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1.
Curr Med Chem ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31580244

RESUMO

Based on three domains of colchicine-site which is conducive to the combination with small molecular compounds, colchicine-site on the tubulin has become a popular target for antitumor, that resulted in a great number of tubulin inhibitors binding to colchicine-site were reported and evaluated over the past years. Here, tubulin inhibitors targeting colchicine-site and their application to antitumor were reviewed from 2015 to 2019. Tubulin inhibitors were classified to ten categories according to structural features, as colchicine derivates, CA-4 analogues, chalcone analogues, coumarin analogs, indole hybrids, quinoline and quinazoline analogs, lignan and podophyllotoxin derivatives, phenothiazine analogs, N-heterocycle hybrids and others. Most of them possessing strong antitumor activity including antiproliferative potential against multi-drug-resistant (MDR) cell lines and anti-vascular properties both in vitro and in vivo. Therefore, in-depth analysis, lots of compounds were listed in tables as multi-target inhibitors, anti-MDR compounds, and inhibitors bearing antitumor activity in vivo. The latest research progress of tubulin inhibitors was demonstrated in this review, providing valuable reference and convenience for the research on tubulin inhibitors in future.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31574957

RESUMO

Adolescents engage in health risk behaviors (HRBs) that influence their current and future health status. Health literacy (HL) is defined as how well a person can get and understand the health information and services, and use them to make good health decisions. HL can be used to participate in everyday activities actively and apply new information to the changing circumstances. HRBs commonly co-occur in adolescence, and few researchers have examined how HL predicts multiple HRBs in adolescence. In this study we examined the subgroups of HRBs, and investigated heterogeneity in the effects of HL on the subgroups. In total, 22,628 middle school students (10,990 males and 11,638 females) in six cities were enrolled by multistage stratified cluster sampling from November 2015 to January 2016. The measurement of HL was based on the Chinese Adolescent Interactive Health Literacy Questionnaire (CAIHLQ). Analyses were conducted with regression mixture modeling approach (RMM) by Mplus. By this study we found four latent classes among Chinese adolescents: Low-risk class, moderate-risk class 1 (smoking/alcohol use (AU)/screen time (ST)), moderate-risk class 2 (non-suicidal self-injury (NSSI)/suicidal behaviors (SB)/unintentional injury (UI)), and high-risk class (smoking/AU/ST/NSSI/SB/UI) which were 64.0%, 4.5%, 28.8% and 2.7% of involved students, respectively. Negative correlations were found between HL and HRBs: higher HL accompanied decreased HBRs. Compared to the low-risk class, moderate-risk class 1 (smoking/AU/ST), moderate-risk class 2 (NSSI/SB/UI), and high-risk class (smoking/AU/ST/NSSI/SB/UI) showed OR (95%CI) values of 0.990 (0.982-0.998), 0.981 (0.979-0.983) and 0.965 (0.959-0.970), respectively. Moreover, there was heterogeneity in the profiles of HRBs and HL in different classes. It is important for practitioners to examine HRBs in multiple domains concurrently rather than individually in isolation. Interventions and research should not only target adolescents engaging in high levels of risky behavior but also adolescents who are engaging in lower levels of risky behavior.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31588722

RESUMO

In many fields, nanoparticles are frequently dispersed onto kinds of nanocarriers integrated into hybrid nanocomposites to acquire advanced performance. However, the nanoparticles usually tend to agglomerate on the surface according to traditional synthetic methods. Besides, the exposed state of loaded nanoparticles and the weak adhesion with the supporters make them fall off during practical application leading to "second agglomeration" of the nanoparticles and attenuated synergistic effects. In this work, we engineered layered bimetallic (Ni-Co) hydroxides into an enclosed nanocages (NCH) derived from metal organic frameworks (MOFs). Zinc hydroxystannate (ZHS) nanoparticles were selected to be confined dispersed within the hollow cavity of the three dimensional nanocages. ZHS nanoparticles were tightly immobilized, monodispersing to form a novel multi-yolk@shell nanostructure with NCH nanocages. To prove the effectiveness of this structural design, the as-synthesized hybrids ZHS@NCH was introduced into epoxy matrix to inquiry its performance. Compared to neat ZHS, neat NCH and physical mixture of ZHS and NCH, ZHS@NCH conferred better flame retardancy, thermal stability and mechanical properties upon the epoxy nanocomposites. With the adding amount of 6 wt.% ZHS@NCH, the UL-94 rating of the nanocomposite was V-0 and the pHRR value were reduced by 69.1 %, while the mechanical properties were slightly influenced. The ingenious synthetic strategy gives insights into uniform distribution of nanoparticles within nanocapsules and enlightens the facile fabrication of multi-yolk@shell nanomaterials.

