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Objective @#This article explores the relationship between congenital tooth agenesis and related gene mutations, providing a reference for early diagnosis of the disease.@*Methods @# Clinical and radiographic examinations of a rare case of congenital tooth agenesis were conducted to evaluate the abnormal morphology and quantity of the teeth, as well as the overall health of the patient. Bidirectional sequencing of the PAX9 and MSX1 genes and whole-exome sequencing were conducted to identify potential genetic abnormalities. Sanger sequencing of the newly discovered mutation site was performed on the proband's son. Subsequently, the impacts of the mutations were evaluated through computational tools and a cell-based gene transfection assay. @*Results @#This is a rare case of tooth agenesis characterized by a congenitally missing first molar, a second molar with one single root and a supernumerary second premolar in the right mandibular dentition. The c.717 C>C/T in PAX9 is synonymous. The c.119C>G in MSX1 is a missense mutation predicted to be “benign” by Polyphen. Through whole-exome sequencing, we found a novel mutation, c.637-7 C>A in intron 3 of the WNT6 gene, which is predicted by MAXENT to influence the splicing of mRNA. Both the proband and his son carry this mutation. A cell-based gene transfection assay demonstrated that it did not alter the mRNA splicing of WNT6. @* Conclusion @#The interaction between single nucleotide polymorphisms may contribute to congenital tooth agenesis.
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Objective @#To explore the etiology, clinical manifestations, diagnosis and treatment of multiple idiopathic root resorption to provide a reference for clinical diagnosis and treatment. @*Methods@# The clinical data of a case of multiple idiopathic root resorption were analyzed retrospectively, and the related literature was reviewed.@*Results@#The patient had no history of orthodontic correction, occlusal trauma, trauma history or other causes of root resorption. Clinical examination revealed full-mouth gingival congestion, redness, a loose texture, and variable degrees of destruction of the alveolar bone. Imaging examination showed that teeth 13, 16, 26, 36, 46 had idiopathic root resorption. The diagnoses were multiple idiopathic root resorption and periodontitis. The pathology tests showed that a large number of osteoclasts were present in the soft tissue surrounding the teeth. Whole-exome sequencing showed that there was a strong correlation between gene mutations (WNT7a and HSPG2) and the present phenotype. Root resorption of teeth without periodontitis was stopped after periodontal treatment during the 19-month follow-up. Tooth 13 was removed, and extraction socket preservation was performed. The etiology of idiopathic root resorption may be related to gene mutations, but it is not clear. At present, there is no effective treatment. @* Conclusion @#Multiple idiopathic root resorption has an unknown etiology, but it may be related to WNT7A and HSPG2 gene mutations. The rate of root resorption can be slowed by controlling periodontal inflammation.
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Objective@#This systematic review and meta-analysis was undertaken to evaluate the efficacy of antibacterial photodynamic therapy (aPDT) in the treatment of periodontitis in type-2 diabetes mellitus (T2DM) patients and to provide better treatment for patients with T2DM complicated with periodontitis.@*Methods@#The PubMed, Cochrane, Embase, Web of Science, CNKI, CBM, and Wanfang databases were searched for relevant randomized controlled trials (RCTs). RevMan 5.3 was applied for the meta-analysis, and a systematic evaluation was conducted.@*Results@#A total of 8 RCTs were included. The results showed that compared to simple subgingival scaling and root planing (SRP), aPDT assisted SRP had a better effect on improving the probing depth (PD) at 3 months after treatment, The difference was statistically significant [WMD=-0.32,95%CI(-0.45, -0.2), P < 0.05], but 6 months after treatment, there was no significant difference in the two groups [ WMD=-0.15,95%CI(-0.40, 0.10),P=0.23]. During the 6-month follow-up period, there were no significant differences in the clinical attachment level (CAL), bleeding on probing (BOP) or hemoglobin A1c (HbA1c) between the two groups (P> 0.05).@*Conclusion@#aPDT-assisted periodontal nonsurgical treatment in T2DM patients can improve PD in the short term but has no significant effect on the improvement of CAL, BOP and HbA1c.
