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1.
Int J Mol Sci ; 20(21)2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31690044

RESUMO

Gene therapy is manipulation in/of gene expression in specific cells/tissue to treat diseases. This manipulation is carried out by introducing exogenous nucleic acids, such as DNA or RNA, into the cell. Because of their negative charge and considerable larger size, the delivery of these molecules, in general, should be mediated by gene vectors. Non-viral vectors, as promising delivery systems, have received considerable attention due to their low cytotoxicity and non-immunogenicity. As research continued, more and more functional non-viral vectors have emerged. They not only have the ability to deliver a gene into the cells but also have other functions, such as the performance of fluorescence imaging, which aids in monitoring their progress, targeted delivery, and biodegradation. Recently, many reviews related to non-viral vectors, such as polymers and cationic lipids, have been reported. However, there are few reviews regarding functional non-viral vectors. This review summarizes the common functional non-viral vectors developed in the last ten years and their potential applications in the future. The transfection efficiency and the transport mechanism of these materials were also discussed in detail. We hope that this review can help researchers design more new high-efficiency and low-toxicity multifunctional non-viral vectors, and further accelerate the progress of gene therapy.

2.
Mol Genet Genomic Med ; : e1032, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31701684

RESUMO

BACKGROUND: The aim of this study was to generate a prognostic model to predict survival outcome in pediatric Wilms tumor (WT). METHODS: The data including mRNA expression and clinical information of pediatric WT patients were downloaded from the Therapeutically Available Research to Generate Effective Treatments (TARGET) database. The differentially expressed genes were identified and a prognostic signature of pediatric WT was generated according to the results of univariate and multivariate Cox analysis. Receiver operating characteristic (ROC) curve was used to evaluate the five-mRNA signature in pediatric Wilms tumor patients. Bootstrap test with 500 times was used to perform the internal validation. RESULTS: We identified 6,964 differentially expressed mRNAs associated with pediatric WT, including 3,190 downregulated mRNAs and 3,774 up-regulated mRNAs. Univariate and multivariate Cox analysis identified five mRNAs (SPRY1, SPIN4, MAP7D3, C10orf71, and SPAG11A) to establish a predictive model. The risk score formula is as follows: Risk score = 0.3036*SPIN4 + 0.8576*MAP7D3 -0.1548*C10orf71 -0.7335*SPRY1 -0.2654*SPAG11A. The pediatric WT patients were divided into low-risk group and high-risk group based on the median risk score (value = 1.1503). The receiver operating characteristic (ROC) curve analysis revealed good performance of the 5-mRNA prognostic model (the area under the curve [AUC] was 0.821). Bootstrap test (Bootstrap resampling times = 500) was used to perform the internal validation and revealed that the AUC was 0.822. REACTOME, KEGG, and BIOCARTA pathway analyses demonstrated that these survival-related genes were mainly enriched in ErbB2 and ErbB3 signaling pathways, and calcium signaling pathway. CONCLUSION: The five-mRNA signature can predict the prognosis of patients with pediatric WT. It has significant implication in the understanding of therapeutic targets for pediatric WT patients. However, further study is needed to validate this five-mRNA signature and uncover more novel diagnostic or prognostic mRNAs candidates in pediatric WT patients.

4.
J Org Chem ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31615204

RESUMO

Many synthetic and supramolecular chiral polymeric systems are known to exhibit the "majority rules effect" (MRE), a positive nonlinear response in which a small enantiomeric excess (ee) of the chiral building blocks leads to unproportionally large chiroptical signals near zero ee. In contrast, the opposite "racemate rules effect" (RRE), a negative nonlinear response in which the chiroptical signals are flat near zero ee, while giving large nonlinear chiroptical responses to ee at high values, has only been occasionally observed. The origin of this unusual ee dependence remains elusive largely because few systems have been established that exhibit this effect. Herein, we present a design approach that enables the development of chiral supramolecular polymers with a pronounced negative nonlinear response akin to RRE. This is achieved by in situ generating a bidentate inducer for supramolecular polymerization that exists in both meso- and homochiral forms upon reacting with chiral guests. The presence of the meso-inducer creates an aggregate structure that has a little response in the circular dichroism (CD) spectra as a function of ee at a particular wavelength, but a homochiral inducer gives large changes in response to ee at this wavelength. This allowed for an RRE-like response to be observed when the CD intensity of the supramolecular polymers was plotted against the ee of the chiral guests that generate the meso- and homochiral inducers without the necessity of the racemic guest preferentially being incorporated into the polymer.

