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@#[摘 要] 目的:探讨溶瘤新城疫病毒(NDV)对IL-6诱导的人胶质母细胞瘤U87MG细胞增殖、迁移和侵袭的作用及其可能的机制。方法:将U87MG细胞分为对照组、IL-6组、NDV组、NDV+IL-6组,其中IL-6组与NDV+IL-6组用75 ng/mL IL-6预处理1 h,其余组用DMEM预处理1 h,后分别用DMEM、75 ng/mL IL-6、1 HU NDV、1 HU NDV+75 ng/mL IL-6处理24 h。MTT法、细胞划痕实验和Transwell侵袭实验分别检测IL-6、NDV对U87MG细胞增殖、迁移和侵袭的影响,WB法检测各组细胞JAK2、p-JAK2、STAT3、p-STAT3和MMP2蛋白的表达水平。结果:与对照组相比,IL-6组细胞迁移率显著升高(P<0.05),侵袭细胞数目显著增多(P<0.01);与IL-6组相比,NDV+IL-6组U87MG细胞增殖率显著降低(P<0.05),细胞迁移率和侵袭细胞数目均显著降低(均P<0.01)。WB实验结果显示,与对照组相比,IL-6组p-STAT3/STAT3比值显著升高(P<0.01),NDV组p-JAK2/JAK2、p-STAT3/STAT3比值显著降低(P<0.05,P<0.01),MMP-2蛋白表达量显著降低(P<0.01);与IL-6组相比,NDV+IL-6组p-STAT3/STAT3比值、MMP-2蛋白表达量均显著降低(均P<0.05)。结论:NDV能抑制IL-6对人脑胶质瘤U87MG细胞迁移和侵袭的诱导作用,其机制可能与JAK2/STAT3信号通路的参与调控有关。
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SUMMARY Primary pigmented nodular adrenocortical disease (PPNAD) is a rare adrenocorticotropin hormone (ACTH)-independent Cushing's syndrome (CS). Pediatric patients with PPNAD typically have unusual skin lesions and slow growth with unknown causes. We present a case of a female Chinese patient with PPNAD caused by the germline PRKACA gene copy number gain of chromosome 19. The patient initially presented with kidney stones, short stature, and obesity. After further testing, it was discovered that the patient had diabetes, mild hypertension, low bone mass, a low ACTH level, and hypercortisolemia, and neither the low-dose or high-dose dexamethasone suppression test was able to inhibit hematuric cortisol, which paradoxically increased. PPNAD was pathologically diagnosed after unilateral adrenalectomy. Chromosome microarrays and whole exon sequencing analyses of the peripheral blood, as well as testing of sectioned adrenal tissue, showed a rise in the copy number of the duplication-containing PRKACA gene on chromosome 19p13.13p13.12, a de novo but not heritable gene defect that causes disease. The clinical signs and symptoms supported the diagnosis of Carney complex (CNC). One significant mechanism of CNC pathogenesis may be the rise in germline PRKACA copy number of chromosome 19. When assessing PPNAD patients for CNC, the possibility of PRKACA gene amplification should be considered. The effect of PRKACA gene amplification on the clinical manifestations of CNC needs to be confirmed by more cases.
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With people's attention and in-depth research on visual quality, many distinctive survey scales have been developed. The use of visual quality questionnaires is a subjective way to evaluate patients' visual quality, an expression of patients' self feelings, and an important part of reflecting visual quality. With objective detection methods, the results are more convincing. Many scales have been introduced into China and have been revised through translation, back translation, and cultural adaptation, playing an indispensable role in the visual quality evaluation system. It is particularly important to assess visual quality through psychological and sociological content, and whether the content can be appropriately combined with the subjective feelings of patients. The core of the visual quality of life survey questionnaire lies in its high repeatability. This article summarizes commonly used visual quality questionnaires, which have been verified in terms of validity, reliability, and responsiveness. The validity of the measurement scale, the consistency of the measurement results, the ability to reflect the smallest meaningful clinical changes after effective medical intervention, and the design characteristics, main application directions, and trends of the scale are listed to provide reference for clinical workers to choose appropriate survey scales.
