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1.
Int J Mol Sci ; 21(6)2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32245267

RESUMO

As emerging evidence suggesting neurodegenerative diseases and metabolic diseases have common pathogenesis, we hypothesized that the neurite outgrowth-controlling collapsin response mediator protein 2 (CRMP2) was involved in energy homeostasis. Therefore, putative roles of CRMP2 in adipocyte differentiation (adipogenesis) and lipid metabolism were explored and addressed in this study. CRMP2 expression profiles were in vitro and in vivo characterized during adipogenic process of 3T3-L1 pre-adipocytes and diet-induced obese (DIO) mice, respectively. Effects of CRMP2 on lipid metabolism and deposits were also analyzed. Our data revealed that CRMP2 expression pattern was coupled with adipogenic stages. CRMP2 overexpression inhibited cell proliferation at MCE phase, and significantly reduced lipid contents by down-regulating adipogenesis-driving transcription factors and lipid-synthesizing enzymes. Interestingly, GLUT4 translocation and the lipid droplets fusion were disturbed in CRMP2-silencing cells by affecting actin polymerization. Moreover, adipose CRMP2 was significantly increased in DIO mice, indicating CRMP2 is associated with obesity. Accordingly, CRMP2 exerts multiple functions in adipogenesis and lipid deposits through mediating cell proliferation, glucose/lipid metabolism and cytoskeleton dynamics. The present study identifies novel roles of CRMP2 in mediating adipogenesis and possible implication in metabolic disorders, as well as provides molecular evidence supporting the link of pathogenesis between neurodegenerative diseases and metabolic abnormalities.

2.
Pain Pract ; 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32237040

RESUMO

In amputees, the majority of residual limb pain ensues due to neuroma(s). Recently, high-resolution ultrasound (US) has substantially facilitated the morphological evaluation of nerves and the surrounding soft tissues/scars contributory in entrapment syndromes. We reported a 57-year-old male, who had received below-knee amputation due to osteomyelitis three years ago, was seen for continuous stabbing and burning sensation at the left residual limb. US examination showed that the terminal end of the deep peroneal nerve was enlarged and encircled by hypoechoic scars. US-guided hydro-dissection was conducted besides the epineurium of the neuroma. After the injection, the numerical rating scale score decreased from 8 to 3, and the numbness was also relieved when putting on the prosthesis. It is noteworthy that one of the superiorities of dextrose (over corticosteroid) is the possibility to use higher volumes for adhesiolysis of the twisting scars. Herein, treatment success lies in introducing the needle at the upper and lower borders of the neuroma to ensure complete relief of the adhesions.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32251112

RESUMO

The developments in technology have improved access to the use of musculoskeletal ultrasound (MSUS) in different clinical settings. Accordingly, MSUS has been applied to a wide range of musculoskeletal problems including inflammatory and degenerative diseases, sport injuries, regional pain syndromes both for clinical practice and research. In this report, we aimed to globally examine the publications on MSUS among different specialties, countries, topics. Sixteen reviewers under the umbrella of EURO-MUSCULUS (European Musculoskeletal Ultrasonography Society Group) and USPRM (Ultrasound Study Group of International Society of Physical and Rehabilitation Medicine) have evaluated approximately 15000 publications on MSUS. We believe that the results of this comparative analysis may provide a holistic snapshot as regards the utility of MSUS, not only for clinicians/academicians but also for the industry. Accordingly, while aiming to further increase their awareness, this paper would possibly guide future investments as well.