4.
Genome ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31600449

RESUMO

Clubroot disease caused by Plasmodiophora brassicae is a challenge to Brassica crop production. Breakdown of resistance controlled by major genes of the Brassica A genome has been reported. Therefore, identification of resistance in the Brassica C genome is needed to broaden the genetic base of resistance in B. napus canola. In this study, we evaluated 135 B. oleracea accessions, belonging to eight variants of this species to identify resistant accessions as well as to identify the genomic regions associated with resistance to two recently evolved P. brassicae pathotypes, F3-14 (3A) and F-359-13 (5X L-G2). Resistance to these pathotypes was observed more frequently in var. acephala (kale) followed by var. capitata (cabbage); few accessions also carried resistance to both pathotypes. Association mapping by using single nucleotide polymorphism (SNP) markers developed through genotyping by sequencing technique identified 10 quantitative trait loci (QTL) from six C genome chromosomes to be associated with resistance to these pathotypes; among these, two QTL associated with resistance to 3A and one QTL associated with resistance to L-G2 carried ≥3 SNP markers. The 10 QTL identified in this study individually accounted 8-18% of the total phenotypic variance. Thus, the results from this study can be used in molecular breeding of Brassica crops for resistance to this disease.

5.
Wei Sheng Yan Jiu ; 48(5): 711-716, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31601309

RESUMO

OBJECTIVE: To examine the association between health literacy( HL) and physical sub-health in middle school students. METHODS: From November 2015 to January 2016, a multi-stage convenient cluster sampling method was adopted to conduct a questionnaire survey among 22 628 middle school students from grade 7 to grade12 in Shenyang, Bengbu, Xinxiang, Ulanqab, Chongqing and Yangjiang, among whom10 990( 48. 6%) were boys and 11 638( 51. 4%) were girls. The Chinese Adolescent Interactive Health Literacy Questionnaire( CAIHLQ), the Multidimensional Sub-health Questionnaire of Adolescents( MSQA) and demographic variables were used to measure the Chinese middle school students ' HL and physical sub-health. RESULTS: The detection rate of physical sub-health was 30. 1%( 6822/22628). High school students reported more physical sub-health than junior school students. The detection rate of physical sub-health in developed area, being only children, resident students, with low socio-economic status was significantly higher detection rate of sub-health than their peers( P< 0. 001). The scores of CAIHLQ was( 104. 06 ± 18. 68). Students who were boys, junior school students, urban residence, only children in family, non-resident students, higher parental education level and lower family income had significantly higher HL scores than the correspnding other students( χ~2= 44. 62, 455. 21, 133. 54, 35. 04, 326. 06, 272. 09, 366. 19 and 572. 35, P < 0. 001). Multiple Logistic regression analysis showed that moderate or low level of overall HL and six dimensions increase the risk of physical sub-health. CONCLUSION: School type, whether it is an economically developed area, whether it is an only child, whether it lives in the school on the study day, and selfassessment of family economic conditions affecting physical sub-health, lower HL may increase the risk of physical subhealth among middle school students.