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To evaluate the predictive value of early warning scores for intensive care unit (ICU) admission in patients with coronavirus disease 2019 (COVID-19). For COVID-19 patients who were admitted to Shijiazhuang People's Hospital from January 2021 to February 2021, national early warning score (NEWS), national early warning score 2 (NEWS2), rapid emergency medicine score (REMS), quick sepsis-related organ failure (qSOFA), altered consciousness, blood urea nitrogen, respiratory rate, blood pressure, and age-65 (CURB-65) were used to evaluate the inpatient condition and the predictive value for ICU admission. A total of 368 patients were included, and 32 patients (8.7%) were transferred to the ICU. The median age was 49.0 (34.0,61.0) years. The scores of NEWS, NEWS2, REMS, and CURB-65 were 1 (0, 2), 1 (0, 2), 4 (2, 6) and 0 (0, 1), respectively. The receiver operating characteristic (ROC) cure (AUC) was used to evaluate the predictive value in detecting patients who are at risk of being transferred to the ICU. Area under the ROC AUC of NEWS was 0.756, sensitivity 65.6%, and specificity 71.3%. ROC AUC of NEWS2 was 0.732, sensitivity 62.5%, and specificity 61.3%. ROC AUC of REMS was 0.787, sensitivity 84.4%, and specificity 64.6%. ROC AUC of CURB-65 was 0.814, sensitivity 81.3%, and specificity 76.8%. The predictive value of NEWS and NEWS2 combined with age were significantly improved. The ROC AUC of NEWS combined with age was 0.885, sensitivity 85.1%, and specificity 75.0%. The ROC AUC of NEWS2 combined with age was 0.883, sensitivity 84.2%, and specificity 75.0%. NEWS and NEWS2 combined with age can be used as a predictive tool for whether COVID-19 patients will be admitted to the ICU.
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Humains , Adulte d'âge moyen , Sujet âgé , COVID-19 , Études rétrospectives , Hospitalisation , Unités de soins intensifs , Courbe ROC , Pronostic , Mortalité hospitalièreRésumé
BACKGROUND: Isolation of nuclei or nuclear proteins is a prerequisite for western blot, nuclear proteome profiling, and other evaluations of nuclear proteins. Here, we developed a simple method for in situ isolation of nuclei or nuclear proteins by in situ removing the extranuclear part of adherent cells via a classical nonionic detergent triton X-100. RESULTS: First, the feasibility of our method was confirmed by confocal microscopy, atomic force microscopy, scanning electron microscopy, dynamic light scattering, immunofluorescence imaging, and time-lapse dynamic observation. Next, the optimal concentration range (approximately 0.1-1% for ~ 10 min) of triton X-100 and the optimal treatment time (< 30 min) of 0.1-1% Triton X-100 for our method were determined via western blotting of eight extra-/ intra-nuclear proteins. Subsequently, the effectiveness, sensitivity, and cytoplasmic contamination of our method were tested by investigating the levels of phosphorylated p65 (a NF-κB subunit) in the nuclei of endothelial or tumor cells treated with/without lipopolysaccharide (LPS) via western blotting and by comparing with a commercial nuclear protein extraction kit (a classical detergent-based method). The data show that compared with the commercial kit our method obtained a higher yield of total nuclear proteins, a higher pP65 level in both control and LPS groups, and much lower content of GAPDH (as a reference for cytoplasmic contamination) in nuclei. CONCLUSIONS: The in situ isolation of nuclei or nuclear proteins from adherent cells in this study is a simple, effective method with less cytoplasmic contamination. This method/strategy has the potential of improving the quality of downstream evaluations including western blotting and proteomic profiling.
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Protéines nucléaires , Lipopolysaccharides , Facteur de transcription NF-kappa B/métabolisme , Octoxinol/pharmacologie , Protéomique , Détergents/pharmacologieRésumé
Objective@#To analyze epidemiological characteristics of campus bullying among primary and middle school students in central China to explore its relation with mental health problems, and to provide a reference for the campus bullying prevention.@*Methods@#Stratified cluster sampling method was used to select primary and middle school 10 581 students from Anyang, Nanyang and Xinxiang cities of Henan Province, Middle School Students Mental Health Scale and the Self designed Scale of Adolescent Bullying Behavior were used to analyze the relationship between mental health problems with campus bullying behavior.@*Results@#The total report rate of bullying penetrator was 12.5% among students in the three cities. Among primary and middle school students with mental health problems such as hostility, interpersonal stress, academic pressure and emotional imbalance, the detection rate of bullying behavior was 24.2%, 20.3%, 19.4% and 20.1%, respectively. The results of multivariate analysis showed that hostility symptoms ( OR =3.78, 95% CI =1.71-8.32), interpersonal stress ( OR =3.50, 95% CI = 1.62 -7.57), academic pressure ( OR = 1.62 , 95% CI =1.21-2.16) and emotional imbalance ( OR =2.80, 95% CI =1.41-5.56) showed a significant impact on campus bullying ( P <0.05).@*Conclusion@#Mental health problems of primary and middle school students are closely related to the occurrence of bullying behavior. It is necessary to pay attention to the mental health education of bullies and intervene bullying behaviors from the source.
