GDC-0152-induced autophagy promotes apoptosis in HL-60 cells.

GDC-0152 is a new type of chemical compound which can downregulate inhibitor of apoptosis protein. We previously reported that GDC-0152 induced apoptosis in HL-60 cells in a caspase-dependent manner. In this study, we have focused on GDC-0152-induced autophagy and the relationship between apoptosis and autophagy. We found that GDC-0152 can evoke autophagy flux as confirmed by the upregulation of LC3 and downregulation of p62. The conversion of LC3I to LC3II verified the existence of autophagy flux further. GDC-0152 induced autophagy through downregulating B cell lymphoma 2 and Bcl-2-interacting myosin-like coiled-coil protein, and upregulating WD-repeat domain phosphoinositide-interacting protein 1. Pretreating HL-60 cells with autophagy inhibitor Bafolimycin A1 reduced GDC-0152-induced apoptosis. However, pretreatment with caspase inhibitor Z-VAD-FMK had no effect on autophagy. Reactive oxygen species were released in GDC-0152-treated HL-60 cells but did not take part in the regulation of autophagy and apoptosis. In conclusion, our findings suggest that GDC-0152-induced autophagy can trigger apoptosis in HL-60 cells.

Prevalence of and risk factors for depressive symptoms among people living with HIV/AIDS receiving antiretroviral treatment in Wuhan, China: a short report.

We aimed to explore the prevalence of and risk factors for depressive symptoms (DS) among people living with HIV/AIDS (PLWHA) receiving antiretroviral treatment (ART) in Wuhan, Hubei, China. A cross-sectional study evaluating adult PLWHA receiving ART in nine designated clinical hospitals was conducted from October to December 2015. The validated Beck Depression Inventory (BDI) was used to assess DS in eligible participants. Socio-demographical, epidemiological and clinical data were directly extracted from the case reporting database of the China HIV/AIDS Information Network. Multinomial regression analysis was used to explore the risk factors for DS. 394 participants were finally included in all analyses. 40.3% were found to have DS with 13.7% having mild DS and 26.6% having moderate to severe DS. The results of multinomial regression analysis suggested that being married or living with a partner, recent experience of ART-related side effects, and/or history of HCV infection were positively associated with mild DS, while increasing age was positively associated with moderate to severe DS.

[Changes in expression of autophagy-related proteins, Beclin-1 and LC3, and effects of rapamycin on their expression in hypoxic-ischemic hippocampus].

OBJECTIVE: To observe changes in the expression of autophagy-related proteins, Beclin-1 and LC3, in the hippocampal tissue of neonatal rats with hypoxic-ischemic brain damage (HIBD) at different time points, and to investigate the effect of rapamycin (Ra) on the expression of the above two proteins. METHODS: A total of 108 7-day-old Sprague-Dawley rats were randomly divided into sham, HIBD, and Ra groups (n=36 each). The HIBD model was established using the modified Rice method. For sham rats, only the left common carotid artery was separated without ligation or hypoxic treatment. For Ra-treated rats, 0.5 mg/kg Ra was administered by an intraperitoneal injection 1 hour before model establishment. The rats were anesthetized and sacrificed to collect brain tissues at 0, 6, 12, 24, 48, and 72 hours after model establishment. Changes in the expression of Beclin-1 and LC3 proteins in rat hippocampus were examined by Western blot. RESULTS: The expression level of Beclin-1 in HIBD rats began to increase at 0 hour, peaked at 24 hours, and then declined thereafter, similar as those of Beclin-1 and LC3-II in Ra-treated rats. The expression level of LC3-II in HIBD rats began to increase at 0 hour, peaked at 12 hours, and then declined thereafter. At all time points, both Beclin-1 and LC3-II expression levels were significantly higher in HIBD and Ra-treated rats than in sham rats (P<0.05); except LC3-II at 12 hours, Beclin-1 and LC3-II expression levels were significantly higher in Ra-treated rats than in HIBD rats (P<0.05). CONCLUSIONS: Hypoxia-ischemia activates autophagy in rat hippocampal cells, while Ra enhances the expression process of autophagy.