6.
Wei Sheng Yan Jiu ; 48(5): 765-771, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31601317

RESUMO

OBJECTIVE: To examine the association of health literacy( HL), screen time and depressive symptoms in middle school students. METHODS: In December 2017, a convenient cluster sampling method was used to select all the students from Junior 1 to Senior 3 in a middle school in Shenyang City in the cooperation area as the subjects. And 1062 valid questionnaires were collected, with the use of the group's self-made questionnaire. The average age of the 1062 students was( 15. 38 ± 1. 74) years old, among which 576 boys and 486 girls were surveyed. Questionnaires survey was conducted to collect information on demographics, health literacy, screen time of study day and depressive symptoms. The Chi-square test was performed according to group differences, and multiple Logistic regression model was used to analyze the association of health literacy( including three dimensions of interpersonal relationship, stress management and mental growth) and screen time and their different combinations and depressive symptoms. RESULTS: The detection rate of depressive symptoms among middle school students was 26. 1%( 277/1062). The prevalence of depressive symptoms among students in high school students, low family income and longer screen time was significantly higher than their peers( χ~2 were 15. 090, 10. 510, 4. 832, P < 0. 05). Data from multiple logistic regression analyses showed that low health literacy, longer screen time and low mental growth were positively correlated with depressive symptoms in middle school students( P < 0. 05). In the same level of health literacy, with the increase of screen time, the higher the detection rate of depressive symptoms of middle school students, the highest detection rate of depressive symptoms of middle school students with longer screen time and low health literacy was 51. 7%( 30/58), and the OR value was 5. 741( 95% CI 2. 999-10. 999). CONCLUSION: Health literacy and screen time are related factors of depressive symptoms. The detection rate of depressive symptoms of middle school students with longer screen time and low health literacy is the highest.

7.
Int J Biol Macromol ; 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31593718

RESUMO

While peptide-directed scaffolds now serve as well-established platforms for biomimetic three-dimensional (3D) extracellular matrices (ECM), challenges still remain for chondrogenesis through direct mediation of stem cells. Here, biocompatible poly (γ-glutamic acid) (γ-PGA) hydrogels with robust mechanical properties were developed based on methacrylate-γ-PGA (γ-PGA-GMA) and cysteamine functionalized γ-PGA (γ-PGA-SH) for cartilage regeneration. The γ-PGA hydrogels demonstrated good self-crosslinking property as well as tunability through conjugation between active thiol groups of γ-PGA-SH and methacrylate moieties of γ-PGA-GMA. The mechanical property, porous structure, swelling, and degradation process of the hydrogels could be controlled by adjusting modified γ-PGA polymers component. The rheological behavior and compression test of γ-PGA hydrogels illustrated a wide processing range in addition to superb mechanical properties. These γ-PGA hydrogels showed excellent elasticity as well as toughness, withstanding more than 70% of mechanical strain. Meanwhile, the stress modulus of γ-PGA hydrogels could be up to 749 kPa. We also studied γ-PGA hydrogels as scaffolds for the 3D culture and chondrogenesis differentiation of rabbit bone marrow-derived mesenchymal stem cells (BMSCs) in vitro. In a rabbit auricular cartilage defect model, BMSCs-laden hydrogel effectively promoted chondrogenesis. Based on these findings, biomimetic γ-PGA-based hydrogels hold promising application as favorable scaffold biomaterials for cartilage tissue regeneration.

8.
Bioorg Chem ; 92: 103219, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31476616

RESUMO

Twenty-four 1,2-diarylbenzimidazole derivatives were designed, synthesized and biologically evaluated. It turned out that most of them were potential anticancer drugs. Among them, compound c24 showed the highest anti-tumor activity (GI50 = 0.71-2.41 µM against HeLa, HepG2, A549 and MCF-7 cells), and low toxicity to normal cells (CC50 > 100 µM against L02 cells). In the microtubule binding assay, c24 showed the most potent inhibition of microtubule polymerization (IC50 = 8.47 µM). The binding ability of compound c24 to tubulin crystal was verified by molecular docking simulation experiment. Further studies on HepG2 and HeLa cells showed that compound c24 could cause mitotic arrest of tumor cells to G2/M phase then inducing apoptosis. To sum up, compound c24 is a promising microtubule assembly inhibitor.

