ABSTRACT
This study compared the effects of Curcuma longa before and after processing with vinegar on the rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation to reveal the mechanism of vinegar processing in improving the role of C. longa in soothing liver and relieving pain. The rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation was established according to the Preparation of the Animal Model of Dysmenorrhea(Draft) and the chronic unpredictable stress me-thod. The changes in the body weight, organ indexes, writhing latency, writhing score, and serum levels of six liver function indicators, sex hormones, pain factors, and blood rheological indicators were measured to evaluate the efficacy of C. longa processed with vinegar or not in treating dysmenorrhea in the rats with syndrome of liver depression and qi stagnation. Compared with the model group, the C. longa group(processed with vinegar or not) showed slow weight loss, increase in writhing latency, and decrease in writhing response(P<0.05). The inhibition rates on writhing in raw C. longa, vinegar-processed C. longa, and positive groups were 33.780%, 64.611%, and 62.466%, respectively. The significantly higher inhibition rate of the vinegar processing group indicated that vinegar-processed C. longa demonstrated more significant therapeutic effect. The vinegar-processed C. longa group showed lower levels of alanine aminotransferase(ALT), alkaline phosphatase(ALP), aspartate aminotransferase(AST), direct bilirubin(DBIL), and total bilirubin(TBIL) and higher level of albumin(ALB)(P<0.05), which indicated that vinegar processing enhanced the therapeutic effect of C. longa on liver injury. The serum levels of estradiol(E_2) and oxytocin(OT) were lower in the vinegar-processed C. longa group(P<0.05), indicating that the vinegar-processed C. longa could regulate the sex hormone levels, reduce the activity of uterine smooth muscle and contraction of uterus, and alleviate the symptoms of dysmenorrhea in rats. Moreover, the vinegar-processed C. longa group showed lower interleukin-6(IL-6) and arginine vasopressin(AVP) levels and higher beta-endorphin(β-EP) level(P<0.05), which indicated that vinegar-processed C. longa regulated the levels of pain factors to exert the pain-relieving effect. Drug intervention decreased the whole blood viscosity low-cut, medium-cut and high-cut values, plasma viscosity, whole blood reduction viscosity low-cut and high-cut values, erythrocyte cumulative pressure, and equation K value of erythrocyte sedimentation rate(P<0.05), and the vinegar-processed C. longa group outperformed other groups. This result indicated that vinegar processing enhanced the function of C. longa in improving the local blood rheology. C. longa processed with vinegar can enter the liver to relieve the da-mage to the heart, liver, kidney, and uterus, repair the liver function, and recover the sex hormone levels and immune function by regulating the levels of sex hormones and pain factors and improving the blood rheology. It activates the pain-relieving mechanism to relieve the pain, protect the liver, and fight inflammation, which is consistent with the theory that vinegar processing facilitates C. longa entering the liver to sooth liver and relieve pain.
ABSTRACT
Liquid chromatography-mass spectrometry was employed to analyze the chemical components in Curcuma longa tuberous roots(HSYJ), C. longa tuberous roots processed with vinegar(CHSYJ), and rat serum after the administration. The active components of HSYJ and CHSYJ absorbed in serum were identified based on the secondary spectrum of database and literature. The targets of primary dysmenorrhea was screened out from database. The protein-protein interaction network analysis, gene ontology(GO) functional annotation, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the common targets shared by the drug active components in serum and primary dysmenorrhea, and the component-target-pathway network was constructed. AutoDock was used to conduct molecular docking between the core components and targets. A total of 44 chemical components were identified from HSYJ and CHSYJ, including 18 absorbed in serum. On the basis of network pharmacology, we identified 8 core components(including procurcumenol, isobutyl p-hydroxybenzoate, ferulic acid, and zedoarondiol) and 10 core targets \[including interleukin-6(IL-6), estrogen receptor 1(ESR1), and prostaglandin-endoperoxide synthase 2(PTGS2)\]. The core targets were mainly distributed in the heart, liver, uterus, and smooth muscle. The molecular docking results showed that the core components were well bound to the core targets, indicating that HSYJ and CHSYJ may exert therapeutic effect on primary dysmenorrhea via estrogen, ovarian steroidogenesis, tumor necrosis factor(TNF), hypoxia-inducible factor-1(HIF-1), IL-17 and other signaling pathways. This study clarifies the HSYJ and CHSYJ components absorbed in serum, as well as the corresponding mechanism, providing a reference for further elucidating the therapeutic material basis and clinical application of HSYJ and CHSYJ.