Decreased expression of LASS2 is associated with worse prognosis in meningiomas.

Homo sapiens longevity assurance homolog 2 of yeast LAG1 (LASS2) has been indicated to have a critical role in various tumors. In the study, we aimed to evaluate the LASS2 expression level in prognostic significance and compare it with commonly used biomarkers: Ki-67, p53 and progesterone receptor (PR) for patients with meningiomas. Firstly, 50 fresh tissues and 143 paraffin-embedded meningiomas samples were analyzed for LASS2 expression by quantitative PCR and immunohistochemistry (IHC), respectively. Subsequently, LASS2 immunostaining was evaluated for its clinical significance. Furthermore, Correlations of LASS2 expression with common biomarkers were assessed. Both PCR and IHC results showed LASS2 was downregulated in high-grade meningiomas in comparison with that of grade I or normal brain (all P < 0.01). IHC results demonstrated LASS2 intensity distribution (ID) score was significantly correlated with tumor size, brain invasion, tumor recurrence and clinical course (all P < 0.01), whereas no correlation of LASS2 ID score with sex or Simpson grade. Moreover, lower LASS2 ID score was strikingly associated with shorter overall and progression-free survival (P < 0.01). Pearson's analysis revealed the ID score was significantly reversely associated with Ki-67 and p53 but not with PR. More importantly,multivariate analyses revealed that LASS2 was an independent prognostic factor (P < 0.05). To our knowledge, it is the first time to investigate the expression of LASS2 and identify it as a potential biomarker for prognosis in meningiomas.

Expression of RACGAP1 in high grade meningiomas: a potential role in cancer progression.

Recently, Rac GTPase-activating protein 1 (RACGAP1) has been shown to have a critical role in various tumors. The aim of the present study was to investigate the expression of RACGAP1 in human meningiomas and to compare these results with the clinicopathological parameters. Thirty-two cases, classified as 13 World Health Organization grade I (40.6 %), 10 grade II (31.3 %) and 9 grade III (28.1 %) primary meningiomas, were selected from our pathological files. Clinico-pathological data, including survival data, were also available. RACGAP1 expression in the meningiomas was measured by real-time quantitative PCR and western blot. Our results showed the level of RACGAP1 expression in grade III meningioma is higher than that of grade I. Higher levels of RACGAP1 mRNA were significantly correlated with tumor size, higher Simpson grade, histological type and clinical course (P < 0.05). Furthermore, the level of RACGAP1 expression mRNA was positively correlated with MIB-1 labeling index in different meningiomas tissue (r(2) = 0.3237, P = 0.0007). Additionally, Kaplan-Meier curves demonstrated a significantly worse survival in patients with high levels of RACGAP1 mRNA (P = 0.008). In conclusion, these findings suggest that RACGAP1 may be used as a potential predictor for tumor proliferative and patient prognosis in meningiomas.

Association between laminin γ1 expression and meningioma grade, recurrence, and progression-free survival.