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Bufonis Venenum,the dried secretion of Bufo bufo gargarizans or B. melanostictus,is toxic and hard with the efficacy of removing toxicity for detumescence and relieving pain. The processing of Bufonis Venenum dates back to the Song dynasty. In addition to the wine-processing,milk-processing and talcum powder-processing,there were some other kinds of processing methods in ancient times,such as baking,calcining,water-soaking and vinegar-processing. Modern studies have shown that the Bufonis Venenum has the main chemical components of bufadienolides,indole alkaloids sterols,and other compounds. It has the pharmacological effects of antitumor,cardiac,antibacterial,and analgesic activities,local anesthesia,and so on. This paper reviews the processing evolution,chemical components and pharmacological effects of Bufonis Venenum,providing references for its special processing and modern research as well as the theoretical basis for the research on its processing mechanism and quality control.
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Animaux , Bufanolide/pharmacologie , Bufonidae , Contrôle de qualitéRésumé
@#AIM: To investigate the relationship between retinal arteriosclerosisand cardiovascular and cerebrovascular diseases in type 2 diabetes mellitus. <p>METHODS:Totally 85 patients with type 2 diabetes mellitus in our hospital from January 2016 to January 2017 were selected as the research subjects. Fundus examination was carried out to determine the classification of ophthalmic arteriosclerosis. The blood glucose level of the patients was detected and the glycosylated hemoglobin,fasting blood glucose and postprandial blood glucose levels were measured. All patients were followed up for at least 1 and a half years, and the cardiovascular and cerebrovascular diseases rate was statistically analyzed during the follow up period. The blood glucose level and cardiovascular and cerebrovascular diseases rate in patients with different ocular fundus arteriosclerosis grades were compared, meanwhile the relationship between ocular fundus arteriosclerosis grades with the blood glucose levels and cardiovascular and cerebrovascular diseases rate were analyzed. <p>RESULTS: Among the 85 patients, 15%(13/85), 52%(44/85)and 33%(28/85)of the patients were classified asocular fundus arteriosclerosis grades Ⅰ, Ⅱ and Ⅲ respectively. The cardiovascular and cerebrovascular diseases rate during the follow up period was 27%(23/85). The glycosylated hemoglobin,fasting blood glucose, postprandial blood glucose and cardiovascular and cerebrovascular diseases rates were all increased with the elevation of ophthalmic arteriosclerosis(<i>P</i><0.05). Spearman correlation analysis showed that the classification of ophthalmic arteriosclerosis in type 2 diabetes mellitus was positively correlated with glycosylated hemoglobin,fasting blood glucose, postprandial blood glucose level and cardiovascular and cerebrovascular diseases rate(<i>r<sub>s</sub></i>=0.875, 0.792, 0.835, 0.878; <i>P</i><0.05). <p>CONCLUSION:Type 2 diabetes mellitus patients has severe fundus arteriosclerosis, which is closely related to blood glucose level and cardiovascular and cerebrovascular diseases.
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Objective To investigate current status of hemodialysis,and qualified status of dialysis water and dia-lysate in a city. Methods Status of hemodialysis in 36 medical institutions in a city which conducted blood purifica-tion programme was surveyed,dialysis water and dialysate were collected to perform microbial detection(including conventional and low temperature culture methods)and on-site ATP detection.Results 13.89% of equipments for water treatment were used less than 1 year,5.56% were used for more than 10 years. 77.78% of medical institu-tions didn't replace sand filtration which had been used for more than 1 year,the replacement time of 72.22% of fil-ter core was less than 3 months,2.78% of reverse water supply pipeline was used for more than 10 years.77.78%of medical institutions used finished A solution,72.22% used finished B solution,22.22% used centrally provided A solution,19.44% used centrally provided B solution,and 8.34% used self-made B solution. Routine microbial detection in 36 medical institutions were qualified,but 80.56% of detection results were"0" value for long period;ATP detection of on-site collected dialysis water and dialysate were all qualified. One specimen for microbial detec-tion under normal temperature exceeded the standard,2 reached the intervention value;4 specimens for microbial detection under low temperature exceeded the standard,6 reached the intervention value;qualified rates of 3 kinds of detection methods among different levels of medical institutions weren't significantly different(all P>0.05).Con-clusion The overall quality of hemodialysis water and dialysate in this city is good,the majority of medical institutions pay attention to the routine maintenance of water treatment equipment,detect the quality of hemodialysis water and dialysate regularly,but microbial detection technique needs to be improved,causes for abnormal results or intervention value of rou-tine detection needs to be analyzed and improved continuously.