9.
Int J Surg ; 71: 132-139, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31561009

RESUMO

BACKGROUND & AIM: Active abdominal compression-decompression cardiopulmonary resuscitation (AACD-CPR), which applies to cardiac arrests with contraindication of standard chest compressions (SCC) CPR, has been utilized in cardiac arrest. However, the efficacy and safety of AACD-CPR still remained controversy. This analysis was designed to comprehensively compare AACD versus SCC-CPR in patients with cardiac arrest. METHODS: We searched the Cochrane Library, PubMed, EMBASE, Web of Science and CNKI up to April 22, 2019. Mean difference (MD) and risk ratio (RR) with its 95% confidence intervals (CIs) were estimated to compare outcomes of the groups. Our primary outcomes were restoration of spontaneous circulation (ROSC) and short-term survival. Two reviewers assessed trial quality and extracted data independently. All statistical analyses were performed using standard statistical procedures provided in Review Manager 5.2 and Stata 12.0. RESULTS: A total of seventeen studies (N = 1647 patients) were identified for the present analysis. Compared with standard CPR, AACD-CPR was superior in restoration of spontaneous circulation (ROSC) and short-term survival, with pooled RRs of 1.38 (95% CI 1.23-1.55; P < 0.00001) and RRs of 2.05 (95% CI 1.69-2.50; P < 0.00001) respectively. In addition, significant superiority of AACD-CPR was found in incidence of fracture, long-term survival, pressure of end-tidal carbon dioxide (PETCO2), coronary perfusion pressure (CPP) and adverse events. No significant difference was observed in incidence of vomiting. CONCLUSIONS: Generally, in this combined analysis we found a statistically significant improvement in survival and ROSC with the use of AACD-CPR as compared with the use of standard CPR. There was also significant improvement in incidence of fracture, long-term survival, PETCO2 and CPP with AACD-CPR in comparison with standard CPR; results were not statistically different between the groups regarding to vomiting rate and adverse events. The standardized, diversified and individualized methods of clinical operation of AACD-CPR need exploration and expectingly serve as a guideline for clinical application of AACD-CPR in the future.

10.
J Pharm Biomed Anal ; 177: 112846, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31522097

RESUMO

The ß-lactam core is a key structure responsible for inducing both IgE-mediated acute-onset hypersensitivity and T-cell-mediated delayed-onset hypersensitivity with penicillins in humans. There is essentially no clinically significant immunologic cross-reactivity noted between the ß-lactam cores of penicillins and cephalosporins based on challenge studies in humans. The side-chains appear to be more important in inducing IgE-mediated acute-onset hypersensitivity and T-cell delayed-onset hypersensitivity with cephalosporins in humans. Despite these clinical findings, the U. S. Food and Drug Administration (FDA) still requires the level of ß-lactam-related antibiotic residues to be controlled at very low levels in manufacturing facilities. Ceftolozane is Merck & Co., Inc., Kenilworth, NJ, USA's (MSD's) 5th generation broad spectrum cephalosporin antibiotic against gram-negative bacteria. In searching for the optimal decontamination method of ceftolozane, most methods were found to be very slow in opening the ß-lactam ring in ceftolozane. Moreover, most of the previously reported decontamination methods applied analytical methods that only monitored the disappearance of the parent molecule as the endpoint of degradation. In this way, many of the ß-lactam-containing degradation products could be overlooked. In order to develop an efficient decontamination solution for ceftolozane, a sensitive ultra high performance liquid chromatography-high resolution-electrospray ionization-tandem mass spectrometry (UHPLC-HRMS/MS) method was first developed to ensure the detection of the ß-lactam ring in all degradation products. Through online UHPLC-UV-HRMS monitoring, 2.5 N KOH in 50% aqueous MeOH or 50% aqueous EtOH was identified as the best condition to fully degrade the ß-lactam ring in ceftolozane. This decontamination could be done within 15 min, even at 100 mg/mL concentration, and thus enable a quick turnaround time for equipment cleaning in the ß-lactam manufacturing facility. This method was also successfully applied to 12 other commercially available ß-lactam antibiotics.