BACKGROUND: Laminins are central components of basement membranes and play important roles in cell adhesion, proliferation, and migration. However, the role of laminins in tumor progression has not been thoroughly investigated in meningiomas. OBJECTIVE: The aim of the present study is to evaluate the expression of laminin γ1 in various grades of meningiomas in Chinese patients. METHODS: In the current study, clinical and pathological data for 32 meningioma patients with various tumor grades were collected. The expression of laminin γ1 in each tumor was assessed by using quantitative real-time polymerase chain reaction (qPCR), Western blot and immunohistochemical analysis and was correlated with the meningioma grade, tumor recurrence and patient survival. Patient prognoses were attained and the progression-free survival was calculated based on the Kaplan-Meier method. A two-sided probability cutoff of 0.05 was chosen for statistical significance. RESULTS: A total of 32 meningioma patients with various pathological subtypes (WHO grade I: 13, grade II: 10 and grade III: 9) were enrolled in this study. The qPCR results showed that laminin γ1 mRNA expression was significantly higher in grade III meningiomas than in grade I meningiomas (p < 0.05), although there was no significant difference in laminin γ1 expression between grade II and grade I meningiomas (p > 0.05). Western blot and immunohistochemistry analysis confirmed that the expression of laminin γ1 protein was relatively higher in grade III meningiomas when compared with grade I meningiomas. Higher levels of laminin γ1 expression in meningiomas are associated with a significantly shorter tumor recurrence time (p < 0.05) and a decreased patient survival time (p < 0.05). CONCLUSIONS: Our results suggest that laminin γ1 is associated with meningioma grades and could play a role in enhancing tumor invasion. Laminin γ1 could be used as a predictor for meningioma recurrence and patient survival. Furthermore, laminin γ1 may represent a druggable molecular target for future therapies for tumors that overexpress this marker.

Study on esophageal cancer radiotherapy dosimetry and position verification for volumetric modulated arc therapy.

BACKGROUND: This study analyzed the respective advantages and disadvantages by comparing volumetric modulated arc therapy (VMAT) and intensity modulated radiotherapy (IMRT) on the dose distribution and position verification distribution characteristics in esophageal cancer radiotherapy, in order to provide the reference for the clinical radiotherapy technology optimization of esophageal cancer. METHODS: A total of 56 cases of patients with esophageal cancer were selected and applied to the Pinnacle three-dimensional radiation treatment planning system (TPS), in order to design a VMAT plan and IMRT plan under the guidance of image-guided radiotherapy (IGRT). The dosimetry and position verification difference were compared between the two groups. RESULTS: Revealed that the target dose distribution of the VMAT plan and IMRT plan meets the requirements in clinical dosimetry for all 56 patients in this study. Under the premise of similar target coverage, the conformal index (CI) of the VMAT plan, homogeneity index (HI), target volume, BODY-PTV radiated volume and spinal cord Dmax, bilateral lung V5, V20 and mean lung dose (MLD), monitor unit (MU) and treatment time (TT), as well as position verification and others, were obviously superior to those in the IMRT plan; and the difference was statistically significant. CONCLUSION: CBCT guided VMAT is a potential effective treatment for esophageal cancer and may be more effective and safer than IMRT.

Identification and verification of key taste components in wampee using widely targeted metabolomics.

Due to the lack of comprehensive evaluation of all metabolites in wampee, the metabolic reasons for taste differences are unclear. Here, two local varieties YF1 (sweet taste) and YF2 (sweet-sour taste), were selected for quality analysis, followed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) based widely targeted metabolomic analysis. YF1 and YF2 were clearly separated by principal component analysis (PCA) and cluster analysis, and 449 metabolites were different between the cultivars, including 29 carbohydrates and 29 organic acids. Among them, d-galactose, d-mannose, and d-fructose 6-phosphate contributed mainly to the sweet taste of the YF1 wampee. l-citramalic acid, 2-hydroxyglutaric acid, and 3-methylmalic acid were the dominant organic acids in YF2 wampee, and therefore, contributed primarily to the sweet-sour taste. The differential metabolites were significantly enriched in the "ascorbate and aldarate metabolism" and "C5-branched dibasic acid metabolism" pathways. Ascorbate played a crucial role in the regulation of sugars and organic acids through those pathways. In addition, high-performance liquid chromatography (HPLC) based quantitative verification exhibited the same specific cultivar variations.

[LASS2 interacts with V-ATPase and inhibits cell growth of hepatocellular carcinoma].