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OBJECTIVE To investigate the underlyingmechanism on the association of red blood cell and gut microbiota in rats induced by High-Fat Diet(HFD).METHODS A total of 36 male Sprague-Dawley rats (180±20g) were randomly divided into two groups. The control group (n=10) was given a normal chow diet(10% calories of fat),and the High-fat diet group(n=26)was given a HFD(60% calo-ries of fat).We recorded body weight,length and detected serum glucose,serum lipids and insulin ev-ery two weeks.The fresh arterial blood was collected during the experiments and blood gases were measured immediately (Radiometer Medical ApS, Denmark).Thehematocrit (Hct) and partial pressure of oxygen(pO2)were detected by the sensor cassette,following themanufacturer′s instructions.The de-tection method was conductivity measurements and current method, respectively. The feces from ce-cum were analyzed by 16S rRNA gene high-throughput sequencing(Illumina Miseq,USA). RESULTS According to the insulin resistance(IR),body weight and body length,the model group was divided into two small groups.(1)IR group,in which IR,body weight and body length were higher than the control group (P<0.05). (2) un-IR group, body weight and body length were higher than the control group (P<0.05),but the IR was not significantly different.In addition,the levels of hematocrit(Hct),checktotalhe-moglobin (ctHb) and check total blood oxygen content (ctO2) showed significantly increased in the IR group when compared with the control group (P<0.05), however, the pO2was not statistically signifi-cant. Furthermore, we identified that the genus Lactobacillus was moderate positive correlation with Hct,ctHb and ctO2(P<0.05).Compared with the control group,the relative abundance of the Lactoba-cillus was significantly lower in IR group(P<0.05).CONCLUSION The high-fat diet induced rats′local tissue hypoxia under the red blood cell increasing,oxygen partial pressure constant and the reduction of Lactobacillus′abundance might be caused by aerobic oxidation and glycolysis inhibition in the meantime.
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OBJECTIVE Oxidative sress is one of the key factor responsible for occurrence and development of hepatic fibrosis, a common consequence of chronic liver injury of multiple etiology. Nuclear factor erythroid 2-related factor 2 (Nrf2) serves as a major regulator of a celular defense system against oxidative stress. Xiaochaihutang (XCHT), a compound of seven botanical extracts used for liver diseases traditionally in East Asia. However, few studies have investigated its anti-hepatic fibrosis effects and pathophysiological mechanism of action. The present study was designed to confirm the anti-hepatic fibrosis effects and explore its potential mechanism of action by investigating the intervention of Nrf2 pathway. METHODS Liver fibrosis was induced by repeated injection of Carbon tetrachloride (CCl4) over a period of 9 weeks. Starting from the 6th week, the animals in treatment groups were given the appropriate dose of XCHT granules and silybin. Biochemical parameters, histological changes of the liver and alpha-smooth muscle actin (α-SMA) were determined. The expressions of Nrf2, Keap1, Nqo1, HO-1, Gclc and Gclm were assessed by RT-PCR and Western blot. RESULTS CCl4 caused a significant fibrosis damage in the rat liver and the liver functions and fibrosis degree were significantly improved by XCHT (5 g·kg- 1 and 10 g·kg- 1). XCHT (5 g·kg- 1 and 10 g·kg- 1) treatment significantly decreased the number of cells labeled with α-SMA antibodies. Moreover, XCHT (5 g·kg-1 and 10 g·kg-1) significantly increase Nqo1, HO-1, Gclc and Gclm expressions in the liver. CONCLUSION These studies establish XCHT is a potentially useful therapeutic agent for treatment of hepatic fibrosis and it might be via regulation of Nrf2 pathway in rats against oxidative stress, making further efforts to inhibiting the activated HSCs. Activation or up-regulation of Nrf2 pathway may be an alternative treatment strategy for liver fibrosis.