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Objective@# To study the changes in levels of interleukin (IL)-6, IL-10, tumor necrosis factor-alpha (TNF-α), and alkaline phosphatase (ALP) in the gingival crevicular fluid (GCF) of patients with severe chronic periodontitis before and after nonsurgical periodontal therapy and to explore the relationship among the levels of these four biomarkers in GCF, their periodontal status and their clinical significance to evaluate the effect of nonsurgical periodontal therapy and periodontitis activity.@*Methods@# In total, 30 patients with severe chronic periodontitis were enrolled in a 1-year longitudinal pilot study (Chinese Clinical Trial Registry: ChiCTR-OCH-13004679). At baseline and 1, 3, 6, and 12 months after nonsurgical therapy, the periodontal clinical indicators plaque index (PLI), probing depth (PD), clinical attachment loss (CAL), sulcus bleeding index (SBI) were recorded. Filter paper strips were used to collect two deep-pocket (probing depth ≥ 6 mm) and two shallow-pocket (probing depth ≤ 4 mm) periodontal sites for each patient and weighed. The levels of interleukin IL-6, IL-10, TNF-α, and ALP in GCF were assessed using enzyme-linked immunosorbent assay. Meanwhile, 30 healthy sites of 15 subjects with healthy periodontium were used as the baseline controls for patients with severe chronic periodontitis.@*Results @#At the baseline, the TNF-α, ALP and IL-6 levels in GCF of the disease sites of patients with periodontitis were significantly higher than those in healthy periodontal sites of the control group (P < 0.001), and the levels of IL-10 were significantly lower than those in the control group (P < 0.001). In patients with severe chronic periodontitis, the levels of TNF-α, ALP and IL-6 in GCF at deep-pocket sites were significantly higher than those at shallow-pocket sites (P <0.001), and the IL-10 levels were significantly lower than those at shallow-pocket sites (P < 0.001). 1, 3, 6, and 12 months after nonsurgical treatment, the levels of TNF-α and ALP in GCF at the shallow- and deep-pocket sites in patients with chronic periodontitis significantly decreased, the level of IL-10 significantly increased (P < 0.005), and the level of IL-6 in GCF at the deep-pocket sites significantly decreased (P < 0.005). However, there was no significant difference in IL-6 level at shallow-pocket sites (P > 0.05). 1, 3, 6, and 12 months after nonsurgical treatment, the periodontal clinical indicators were improved compared with the baseline. In addition, there was a significant correlation between the levels of these four biomarkers and the periodontal clinical parameters (P < 0.05). During the two follow-up visits after nonsurgical periodontal therapy, the sites with more than 2-mm increase in attachment loss had significant differences in the levels of the four biomarkers in the GCF compared with the previous visit time (P < 0.005).@*Conclusion@#The detection of the levels of these four biomarkers in GCF has strong clinical significance for assessing the severity of periodontitis and the efficacy of nonsurgical periodontal therapy. Increased levels of TNF-α, ALP, and IL-6 and decreased IL-10 levels in GCF may indicate periodontitis progression at this site.
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Objective@#To explore the changes of awareness of tuberculosis and access to tuberculosis-related information among students in Zhejiang Province.@*Methods@#There were 554 students younger than 30 y were included in the study during April to sept. of 2014 and during sept. to Nov. of 2018. Univariate and multivariate Logistic regression were conducted to find the related factors of knowing about tuberculosis and related knowledge. Chi-square test was used to analyze the changes of ways access to tuberculosis-related information.@*Results@#There were 440 participants (79.4%) aware of tuberculosis, including 215(85.7%) in 2014 and 225(74.3%) in 2018. The factors affecting awareness on tuberculosis were female ( AOR=1.60, 95%CI =1.04-2.47) vs male; and junior middle school( AOR=1.99, 95%CI =1.03-3.85), high school( AOR=3.27, 95%CI =1.57-6.81), college or higher ( AOR=6.73,95%CI =2.55-17.76) vs primary school or lower; year 2018 ( AOR=0.50, 95%CI =0.31-0.80) vs 2014. There was no significant statistical difference in the overall knowledge scores of tuberculosis between the students in the two surveys. In 2018, the proportion of tuberculosisrelated information accessed from the Internet (forum, WeChat, Weibo.) and community activities (assembly promotion)(75.10%, 26.70%) was higher than that of 2014(36.20%, 13.10%)( χ 2=68.88, 12.79, P <0.05).@*Conclusion@#The proportion of students aware of tuberculosis and TB control in Zhejiang Province were not significantly improved. Higher proportion of students get tuberculosis-related information from the new media. Therefore, it is necessary to strengthen health education of tuberculosis in schools, especially through the usage of new media apart from traditional pathways.