5.
Mol Diagn Ther ; 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31630374

RESUMO

BACKGROUND: Hereditary spastic paraplegia (HSP) refers to a group of neurodegenerative disorders characterized by bilateral weakness, spasticity, and hyperreflexia in the lower limbs. The autosomal dominant HSP (ADHSP) predominantly presents as the pure form, but the clinical profiles and causal genetic variants underlying ADHSP are complex, and many remain unknown. METHODS: A cohort of 15 Chinese HSP pedigrees (including 35 patients and their 22 relatives) were screened by multiplex ligation-dependent probe amplification (MLPA) or whole-exome sequencing (WES). Neurological assessments were also conducted. RESULTS: The main subtypes of HSP above detected in our cohort were SPG4, SPG3A, and SPG6. Fifteen HSP-inducing mutations were identified, among which six were novel mutations: SPAST c.1277T>C, c.1292G>C, c.1562T>C, and c.1693A>T, NIPA1 c.748A>C, and KIDINS220 c.4448C>G. As expected, the most common presentation of the ADHSP cases was the pure form, manifesting spasticity of lower limbs and hyperreflexia, as well as pyramidal signs. Differing substantially from previous reports for KIDINS220 variants, our study family exhibited autosomal dominant inheritance, and only presented with spastic paraplegia, with no signs of intellectual disability, nystagmus, or obesity. CONCLUSION: Our work reveals a non-classical spastic paraplegia, intellectual disability, nystagmus, and obesity phenotype for a KIDINS220 mutation, which broadens both the clinical and genetic spectrum for ADHSP. Beyond underscoring the utility of using both MLPA and WES in studies of HSP, our work deepens the scientific understanding of phenotypes for ADHSP and defines new genetic variants to facilitate future diagnoses.

6.
Aging (Albany NY) ; 11(20): 8760-8776, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31659144

RESUMO

Adipose tissue-derived adipokines mediate various kind of crosstalk between adipose tissue and other organs and thus regulate metabolism balance, inflammation state as well as disease progression. In particular, omentin-1, a newly found adipokine, has been reported to exhibit anti-calcification effects in vitro and in vivo. However, little is known about the function of endogenous adipose tissue-derived omentin-1 in arterial calcification and the detailed mechanism involved. Here, we demonstrated that global omentin-1 knockout (omentin-1-/-) resulted in more obvious arterial calcification in 5/6-nephrectomy plus high phosphate diet treated (5/6 NTP) mice while overexpression of omentin-1 attenuated attenuates osteoblastic differentiation and mineralisation of VSMCs in vitro and 5/6 NTP-induced mice arterial calcification in vivo. Moreover, we found that omentin-1 induced AMPK and Akt activation while inhibition of AMP-activated protein kinase (AMPK) and Akt signaling reversed the anti-calcification effect induced by omentin-1 both in vitro and in vivo. Our results suggest that adipose tissue-derived omentin-1 serves as a potential therapeutic target for arterial calcification and cardiovascular disease.

7.
Arch Insect Biochem Physiol ; 102(3): e21593, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31612553

RESUMO

The diamondback moth, Plutella xylostella, is one of the most destructive pests worldwide and its management relies exclusively on frequent application of chemical insecticides. Resistance to common insecticides is now widespread, and novel classes of insecticides are needed. Entomopathogenic bacteria and their related products play an important role in the management of this pest. In the present work, one bacterial strain was separated from infected pupae of P. xylostella collected from field and its pathogenicity was evaluated. On the basis of the 16S ribosomal RNA sequencing, BLASTN, and phylogenetic analysis, this bacterial isolate was identified as Pseudomonas cedrina. Oral administration of P. cedrina at levels above 10,000 CFU/ml gave significant mortality to P. xylostella larvae. The pathogenicity was also observed by reduced longevity and fecundity in adult females. However, when live bacterial cells were removed, the cultured broth lost any pathogenicity. In response to the bacterial infection, P. xylostella expressed antimicrobial and stress-associated genes. A mixture treatment of P. cedrina and Bacillus thuringiensis showed an additive effect on larval mortality of P. xylostella. These results indicated that P. cedrina is an opportunistic entomopathogen without secretion of toxins. Furthermore, the additive effect of P. cedrina and B. thuringiensis provide a new insight to develop new strategy for controlling P. xylostella.