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<p><b>OBJECTIVE</b>To investigate the effect of glutaryl-CoA dehydrogenase (GCDH) gene silencing and accumulation of lysine metabolites on the viability of hepatocytes.</p><p><b>METHODS</b>BRL cells were divided into normal control group, negative control group, and GCDH silencing group. The shRNA lentiviral vector for silencing GCDH gene was constructed, and the BRL hepatocytes in the GCDH silencing group and the negative control group were infected with this lentivirus and negative control virus respectively, and then cultured in a medium containing 5 mmol/L lysine. Immunofluorescence assay was used to measure the infection efficiency of lentivirus. Western blot was used to measure the expression of GCDH protein. MTT assay was used to evaluate cell viability. Hoechest33342 staining was used to measure cell apoptosis. Western blot was used to measure the expression of Caspase-3, an index of cell apoptosis.</p><p><b>RESULTS</b>The lentivirus constructed effectively silenced the GCDH gene in hepatocytes (P<0.01). MTT assay and Hoechest 33342 staining showed no significant differences in cell viability and apoptosis between groups (P>0.05). There was also no significant difference in the expression of Caspase-3 protein between groups (P>0.05).</p><p><b>CONCLUSIONS</b>GCDH gene silencing and accumulation of lysine metabolites may not cause marked hepatocyte injury.</p>
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Animaux , Rats , Aminoacidopathies congénitales , Anatomopathologie , Thérapeutique , Apoptose , Encéphalopathies métaboliques , Anatomopathologie , Thérapeutique , Caspase-3 , Métabolisme , Survie cellulaire , Cellules cultivées , Technique d'immunofluorescence , Extinction de l'expression des gènes , Glutaryl-CoA dehydrogenase , Génétique , Hépatocytes , Anatomopathologie , Lysine , MétabolismeRésumé
<p><b>BACKGROUND</b>In the past decades, studies on infant anemia have mainly focused on rural areas of China. With the increasing heterogeneity of population in recent years, available information on infant anemia is inconclusive in large cities of China, especially with comparison between native residents and floating population. This population-based cross-sectional study was implemented to determine the anemic status of infants as well as the risk factors in a representative downtown area of Beijing.</p><p><b>METHODS</b>As useful methods to build a predictive model, Chi-squared automatic interaction detection (CHAID) decision tree analysis and logistic regression analysis were introduced to explore risk factors of infant anemia. A total of 1091 infants aged 6-12 months together with their parents/caregivers living at Heping Avenue Subdistrict of Beijing were surveyed from January 1, 2013 to December 31, 2014.</p><p><b>RESULTS</b>The prevalence of anemia was 12.60% with a range of 3.47%-40.00% in different subgroup characteristics. The CHAID decision tree model has demonstrated multilevel interaction among risk factors through stepwise pathways to detect anemia. Besides the three predictors identified by logistic regression model including maternal anemia during pregnancy, exclusive breastfeeding in the first 6 months, and floating population, CHAID decision tree analysis also identified the fourth risk factor, the maternal educational level, with higher overall classification accuracy and larger area below the receiver operating characteristic curve.</p><p><b>CONCLUSIONS</b>The infant anemic status in metropolis is complex and should be carefully considered by the basic health care practitioners. CHAID decision tree analysis has demonstrated a better performance in hierarchical analysis of population with great heterogeneity. Risk factors identified by this study might be meaningful in the early detection and prompt treatment of infant anemia in large cities.</p>
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Femelle , Humains , Nourrisson , Mâle , Anémie , Épidémiologie , Pékin , Épidémiologie , Chine , Épidémiologie , Études transversales , Arbres de décision , Modèles logistiques , Modèles théoriques , Facteurs de risqueRésumé
AIM:To study the effect of posterior sub - Tenon's capsule injection of triamcinolone acetonide ( TA ) in treatment of patients with diffuse diabetic macular edema ( DME) before panretinal photocoagulation ( PRP) . METHODS:Retrospective analysis of the clinical data of 96 cases (96 eyes) with DME treated in our hospital from October 2008 to May 2012, and the patients were divided into the study group and control group, each group with 48 cases ( 48 eyes ) , the control group were only treated with PRP, and for the study group, TA was injected one week before PRP. At 6mo after treatment, best-corrected visual acuity ( BCVA) and retinal thickness changes of two groups were compared, the changes of intraocular pressure in two groups was analyzed. RESULTS:After treatment, two groups were followed up for 6mo, compared with before treatment, the expression of BCVA in control group was reduced, and rise in the study group, with significant difference between the two groups (P0. 05), the study group had foveal thickness reduction of 9. 6μm, the control group was increased by 31. 9μm, with significant difference (P0. 05).CONCLUSION:TA injection in patients with diffuse DME before PRP is safe and effective, and it is superior to simple PRP therapy, and it can be applied in primary hospital.