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PURPOSE: The intermediate stage of hepatocellular carcinoma (HCC) (Barcelona Clinic Liver Cancer [BCLC] B) comprises a highly heterogeneous population, and the treatment strategy is still controversial. Because of the heterogeneity, a subclassification of intermediate-stage HCCs was put forward by Bolondi according to the ‘beyond Milan and within up-to-7' criteria and Child-Pugh score. In this study, we aim to analyze the prognosis of BCLC-B stage HCC patients who received hepatic resection according to the Bolondi's subclassification. MATERIALS AND METHODS: One thousand and one hundred three patients diagnosedwith HCC and treatedwith hepatic resectionwere enrolled in our hospital between 2006 and 2012. According to Bolondi's subclassification, the BCLC-B patients were divided into four groups. Recurrence-free survival (RFS) and overall survival (OS) were analyzed. RESULTS: According to Bolondi's subclassification, the BCLC-B patients were divided into four groups: B1 (n=41, 18.7%), B2 (n=160, 73.1%), B3 (n=11, 5.0%), and B4 (n=7, 3.2%). Significant difference was observed between B1 and other groups (B1 vs. B2, p=0.022; B1 vs. B3, p < 0.001; B1 vs. B4, p < 0.001), but no difference for B2 vs. B4 (p=0.542) and B3 vs. B4 (p=0.542). In addition, no significant differences were observed between BCLC-A and BCLC-B1 group for both RFS (p=0.087) and OS (p=0.643). In multivariate analysis, BCLC-B subclassification was not a risk factor for both OS (p=0.263) and RFS (p=0.892). CONCLUSION: In our study, HCC patients at B1 stagewere benefited from hepatic resection and had similar survival to BCLC-A stage patients. Our study provided rationality of hepatic resection for selected BCLC-B stage HCC patients instead of routine transarterial chemoembolization.
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Humains , Carcinome hépatocellulaire , Hépatectomie , Tumeurs du foie , Analyse multifactorielle , Caractéristiques de la population , Pronostic , Facteurs de risqueRÉSUMÉ
OBJECTIVE@#To study the features of serum metabolites in preterm infants based on gas chromatography-mass spectrometry (GC-MS), and to find differentially expressed metabolites in the serum of preterm infants.@*METHODS@#Serum samples were collected from 19 preterm infants and 20 full-term infants before feeding. GC-MS was used to measure metabolic profiles, and the metabolic features of 397 serum metabolites in preterm infants were analyzed.@*RESULTS@#There was a significant difference in serum metabolic features between the preterm and full-term infants before feeding. There were significant differences between the full-term and preterm infants in the levels of metabolites such as O-phosphonothreonine, digicitrin, tannic acid, and fructose-1,6-diphosphate (P<0.01), suggesting that the above differentially expressed metabolites were highly differentiated between the preterm and full-term infants. Most differentially expressed metabolites were involved in the metabolic pathways such as ABC transporters, β-alanine and pyrimidines and were correlated with some clinical parameters (albumin and total bilirubin) (P<0.05).@*CONCLUSIONS@#There is a significant difference in serum metabolites between preterm and full-term infants before feeding. Metabolomics plays an important role in improving metabolic disorders and exploring metabolism-related diseases in preterm infants.