8.
Cell Death Dis ; 10(10): 728, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31570698

RESUMO

Hypertriglyceridemia severity is linked to acute pancreatitis prognosis, but it remains unknown why a portion of severe hypertriglyceridemia patients do not develop severe acute pancreatitis. To investigate whether hypertriglyceridemia subtypes affect acute pancreatitis progression, we analyzed two genetically modified hypertriglyceridemia mouse models-namely, glycosylphosphatidylinositol high-density lipoprotein binding protein 1 knockout (Gpihbp1-/-) and apolipoprotein C3 transgenic (ApoC3-tg) mice. Acute pancreatitis was induced by 10 intraperitoneal caerulein injections. Biochemical assays and pathological analysis were performed for the severity evaluation of acute pancreatitis. Plasma triglyceride-rich lipoproteins (TRLs), including chylomicrons and very low-density lipoprotein (VLDL), were collected via ultracentrifugation to evaluate their cytotoxic effects on primary pancreatic acinar cells (PACs). We found that the particle sizes of Gpihbp1-/- TRLs were larger than ApoC3-tg TRLs. Severe pancreatic injury with large areas of pancreatic necrosis in the entire lobule was induced in Gpihbp1-/- mice when plasma triglyceride levels were greater than 2000 mg/dL. However, ApoC3-tg mice with the same triglyceride levels did not develop large areas of pancreatic necrosis, even upon the administration of poloxamer 407 to further increase triglyceride levels. Meanwhile, in the acute pancreatitis model, free fatty acids (FFAs) in the pancreas of Gpihbp1-/- mice were greater than in ApoC3-tg mice. TRLs from Gpihbp1-/- mice released more FFAs and were more toxic to PACs than those from ApoC3-tg mice. Chylomicrons from patients showed the same effects on PACs as TRLs from Gpihbp1-/- mice. Gpihbp1-/- mice with triglyceride levels below 2000 mg/dL had milder pancreatic injury and less incidence of pancreatic necrosis than those with triglyceride levels above 2000 mg/dL, similar to Gpihbp1-/-mice with triglyceride levels above 2000 mg/dL but with fenofibrate administration. These findings demonstrated that hypertriglyceridemia subtypes with large TRL particles could affect acute pancreatitis progression and that chylomicrons showed more cytotoxicity than VLDL by releasing more FFAs.

9.
Eur Neurol ; : 1-8, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31618739

RESUMO

INTRODUCTION: Several studies have identified a number of genes associated with Parkinson's disease (PD). Genomic rearrangements (exon dosage variations) in these genes have emerged as significant, causing mutations. However, exon dosage variations in several PD genes were rarely investigated in Chinese patients. OBJECTIVE: This study was aimed at determining the prevalence of PD-causing genes' exon rearrangements in Chinese sporadic early-onset PD (EOPD) patients. METHODS: A total of 150 Chinese sporadic EOPD patients and 100 healthy controls were enrolled. Multiplex ligation-dependent probe amplification (MLPA) was used to detect exon dosage in PD genes, including SNCA, PARKIN, UCHL1, PINK1, DJ1, LRRK2, and ATP13A2. Positive results were verified by real-time quantitative polymerase chain reaction. And exon sequencing was employed to screen for subtle mutations. Novel exon dosage variations were screened in families and controls. RESULTS: PARKIN exon rearrangements were detected in 10 (6.7%) patients, including a novel heterozygous duplication of PARKIN exons 1-4. Clinical investigation showed that the percentage of individuals with PARKIN exon rearrangements was higher in the younger patients. Notably, the MLPA screening detected a heterozygous deletion of UCHL1 exon 1 in a patient. MLPA analysis in the family detected the deletion in an asymptomatic sister, indicating incomplete penetrance. CONCLUSION: Exon copy number variations (CNVs) in the PARKIN gene are relatively common among Chinese sporadic EOPD patients, whereas exon CNVs in other known PD genes can also be detected. Our findings demonstrate that it is important to perform exon dosage analysis for several known PD genes to obtain a better mechanistic insight into PD pathogenesis.