Subject(s)
Female , Humans , Animals , Rats , Acetic Acid , Curcuma , Dysmenorrhea , Molecular Docking Simulation , Tumor Necrosis Factor-alpha , Cyclooxygenase 2ABSTRACT
Objective: The Huanghuai (HH), which is made from the dried roots of Scutellaria baicalensis (Huangqin in Chinese) and the dried flowers and buds of Sophora japonica (Huaihua in Chinese), is a traditional Chinese formula used to treat dysfunctional uterine bleeding (DUB) (Benglou in Chinese) and proven to treat hemostasis effectively in our previous study. Network pharmacology and molecule docking were performed to study the underlying mechanism of Huanghuai (HH), and pharmacodynamic experiments were conducted to verify its curative effect. Methods: TCMSP, UniProt, GeneCards, STRING, DAVID databases, and Cytoscape 3.7.2 were utilized for the construction of a compound-target-pathway network. Docking the potential effective components with potential targets. The HPLC analysis of the potential effective components was performed. In vivo, the hot plate test model was used to study the analgesic activity, the egg white was used to study the swollen reaction in the sole in mice, and the hemostasis effect was studied by the capillary method, tail-breaking method and abortion uterus test. Results: The results showed that six compounds (acacetin, beta-sitosterol, wogonin, baicalein, kaempferol and quercetin) and four potential targets (PTGS2, AKT1, TP53 and TNF) in the compound-target-pathway network were the potential material basis for HH to treat DUB. It can be seen that the binding energy of the acacetin, wogonin, baicalein, beta-sitosterol, kaempferol and quercetin in HH docked with the receptor proteins PTGS2, AKT1, TP53, and TNF were far less than −5.0 kJ/mol, which means the molecules have low conformational energy, stable structure and high binding activity. And the result of HPLC analysis showed that acacetin, wogonin, baicalein, kaempferol and quercetin were the potential effective components of the hemostasis mechanism of HH, beta-sitosterol was removed due to low content. In vivo testing of the potential effective components, it revealed that the group of potential effective components identified by HPLC could increase the pain threshold, inhibit the swelling hind paws of mice induced by egg white, reduce the bleeding time and clotting time, reduce uterine bleeding, decrease the uterine weight, increase the content of Ca and ET-1, and reduce the content of NO in uterine homogenate tissue, and decrease of E
ABSTRACT
Objective: To explore the potential material basis of Kangbingdu Granules for the treatment of coronavirus disease 2019 (COVID-19) through network pharmacology and molecular docking technology. Methods: The chemical constituents and action targets of Isatidis Radix, Forsythiae Fructus, Gypsum Fibrosum, Anemarrhenae Rhizoma, Phragmitis Rhizoma, Rehmanniae Radix Praeparata, Pogostemon cablin, Acoritataninowii Rhizoma and Curcumae Radix in Kangbingdu Granules were searched by TCMSP. The gene corresponding to the target was searched by UniProt database, and Cytoscape 3.6.1 was used to build a medicinal material-compound-target (gene) network. DAVID was used to perform gene ontology (GO) function enrichment analysis and KEGG pathway enrichment analysis to predict its mechanism. Molecular docking of the top 15 components was carried out in the medicinal material-compound-target network with SARS-CoV-2 3CL hydrolase, and molecular docking with bicuculline, luteolin, quercetin and angiotensin-converting enzyme II (ACE2) was performed. Results: The medicinal material-compound-target (gene) network contained eight medicinal materials, 75 compounds and 255 targets. GO function enrichment analysis revealed 161 GO items (P < 0.05), including 65 biological process (BP) items, 36 cell composition (CC) items, and 60 molecular function (MF) items. KEGG pathway enrichment screened 131 signaling pathways (P < 0.05). The results of molecular docking showed that the core active compounds such as bicuculline, luteolin, and quercetin in the Kangbingdu Granules had similar affinities with those recommended by COVID-19. Conclusion: The active compounds in Kangbingdu Granules can interact with angiotensin-converting enzyme II (ACE2) via targets PTGS2, HSP90AB1, and PTGS1 to regulate multiple signaling pathways, thereby exerting therapeutic effects on COVID-19.