Homo sapiens longevity assurance homologue 2 (LASS2) is a novel gene isolated from a human liver cDNA library by our laboratory, and it is a human homologue of the yeast longevity assurance gene LAG1 (Saccharomyces cerevisiae longevity assurance gene). According to our previous results, LASS2 could interact with subunit c of vacuolar type H(+)-ATPase (V-ATPase), and the overexpression of LASS2 could inhibit the cell growth of a human hepatocellular carcinoma (HCC) cell line, SMMC-7721. In order to understand the role of the interaction between LASS2 and V-ATPase in HCC cell growth, we transiently transfected plasmid pCMV-HA2-LASS2 into HCCLM3, a HCC cell line without the significant expression of endogenous LASS2. The pH-sensitive fluorescence probes, BCECF and BCECF-AM, were used to measure the intracellular and extracellular H(+) concentrations of HCCLM3 cells respectively. The effect of LASS2 gene on apoptosis was evaluated with Annexin-V/FITC and propidium iodide (PI) by flow cytometry. Western blot was used to detect cytochrome c (Cyt c) in the cytosol and mitochondria, as well as pro-caspase-3 in cytosol. The results showed that the cell growth of LASS2-transfected HCCLM3 cells was significantly inhibited compared with that of the mock control. LASS2 transfection increased intracellular H(+) concentration of HCCLM3 cells, while decreased extracellular H(+) concentration. Moreover, LASS2 transfection significantly enhanced the apoptosis of HCCLM3 cells. In LASS2-transfected cells, the amounts of Cyt c increased in the cytosol, while decreased in the mitochondria. Meanwhile, the expression of pro-caspase-3 in the cytosolic extracts was decreased. These results implicate that LASS2 gene might increase intracellular H(+) of HCC cells via the interaction with V-ATPase, thereby inducing cell apoptosis through mitochondrial pathway.

MiR-451a attenuates doxorubicin resistance in lung cancer via suppressing epithelialmesenchymal transition (EMT) through targeting c-Myc.

Chemoresistance is still a major obstacle for lung cancer treatment. Increasing studies have demonstrated that microRNAs (miRNAs) are essential meditators of chemoresistance during cancer progression. MiR-451a is reported to be a tumor suppressor during cancer development. However, its effects on lung cancer and drug resistance in lung cancer are still unclear. In the study, the results showed that miR-451a exhibited a significant role in suppressing the drug resistance in lung cancer cells when treated with doxorubicin (DOX) through alleviating epithelialmesenchymal transition (EMT), as evidenced by the markedly reduced expression of N-cadherin and Vimentin, while the enhanced expression of E-cadherin. In addition, miR-451a over-expression markedly promoted the sensitivity of lung cancer cells to DOX treatments, and also disrupted the EMT of lung cancer cells. Mechanistically, miR-451a was found to directly target c-Myc to affect the EMT and drug resistance in lung cancer cells in response to DOX incubation. Furthermore, c-Myc knockdown markedly elevated the sensitivity of lung cancer cells to DOX, whereas over-expressing c-Myc markedly reversed the anti-tumor role of DOX, which was slightly diminished by miR-451a mimic. The in vivo experiments confirmed that miR-451a promoted the sensitivity of lung cancer cells-derived tumors to DOX treatment by reducing c-Myc. Therefore, our results revealed a new insight into DOX resistance of lung cancer cells and miR-451a could be considered as a potential therapeutic target to overcome drug resistance in lung cancer.

Percutaneous treatment with drug-eluting stent vs bypass surgery in patients suffering from chronic stable angina with multivessel disease involving significant proximal stenosis in left anterior descending artery.