10.
J Biomed Mater Res A ; 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31628823

RESUMO

Cell-material interactions and compatibility are important aspects of bioactive materials for bone tissue engineering. Phosphate glass fiber (PGF) is an attractive inorganic filler with fibrous structure and tunable composition, which has been widely investigated as a bioactive filler for bone repair applications. However, the interaction of osteoblasts with PGFs has not been widely investigated to elucidate the osteogenic mechanism of PGFs. In this study, different concentrations of short PGFs with interlaced oriented topography were cocultured with MC3T3-E1 cells for different periods, and the synergistic effects of fiber topography and ionic product of PGFs on osteoblast responses including cell adhesion, spreading, proliferation, and osteogenic differentiation were investigated. It was found that osteoblasts were more prone to adhere on PGFs through Vinculin protein, leading to enhanced cell proliferation with polygonal cell shape and spreading cellular actin filaments. In addition, osteoblasts incubated on PGF meshes showed enhanced alkaline phosphatase activity, extracellular matrix mineralization, and increased expression of osteogenesis-related marker genes, which could be attributed to the Wnt/ß-catenin/Runx2 signaling pathway. This study elucidated the possible mechanism of PGF on triggering specific osteoblast behavior, which would be highly beneficial for designing PGF-based bone graft substitutes with excellent osteogenic functions.

11.
Int J Cancer ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31577838

RESUMO

Peritoneal metastasis is a critical feature and clinical challenge in epithelial ovarian cancer (EOC). We previously identified a novel long noncoding RNA (lncRNA, TC0101441) in epithelial ovarian cancer (EOC) using microarrays. However, the impact of TC0101441 on EOC metastasis and prognosis remains unclear. TC0101441 expression in EOC tissues and its correlation with clinicopathological factors and prognosis were examined. A series of in vitro and in vivo assays were performed to elucidate the roles and mechanism of TC0101441 in EOC metastasis. We found that TC0101441 levels were elevated in EOC tissues compared with those in normal controls and significantly correlated with an advanced clinical stage and lymph node metastasis. TC0101441 was determined to be an independent prognostic predictor of overall survival (OS) and disease-free survival (DFS). Furthermore, loss-of-function assays showed that TC0101441 promoted the invasive and metastatic capacities of EOC cells both in vitro and in vivo. Mechanistically, the prometastatic effects of TC0101441 were linked to the induction of epithelial-mesenchymal transition (EMT). Importantly, KiSS1 was identified as a downstream target gene of TC0101441 and was downregulated by TC0101441 in EOC cells. After TC0101441 was silenced, the corresponding phenotypes of EOC cell invasion and EMT were reversed by the overexpression of KiSS1. Taken together, our data suggest that TC0101441 functions as a potential promigratory/invasive oncogene by promoting EMT and metastasis in EOC through downregulation of KiSS1, which may represent a novel prognostic marker and therapeutic target in EOC. This article is protected by copyright. All rights reserved.

12.
Cells ; 8(9)2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31487778

RESUMO

RATIONALE: While high low-density lipoprotein cholesterol (LDL-C) and low high-density lipoprotein cholesterol (HDL-C) levels are positively associated with cardiovascular events, it is still unclear whether familial hypercholesterolemia (FH) and Tangier's disease (TD), caused by mutations in LDLR and ABCA1, respectively, influence ischemic stroke (IS) in humans. OBJECTIVE: We sought to establish an easier, more effective, and time-saving method to induce IS, then studied the precise effects of different types of lipoproteins on IS. METHODS AND RESULTS: A new technique termed contralateral middle cerebral artery occlusion (c-MCAO) was introduced to human-like hamster models to induce IS. Compared to traditional distal MCAO (d-MCAO) induced by electrocoagulation, c-MCAO resulted in a more severe IS with larger infarct sizes and more blood-brain barrier (BBB) disruption after 24 h. It was shown that c-MCAO markedly elicited an increase in brain infarct volume and BBB leakage in both homozygous LDLR (LDLR-/-) and ABCA1 knockout (ABCA1-/-) hamsters, but not in heterozygous LDLR knockout (LDLR+/-) hamsters when compared to wild-type (WT) controls. CONCLUSIONS: Using human-like genetically engineered hamsters, our findings demonstrated that both high LDL-C level caused by homozygous LDLR deficiency and severe low HDL-C level caused by deleting ABCA1 were risk factors of IS. As such, we believe the development of this novel IS hamster model is suitable for future ischemic/reperfusion studies.