ABSTRACT
To evaluate the relationship of volumetric changes and endoleaks after endovascular aneurysm repair(EVAR)for abdominal aortic aneurysms(AAAs). We retrospectively evaluated the clinical and imaging data of 54 patients who had underwent EVAR within 1 month after their aneurysms were detected.All patients received abdominal and pelvic enhanced computed tomography(CTA)for two follow-up visits in Peking Union Medical College Hospital from July 2014 to February 2019.Three-dimensional volumes and maximum diameters on axial CT of the aortic aneurysms were calculated by dedicated semi-automated 3D segmentation software before surgery(V and D),in the 4 postoperative month(Vand D),and in the 12 postoperative month(Vand D),respectively.The presence or absence of endoleak for each patient with the V/V,V/V,and V/V were calculated to assess the significance of volume changes with respect to endoleaks and the correlation between volume changes and maximum diameter changes on axial CT images. Of the 54 patients,endoleaks were found in 11 patients at the first follow-up visit(4 months after surgery),among whom 8 patients were arranged a second follow-up visit(12 months after surgery),during which endoleaks were found in 5 patients.Fifteen of 43 non-leaked patients underwent a second CTA examination,which revealed endoleak in one case.Patients who did exhibit endoleaks[ =11,V/V=1.086(1.033,1.116)]showed significant increases in aneurysm volume when compared with those who did not exhbit endoleaks[ =43,V/V=1.019(0.970,1.065)]at the first follow-up visit(=-2.695,=0.007),although no significant difference was found with regard to volume changes between endoleaks(=6,V/V=1.1±0.2,V/V=1.0±0.1)and non-endoleaks(=17,V/V=1.0±0.1,V/V=1.0±0.1)at the second follow-up visit(=0.725,=0.476)as well as between these two follow-up visits(=-0.021,=0.984).V and D were moderately correlated with V and D,respectively(=0.5,<0.001)and strongly correlated with V and D,respectively(=0.8,<0.001).V and D were strongly correlated with V and D,respectively(=0.8,<0.001). The changes of aneurysm volume cannot reliably reflect the occurrence of endoleaks.The change of maximum axial diameter of aneurysm has certain correlation with the changes of aneurysm volume.
ABSTRACT
OBJECTIVE@#To investigate the effect of lncRNA-CASC2 (CASC2) /miR-155-5p/APC axis to the progression of non-Hodgikn lymphoma (NHL).@*METHODS@#The expression level of CASC2 and miR-155-5p in NHL cell lines were examined by qRT-PCR. Dual-luciferase reporter gene assay was used to verify the relationship between miR-155-5p, CASC2 and APC. The effects of CASC/miR-155-5p/APC axis to the proliferation, invasion and apoptosis of NK-92 cells were detected by MTT, Transwell assay and flow cytometry assay, respectively.@*RESULTS@#CASC2 was downregulated in NHL cell lines. Overexpression of CASC2 could inhibit the proliferation and invasion of NK-92 cells, and promote its apoptosis. Dual-luciferase reporter gene assay confirmed that there was a targeting relationship between miR-155-5p, CASC2 and APC. The restoration experiments proved that knockdown of both miR-155-5p and CASC2 or APC could restore the inhibitory effect of miR-155-5p silencing to the biological behavior of NK-92 cells.@*CONCLUSION@#Overexpression of CASC2 suppresses the proliferation and invasion of NK-92 cells, promote the apoptosis of NK-92 cells via targeting miR-155-5p and upregulating APC expression.