4.
J Virol ; 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32132234

RESUMO

A novel lytic bacteriophage ValSw3-3, which efficiently infects pathogenic strains of Vibrio alginolyticus, was isolated from sewage water and characterized by microbiological and in silico genomic analyses. Transmission electron microscopy indicated that ValSw3-3 had the morphology of siphoviruses. This phage can infect four species in the Vibrio genus and has a latent period of 15 min and a burst size of 95 ± 2 PFU/infected bacterium. Genome sequencing results show that ValSw3-3 has a 39,846-bp double stranded DNA genome with a GC content of 43.1%. The similarity between the genome sequences of ValSw3-3 and other phages recorded in GenBank database was below 50% (42%), suggesting that ValSw3-3 significantly differed from previously reported phages at the DNA level. Multiple genome comparisons and phylogenetic analysis based on major capsid protein revealed that phage ValSw3-3 was grouped in a clade with other five phages, including Listonella phage phiHSIC (NC_006953.1), Vibrio phage P23 (MK097141.1), Vibrio phage pYD8-B (NC_021561.1), Vibrio phage 2E1 (KX507045.1), and Vibrio phage 12G5 (HQ632860.1), which was distinct from all known genera within the Siphoviridae family that have been ratified by ICTV. An in silico proteomic comparison of diverse phages from the Siphoviridae family supported this clustering result and suggested that ValSw3-3, phiHSIC, P23, pYD8-B, 2E1, and 12G5 could be classified as a novel genus cluster of Siphoviridae A subsequent analysis of core genes also revealed the common genes shared within this new cluster. Overall, these results provide a characterization of Vibrio phage ValSw3-3 and support our proposal of a new viral genus within the family Siphoviridae ImportancePhage therapy has been considered as a potential alternative to antibiotic therapy in treating bacterial infections. For controlling the vibriosis-causing pathogen, Vibrio alginolyticus, well documented phage candidates are still lacking. Here we characterize a novel lytic Vibrio phage ValSw3-3 based on its morphology, host range and infectivity, growth characteristics, stability under various conditions, and genomic features. Our results show that ValSw3-3 could be a potent candidate for phage therapy to treat V. alginolyticus infections due to its strong infectivity and better pH and thermal stability compared with previously reported Vibrio phages. Moreover, genome sequence alignments, phylogenetic analysis, in silico proteomic comparison, and core-gene analysis all support that this novel phage ValSw3-3 and five unclassified phages form a clade distant from other known genera ratified by ICTV. We thus propose a new viral genus within the Siphoviridae family to accommodate this clade with ValSw3-3 as a representative member.

5.
Sci Rep ; 10(1): 3953, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32127576

RESUMO

Recent advances in high-throughput genomic technologies have nurtured a growing demand for statistical tools to facilitate identification of molecular changes as potential prognostic biomarkers or drugable targets for personalized precision medicine. In this study, we developed a web-based interactive and user-friendly platform for high-dimensional analysis of molecular alterations in cancer (HDMAC) (https://ripsung26.shinyapps.io/rshiny/). On HDMAC, several penalized regression models that are suitable for high-dimensional data analysis, Ridge, Lasso and adaptive Lasso, are offered, with Cox regression for survival and logistic regression for binary outcomes. Choice of a first-step screening is provided to address the multiple-comparison issue that often arises with large-volume genomic data. Hazard ratio or estimated coefficient is provided with each selected gene so that a multivariate regression model may be built based on the genes selected. Cross validation is provided as the method to estimate the prediction power of each regression model. In addition, R codes are also provided to facilitate download of whole sets of molecular variables from TCGA. In this study, illustration of the use of HDMAC was made through a set of data on gene mutations and a set on mRNA expression from ovarian cancer patients and a set on mRNA expression from bladder cancer patient. From the analysis of each set of data, a list of candidate genes was obtained that might be associated with mutations or abnormal expression of genes in ovarian and bladder cancers. HDMAC offers a solution for rigorous and validation analysis of high-dimensional genomic data.

6.
Arch Osteoporos ; 15(1): 54, 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32221755

RESUMO

PURPOSE: Recently, trabecular bone score (TBS) has emerged as an important supplementary assessment tool in osteoporosis diagnosis and management. The high incidence of fragility fracture within the non-osteoporotic range of bone mineral density (BMD), among systemic lupus erythematosus (SLE) patients, highlights the crucial role of bone microarchitecture in osteoporosis. This study aimed to evaluate whether TBS identified existing vertebral fractures (VF) more accurately than BMD in SLE patients. METHODS: This study enrolled 147 SLE patients from the Asia Pacific Lupus Collaboration (APLC) cohort, who had BMD and TBS assessed from January 2018 until December 2018. Twenty-eight patients sustaining VF and risk factors associated with increased fracture occurrence were evaluated. Independent risk factors and diagnostic accuracy of VF were analyzed by logistic regression and ROC curve, respectively. RESULT: The prevalence of vertebral fracture among SLE patients was 19%. BMD, T-score, TBS, and TBS T-score were significantly lower in the vertebral fracture group. TBS exhibited higher positive predictive value and negative predictive value than L spine and left femur BMD for vertebral fractures. Moreover, TBS had a higher diagnostic accuracy than densitometric measurements (area under curve, 0.811 vs. 0.737 and 0.605). CONCLUSION: Degraded microarchitecture by TBS was associated with prevalent vertebral fractures in SLE patients. Our result suggests that TBS can be a complementary tool for assessing vertebral fracture prevalence in this population.