11.
BMC Public Health ; 19(1): 1259, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31510983

RESUMO

BACKGROUND: Lower health literacy (HL) has been known to be involved in a range of common mental and physical disorders among adolescent students. Ample studies indicated low HL is associated with a series of chronic diseases even psychological diseases, nevertheless, little is known about this relationship among adolescents. In this context, the study aimed to examine associations between psychosomatic symptoms (physical and psychological symptoms) and HL in junior and senior high school students in China, and to provide guidance for improving the physical and mental health in Chinese adolescents. METHODS: A total of 22,628 junior and high school students in China were enrolled in this study. HL and psychosomatic symptoms were measured by self-report validated questionnaires. Multiple linear regression analyses were conducted to examine the associations between six sub-scales of HL and physical / psychological symptoms. RESULTS: Multiple linear regression analysis demonstrated that the sub-scales of HL showed a significantly negative association with physical symptoms and psychological symptoms (P <  0.05 for each). Physical symptoms was most strongly associated with IR (ß = - 0.134), followed by SM (ß = - 0.093), DB (ß = - 0.059), SA (ß = - 0.058) and PA (ß = - 0.054). No statistically significant difference was found between HA and physical symptoms (P > 0.05). Meanwhile, psychological symptoms were most strongly associated with IR (ß = - 0.160), followed by SA (ß = - 0.129), SM (ß = - 0.069), DB (ß = - 0.031), HA (ß = - 0.026) and PA (ß = - 0.021). CONCLUSION: These results indicated the importance of identifying the association of HL with physical and psychological symptoms, and provided the evidence that lower HL may serve as a critical and independent risk factor for poor health outcomes. Meanwhile, to maintain students' desirable healthy status public health efforts for enhancing their HL level are urgently needed in adolescents.

12.
Hum Genomics ; 13(1): 50, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519209

RESUMO

BACKGROUND: Pre-eclampsia (PE) is regarded as the leading cause of maternal and neonatal morbidity and mortality. Nevertheless, the potential mechanism for the regulation of trophoblast behaviors and the pathogenesis of PE remain largely elusive. Recently, accumulating evidence emphasized that aberrant expression of long non-coding RNAs (lncRNAs) functions as imperative regulators in human diseases, including PE. Thus, identifying PE-related specific lncRNAs to uncover the underlying molecular mechanism is of much significance. However, the functional roles and underlying mechanisms of lncRNAs in PE progression remain unclear. METHOD: Placenta tissues obtained from patients with PE and healthy pregnant women were performed to measure TUG1 expression by qRT-PCR analysis. Transient transfections were conducted to alter TUG1 expression. Cell Counting Kit-8 (CCK-8) and flow cytometry assays were carried out to assess cell proliferation and apoptosis, respectively. Transwell and tube formation assays were performed to measure the capacity of cell invasion and angiogenesis. Moreover, the luciferase reporter assay was subjected to verify the binding relationship between TUG1 and miR-29b. Western blot analysis was performed to detect the expression of key proteins in the PI3K/AKT and ERK pathway. RESULTS: Here, we identified a lncRNA, TUG1, which was notably decreased in placental samples of PE patients. Functional experiments of loss- or gain-of-function assays also verified that ectopic expression of TUG1 promoted cell proliferation, invasion, and angiogenesis, but negatively regulated cell apoptosis, whereas TUG1 inhibition presented the opposite effects. Furthermore, mechanistic researches revealed that TUG1 could act as a molecular sponge for miR-29b, thus regulating MCL1, VEGFA, and MMP2 to modulate PE development. CONCLUSIONS: Taken together, our findings demonstrated that TUG1 exerts as a critical role in PE progression, which might furnish a novel therapeutic marker for PE treatment.