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Humains , Nouveau-né , Chromatographie gazeuse-spectrométrie de masse , Prématuré , Voies et réseaux métaboliques , Métabolome , MétabolomiqueRÉSUMÉ
Objective@#To investigate the distribution and proportion of M1/M2 macrophages in the periodontal tissues of rats with and without periodontitis.@*Method@#Twelve Sprague-Dawley rats were randomly divided into a chronic periodontitis group (CP, n = 6) and a periodontal health group (PH, n = 6). The periodontitis model was induced at the first mandibular molar using a stainless steel ligature and was confirmed by histological analysis. M1 macrophages were labeled with inducible nitric oxide synthase (iNOS), and M2 macrophages were labeled with CD163. The distributions of M1 and M2 macrophages in the two groups were determined via immunohistochemistry and immunofluorescence, and the M1/M2 ratios were compared between the two groups.@*Results @#The M1 type macrophage count in the PH group was 12.17 ± 1.40, and the M1 macrophage count in the CP group was 40.00 ± 3.20; there was a statistically significant difference between the two groups (t = 7.96, P<0.0001). The M2 macrophage count in the PH group was 4.50 ± 1.09, and the M2 type macrophage count in the CP group was 5.33 ± 0.67. There was no statistically significant difference between the two groups (t = 0.65, P = 0.53). The M1/M2 ratio in the CP group was 3.72 ± 1.08, and the M1/M2 ratio in the PH group was 8.31 ± 1.37; there was a statistically significant difference between the two groups (t = 2.63, P= 0.025).@*Conclusion@#During periodontitis, M1 macrophages increased significantly and were widely distributed; they may be involved in the progression of periodontitis and may be closely related to the destruction of the cementum.
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@#Objective To summarize the mid-term follow-up results and postoperative aortic remodeling of treating blunt aortic injuries (BAI) with thoracic endovascular aortic repair (TEVAR). Methods A retrospective study was conducted on BAI patients treated with TEVAR, who were admitted into the Department of Vascular Surgery in Zhongshan Hospital, Affiliated to Fudan University between September 2003 and December 2015. There were 15 males and 9 females at an average age of 45.6±14.0 years. The mechanism of BAI was mainly auto car crash. Totally 25 entry tears were detected and most of them were located at the aortic isthmus. Results Twenty-four BAI patients survived and eventually went through TEVAR. One patient died of pulmonary embolism 1 week post-TEVAR. Rate of technical success, clinical success and perioperative mortality was 100.0%, 95.8%, and 4.2%, respectively. Nineteen patients were followed up with a mean time of 35.1(13-87) months. All of them survived this period. Based on the follow-up imaging of CTA, 18 of them revealed no endoleak or stent migration, and 1 patient of transection still had perfusion of distal false lumen at the abdominal aorta. None of the aortic segments measured in this study showed expansion of ≥5 mm during follow-up. The aorta remodeled well in 94.7% of them. Conclusion TEVAR for treating BAI appears feasible with high rates of technical and clinical success rates. The mid-term follow-up results seems satisfying, but the long-term results are yet to be assessed with further follow-up.
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Arteriovenous fistula stenosis developed in 32 patients who received hemodialysis from April 2014 to April 2016, including 24 cases of autologous arteriovenous fistula ( AVF) and 8 cases of artificial vessel arteriovenous fistula ( AVG).In AVF patients, there were 20 cases with blood flow decreasing and 4 cases of venous hypertension , while in AVG patients there were no cases with blood flow decreasing and 8 cases with venous pressure increasing (χ2 =17.77, P0.05].The blood pressure was decreased after PTA treatment [( 71.2 ±7.9 ) vs.( 170.4 ± 15.7) mmHg, t=34.62, P0.05].
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Objective To evaluate the efficacy of flexible ureteroscopy combined with holmium laser lithotripsy for the treatment of subrenal calyx calculus, and comparing with digital flexible ureteroscope and modular flexible ureteroscope with holmium lithotripsy for the difference of the efficacy of the treatment of subrenal calyx calculus. Methods Review of the clinical data of 93 patients with subrenal calyx calculus, of which 48 cases were treated with digital flexible ureteroscope (digital flexible ureteroscope group, DFU group), 45 cases with modular flexible ureteroscope treatment (modular flexible ureteroscope group, MFU group), lithotripsy effect and complications were compared between the two groups. Results The mean operation time, one-session stone-free rate were significantly different between the two groups (P < 0.05). No significant differences in hospital stay, the success rate of looking for calculus, complication and hospitalization expense (P > 0.05). Conclusion With digital flexible ureteroscope and modular flexible ureteroscope treatment of subrenal calyx calculus all are safe and effective. The use of DFU than the use of MFU in the treatment of subrenal calyx calculus operation time is shorter, stone-free rateis higher, the effect is better. There is little difference between their hospitalization expenses, but the use of MFU can reduce the cost of the department.