7.
Appl Ergon ; 85: 103069, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32174357

RESUMO

The prevalence of musculoskeletal (MSK) symptoms in radiographers is high, similar to other healthcare occupations that involve high levels of physical exertion (e.g. patient handling; grasping and moving equipment). Reports of interventions to reduce MSK discomfort in radiographers are limited. A participatory approach was used to investigate daily challenges, needs, and opportunities for developing interventions to address exposures to many of the risk factors that contribute to MSK symptoms in radiographers. In this paper, we present the expressed needs of experienced radiographers (including assistance with patient handling, security, supportive design of equipment and work spaces), along with their evaluations of several intervention concepts intended to address some of those needs. We also report results from tests of three prototype interventions stemming from this participatory process that demonstrate the potential for new engineering control concepts to reduce the physical effort associated with some of the most common tasks radiographers perform.

8.
Environ Int ; 138: 105602, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32120057

RESUMO

Few studies have assessed the association between fine particulate matter (PM2.5) exposure during pregnancy and infancy and pediatric rheumatic diseases (PRDs). The goal of this study was to investigate the association of PM2.5 with PRDs, and to explore sensitive windows of exposure. Therefore, we conducted a cohort-based case-control study to investigate the association between weekly exposure to PM2.5 and PRDs in Taiwan. Our birth cohort consisted of infants born in 2004-2014 (n = 1,991,592) who were followed from conception to the end of 2015. There were 2363 cases of incident PRDs in children, and 23,630 children served as controls using density matching (1:10) based on date of birth, gender, and gestational week. We used a linear mixed effect (LME) model to incorporate the aerosol optical depth (AOD), meteorological variables, and land-use data to predict daily PM2.5 concentrations. We also performed conditional logistic regression with distributed lag non-linear models (DLNMs) to assess the effects of weekly average PM2.5 on PRDs, as well as dose-response relationships. In DLNMs, exposure to PM2.5 during pregnancy (11-40 weeks) or infancy (1-14 weeks after birth) was associated with incident PRDs adjusting for potential confounding factors, and for carbon monoxide and sulfur dioxide. In the dose-response association, the odds ratios of PRDs were significantly increased for PM2.5 exposures between 26 and 54 µg/m3. In addition, exposure to PM2.5 above 81 µg/m3 dramatically increased the risk of PRDs. In conclusions, our study provides new data to suggest that PM2.5 exposure from 11-40 gestational weeks to 1-14 weeks after birth can increase the risk for PRDs in a non-linear dose-response fashion.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32115237

RESUMO

OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease that develops mainly in women of reproductive age. We aimed to explore the risk of pregnancy complications in Asian patients with SLE. METHODS: From January 2005 to December 2014, we conducted a nationwide case-control study, using Taiwan's National Health Insurance Research Database. Obstetric complications and perinatal outcomes in SLE patients were compared with those without SLE. RESULTS: 2059 SLE offspring and 8236 age-matched, maternal healthy controls were enrolled. We found increased obstetric and perinatal complications in SLE population compared with healthy controls. SLE patients exhibited increased risk of preeclampsia/eclampsia (8.98% vs.1.98%, odds ratio [OR]: 3.87, 95% confidence interval [95% CI]: 3.08-4.87, p<0.0001). Their offspring tended to have lower Apgar scores (<7) at both 1 min (10.7% vs. 2.58%, p<0.0001) and 5 min (4.25% vs. 1.17%, p<0.0001), as well as higher rates of intrauterine growth restriction (IUGR, 9.91% vs. 4.12%, OR: 2.24, 95% CI: 1.85-2.71, p<0.0001), preterm birth (23.70% vs 7.56%, OR: 3.00, 95% CI: 2.61-3.45, p<0.0001), and stillbirth (4.23% vs. 0.87%, OR: 3.59, 95% CI: 2.54-5.06, p<0.0001). The risks of preterm birth and stillbirth were markedly increased in SLE patients with concomitant preeclampsia/eclampsia or IUGR. Preterm birth of SLE patients was 1~4 gestational weeks earlier than that of healthy controls and the peak occurrence of stillbirth in SLE population was at 20~30 gestational weeks. CONCLUSIONS: Asian SLE patients exhibited increased risks of maternal complications and adverse birth outcomes. Frequent antenatal visits before 20 gestational weeks are recommended in high-risk SLE patients.