13.
Cell Death Differ ; 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31527798

RESUMO

Sonic hedgehog (SHH) signaling is crucial for the maintenance of the physiological self-renewal of granule neuron progenitor cells (GNPs) during cerebellar development, and its dysregulation leads to oncogenesis. However, how SHH signaling is controlled during cerebellar development is poorly understood. Here, we show that Trim32, a cell fate determinant, is distributed asymmetrically in the cytoplasm of mitotic GNPs, and that genetic knockout of Trim32 keeps GNPs at a proliferating and undifferentiated state. In addition, Trim32 knockout enhances the incidence of medulloblastoma (MB) formation in the Ptch1 mutant mice. Mechanistically, Trim32 binds to Gli1, an effector of SHH signaling, via its NHL domain and degrades the latter through its RING domain to antagonize the SHH pathway. These findings provide a novel mechanism that Trim32 may be a vital cell fate regulator by antagonizing the SHH signaling to promote GNPs differentiation and a tumor suppressor in MB formation.

15.
Nat Commun ; 10(1): 3624, 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31399580

RESUMO

Solution-processable perovskites show highly emissive and good charge transport, making them attractive for low-cost light-emitting diodes (LEDs) with high energy conversion efficiencies. Despite recent advances in device efficiency, the stability of perovskite LEDs is still a major obstacle. Here, we demonstrate stable and bright perovskite LEDs with high energy conversion efficiencies by optimizing formamidinium lead iodide films. Our LEDs show an energy conversion efficiency of 10.7%, and an external quantum efficiency of 14.2% without outcoupling enhancement through controlling the concentration of the precursor solutions. The device shows low efficiency droop, i.e. 8.3% energy conversion efficiency and 14.0% external quantum efficiency at a current density of 300 mA cm-2, making the device more efficient than state-of-the-art organic and quantum-dot LEDs at high current densities. Furthermore, the half-lifetime of device with benzylamine treatment is 23.7 hr under a current density of 100 mA cm-2, comparable to the lifetime of near-infrared organic LEDs.

16.
Sci Adv ; 5(8): eaaw0982, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31467971

RESUMO

Carboncones, a special family of all-carbon allotropes, are predicted to have unique properties that distinguish them from fullerenes, carbon nanotubes, and graphenes. Owing to the absence of methods to synthesize atomically well-defined carboncones, however, experimental insight into the nature of pure carboncones has been inaccessible. Herein, we describe a facile synthesis of an atomically well-defined carboncone[1,2] (C70H20) and its soluble penta-mesityl derivative. Identified by x-ray crystallography, the carbon skeleton is a carboncone with the largest possible apex angle. Much of the structural strain is overcome in the final step of converting the bowl-shaped precursor into the rigid carboncone under mild reaction conditions. This work provides a research opportunity for investigations of atomically precise single-layered carboncones having even higher cone walls and/or smaller apex angles.

17.
Sci Adv ; 5(8): eaaw8904, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31467976

RESUMO

The recent discovery of ferromagnetism in two-dimensional (2D) van der Waals (vdW) materials holds promises for spintronic devices with exceptional properties. However, to use 2D vdW magnets for building spintronic nanodevices such as magnetic memories, key challenges remain in terms of effectively switching the magnetization from one state to the other electrically. Here, we devise a bilayer structure of Fe3GeTe2/Pt, in which the magnetization of few-layered Fe3GeTe2 can be effectively switched by the spin-orbit torques (SOTs) originated from the current flowing in the Pt layer. The effective magnetic fields corresponding to the SOTs are further quantitatively characterized using harmonic measurements. Our demonstration of the SOT-driven magnetization switching in a 2D vdW magnet could pave the way for implementing low-dimensional materials in the next-generation spintronic applications.