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Objective To evaluate the efficacy of flexible ureteroscopy combined with holmium laser lithotripsy for the treatment of subrenal calyx calculus, and comparing with digital flexible ureteroscope and modular flexible ureteroscope with holmium lithotripsy for the difference of the efficacy of the treatment of subrenal calyx calculus. Methods Review of the clinical data of 93 patients with subrenal calyx calculus, of which 48 cases were treated with digital flexible ureteroscope (digital flexible ureteroscope group, DFU group), 45 cases with modular flexible ureteroscope treatment (modular flexible ureteroscope group, MFU group), lithotripsy effect and complications were compared between the two groups. Results The mean operation time, one-session stone-free rate were significantly different between the two groups (P < 0.05). No significant differences in hospital stay, the success rate of looking for calculus, complication and hospitalization expense (P > 0.05). Conclusion With digital flexible ureteroscope and modular flexible ureteroscope treatment of subrenal calyx calculus all are safe and effective. The use of DFU than the use of MFU in the treatment of subrenal calyx calculus operation time is shorter, stone-free rateis higher, the effect is better. There is little difference between their hospitalization expenses, but the use of MFU can reduce the cost of the department.
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The present study was aimed to investigate the underlying mechanisms of the protective effect of proanthocyanidin (Pro) against hypoxia/reoxygenation (H/R) injury in H9C2 cells with a focus on Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway. H9C2 cells were randomly assigned to 5 groups, including the control group (Con), the H/R-injured group (H/R), the Pro-treated group (H/R+Pro), the JAK2 siRNA-treated group (H/R+Pro+JAK2 siRNA) and the JAK2 siRNA control group (H/R+JAK2 siRNA). The cells were pretreated with Pro (40 µmol/L) for 8 h before 2 h of hypoxia and 4 h of reoxygenation. Cellular viability and apoptosis rate were detected by MTT and TUNEL methods, and superoxide generation was measured. JAK2/STAT3 signaling, oxidative stress markers and endoplasmic reticulum stress markers were also detected by Western blot. We found that Pro treatment significantly improved cellular viability and reduced apoptosis rate in H/R-treated H9C2 cells. In addition, Pro treatment significantly up-regulated the phosphorylation levels of JAK2 and STAT3, down-regulated the superoxide generation, gp91, glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP) and caspase-12 expression. However, these protective effects of Pro were all attenuated by JAK2 siRNA administration. Taken together, we demonstrated that Pro protects H9C2 cells against H/R-induced oxidative stress and endoplasmic reticulum stress injury via JAK2/STAT3 signaling pathway.
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Animaux , Rats , Apoptose , Hypoxie cellulaire , Lignée cellulaire , Survie cellulaire , Stress du réticulum endoplasmique , Méthode TUNEL , Janus kinase 3 , Oxydoréduction , Phosphorylation , Proanthocyanidines , Agents protecteurs , Petit ARN interférent , Facteur de transcription STAT-3 , Transduction du signal , Régulation positiveRÉSUMÉ
In order to explore the change rule of myoblast stem cells (satellite cells, SCs) in the denervated and re-innervated muscle and to investigate the cellular mechanism of the morphological and functional changes of the muscle, denervated muscle atrophy and nerve regeneration models were established in one-month-old rats. Postoperative indexes such as muscle wet weight, cell section areas, content of collagen fibers and DNA, electrophysiology, numbers of SCs in the triceps muscle of calf were dynamically tested. After denervation, the muscle wet weight and cell area reduced rapidly, and the collagen fiber content increased slowly. The number of SCs increased at first, and then declined suddenly two months later. From 4 to 5 weeks after re-neuralization, muscle action potentials could be evoked, but the best innervation effect was found in the groups, which received re-neuralization at 2 months and 3 months after denervation. Denervation causes a progressive progress of muscle atrophy. SCs proliferate within 3 months after denervation, and then atrophy becomes irreversible from 4 months. At 4 or 5 weeks after re-neuralization, muscle action potentials can be evoked. Re-neuralization at 2 months and 3 months after denervation can achieve a good effect on the functional recovery of the atrophic muscle.