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AMYLOIDOSIS is a benign process which can have systemic involvement. Though larynx is the common site of localized amyloidosis in the head and neck region,1 it was seldom reported with heterochronous implication of bilateral ventricles. Here we report a case of laryngeal amyloidosis heterochronously localized at bilateral ventricles with tracheobronchial involvement. Combined with our experience we reviewed the literature, and discuss the pertinent managements of this condition.
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Adulte , Humains , Mâle , Amyloïdose , Imagerie diagnostique , Anatomopathologie , Chirurgie générale , Maladies des bronches , Imagerie diagnostique , Anatomopathologie , Chirurgie générale , Maladies du larynx , Imagerie diagnostique , Anatomopathologie , Chirurgie générale , Laryngoscopie , Radiographie , Tomodensitomètre , Maladie de la trachée , Imagerie diagnostique , Anatomopathologie , Chirurgie générale , Résultat thérapeutiqueRésumé
Objective To analyze the clinical characteristics of 7 pediatric patients with C3 glomerulonephritis (C3-GN).Methods The clinical manifestations,pathological features,therapies,prognosis of patients from Jun.2006 to Nov.2011 were analyzed retrospectively.Results All of the patients were presented as acute nephritic syndrome,and 4 patients with macroscopic hematuria,other 3 cases with severe proteinuria.Five patients with eyelid edema.All the patients showed decreased level of serum complement C3,while serum complement C4 was normal.Investigations showed elevation of 24 h urine protein,5 patients with elevated antistreptolysin O titers.Three patients with renal dysfunction.Isolated C3 deposition in mesangial and endothelial areas(+ +-+ + +) was confirmed by immunofluorescence.Light microscope revealed membrane proliferative glomerulonephritis and mesangial proliferative glomerulonephritis.Electron microscope showed swelling and hyperplasia of endothelial cells without electron-dense deposition or podocyte foot fusion.Based on conventional treatment,administration of immunosuppressant was performed in 3 patients with severe pathological changes.After a follow-up of 2 months to 5 years,the prognosis seems to be benign.Conclusions Children with C3-GN are usually presented as acute nephritic syndrome,characterized by isolate C3 deposition in immunofluorescence.Electron microscope showed lesion of endothelial cells,while no electron-dense deposits in mesangial and endothelial areas.The mechanism may be associated with dysregulation of alternative complement pathway,and seems had a good short-term prognosis.
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OBJECTIVE@#To identify novel drug targets for treatment of Plasmodium falciparum.@*METHODS@#Local BLASTP were used to find the proteins non-homologous to human essential proteins as novel drug targets. Functional domains of novel drug targets were identified by InterPro and Pfam, 3D structures of potential drug targets were predicated by the SWISS-MODEL workspace. Ligands and ligand-binding sites of the proteins were searched by Ef-seek.@*RESULTS@#Three essential proteins were identified that might be considered as potential drug targets. AAN37254.1 belonged to 1-deoxy-D-xylulose 5-phosphate reductoisomerase, CAD50499.1 belonged to chorismate synthase, CAD51220.1 belonged to FAD binging 3 family, but the function of CAD51220.1 was unknown. The 3D structures, ligands and ligand-binding sites of AAN37254.1 and CAD50499.1 were successfully predicated.@*CONCLUSIONS@#Two of these potential drug targets are key enzymes in 2-C-methyl-d-erythritol 4-phosphate pathway and shikimate pathway, which are absent in humans, so these two essential proteins are good potential drug targets. The function and 3D structures of CAD50499.1 is still unknown, it still need further study.