18.
Bosn J Basic Med Sci ; 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31465718

RESUMO

Presbycusis, or age-related hearing loss, is a prevalent disease that severely affects the physical and mental health of the elderly. Oxidative stress and mitochondrial (mt)DNA deletion mutation are considered as major factors in the pathophysiology of age-related hearing loss. The 4977-bp deletion in human mtDNA (common deletion, corresponding to the 4834-bp mtDNA deletion in rats) is suggested to be closely associated with the pathogenesis of age-related hearing loss. Superoxide dismutase 2 (SOD2), an isoform of SOD that is exclusively expressed in the intracellular mitochondrial matrix, plays a crucial role in oxidative resistance against mitochondrial superoxide. Previous research has shown that methylation of the promoter region of the SOD2 gene decreased the expression of SOD2 in marginal cells (MCs) extracted from the inner ear of rats subjected to D-galactose-induced mtDNA4834 deletion. However, the relationship between SOD2 methylation and mtDNA4834 deletion under oxidative stress remains to be elucidated. Herein, an oxidative damage model was established in the extracted MCs using hydrogen peroxide (H2O2), which increased the methylation level of SOD2 and the copy number of mtDNA4834 mutation in MCs. Decreasing the methylation level of SOD2 using 5-azacytidine, a DNA methylation inhibitor, reduced oxidative stress and the copy number of mtDNA4834 mutation and inhibited H2O2-induced apoptosis. The present work demonstrates that decreasing the methylation of SOD2 suppresses the mtDNA4834 deletion in MCs under oxidative stress and provides potential insights to the intervention therapy of aging-related hearing loss.

19.
Behav Brain Res ; 376: 112172, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31445977

RESUMO

Emerging evidence suggest that neuromodulators are the critical factor involved in depression. This study aimed to investigate the effects of unpredictable chronic mild stress (CUMS) and n-3 polyunsaturated fatty acids (n-3 PUFAs) on central nervous system. The depressive-like behaviors induced by CUMS were assessed by sucrose preference test (SPT), open field test (OFT) and forced swimming test (FST). High-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was used to quantify the levels of neurotransmitters and their metabolites involved in serotonergic, dopaminergic, noradrenergic, GABAergic neurotransmitter systems in hippocampus and prefrontal cortex. Repeated CUMS caused depressive-like behaviors of rats, associated with the alteration of neurotransmitters in brain, including the decreasing DA level, the increasing NE and GABA level, and the increasing 5-HT turnover rate in hippocampus, which could be partly alleviated by sufficient n-3 PUFAs supplementation. The influence of stress and diet on neurotransmitters in the prefrontal cortex was slight. However, it was obvious that supplementary of n-3 PUFAs relieved the decreasing DA/NE between-metabolite ratio 1,2 and DA/5-HT between-metabolite ratio 1,2 in the prefrontal cortex caused by CUMS. Altered neurotransmitter turnover rates and between-metabolite ratios in brain may be better predictors in depression and antidepressant treatment compared with monoamine neurotransmitters.

20.
Sci Rep ; 9(1): 10089, 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300660

RESUMO

Osteoporosis medication in fragility fracture patients is associated with better outcomes. However, limited studies have investigated whether fracture types affect outcomes among patients undergoing treatment. We performed a secondary data analysis on participants from a fracture liaison service and an osteoporosis medication management service. Participants (n = 974) were regrouped into hip fracture (HF), vertebral fracture (VF), HF + VF, and NO HF/VF groups at baseline. Bivariate and multivariate logistic regressions were performed to identify baseline correlates on one-year mortality, incident refractures, and falls. Baseline characteristics were different among fracture groups. The HF group was oldest, with the lowest body mass index (BMI), lowest FRAX® T-score and had the highest 10-year fracture risk. After intervention, the HF group still had the highest mortality, but the HF + VF group had the highest refracture and incident fall rates. In the multivariate regression analysis, prevalent HF and VF, lower BMI and albumin level, and having chronic kidney disease or cancer were associated with higher mortality rates. HF + VF patients had the highest refracture risk. Prevalent HF and VF, older age and higher BMI, and having cancer or osteoarthritis were associated with a greater fall risk. HF and VF are associated with adverse outcomes, even under an optimal fracture care.

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