Con el fin de explorar la regla de cambio de las células precursoras mioblásticas (células satélite, CSs) en el músculo denervado y re-inervado e investigar el mecanismo celular de los cambios morfológicos y funcionales del músculo, se establecieron, en ratas de un mes de edad, modelos de atrofia del músculo denervado y regeneración del nervio. Fueron examinados de manera dinámica índices postoperatorios tales como, el peso húmedo del músculo, áreas celulares de la sección, contenido de fibras de colágeno y ADN, electrofisiología, número de CSs en el músculo tríceps de las crías. Luego de la denervación, el peso del músculo húmedo y el área celular se redujeron rápidamente, mientras que el contenido de fibras colágenas aumentó lentamente. El número de CSs aumentó al inicio, pero más tarde, a los dos meses, disminuyó repentinamente. Entre las 4 a 5 semanas después de la reneuralización, los potenciales de acción muscular pudieron ser evocados, pero el mejor efecto de inervación se encontró en los grupos que recibieron reneuralización a los 2 y 3 meses después de la denervación. La denervación causó un avance progresivo de la atrofia muscular. Las CSs proliferaron dentro de los primeros 3 meses post-denervación, y luego de los 4 meses la atrofia fue irreversible. A las 4 o 5 semanas después de la reneuralizacón, los potenciales de acción muscular pueden ser evocados. La reneuralización a los 2 y 3 meses después de la denervación puede lograr un buen efecto en la recuperación funcional del músculo atrófico.
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Animaux , Rats , Muscles squelettiques/cytologie , Muscles squelettiques/innervation , Cellules satellites du muscle squelettique , Régénération , Cellules souches , Amyotrophie , Dénervation musculaireRÉSUMÉ
Podophyllotoxin (PPT) and its derivatives exert significant anti-cancer activities, and one derivative etoposide is often utilized to treat various cancers in the clinic. The aim of the present study is to investigate the inhibitory effects of PPT on major cytochrome P450 (CYP) isoforms in human livers. Inhibition of CYP3A4, CYP2C9, CYP2C8, CYP2D6, CYP2E1 and CYP2A6 by PPT was investigated in the human liver microsomal system. Time-dependent inhibition of CYP3A4 by PPT was also evaluated. The results showed that PPT strongly exhibited inhibitory effects on CYP3A4 and CYP2C9 in a concentration-dependent manner. Half inhibition concentration (IC50) was 1.1±0.3 and 4.6±0.3 μM for CYP3A4 and CYP2C9, respectively. Inhibition kinetic analysis showed that PPT exhibited competitive inhibition towards CYP3A4 and CYP2C9 with Ki of 1.6 and 2.0 μM, respectively. Additionally, PPT exerted time-dependent inhibition towards CYP3A4 and the kinetic parameters were 4.4±2.1 μM and 0.06±0.01 min–1 for KI and kinact, respectively. Our experimental data indicate that potential drug–drug interaction (DDI) might exist when PPT is co-administered with the substrates which mainly undergo CYP3A4- or CYP2C9-mediated metabolism.
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Objective : The aim of this study was to revision hip arthroplasties in ankylosing spondylitis. Materials and Methods: We performed 21 revision hip arthroplasty in 16 patients with ankylosing spondylitis (AS) using S-ROM modular femoral stem. At the final follow-up, all patients were able to ambulate without any walking aids. Results: The mean Harris hip score improved from 57.2 (35 to 74) pre-operatively to 90.2 points (73 to 100) post-operatively, and the outcome was classified as good or excellent in 17 hips (81%). Fixation of the femoral component was classified as stable with bone ingrowth in 15 hips (71.4%), stable with fibrous ingrowth in 2 hips (9.5%), and radiolucent loosening in 4 hips (19.1%). Five hips developed a pedestal at the tip of femoral component. Femoral osteolysis was found in 3 hips (14.2%): 3 hips in Gruen zones 1 and 7, one hip in zone 7, and two hips in zone 1. One hip underwent acetabular revision because of breakage of polyethylene liner, and the well-fixed femoral component was left in situ. Thigh pain developed in 1 patient (6.2%). Kaplan-Meier survival was 81% at 64 months, with radiographic loosening as an end-point when two hips were at risk. Conclusion: Satisfactory results of midterm clinical and radiographic follow-up can be achieved using S-ROM modular femoral stem for revision of femoral stem in ankylosing spondylitis.