13.
Cancer Epidemiol ; 63: 101586, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31522131

RESUMO

BACKGROUND: Forecast of disease burden in lung cancer is an important health agenda. One of the main challenges is to predict the evolution of trends in disability-adjusted life year (DALY) of lung cancer so as to anticipate the future burden and to coordinate the supply of sufficient health services and care. METHODS: Using 2004-2013 cancer registry data in Guangzhou, we fitted Bayesian age-period-cohort models with age, period, and cohort effects to analyze trends of lung cancer among women, and then made forecast for DALY of lung cancer until 2030. RESULTS: During 2004-2013, there was an annual average of 10,582 DALYs for lung cancer (15.84% of total DALY). In 2014-2030, DALY is expected to reach 234,752 person-years for lung cancer (12.25% of total DALY), with an annual mean of 13,809 DALYs. Lung cancer crude DALY rate is projected to rise steadily from 257.56 (95% uncertainty interval: 165.97-361.22) in 2014 to 316.99 (219.96-419.41) per 100,000 women in 2030, and the rise is mainly seen in 45-64 years age group. Lung cancer DALY rate remains the highest in the 65-89 years age group. CONCLUSIONS: Women at 65-89 years carry the highest lung cancer burden among other age groups in Guangzhou. The DALY rate of lung cancer is projected to increase most precipitously for the 45-64 years age group. This indicates that concerted efforts are needed to develop adequate cancer services, and to reassess health resources for control and care of lung cancer in these populations.

14.
Opt Express ; 27(16): 22508-22521, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31510542

RESUMO

A rigorous homogenization theory is developed to characterize the effective conductivity tensor of periodic graphene ribbons. This way, the obtained conductivity simplifies the study of the exotic scattering properties of periodic graphene ribbons. As a typical example, we find that the performance of reflective dichroism from the designed graphene ribbons can be enhanced (up to a maximum linear dichroism of 0.98) when the total internal reflection happens. Moreover, by rotating its optical axis, the functionality of the periodic graphene ribbon can change from an absorber for linearly polarized waves to another absorber for circularly polarized waves (maximum circular dichroism of 0.93). The revealed indispensable property of graphene ribbons in controlling the reflective dichroism indicates their promising wide applications including energy harvesting and optical sensing.

15.
Anticancer Drugs ; 30(10): 973-982, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31503014

RESUMO

Fibroblast growth factor-2 (FGF2) is a protein ligand, which exerts essential roles in development, angiogenesis, and tumor progression via activation of the downstream signaling cascades. Accumulating evidence has demonstrated that FGF2 is involved in the progression of ovarian cancer, providing a novel potential target for ovarian cancer therapy. In this study, we showed that FGF2 is significantly increased in ovarian tumors, and is negatively associated with the overall survival of ovarian cancer by database analysis. A short peptide obtained from a heptapeptide phage display library suppressed FGF2-induced proliferation, migration, and invasion of the p53-null epithelial ovarian cancer (EOC) cells. Further investigations revealed that the short peptide antagonized the effects of FGF2 on G0/G1 to S cell phase promotion, cyclin D1 expression, and MAPK and Akt signaling activation, which might contribute to the mechanism underlying the inhibitory effects of the short peptide on the aggressive phenotype of the ovarian cancer cells triggered by FGF2. Moreover, the short peptide might have the potentials of reversing FGF2-induced resistance to the doxorubicin via downregulation of the antiapoptotic proteins and counteracting of the antiapoptotic effects of FGF2 on p53-null EOC cells. Taken together, the short peptide targeting FGF2 may provide a novel strategy for improving the therapeutic efficiency in a subset of EOC.