BACKGROUND: The aim of the present study was to compare the effects of drug-eluting stents (DES) and coronary artery bypass grafting (CABG) in patients suffering from chronic stable angina with multivessel disease, involving significant proximal stenosis in the left anterior descending artery (LAD). METHODS AND RESULTS: All consecutive patients suffering from chronic stable angina with multivessel disease involving significant proximal LAD stenosis underwent DES implantation (n=600) or CABG (n=709) at our institution. At 2 years, the unadjusted mortality was significantly lower in the DES group than in the CABG group (2.2% vs 5.2%, P=0.004), but the adjusted risk of death was similar (odds ratio (OR) 0.74, 95%CI 0.28-1.97, P=0.555). Furthermore, both the adjusted rate of nonfatal myocardial infarction and cerebrovascular events was also comparable. However, the unadjusted and adjusted risk of major adverse cardiac cerebrovascular events in the DES was significantly higher than in the CABG (13.3% vs 9.6%, OR 2.71, 95%CI 1.56-4.74, P<0.001), which is probably attributed to the higher subsequent revascularization rate after DES implantation. CONCLUSIONS: DES showed comparable long-term mortality for the treatment of multivessel disease involving significant proximal stenosis in LAD in comparison with CABG.

Autophagy-regulated AMPAR subunit upregulation in in vitro oxygen glucose deprivation/reoxygenation-induced hippocampal injury.

Autophagy has been implicated to mediate experimental cerebral ischemia/reperfusion-induced neuronal death; the underlying molecular mechanisms, though, are poorly understood. In this study, we investigated the role of autophagy in regulating the expression of AMPAR subunits (GluR1, GluR2, and GluR3) in oxygen glucose deprivation/reperfusion (OGD/R)-mediated injury of hippocampal neurons. Our results showed that, OGD/R-induced hippocampal neuron injury was accompanied by accumulation of autophagosomes and autolysosomes in cytoplasm alongside a dramatic increase in expression of autophagy-related genes, LC3 and Beclin 1 and increased intracellular Ca2+ levels. Pre-treatment with autophagy inhibitor 3-methyladenine (3-MA) significantly reduced this effect. Moreover, the OGD/R-induced upregulation of mRNA and protein expressions of GluR1, GluR2, and GluR3 were also effectively reversed in cells pretreated with 3-MA. Our findings indicate that OGD/R induced the expression of GluRs by activating autophagy in in vitro cultured hippocampal neurons, which could be effectively reversed by the administration of 3-MA.

Age-sex distribution of patients with high-sensitivity troponin T levels below the 99th percentile.

BACKGROUND: Recently, very low concentrations of high-sensitivity cardiac troponin T (hs-cTnT), below the 99th percentile, have been used to immediately exclude acute myocardial infarction in certain patients without taking their age and sex into consideration. RESULTS: The hs-cTnT values below the 99th percentile (≤ 14 ng/L) were higher in men (p = 0.000) and significantly increased with age (p = 0.000) among both men and women. In addition, hs-cTnT was positively associated with age (r = 0.459, p = 0.000), myoglobin (r = 0.392, p = 0.000), and creatine kinase-MB (r = 0.133, p = 0.000). Moreover, males were younger (p = 0.001) and had higher myoglobin (p = 0.000) and creatine kinase-MB (p = 0.000) concentrations than females. MATERIALS AND METHODS: A total of 5585 consecutive subjects who presented with non-traumatic chest pain/discomfort to the inpatient, outpatient, or emergency department and who underwent high-sensitivity troponin T, myoglobin and creatine kinase-MB testing at presentation, with hs-cTnT below the 99thpercentile (≤ 14 ng/L), were eligible for enrollment. CONCLUSIONS: We suggest that patients' age, sex and levels of myocardial injury biomarkers should be taken into consideration when ruling out acute myocardial infarction and/or adverse prognostic implications in patients who have very low hs-cTnT concentrations.

Relationship between true fasting plasma insulin level and angiographic characteristics of coronary atherosclerosis.