Subject(s)
Humans , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Lymphoma, Non-Hodgkin/genetics , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Tumor Suppressor Proteins/geneticsABSTRACT
Objective To study the anatomical variations of the origin of uterine artery(UA)by three-dimensional(3D)reconstructed computed tomography angiography(CTA)and facilitate the preoperative evaluation for gynecological surgeries or interventional therapies. Method The CTA findings of 112 patients with an average age of(31.4±6.6)years old who had received a pelvic CTA and undergone 3D reconstruction of the uterine artery were retrospectively analyzed. Results The average uterine volume was(95.6±26.8)cm .Of the UA 224 sides,144 sides(64.3%)arose from the interior gluteal artery and 51(22.8%)from internal iliac artery;in 29 sides(12.9%),the uterine artery,the inferior gluteal and the superior gluteal arteries arising as a trifurcation.The origin of UA was consistent between left and right sides in 68 patients(60.7%)and not in 44 patients(39.3%). Conclusion As a rapid,noninvasive,and economic technique,CTA can effectively display the anatomical variations of the origin of UA and thus can be used to guide interventional therapies and gynaecological surgeries.
Subject(s)
Adult , Female , Humans , Computed Tomography Angiography , Imaging, Three-Dimensional , Pelvis , Retrospective Studies , Uterine Artery , Diagnostic Imaging , UterusABSTRACT
Textbook evaluation is of great significance in teaching studies and activities. By taking the establishment of evaluation index system forExperimental Acupuncture-moxibustion Science as an example, this article discussed the process and method of adopting the analytic hierarchy process for textbook evaluation: 3 levels, 4 dimensions, and 20 evaluation indexes were developed for the evaluation ofExperimental Acupuncture-moxibustion Science textbook, and each component of the indexes was assigned weight, based on which, a scale was established and preliminarily evaluated, in order to provide reference for the evaluation of the textbooks of traditional Chinese medicine.
ABSTRACT
Textbook evaluation is of great significance in teaching studies and activities. By taking the establishment of evaluation index system forExperimental Acupuncture-moxibustion Science as an example, this article discussed the process and method of adopting the analytic hierarchy process for textbook evaluation: 3 levels, 4 dimensions, and 20 evaluation indexes were developed for the evaluation ofExperimental Acupuncture-moxibustion Science textbook, and each component of the indexes was assigned weight, based on which, a scale was established and preliminarily evaluated, in order to provide reference for the evaluation of the textbooks of traditional Chinese medicine.