11.
J Clin Epidemiol ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32169597

RESUMO

OBJECTIVE: To evaluate the performance of machine learning (ML) algorithms and to compare them to logistic regression for the prediction of risk of cardiovascular diseases (CVD), chronic kidney disease (CKD), diabetes (DM), and hypertension (HTN) and in a prospective cohort study using simple clinical predictors. STUDY DESIGN AND SETTING: We conducted analyses in a population-based cohort study in Asian adults (n=6,762). Five different ML models were considered: single-hidden-layer neural network, support vector machine, random forest, gradient boosting machine and k-nearest neighbour, and were compared to standard logistic regression. RESULTS: The incidences at 6-year of CVD, CKD, DM, and HTN cases were 4.0%, 7.0%, 9.2%, and 34.6%, respectively. Logistic regression reached the highest AUC for CKD (0.905 [0.88, 0.93]) and DM (0.768 [0.73, 0.81]) predictions. For CVD and HTN, the best models were neural network (0.753 [0.70, 0.81]) and support vector machine (0.780 [0.747, 0.812]), respectively. However, the differences with logistic regression were small (less than 1%) and non-significant. Logistic regression, gradient boosting machine and neural network were systematically ranked among the best models. CONCLUSION: Logistic regression yields as good performance as ML models to predict the risk of major chronic diseases with low incidence and simple clinical predictors.

12.
Pharmaceuticals (Basel) ; 13(3)2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32197544

RESUMO

This network meta-analysis aimed to integrate the available direct and indirect evidence on regenerative injections-including 5% dextrose (D5W) and platelet-rich plasma (PRP)-for the treatment of carpal tunnel syndrome (CTS). Literature reports comparing D5W and PRP injections with non-surgical managements of CTS were systematically reviewed. The main outcome was the standardized mean difference (SMD) of the symptom severity and functional status scales of the Boston Carpal Tunnel Syndrome Questionnaire at three months after injections. Ranking probabilities of the SMD of each treatment were acquired by using simulation. Ten studies with 497 patients and comparing five treatments (D5W, PRP, splinting, corticosteroid, and normal saline) were included. The results of the simulation of rank probabilities showed that D5W injection was likely to be the best treatment, followed by PRP injection, in terms of clinical effectiveness in providing symptom relief. With respect to functional improvement, splinting ranked higher than PRP and D5W injections. Lastly, corticosteroid and saline injections were consistently ranked fourth and fifth in terms of therapeutic effects on symptom severity and functional status. D5W and PRP injections are more effective than splinting and corticosteroid or saline injection for relieving the symptoms of CTS. Compared with splinting, D5W and PRP injections do not provide better functional recovery. More studies investigating the long-term effectiveness of regenerative injections in CTS are needed in the future.

13.
J Immunol Res ; 2020: 8640719, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32149159

RESUMO

Adult-onset Still's disease (AOSD) is a rare and inflammatory disorder characterized by spiking fever, rash, arthritis, and multisystemic involvement. HLA has been shown to be associated with AOSD; however, it could not explain the innate immunity and autoinflammatory characteristics of AOSD. To assess the genetic susceptibility of AOSD, we conducted a genome-wide association study (GWAS) on a cohort of 70 AOSD cases and 688 controls following a replication study of 36 cases and 200 controls and meta-analysis. The plasma concentrations of associated gene product were determined. The GWAS, replication, and combined sample analysis confirmed that SNP rs11102024 on 5'-upstream of CSF1 encoding macrophage colony-stimulating factor (M-CSF) was associated with AOSD (P = 1.20 × 10-8, OR (95% CI): 3.28 (2.25~4.79)). Plasma levels of M-CSF increased in AOSD patients (n = 82, median: 9.31 pg/mL), particularly in the cases with activity score ≥ 6 (n = 42, 10.94 pg/mL), compared to the healthy donors (n = 68, 5.31 pg/mL) (P < 0.0001). Patients carrying rs11102024TT genotype had higher M-CSF levels (median: 20.28 pg/mL) than those with AA genotype (6.82 pg/mL) (P < 0.0001) or AT genotype (11.61 pg/mL) (P = 0.027). Patients with systemic pattern outcome were associated with elevated M-CSF and frequently observed in TT carriers. Our data suggest that genetic variants near CSF1 are associated with AOSD and the rs11102024 T allele links to higher M-CSF levels and systemic outcome. These results provide a promising initiative for the early intervention and therapeutic target of AOSD. Further investigation is needed to have better understandings and the clinical implementation of genetic variants nearby CSF1 in AOSD.