BACKGROUND: Reports about the relationships between specific insulin concentration and coronary heart disease risk are controversial. HYPOTHESIS: The objective of this study was to examine the association between insulin level and the severity of coronary atherosclerosis. METHODS: The study population consisted of 507 consecutive patients (376 men and 131 women) who underwent coronary angiography for suspected or known coronary atherosclerosis. The patients' habits of smoking and drinking were investigated, and anthropometric measurements including body mass index, systolic and diastolic blood pressures, as well as plasma measurements including lipids and blood glucose were taken. The true insulin level was measured using a highly sensitive two-site sandwich ELISA. The severity of coronary atherosclerosis was defined by the Gensini score system. The statistical methods including Kruskal-Wallis test, chi-square analysis, Spearman correlation analysis, and multivariate stepwise linear regression analysis were employed to explore the relationship between specific insulin level and coronary atherosclerosis. RESULTS: When the Gensini score was examined as a categorical variable classified by tertile values, subjects with a high Gensini score had significantly higher values of fasting plasma specific insulin level (p = 0.022). The Spearman correlation analysis suggest that the Gensini score correlated significantly with true insulin (mIU/l) (r = 0.095, p = 0.033). However, the results from the multivariate stepwise linear regression analysis show that the association between specific insulin level and severity of coronary atherosclerosis lost its significance. CONCLUSIONS: The level of plasma fasting specific insulin was associated significantly with the severity of coronary atherosclerosis, as measured by Gensini score, but hyperinsulinemia showed no association with the severity of coronary atherosclerosis in multivariate analyses.

Determination of trace aluminum by fluorescence quenching method based on catalysis of potassium chlorate oxidizing alizarin red.

A new method for the determination of trace aluminum has been proposed. It is based on the fact that alizarin red can emit strong and stable fluorescence at 80 degrees C for 30 min and Al(3+) can effectively catalyze potassium chlorate oxidizing alizarin red to form non-fluorescence complex which cause the fluorescence quenching. The linear dynamic range of this method is 0.040-4.00 ngl(-1) with a detection limit of 5.3 pgl(-1). The regression equation can be expressed as DeltaI(f)=8.731+21.73c(Al(3+)) (ngl(-1)), with the correlation coefficient r=0.9992 (n=6). This sensitive, rapid and accurate method has been applied to the determination of trace aluminum(III) in human hair and tea samples successfully. What is more, the mechanism of catalyzing potassium chlorate oxidizing alizarin red by the fluorescence quenching method is also discussed.

Alpha-synuclein is a potential biomarker in the serum and CSF of patients with intractable epilepsy.

PURPOSE: Intractable epilepsy is a brain disorder characterized by recurrent seizures and intracellular alpha-synuclein (αS) deposits; however, the neurobiological basis of this protein accumulation is still poorly understood. This is the first study aiming to assess whether the increase of αS concentrations in the serum and CSF (cerebrospinal fluid) could serve as a marker for αS deposition in the brain and diagnosis of epilepsy. METHODS: This investigation enrolled 67 epileptic patients (40 with intractable epilepsy; 13 with newly diagnosed epilepsy, and 14 with non-intractable epilepsy). CSF and serum samples were collected from each patient and were assessed by ELISA. RESULTS: It was established that the concentration of αS in the CSF and serum was elevated in the epilepsy patients, as compared to the control. However, the results of the subgroup analysis revealed that levels of αS in the serum and CSF were increased in the intractable epileptic patients (CSF: 11.12 ± 4.18 ng/ml; serum: 52.93 ± 22.11 ng/ml), whereas there was no difference in the groups with the newly diagnosed (CSF: 34.998 ± 14.96 ng/ml; serum: 7.77 ± 3.41 ng/ml) and non-intractable epilepsy (CSF: 8.93 ± 4.83 ng/ml; serum: 34.11 ± 17.53 ng/ml). CONCLUSION: Overall, we found that the rise of the αS content in the serum and CSF may facilitate the identification of intractable epilepsy; therefore, the determination of αS rates may serve as a valuable prognostic marker in the clinical assessment.

[Study on plant pigments by photoacoustic spectroscopy].

Six plant pigments separated by paper chromatography have been measured by photoacoustic spectroscopy (PAS). Their PA spectra are compared with the corresponding absorption spectra, which indicate that PAS is a convenient and effective method for identifying plant pigment. The sorts of marine algae are numerous and pigments in marine algae have certain characteristics. The PA spectra of green, red and brown algae have been reported. Pigment characteristics in these algae are identified by their second derivative PA spectra.