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OBJECTIVE: Metallothionein 3 (MT-3) has been shown to protect against apoptotic neuronal death in the brains of patients with Alzheimer's disease. Zinc is a potent inhibitor of caspase-3 and its deficiency was found to promote apoptosis. Here, we measured the zinc and copper content in the brains of senescence-accelerated mouse/PRONE8 (SAMP8) and sought to investigate the effect of MT-3 on the apoptosis of neurons in the hippocampal CA1 region of these mice. METHOD: The zinc and copper content in the brain samples of SAMP8 and normal control SAMR1 mice were determined using an atomic absorption spectrophotometer. The mice were administered intraperitoneally for four weeks with MT-3 or MT1 and thereafter apoptosis was measured using the TUNEL method and the expression of anti-apoptotic protein Bcl-2 and proapoptotic protein Bax was examined by immunohistochemistry. RESULTS: Compared with that in SMAR1 mice, the content of zinc in the brains of SAMP8 mice was significantly reduced (P<0.05). Moreover, significant levels of apoptosis of neurons were observed in the hippocampus of SAMP8 mice, which, compared with those in SMAR1 mice, also showed significantly lower levels of Bcl-2 and higher levels of Bax (P<0.05). MT-3 increased zinc concentration in the hippocampus of SAMP8 mice and also significantly decreased apoptosis in these neurons dose-dependently and increased the levels of Bcl-2 and decreased the levels of Bax. CONCLUSION: MT-3 could attenuate apoptotic neuron death in the hippocampus of SAMP8, suggesting that the protein may lessen the development of neurodegeneration.
OBJETIVO: Metalotioneína 3 (MT-3) tem mostrado proteção contra a apoptose neuronal em cérebros de pacientes com doença de Alzheimer. Zinco é um potente inibidor da caspase-3, e sua deficiência pode promover a apoptose. No presente trabalho, foram dosados os níveis de zinco e cobre nos cérebros de camundongos PRONE8 com envelhecimento acelerado (SAMP8), visando investigar o efeito da MT-3 na apoptse dos neurônios da região hipocampal CA1 destes camundongos. MÉTODO: Os níveis de zinco e cobre em amostras cerebrais de camundongos SAMP8 e de controles normais SAMR1 foram determinados por absorção atômica em espectrofotometria. Foram administradas MT-3 ou MT-1 intraperitoneais durante quatro semanas, sendo em seguida avaliada a apoptose pelo método TUNEL , enquanto a expressão da proteína anti-apoptótica Bcl-2 e a proteína pró-apoptótica Bax foram avaliadas por imunohistoquímica. RESULTADOS: Em comparação aos camundongos SMAR1, o nível de zinco nas amostras cerebrais dos camundongos SAMP8 estava significativamente diminuído (P<0.05). Além disto, níveis significativos de apoptose foram observados no hipocampo dos camundongos SAMP8, o que, em comparação com os níveis em camundongos SMAR1, também mostrava níveis significativamente mais baixos de Bcl-2 e níveis mais altos de Bax (P<0.05). MT-3 aumentou a concentração de zinco no hipocampo dos camundongos SAMP8, além de diminuir significativamente a apoptose destes neurônios, de uma forma dose-dependente, ao mesmo tempo que aumentou níveis de Bcl-2 e diminuiu níveis de Bax. CONCLUSÃO: MT-3 pode atenuar a morte neuronal apoptótica no hipocampo de SAMP8, o que sugere que esta proteína possa diminuir a neurodegeneração.