16.
Int J Biochem Cell Biol ; 116: 105610, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31518663

RESUMO

It has been proposed that the aberrant expressions of the classical apoptosis-related genes and the subsequent decrease of apoptosis contribute to the development of cisplatin resistance in gastric cancer. However, little is known about the correlation and the molecular regulation mechanisms of cisplatin and the apoptosis-related gene expressions. Herein, we first identified the expressions of the anti-apoptotic BCL2 and the prostaglandin-endoperoxide synthase-2 (PTGS2) genes, which were abundant in the gastric carcinoma and associated with poor patient survival, were closely related with the resistance against cisplatin. Further investigations revealed that PTGS2 served as an essential mediator involved in the developing process of the resistance against cisplatin via mediating the inhibition effects of cisplatin on BCL2 expression. Mechanistically, cisplatin induced PTGS2 expression through ROS/NF-κB pathway. In addition, PTGS2 mediated cisplatin-induced BCL2 expression and subsequent resistance to apoptosis via PGE2/EP4/MAPKs (ERK1/2, P38) axis. Analysis of the clinical specimens demonstrated that PTGS2 and BCL2 were positively correlated in human gastric cancer. Moreover, in the xenograft models, inhibition of PTGS2 by celecoxib significantly augmented the cytotoxic efficacy of cisplatin in the resistant gastric cancer via suppression of PTGS2 and BCL2 expressions regulated by ERK1/2 and P38 signal axis, suggesting PTGS2 might be employed as an adjunctive therapeutic target for reversal of the chemoresistance in a subset of cisplatin resistant gastric cancer.

17.
J Pediatr Endocrinol Metab ; 32(10): 1121-1129, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31539362

RESUMO

Introduction Growing evidence indicates that circulating concentrations of insulin-like growth factor 1 (IGF-I), along with IGF-I relative to IGF-binding proteins (IGFBP), are associated with an increased risk of cancer. In accord, regular exercise is linked with a lower risk of cancer. Purpose To assess the effects of a 16-week home-based strength training (HBST) program on serum IGF-I, IGFBP-1 and IGFBP-3. Methods A total of 32 obese Latino adolescent males (aged 14-18 years) were randomized into a twice-weekly HBST (n = 16) or a control group (C, n = 16) for 16 weeks. The following were measured at pre- and post-intervention: IGF-I, IGFBP-1 and IGFBP-3, glucose/insulin indices by oral and/or intravenous (IV) glucose tolerance tests, strength by one-repetition maximum (1RM), dietary intake by 3-d records, body composition by DEXA and physical activity using the Actigraph GT1X. The generalized linear model (GLM) was used to assess differences in changes among outcome measures between the HBST and C groups. Results Exercise adherence in the HBST group was 89%. IGF-1 showed a trend for significant within-subject improvements (p = 0.078) but no significant within-subject or between-subject differences for IGFBP-1, IGFBP-3 two-glucose, fasting glucose or 2-h glucose (p > 0.05). There was a significant decrease (p > 0.05) in fasting glucose in the C group (p = 0.02) and also in the intervention group (p = 0.03) between baseline and follow-up testing. A significant difference was also found in the C group for 2-h glucose with an increase at follow-up testing (p = 0.04). Conclusions Though not statistically significant (p < 0.05), the results indicated that a 16-week HBST program decreased IGF-I and increased IGFBP-1, along with IGFBP-3, concentrations among overweight/obese Latino boys. However, further studies should consider increasing either the dose or the duration of the intervention to elicit greater improvements in this at-risk pediatric population.

18.
J Appl Clin Med Phys ; 20(9): 31-41, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31483573

RESUMO

PURPOSE: To investigate the fixed-jaw intensity-modulated radiotherapy (F-IMRT) and tangential partial volumetric modulated arc therapy (tP-VMAT) treatment plans for synchronous bilateral breast cancer (SBBC). MATERIALS AND METHOD: Twelve SBBC patients with pTis-2N0M0 stages who underwent whole-breast irradiation after breast-conserving surgery were planned with F-IMRT and tP-VMAT techniques prescribing 42.56 Gy (2.66 Gy*16f) to the breast. The F-IMRT used 8-12 jaw-fixed tangential fields with single (sF-IMRT) or two (F-IMRT) isocenters located under the sternum or in the center of the left and right planning target volumes (PTVs), and tP-VMAT used 4 tangential partial arcs with two isocenters located in the center of the left and right PTVs. Plan evaluation was based on dose-volume histogram (DVH) analysis. Dosimetric parameters were calculated to evaluate plan quality; total monitor units (MUs), and the gamma analysis for patient-specific quality assurance (QA) were also evaluated. RESULTS: For PTVs, the three plans had similar Dmean and conformity index (CI) values. F-IMRT showed a slightly better target coverage according to the V100% values and demonstrated an obvious reduction in V105% and Dmax compared with the values observed for sF-IMRT and tP-VMAT. Compared with tP-VMAT, sF-IMRT was slightly better in terms of V100% , V105% and Dmax . In addition, F-IMRT achieved the best homogeneity index (HI) values for PTVs. Concerning healthy tissue, tP-VMAT had an advantage in minimizing the high dose volume. The MUs of the tP-VMAT plan were decreased approximately 1.45 and 1 times compared with the sF-IMRT and F-IMRT plans, respectively, and all plans passed QA. For the lungs, heart and liver, F-IMRT achieved the smallest values in terms of Dmean and showed a significant difference compared with tP-VMAT. Simultaneously, sF-IMRT was also superior to tP-VMAT. For the coronary artery, tP-VMAT achieved the lowest Dmean , while the value for F-IMRT was 2.24% lower compared with sF-IMRT. For all organs at risk (OARs), tP-VMAT was superior at the high dose level. In contrast, sF-IMRT and F-IMRT were obviously superior at the low dose level. The sF-IMRT and F-IMRT plans showed consistent trends. CONCLUSION: All treatment plans for the provided techniques were of high quality and feasible for SBBC patients. However, we recommend F-IMRT with a single isocenter as a priority technique because of the tremendous advantage of local hot spot control in PTVs and the reduced dose to OARs at low dose levels. When the irradiated dose to the lungs and heart exceed the clinical restriction, two isocenter F-IMRT can be used to maximize OAR sparing. Additionally, tP-VMAT can be adopted for improving cold spots in PTVs or high-dose exposure to normal tissue when the interval between PTVs is narrow.