14.
Pain Manag ; 10(2): 97-106, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32162601

RESUMO

Ultrasound (US) imaging has become one of the most useful modalities to assess peripheral nerve disorders. Nowadays, it is as important as nerve conduction studies and electromyography for peripheral nerve entrapment. Additionally, US is also helpful in guiding a possible intervention. As peripheral nerves are tiny, palpation-guided injections are really challenging for precisely targeting the nerves. By using US, perineural injections have significantly become safe and effective. Recently, US-guided hydrodissection has emerged as the mainstream for nerve entrapment. Accordingly, this review aims to summarize and update the mechanism and evidence regarding this imperative procedure for neuropathic pain management. Furthermore, the pathogenesis, anatomic features, US findings and histological correlations of nerve entrapment syndromes will also be discussed in this article.

15.
Chemosphere ; 250: 126316, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32120153

RESUMO

Per- and polyfluoroalkyl substances (PFASs) are artificial refractory organic pollutants which are widely presented in aqueous environment. Due to the unquiet strength of the highly polarized carbon-fluorine bond (C-F) and their hydrophobic/lipophobic feature as well as biological persistence properties, the remediation and treatment of PFASs is a big challenge. Preliminary studies indicate that a few kinds of technical approaches could remove or transfer PFASs, but the effectiveness is not high as expected or limited while most of the techniques are only tested at laboratory scale. A review of existing treatment technologies was thus conducted for the purpose to outlook these technologies, and more importantly, to propose the foreseeable technique. As such, a constructed wetland-microbial fuel cell (CW-MFC) technology was recommended, which is a newly emerged technology by integrating physical, chemical and enhanced biological processes plus the wetland plants function with strong eco-friendly feature for a comprehensive removal of PFASs. It is expected that the review can strengthen our understanding on PFASs' research and thus can help selecting reasonable technical means of aqueous PFASs control.

16.
Int J Mol Sci ; 21(5)2020 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-32121388

RESUMO

Lapatinib (LAP) and sorafenib (SOR) are multitargeted tyrosine kinase inhibitors (TKIs) with antineoplastic properties. In clinical observations, LAP and SOR may contribute to QTc prolongation, but the detailed mechanism for this has been largely unexplored. In this study, we investigated whether LAP and SOR affect the activities of membrane ion channels. Using a small animal model and primary cardiomyocytes, we studied the impact of LAP and SOR on Na+ and K+ currents. We found that LAP-induced QTc prolongation in mice was reversed by isoproterenol. LAP or SOR suppressed the amplitude of the slowly activating delayed-rectifier K+ current (IK(S)) in H9c2 cells in a time- and concentration-dependent fashion. The LAP-mediated inhibition of IK(S) was reversed by adding isoproterenol or meclofenamic acid, but not by adding diazoxide. The steady-state activation curve of IK(S) during exposure to LAP or SOR was shifted toward a less negative potential, with no change in the gating charge required to activate the current. LAP shortened the recovery from IK(S) deactivation. As rapid repetitive stimuli, the IK(S) amplitude decreased; however; the LAP-induced inhibition of IK(S) remained effective. LAP or SOR alone also suppressed inwardly rectifying K+ and voltage-gated Na+ current in neonatal rat ventricular myocytes. The inhibition of ionic currents during exposure to TKIs could be an important mechanism underlying changes in QTc intervals.