Clinical study on the posterior occlusal plane and morphology of temporomandibular joint / Estudio clínico sobre el plano oclusal posterior y la morfología de la articulación temporomandibular

The objective of the study was to investigate the morphological features of the temporomandibular joint in adult patients with posterior occlusal plane and different inclinations. Fifty five skeletal I occlusion patients with average were included, shooting CBCT in the intercuspal position, divided into 3 groups according to OPP-FH angle, and measurement of the temporomandibular joint morphology was calculated with cone beam computed tomography (CBCT) special software Invivo 5.0, Statistical analysis of three groups of data using SPSS23.0. The condyle usually locates in the middle of the fossa, the maximum axial area of the condyle (A) was statistically significant between the group 1 and the group 3. The internal and external diameter (MD) of the condyle was statistically significant between group 1 and group 3, and group 2 and group 3. The bilateral TMJ morphological features of the three groups were basically symmetrical. The position of the condyle in the fossa is mostly centered, and some of the posterior, the maximum axial area and the internal and external diameter of the condyle are different in three groups.

El objetivo de este estudio fue investigar las características morfológicas de la articulación temporomandibular (ATM) en pacientes adultos con plano oclusal posterior y diferentes inclinaciones. Se incluyeron 55 pacientes con oclusión esquelética tipo I, visualizados por tomografía computarizada de haz cónico (CBCT) en posición intercuspiana, y se dividieron en 3 grupos según el ángulo OPP-FH. La medición morfológica de la articulación temporomandibular se calculó con CBCT y mediante el software especial Invivo 5.0. El análisis estadístico de datos se realizó con el software SPSS 23.0. El cóndilo de la mandíbula generalmente se ubica en el centro de la fosa; el área axial máxima del cóndilo de la mandíbula (A) fue estadísticamente significativa entre los grupos 1 y 3. Los datos de los diámetros medial y lateral (DM) del cóndilo de la mandíbula fueron estadísticamente significativos entre los grupos 1 y 3 y los grupos 2 y 3. Las características morfológicas de la ATM de los tres grupos fueron básicamente simétricas. La posición del cóndilo de la mandíbula en la fosa fue principalmente centrada, y parte del área axial máxima, posterior y los diámetros medial y lateral del cóndilo de la mandíbula fueron diferentes en los tres grupos.

Histone acetyltransferase inhibitor II induces apoptosis in glioma cell lines via the p53 signaling pathway.

BACKGROUND: Histone acetyltransferase (HAT) inhibitors can inhibit proliferation and induce apoptosis in cancer cell lines. The novel cell-permeable p300/CREB-binding protein (CBP)-selective HAT inhibitor HATi II can reduce histone H3 acetylation and induce chromatin condensation in HeLa cells. Here, we examined the effects and mechanism of action of HATi II in glioma cell lines. METHODS: Cell viability was assessed using the CCK-8 assay. Cell cycle analysis was performed using flow cytometry. Apoptosis was evaluated using Annexin V staining and flow cytometry, Hoechst 33342 staining and the TUNEL assay. Expression and cleavage of caspase-3, caspase-9 and poly ADP-ribose polymerase (PARP) were assessed by Western blotting. Statistical analysis was performed using two-tailed Student's t-tests. The gene expression profiles of U251 glioma cells treated with HATi II or DMSO were analyzed using the Arraystar Human 8 x 60 K LncRNA/mRNA expression array; data was analyzed using MEV (Multi Experiment View) cluster software. Datasets representing genes with altered expression profiles (≥2-fold) derived from the cluster analyses were subjected to gene ontology and pathway analysis. RESULTS: HATi II inhibited the proliferation of U251, U87, HS683 and SHG44 cells in a dose-dependent manner. HATi II induced cell cycle arrest at the G2/M phase, and induced significant levels of apoptosis, apoptotic body formation and DNA fragmentation in HATi II-treated U251 and SHG44 cells. HATi II induced cleavage of caspase-3, caspase-9 and PARP in U251 and SHG44 cells. In HATi II-treated U251 cells, 965 genes were upregulated, 984 genes were downregulated and 3492/33327 lncRNAs were differentially expressed. GO analysis showed the differentially expressed genes with known functions are involved in a variety of processes; alcoholism, p53 signaling pathway, cytokine-cytokine receptor interaction and transcriptional mis-regulation in cancer were the four most significant pathways. Upregulation of p53 signaling pathway-related genes in HATi II-treated cells was confirmed by quantitative RT-PCR and Western blotting. CONCLUSIONS: HATi II inhibits proliferation and induces apoptosis via the caspase-dependent pathway in human glioma cell lines, possibly by activating the p53 signaling pathway. HATi II deserves further investigation as a novel treatment for glioma.