ABSTRACT
Objective To evaluate the changes in epithelial thickness profile and its relationship with diopter following small incision lenticule extraction (SMILE) for moderate and high myopia.Methods Together 46 myopia or myopic astigmatism (92 eyes) who underwent SMILE were included under the informed consent from January 2016 to March 2017 and were decided into 2 groups according to the diopter:moderate myopia group (58 eyes)and high myopia group (34 eyes).Epithelial thickness profile was measured using spectral-domain optical coherence tomography at different corneal zones (0-2 mm,＞ 2-5 mm and ＞ 5-6 mm cornea) preoperatively before surgery and 1 month and 6 months after surgery for observing the changes in epithelial thickness and its correction with diopter.Results The mean epithelial thickness in the central zone was (55.68 ± 3.61) μm before surgery,and,6 months after surgery,it was thickened by (3.85-±3.99),(3.46 ±3.29) and (2.85 ±3.18) μm in the 0-2 mm,＞2-5 mum and ＞5-6 mm cornea respectively,and the difference was statistically significant among the three zones (P ＜ 0.01).After surgery for 6 months,the epithelial thickness in the high myopia group was thickened more obviously compared with the moderate myopia group (t =1.440,P =-0.047).And no correlation was found between changes in the epithelial thickness at 0-2 mm cornea and diopter after surgery(moderate myopia group:r =0.219,P=0.633;high myopia group:r =0.197,P =0.585).Conclusion Significant epithelial thickening was observed after SMILE,presenting the thickened epithelium.The higher the diopter was,the more thickened the epithelium was.The epithelial changes does not appear to affect the diopter after SMILE.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the prevalence and subtype distribution of human papillomavirus (HPV) infection and its correlation with age among women in Beijing urban area, and provide some epidemiological evidence for the clinical application of HPV vaccines.</p><p><b>METHODS</b>We collected cervical specimens from 1999 women in the Outpatient Department of our hospital, performed genetyping of HPV-DNA, and analyzed the incidence of HPV infection in different age groups.</p><p><b>RESULTS</b>HPV infection was detected in 502 (25.2%) of the 1999 women patients, with 391 (19.6%) cases of high-risk HPV, which included 326 (83.4%, 326/391) cases of single infection. HPV-16 was the most common type (21.2%, 69/326), followed by HPV-52 (19.3%, 63/326) and HPV-58 (16.0%, 52/326). The prevalence of HPV infection was the highest among the women aged 41 -50 years and the lowest among those over 60 years.</p><p><b>CONCLUSION</b>The subtype- and age-specific distribution of HPV infection among women in Beijing urban area shows an obvious heterogeneity, which deserves due consideration in the clinical application of HPV vaccines.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Middle Aged , Young Adult , Age Distribution , China , Epidemiology , Genotype , Papillomaviridae , Classification , Genetics , Papillomavirus Infections , EpidemiologyABSTRACT
Objective To explore the role of white matter injuries in the schizophrenia induced by the NMDA re-ceptor antagonist. Methods Adult male C57BL/6J mice (8 week old) were equally divided into four groups. One group was sub-chronically treated with saline solution, and the other three groups were intraperitoneally treated with MK-801 at dose of 0.025 mg/mL (M1), 0.050 mg/mL (M2) and 0.100 mg/mL (M3) in a volume 10 ml per kilogram body weight. All ani-mals were tested using Morris water maze at the 9th-15th day and using the Hole Board exploration as well as Rota Rod performance tests on the 16th day. The myelin basic protein (MBP) and the ultrastructure of the myelin sheaths in the cor-pus callosum were then examined using immunohistochemical methods, transmission electron microscope technique and stereological methods. Results The repeated sub-chronic MK-801 treatment did not induce impairment of spatial learning and memory in Morris water maze. The MK-801 treatment at 0.25 mg/kg and 1.00 mg/kg but not at 0.50 mg/kg resulted in less exploration to a new environment. The myelin staining with anti-MBP antibody was less intense in all three schizo-phrenic groups when compared to saline control group (P<0.01). Furthermore, MK-801 treatment caused pathological al-terations of the myelin sheaths including segmental demyelination of myelinated fibers and splitting of myelin sheath lamel- lae in schizophrenic groups. The ratio of the injured myelinated nerve fibers in the corpus callosum of MK-801 treated mice [M3 group, (22.42 ± 4.24)%] was significantly higher when compared to the control mice [(3.84 ± 1.35)%,P<0.01)]. Conclusions The present study demonstrated the white matter damages, mainly low MBP expression and segmental demye-lization in the corpus callosum in the mice sub-chronic treated with MK-801, indicating that the white matter changes might be involved in the schizophrenia induced by NMDA antagonist.
