemistry , Plant Extracts/pharmacology , Receptors, Vascular Endothelial Growth Factor/genetics , Subarachnoid Hemorrhage/drug therapy , Animals , Arteries , Disease Models, Animal , Dose-Response Relationship, Drug , Plant Extracts/administration & dosage , RNA, Messenger/analysis , Rats , Rats, Wistar , Up-Regulation/drug effects , Vascular Endothelial Growth Factor Receptor-1/genetics , Vascular Endothelial Growth Factor Receptor-2/geneticsABSTRACT
This study was aimed to evaluate the influence of an antagonist of heme oxygenase, zinc protoporphyrin IX (ZnPPIX), on the production of endogenous carbon monoxide (CO) and the secondary cerebral injury after subarachnoid hemorrhage (SAH). Wistar rats were divided into non-SAH, SAH, and ZnPPIX groups. Autologus arterial hemolysate was injected into rat cisterna magna to induce SAH. CO and cyclic guanosine monophosphate (cGMP) levels in the brain, and lactate dehydrogenase (LDH) activity in serum were determined 24 hours and 72 hours after cisternal injection. It was found that 24 hours and 72 hours after SAH, the CO contents in SAH group were increased by 20.76% and 37.36%, respectively. CO content in ZnPPIX group was statistically lower than that in SAH group. No obvious change of cGMP content in SAH group was found. However, cGMP content in ZnPPIX group was lower than that in SAH group. Serum LDH activity increased significantly after induction of SAH. LDH activity in ZnPPIX group increased to a greater extent. It was concluded that ZnPPIX aggravates the cerebral injury secondary to experimental SAH by inhibiting the production of endogenous CO. The activation of HO/CO pathway is an intrinsic protective mechanism against cerebral ischemic injury after SAH.
Subject(s)
Brain Ischemia/etiology , Heme Oxygenase (Decyclizing)/antagonists & inhibitors , Protoporphyrins/pharmacology , Subarachnoid Hemorrhage/complications , Animals , Brain Ischemia/metabolism , Carbon Monoxide/analysis , Carbon Monoxide/metabolism , Cyclic GMP/analysis , L-Lactate Dehydrogenase/analysis , Protoporphyrins/administration & dosage , Rats , Rats, Wistar , Time FactorsABSTRACT
To investigate the changes in bcl-2, bax expression and neuron apoptosis in the hippocampus after the blockade of cervical lymphatics, the model of lymphostatic encephalopathy was established by occluding and removing both the superficial and deep cervical lymph nodes in rats. The animals were sacrificed at 1, 2, 3, 5, 7 and 14 d after operation. H and E staining was used to observe the structure of brain tissues and TUNEL staining was used to detect in situ cell apoptosis in the hippocampus. The expression of bcl-2 and bax in the hippocampus were examined by RT-PCR. The results showed that cerebroedema appeared at day 2 and was most serious at day 5 after the blockade of cervical lymphatics. The number of TUNEL positive cells began to increase at day 2 and reached the maximum at day 5. The expression of bax began to increase at day 1 and reached the maximum at day 2. The expression of bcl-2 began to decrease at day 1 and dropped to the minimum at day 5. The items mentioned above recovered to control level at day 14. These results suggest that lymphostatic encephalopathy following the blockade of cervical lymphatics result in changes in bcl-2 and bax expression in the hippocampus and that apoptosis is the main form of neuron death.
Subject(s)
Apoptosis/physiology , Hippocampus/metabolism , Lymphatic System/physiology , Proto-Oncogene Proteins c-bcl-2/metabolism , bcl-2-Associated X Protein/metabolism , Animals , Female , Hippocampus/pathology , Lymph Node Excision , Male , Neck , Neurons/cytology , Proto-Oncogene Proteins c-bcl-2/genetics , Random Allocation , Rats , Rats, Wistar , bcl-2-Associated X Protein/geneticsABSTRACT
Single Objective Genetic Algorithm (SGA) optimization process usually needs a large number of objective function evaluations before converging towards global optimum or a near-optimum. The SGA is used as automatic calibration method for a wide range of numerical models. However, the evaluation of the quality of solutions is very time-consuming in many real-world numerical model calibration problems. The algorithm SGA-1NN-PCA, an effective and efficient dynamic approximation model to reduce the number of actual fitness evaluations, is presented in this paper. Training data of 1NN classifier are produced from early generations. 1-Nearest Neighbor (1NN) classifier is used to predict objective function values for evaluations. Principal Component Analysis (PCA) linearly transforms high-dimensional optimization parameters into low-dimensional optimization parameters to save test time for 1NN. The test results show that the proposed method only requires about 25 percent of actual fitness evaluations of the SGA.
ABSTRACT
This study was aimed at investigating the effects of extract of Ginkgo biloba (EGb) on cerebral vasospasm and microcirculatory perfusion after subarachnoid hemorrhage (SAH). An endovascular piercing method was used to induce Wistar rat SAH models, and animals were divided into sham-operated, vehicle controls, and EGb-treated groups. EGb was injected intraperitoneally 30 minutes before operation and was repeated every 6 hours, with a single dose of 15 mg/kg bw. Diameters of basilar arteries before and after operation were measured. Microcirculatory blood perfusion of parietal lobe cortex was detected using a laser Doppler flow-meter probe within 24 hours. Endothelin-1 levels in both plasma and brain tissue were detected at different time points. The results showed that SAH caused an immediate drop in microcirculatory blood flow in vehicle controls, which persisted for 24 hours. Endothelin-1 levels in both plasma and brain tissue increased after SAH. EGb partly reversed spasms of the basilar artery and antagonized a drop in microcirculatory blood flow. EGb also prevented an increase in endothelin-1 both in plasma and in brain tissue. In conclusion, EGb, by antagonizing the overproduction of endo- thelin-1, partly reverses cerebral vasospasm and improves microcirculation, and thus relieves secondary ischemic brain injury after experimental SAH.