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Animaux , Mâle , Souris , Apoptose/effets des médicaments et des substances chimiques , Inhibiteurs de croissance/pharmacologie , Hippocampe/effets des médicaments et des substances chimiques , Protéines de tissu nerveux/pharmacologie , Neurones/effets des médicaments et des substances chimiques , Vieillissement , Chimie du cerveau , /antagonistes et inhibiteurs , /déficit , Cuivre/analyse , Hippocampe/métabolisme , Hippocampe/anatomopathologie , Métallothionéine/pharmacologie , Neurones/métabolisme , Neurones/anatomopathologie , /analyse , Spécificité d'espèce , Zinc/analyse , Zinc/déficit , /analyseRÉSUMÉ
Suberonylanilide hydroxamic acid (SAHA)is an orally administered histone deacetylase inhibitor (HDACI) that has shown significant antitumour activity in a variety of tumour cells.To identify proteins involved in its antitumour activity,we utilized a proteomic approach to reveal protein expression changes in the human cervical cancer cell line HeLa following SAHA treatment.Protein expression profiles were analysed by 2-dimensional polyacrylamide gel electrophoresis (2-DE) and protein identification was performed on a MALDI-Q-TOF MS/MS instrument.As a result,a total of nine differentially expressed proteins were visualized by 2-DE and Coomassie brilliant blue (CBB) staining.Further,all the changed proteins were positively identified via mass spectrometry (MS)/MS analysis. Of these,PGAM1 was significantly downregulated in HeLa cells after treatment with SAHA. Moreover,PGAM1 has been proven to be downregulated in another cervical cancer cell line (CaSki) by western blot analysis.Together,using proteomic tools,we identified several differentially expressed proteins that underwent SAHA-induced apoptosis. These changed proteins may provide some clues to a better understanding of the molecular mechanisms underlying SAHA-induced apoptosis in cervical cancer.
Sujet(s)
Séquence d'acides aminés , Antinéoplasiques/pharmacologie , Femelle , Analyse de profil d'expression de gènes , Régulation de l'expression des gènes tumoraux/effets des médicaments et des substances chimiques , Cellules HeLa , Humains , Acides hydroxamiques/pharmacologie , Données de séquences moléculaires , Protéines tumorales/composition chimique , Protéome , Tumeurs du col de l'utérus/traitement médicamenteuxRÉSUMÉ
The change of the expression of Cyclins in neurons of rats after focal cerebral ischemia was investigated. Ischemia was induced by temporary middle cerebral artery occlusion (MCAO). The experimental rats induced by MCAO were sacrificed on 7th and 14th day after reperfusion. The brain was taken out at 7th and 14th day after injury, and the expression of Cyclin D1>, E, A and B1> in neu- rons of cerebral cortex or hippocampal Cal region was detected by immunofluorescence and confo- cai microscope. The results showed that after MCAO, in the ipsilateral CAI subfield of hippocampus the expression of Cyclin D1, E, A and B1 in neurons was significantly gradually up-regulated at 7th and 14th day after reperfusion (P<0.05) as compared with that in control group. In the ipsilateral cerebral cortex the expression of Cyclin D1 and B1 in neurons was notably gradually down-regulated at 7th and 14th day, and that of Cyclin E and A was significantly up-regulated at 14th day after reper- fusion as compared with that in control group (all P<0.05). It was concluded that there was a differ- ential sensitivity among neurons from different brain regions to ischemic injury. But all of them re-enter into cell cycle after MCAO.
RÉSUMÉ
Hybridization tests of laboratory-raised, isolines of Anopheles minimus, species A and C were conducted by induced copulation. The three isolines were established based on three morphological variants of wild-caught, fully engorged females and two distinct types of metaphase chromosomes. They were An. minimus species A: V form (X1,Y1), M form (X2,Y1); species C: P form (X3,Y2). The results of reciprocal and back crosses indicated that the two morphologically variant forms of species A were genetically compatible, providing viable progeny and completely synaptic salivary gland polytene chromosomes, whereas they were genetically incompatible with species C and/or the P form. Hybrid progeny was only obtained from both forms of species A females x species C males, but asynaptic salivary gland polytene chromosomes on 3L and partial development of ovarian follicles in females were seen. Back crosses of F1 hybrid males with parental species A females provided viable progeny, while back crosses of F1 hybrid females with parental species C males provided progeny of low viability and adult males with abnormal spermatozoa, suggesting the partial reproductive isolation of An. minimus species A and C.