Morphological changes of skeletal class III malocclusion in mixed dentition with protraction combined activities / Cambios morfológicos en maloclusión de la clase esquelética III en dentición mixta con actividades combinadas de protracción

The objective of the study was to investigate the morphological changes of skeletal class III malocclusion in mixed dentition with light force protraction combined activities. Randomly selected 30 cases of orthodontics in Shanxi Medical University orthodontics patients (ages: 6-10 years) of the lateral cephalograms. Using the oral maxillary casting type of pre-traction device, according to the condition of maxillary dentition to select the corresponding activities of the movable expansion appliance, each side of the force of about 150-200 g, requiring patients to wear 10-12 hours a day, the appliance should be removed after reaching normal occlusion. The correlation cephalometric profile of the cranial lateral radiographs before and after orthodontic treatment was measured. All patients with skeletal class III malocclusion were improved, concave type became direct type, measurements SNA, ANB, A-Ptm, MP-SN, ANS-Me/N-Me increased, maxillary advancement and reconstruction are more obvious; mandible rotates clockwise; the increase of lip inclination of anterior teeth compensatory changes, lower anterior tooth inclination changes smaller; upper lip forward, nasolabial angle decreased, improved appearance significantly. Light force protraction combined activities can make the mixed dentition of skeletal class III malocclusion in patients with significant improvement in profile appearance.

El objetivo de este estudio fue investigar los cambios morfológicos de la maloclusión clase esquelética III, en la dentición mixta, con actividades combinadas de protracción de la fuerza ligera. Se seleccionaron aleatoriamente 30 casos de ortodoncia en pacientes de ortodoncia de la Universidad Médica de Shanxi (edades: 6-10 años) a partir de cefalogramas laterales, utilizando el tipo de dispositivo de pretracción de vaciado maxilar oral, de acuerdo con la condición de la dentición maxilar para seleccionar las actividades correspondientes del dispositivo de expansión móvil, cada lado con fuerza de alrededor de 150-200 g, requiriendo que los pacientes los utilizaran de 10 a 12 horas al día. El dispositivo debía ser retirado después de alcanzar la oclusión normal. Se midió el perfil cefalométrico de correlación de las radiografías laterales craneales, antes y después del tratamiento ortodóncico. Se observó mejoramiento en todos los pacientes con maloclusión de clase esquelética. Las mediciones SNA, ANB, APtm, MP-SN, ANS-Me / N-Me aumentaron, el avance y la reconstrucción maxilar fueron los cambios más significativos; la mandíbula giró en el sentido de las agujas del reloj, se observó un aumento de la inclinación labial de los dientes anteriores. Fue reducida la inclinación anterior del diente inferior, el ángulo nasolabial disminuyó y en general mejoró significativamente la apariencia. Las actividades combinadas de protrusión de la fuerza radiante pueden llevar a una mejora signficativa en el perfil de pacientes con dentición mixta de maloclusión clase III.