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Humains , Antipaludiques , Utilisations thérapeutiques , Ligands , Paludisme à Plasmodium falciparum , Traitement médicamenteux , Conformation moléculaire , Plasmodium falciparum , Chimie , Protéines , Chimie , Similitude structurale de protéinesRésumé
<p><b>OBJECTIVE</b>To study changes of glycolipid metabolism and adipocyte function in an catch-up growth intrauterine growth retardation (IUGR) rat model.</p><p><b>METHODS</b>IUGR rat model was established by maternal nutrition restriction during pregnancy. Newborn IUGR pups were used as IUGR group, and normal newborn pups were used as control group (appropriate for gestational age, AGA group). At age of 12 weeks, plasma samples were collected for the test of triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), adiponectin and acylation stimulating protein (ASP). Oral glucose tolerance test (OGTT) was performed for the test of glucose and insulin levels, and insulin resistance index (IRI) was calculated. Expression of glucose transfer 4 (GLUT-4) in adipocytes was examined by confocal microscopy.</p><p><b>RESULTS</b>Body weight and BMI in the IUGR group were significantly higher than in the AGA group by 12 weeks (P<0.01), and plasma TC, TG and LDL-C levels in the IUGR group were higher than in the AGA group, but HDL-C was lower (P<0.05). In the OGTT test, blood glucose level and IRI score in the IUGR group were higher than in the AGA group (P<0.05). Compared with the AGA group, the IUGR group had a higher ASP level (P<0.05) and a lower adiponection level (P<0.05). GLUT4 expression in the adipocytes was significantly lower in the IUGR group than in the AGA group (P<0.05).</p><p><b>CONCLUSIONS</b>Catch-up growth may be obviously noted in IUGR rats after birth. Both hyperlipidaemia and insulin resistance occur at age of 12 weeks. Dysfunction of adipocytes decreased expression of GLUT-4 may be risk factors for insulin resistance in IUGR rats.</p>
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Animaux , Femelle , Mâle , Rats , Adipocytes , Physiologie , Glycémie , Indice de masse corporelle , Poids , Métabolisme glucidique , Retard de croissance intra-utérin , Transporteur de glucose de type 4 , Métabolisme lipidique , Rat Sprague-DawleyRésumé
Background: Viral vectors can produce longer-lasting effects than a recombinant protein. Objective: Develop a system of sustained GH1 (a human growth hormone gene) transfer and expression in baby hamster kidney cell (BHK-21) line using recombinant adeno-associated viral vectors pseudotyped with viral capsids from serotype 1 (rAAV2/1). Methods: The expression of GH1 in vitro was examined by reverse transcription polymerase chain reaction and Western blot analysis. Effects of GH1 on cell proliferation were measured by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl-tetrazolium bromide (MTT) experiments. Mice serum IGF-1 and blood glucose, after injection of virus infected BHK-21 cells, were measured by enzyme-linked immunosorbent assays. Results: rAAV2/1-mediated GH1 gene transfer occurred effectively in vitro after 48 hours of transduction at 1 105 vg/mL (multiplicities of infection). MTT experiments indicated notable effects of the GH1 gene on cell proliferation in vitro. Subsequent animal experiment suggested that the injection of virus infected BHK-21 cells might induce increase of serum IGF-1. Conclusion: Our study shows the feasibility of rAAV2/1-mediated GH gene delivery in vitro, applicable for future experimental and clinical investigations.
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<p><b>OBJECTIVE</b>To definite the etiopathogenisis by carrying out the genome-wide copy number variation analysis for a suspect patient with Prader-Willi syndrome.</p><p><b>METHODS</b>The peripheral blood was collected from the patient who was diagnosed as having Prader-Willi syndrome, as well as his parents for conventional cytogenetic G-banding and high resolution chromosome assay. Genomic DNA of the child patient was extracted from the blood to perform the genome-wide copy number variation analysis.</p><p><b>RESULTS</b>There was a heterozygosis deletion of a 5Mb region in chromosome 15q11.2-q13.1 by the genome-wide copy number variation analysis, but no abnormality was observed in high resolution chromosome assay in the child patient and his parents. Baylay and Gesell developmental scale was assessed regularly; the results suggested that the IQ of the child patient was 60-70, according with the clinical feature of Prader-Willi syndrome.</p><p><b>CONCLUSION</b>The heterozygosis deletion in chromosome 15q11.2-q13.1 is the cause of Prader-Willi syndrome in this family. Further molecular genetics detection can make up for the insufficiency in cytogenetics methods, when no abnormality is observed at the level of cytogenetics in patients with Prader-Willi syndrome.</p>