ABSTRACT
This study was purposed to analyse the immunophenotypic characteristics of chronic myelomonocytic leukemia (CMML), myelodysplastic syndromes (MDS) and acute monocytic leukemia (AML-M5b) by using multiparameter flow cytometry, and to explore its significance in diagnosis and differential diagnosis. The immunophenotypic characteristics of bone marrow samples from 14 CMML patients, 48 MDS patients, 46 AML-M5b patients and 18 normal persons were analyzed and compared by multiparametric flow cytometry. The results showed that the ratio of monocytes in CMML patients was obviously higher than that in MDS, AML-M5b patients and normal persons (P < 0.05), but there was no statistically significant difference between bone marrow samples of MDS and AML-M5b patients as well as normal persons. The ratio of blast cells in MDS patients was obviously higher than that in normal persons (P < 0.05), but did not show significant difference as compared with CMML patients. The ratio of mature granulocytes in AML-M5b patients was obviously lower than that in CMML and MDS patients as well as normal person bone marrow (P < 0.05). Certain differences of CD45/SSC characteristics in MDS, AML-M5b and CMML patients were found in comparison with normal persons. The abnormal expression of CD2, CD56, and CD14 tailing phenomenon were observed in CMML patients in comparison with bone marrow samples of MDS, AML-M5b and normal persons (P < 0.05). Lack and decrease of CD15 expression in MDS and CMML patients was significant different from AML-M5b and normal persons marrow, abnormal expression rate of CD15 in CMML patients was higher than that in MDS patients (P < 0.05), the CD13/CD11b/CD16 abnormal expression of granulocytes was seen in both CMML and MDS patients, but there was no statistically significant difference between them. Other antigens showed abnormality of varying degrees, but did not have any statistical significance. It is concluded that MDS, CMML and AML-M5b displayed a certain degree of similarity, and also possess their own immunophenotype characteristics. Comprehensive analysis of immunophenotype by multiparameter flow cytometry may be important for differential diagnosis among CMML, MDS and AML-M5b. High percentage of monocytes, abnormal coexpression of CD2, CD56 and CD14 tailing phenomenon, lack or decrease of CD15 as well as abnormal expression of CD13/CD11b/CD16 in granulocytes may play important roles in diagnosis of CMML.
Subject(s)
Humans , Case-Control Studies , Flow Cytometry , Methods , Immunophenotyping , Methods , Leukemia, Monocytic, Acute , Diagnosis , Allergy and Immunology , Leukemia, Myelomonocytic, Chronic , Diagnosis , Allergy and Immunology , Myelodysplastic Syndromes , Diagnosis , Allergy and ImmunologyABSTRACT
In order to investigate the expression and the relationship of ubiquitin associated protein 1 (ubap1) gene and tumor-suppressor gene p16 in acute leukemia, 68 cases of acute leukemia and 22 control cases were selected in this experiment, FQ-PCR technique was used to detect the mRNA expression level of ubap1 gene and p16 gene in their bone marrow cells. The results showed that as compared with the control group, the ubap1 gene in acute leukemia group highly expressed (p<0.01), while the p16 gene lowly expressed (p<0.01). But grouping of patients according to FAB revealed that as compared with the control group, the ubap1 gene expression displayed statistical difference only in M4 and M5 of adult AML (p<0.05), while the p16 gene expression in all groups of adult AML showed significant difference (p<0.05) except M1 and M2. In addition to this, the ubap1 gene and p16 gene mRNA expression in AL was not relate with chromosome abnormality (p>0.05). A negative correlation (r=-0.827, p<0.01) was found between the ubap1 gene and p16 gene mRNA expressions in the control group. It is concluded that the upregulation of ubap1 gene expression mainly and the downregulation of p16 gene expression mainly may simultaneously participate in the pathogenesis of acute leukemia. High expression of ubap1 gene influences the M4 and M5 subtypes in AML. This discovery provides important theoretical basis for the further investigation of pathogenesis and targeting therapy of AL.
Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young Adult , Bone Marrow Cells , Metabolism , Carrier Proteins , Genetics , Case-Control Studies , Cyclin-Dependent Kinase Inhibitor p16 , Genetics , Gene Expression , Leukemia , Genetics , Metabolism , Pathology , RNA, Messenger , GeneticsABSTRACT
<p><b>OBJECTIVE</b>Benzodiazepines (BDZ) have many effects on various kinds of epilepsies, but long-term treatment with BDZ often leads to drug tolerance. This study aimed to seek drugs which can reverse the tolerance of flurazepam (FZP), and to explore the role of neuropeptide Y (NPY) in the reversal effect.</p><p><b>METHODS</b>A rat model of anticonvulsant tolerance to FZP was prepared. The rats with FZP tolerance were randomly assigned to seven groups: FZP-tolerance, and nifedipine, levetiracetam, topiramate, flumazenil, L-NAME and pyridoxamine treatment groups. The tolerance to FZP was evaluated through pentylenetetrazol (PTZ) infusion into a tail vein. The latency to onset of clonic seizure and the PTZ threshold were recorded. The mRNA of NPY receptor Y2 in the hippocampus was determined by RT-PCR, and the distribution of NPY in the hippocampus was examined by immunohistochemistry.</p><p><b>RESULTS</b>In comparison with the blank control group, the average latency to the onset of clonic seizure was shortened, the average PTZ threshold decreased and the expression of NYT and NPY receptor Y2 mRNA decreased significantly in the FZP-tolerance group (p<0.01). In comparison with the FZP-tolerance group, the average latency to onset of clonic seizure was prolonged by 2 times and the average PTZ threshold doubled in the topiramate treatment group. The average latency to onset of clonic seizure was prolonged by 1 time and the average PTZ threshold increased 1 time in the nifedipine, the levetiracetam and the flumazenil treatment groups. The mRNA expression of NPY receptor Y2 increased by 1 or 2 times in the flumazenil, the nifedipine and the topiramate treatment groups when compared with the FZP-tolerance group.</p><p><b>CONCLUSIONS</b>Nifedipine, levetiracetam, topiramate and flumazenil can reverse the anticonvulsant tolerance to flurazepam. NPY may play a role in mediating the reversal effect.</p>
Subject(s)
Animals , Male , Rats , Anticonvulsants , Pharmacology , Drug Tolerance , Flurazepam , Pharmacology , Hippocampus , Chemistry , Neuropeptide Y , Physiology , Pentylenetetrazole , RNA, Messenger , Rats, Sprague-Dawley , Reaction Time , Receptors, Neuropeptide Y , Genetics , Seizures , Drug TherapyABSTRACT
The objective of this study was to investigate the immunophenotypic subtype profiles of 192 patients with acute myeloid leukemia (AML) and its association to cytogenetics and clinical features. Immunophenotyping of 192 patients was performed by flow cytometry using a panel of monoclonal antibodies. The karyotypes in 125 out of 192 cases were analyzed by G-banding technology. The results showed that CD33, CD13, myeloperoxidase (MPO) and CD117 were the most commonly expressed antigens in AML. CD117 expressed in 84.6% of AML-M3 cases. A combination of intensive autofluorescence, both CD34- and HLA-DR-, and high expression of CD13, CD33 and MPO had significant value for AML-M3 diagnosis. CD14 expressed only in AML-M4 and AML-M5, and both intensive positivity of CD64 and CD15 with high expression of HLA-DR may suggest great possibility for diagnosis of AML-M5. Lymphoid marker expression was documented in 47.9% of the 192 AML cases. CD56 (26.0%) and CD7 (20.8%) were the most commonly expressed lymphoid markers in AML patients, followed by CD19 (9.9%) and CD2 (7.3%). Abnormal karyotypes were detected in 76 out of 125 cases (60.8%). Correlation test showed that t(8;21) was found only in 17 cases of AML-M2 and strongly associated with the individual or combinational expressions of CD15/CD19/CD56. And 28 cases of t(15;17) were found in AML-M3; 2 cases of inv(16) were found in AML-M4EO. Higher CD34 positivity was found in LymAg+ group (77.2%) than that in LymAg- group (48.0%). It is concluded that immunophenotype analysis is useful for AML diagnosis and classification, and the immunophenotype has close relevance to the abnormal cytogenetic changes and clinical features in AML. The results suggested that a new prognostic scoring system that integrated the morphology, cytogenetic abnormalities and immunophenotype parameters would benefit the diagnosis, classification, and estimation of prognosis in AML patients.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young Adult , Cytogenetics , Immunophenotyping , Leukemia, Monocytic, Acute , Genetics , Allergy and ImmunologyABSTRACT