17.
Int J Cardiol ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-32005451

RESUMO

BACKGROUND: Anthracycline anticancer drugs such as epirubicin and doxorubicin may induce myocardial dysfunction, leading to poor prognosis. Early detection of minor left ventricular (LV) myocardial dysfunction is important for the prevention of anthracylcine-induced cardiotoxicity. Using layer-specific speckle tracking echocardiography (STE), we investigated the progressive distribution of myocardial dysfunction in both breast cancer patients and an animal toxicity model. METHODS: Patients with preserved LV ejection fraction (LVEF) preparing for epirubicin chemotherapy (N = 125) were prospectively enrolled. Layer-specific STE, including LV longitudinal and circumferential strains on subepicardium and subendocardium, were evaluated at baseline and after the first cycle, third cycle and six months of epirubicin therapy. A decline of LVEF above 10% to <55% at six months was defined as cardiotoxicity. These same strain measures were obtained in doxorubicin-treated rats and the distribution of myocardial fibrosis evaluated. RESULTS: In patients developing cardiotoxicity, LV longitudinal strain on subendocardium (LVLSendo) was significantly reduced after three cycles of therapy despite no significant changes in conventional LV systolic, diastolic parameters as well as LV circumferential strains at that moment. Compared to conventional echocardiographic parameters, LVLSendo was significantly predictive of cardiotoxicity. Declines in LVLSendo were also observed in doxorubicin-treated rats at an early stage. These reductions also predicted significant fibrosis in the subendocardial layer. CONCLUSION: LVLSendo is useful for the early detection of minor cardiac dysfunction during chemotherapy, thereby implicating endocardial involvement in the development of cardiotoxicity.

18.
Biochim Biophys Acta Gen Subj ; 1864(7): 129548, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32035161

RESUMO

BACKGROUND: Radiation exposure of tissues is associated with inflammatory cell influx. Myeloperoxidase (MPO) is an enzyme expressed in granulocytes, such as neutrophils (PMN) and macrophages, responsible for active chlorine species (ACS) generation. The present study aimed to: 1) determine whether exposure to γ-irradiation induces MPO-dependent ACS generation in murine PMN; 2) elucidate the mechanism of radiation-induced ACS generation; and 3) evaluate the effect of the synthetic lignan LGM2605, known for ACS scavenging properties. METHODS: MPO-dependent ACS generation was determined by using hypochlorite-specific 3'-(p-aminophenyl) fluorescein (APF) and a highly potent MPO inhibitor, 4-aminobenzoic acid hydrazide (ABAH), and confirmed in PMN derived from MPO-/- mice. Radiation-induced MPO activation was determined by EPR spectroscopy and computational analysis identified tyrosine, serine, and threonine residues near MPO's active site. RESULTS: γ-radiation increased MPO-dependent ACS generation dose-dependently in human MPO and in wild-type murine PMN, but not in PMN from MPO-/- mice. LGM2605 decreased radiation-induced, MPO-dependent ACS. Protein tyrosine phosphatase (PTP) and protein serine/threonine phosphatase (PSTP) inhibitors decreased the radiation-induced increase in ACS. Peroxidase cycle results demonstrate that tyrosine phosphorylation blocks MPO Compound I formation by preventing catalysis on H2O2 in the active site of MPO. EPR data demonstrate that γ-radiation increased tyrosyl radical species formation in a dose-dependent manner. CONCLUSIONS: We demonstrate that γ-radiation induces MPO-dependent generation of ACS, which is dependent, at least in part, by protein tyrosine and Ser/Thr dephosphorylation and is reduced by LGM2605. This study identified for the first time a novel protein dephosphorylation-dependent mechanism of radiation-induced MPO activation.

19.
Mol Inform ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32077235

RESUMO

Flash points of organic molecules play an important role in preventing flammability hazards and large databases of measured values exist, although millions of compounds remain unmeasured. To rapidly extend existing data to new compounds many researchers have used quantitative structure-property relationship (QSPR) analysis to effectively predict flash points. In recent years graph-based deep learning (GBDL) has emerged as a powerful alternative method to traditional QSPR. In this paper, GBDL models were implemented in predicting flash point for the first time. We assessed the performance of two GBDL models, message-passing neural network (MPNN) and graph convolutional neural network (GCNN), by comparing against 12 previous QSPR studies using more traditional methods. Our result shows that MPNN both outperforms GCNN and yields slightly worse but comparable performance with previous QSPR studies. The average R 2 and Mean Absolute Error (MAE) scores of MPNN are, respectively, 2.3 % lower and 2.0 K higher than previous comparable studies. To further explore GBDL models, we collected the largest flash point dataset to date, which contains 10575 unique molecules. The optimized MPNN gives a test data R 2 of 0.803 and MAE of 17.8 K on the complete dataset. We also extracted 5 datasets from our integrated dataset based on molecular types (acids, organometallics, organogermaniums, organosilicons, and organotins) and explore the quality of the model in these classes.

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