19.
Epilepsy Behav ; 98(Pt A): 173-187, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31377659

RESUMO

Epilepsy is a serious neurological disorder posing a severe burden to our society. Cognitive deficits are very common comorbidities of epilepsy. It is known that enhanced cognition has been demonstrated as an indicator for successful treatment of epilepsy. Physical exercise shows a positive consequence on cognition in healthy individuals and improves health and life conditions in people with epilepsy. However, there is no direct evidence to determine the role and the potential mechanism of physical exercise on the cognitive impairment and the relationship of susceptibility to seizures. The goal of the current investigation was to explore whether sustained physical exercise improves the cognitive dysfunction and simultaneously decreases the susceptibility to seizures in rats with epilepsy. Rats were treated with pentylenetetrazole (PTZ) (35 mg/kg, i.p. [intraperitoneally]) for 36 days to induce chronic epilepsy. During the induction period, rats were exposed to voluntary wheel running or forced swimming 30 min prior to each PTZ injection from the 16th day. The cognition of rats was evaluated by object recognition test and passive avoidance test. The susceptibility to seizures was evaluated by seizure frequency and duration. The levels of synaptic-related proteins including PSD95 (postsynaptic density 95), Synapsin, GluA1, and BDNF (brain-derived neurotrophic factor) were measured to evaluate the hippocampal synaptic plasticity. Furthermore, the GAD67 (glutamic acid decarboxylase) levels and GABA (γ-aminobutyric acid)ergic function in PTZ-treated rats were also determined. Finally, antagonist of GABAAR (GABAA receptors) bicuculline was used to explore the reversal effects of physical activity on seizures and cognition. The results showed that rats subjected to voluntary wheel running or forced swimming showed a significant reduction of seizure frequency and duration in PTZ-treated group relative to rats without running or swimming. In addition, both running and swimming improved cognitive function as measured by enhanced performance in object recognition test and passive avoidance test. Furthermore, the reduced levels of synaptic-related proteins and GABAergic function were reversed by exercise compared with rats without exercise. Moreover, antagonism of hippocampal CA3 (cornu ammonis 3) GABAergic neurons blocks the reversal effects of physical activity on seizures and cognition in PTZ-treated rats. These data showed that chronic physical exercise reduced the frequency of seizures and improved the cognitive function in a rat model of chronic epilepsy through normalization of CA3 synaptic plasticity and GABAergic function. Our findings suggest that chronic physical exercise has beneficial effects on controlling seizure through enhancement of cognition and highlights the possibility to translate into reduced seizure recurrence in people with epilepsy.

20.
Nanoscale ; 11(35): 16241-16244, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31454010

RESUMO

In this work, a novel and general comparator was constructed based on cascaded strand displacement reactions and DNA hybridization and its potential in intelligently weighing the quantitative predominance of two targets was explored in a complex biological matrix, which not only enriches the information processing mode of DNA computation but also provides an instructive way to deal with quantitative analyzing tasks in further DNA-based logic sensors.

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