Near-tetraploidy is a rare cytogenetic abnormality in myelocytic malignancies in children, and its significance is unknown. To investigate the characteristics of near-tetraploidy in a child with acute myelogenous leukemia (AML-M4), bone marrow smears were prepared for morphological analysis. Bone marrow samples were collected for flow cytometry, and prepared by short-term (24 hrs) unstimulated culture and R-banding for conventional cytogenetic assay. In this case, the morphological analysis of bone marrow cells showed large and prominent nuclei. The chromosomal analysis (R-banding) demonstrated a near-tetraploidy. Combined with morphological and immunophenotypic results, AML-M4 was confirmed. The patient was given four cycles of chemotherapy, and finally achieved clinical remission. However, the duration achieving the remission in the child was longer than AML children with normal karyotype. It is believed that near-tetraploid karyotype may have a great significance to the therapy and prognosis.
Subject(s)
Child , Female , Humans , Bone Marrow Cells , Pathology , DNA, Neoplasm , Immunophenotyping , Leukemia, Myeloid, Acute , Genetics , Polyploidy , Precursor Cell Lymphoblastic Leukemia-Lymphoma , GeneticsABSTRACT
Wnt/beta-catenin is the most important and more understanding pathway in Wnt pathways, which is closely related to pathogenesis and development of many solid tumors. Recently, researches discovered that Wnt/beta-catenin signal pathway may be involved in malignant hematopoiesis, and abnormally activated in many hematological-malignancies. This article reviews the newest studies on relationship between Wnt/beta-catenin signal pathway and hematological malignancies (multiple myeloma, chronic myeloid leukemia, chronic lymphocytic leukemia, acute leukemia and so on) in order to reveal the related pathogenesis of hematological malignancies and provide new opinions for target therapy of these diseases.
Subject(s)
Humans , Hematologic Neoplasms , Metabolism , Signal Transduction , Wnt Proteins , Metabolism , beta Catenin , MetabolismABSTRACT
This study was aimed to quantitatively detect the levels of beta-catenin and cyclin D1 mRNA in various subgroups of acute myeloid leukemia (AML) and to analyze their potential relationship, so as to provide theoretical basis for exploring the role of Wnt/beta-catenin pathway in the pathogenesis of AML. Real time fluorescent quantitative RT-PCR was used to detect the relative expression levels of beta-catenin and cyclin D1 mRNA, to analyze changes of the two gene expressions and their relationship. The results showed that the beta-catenin mRNA expression level in BMMNC of AML patients was significantly higher than that in benign blood disease patients (p < 0.05), but no statistical difference was found among the various subgroups of AML (p > 0.05). In AML there was overexpression of cyclin D1 mRNA, and its expression level was significantly higher than that in benign blood disease group (p < 0.05), but there was no statistical difference among the subtypes of AML. The expression levels of beta-catenin and cyclin D1 were correlated each other in AML-M(1), M(2) and M(4) (r values were 0.822, 0.627, 0.712 respectively; p values were 0.001, 0.020, 0.002 respectively). It is concluded that the over-expressions of beta-catenin and cyclin D1 exit in AML patients, and the significant correlation appears in part of the subgroups, which means that the Wnt/beta-catenin pathway is aberrantly activated in AML, probably activating the downstream target gene cyclin D1 and participating in the regulation of cell cycle disturbance and abnormal proliferation of leukemic cells.