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1.
Huan Jing Ke Xue ; 41(5): 2166-2176, 2020 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608834

RESUMO

To explore the effect mechanism of the artificial mixing process on the temporal and spatial succession of algae community structure in a water body, this study used water-lifting aerators to induce in-situ artificial mixing of the water body of Jinpen Reservoir, and in-situ spot physical-chemical parameters and algae of the water body of the reservoir were observed during an artificial mixing process. A total of 51 species of 28 genera of 6 families of algae were identified in the water body of the Jinpen Reservoir. The artificial mixing effect of the water-lifting aerators significantly inhibited the growth of algae in the water, and had a significant impact on the community structure. Before activation of the water-lifting aerators, algae were mainly distributed in the surface water body, and Chlorella vulgaris was the dominant species. With the operation of the water-lifting aerators, the algal density of surface water body decreased significantly, and the vertical distribution of the algae density in the water body tended to be uniform. The dominant species tended to succeed in Cyclotella sp. This study used the method of redundancy analysis, combined with critical depth theory and the characteristics of algae growth, to analyze the relationship between the spatial-temporal succession of algae community structure and the changes in the main physical-chemical parameters in Jinpen Reservoir during the artificial process. The analysis results showed that the artificial mixing of the water-lifting aerators mainly affects the temporal and spatial succession of the algae community structure by rapidly destroying the thermal stratification stability of the water body and significantly increasing the water mixing depth.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(3): 717-723, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32552926

RESUMO

OBJECTIVE: To investigate the clinical significance of AML patients with 11q23/MLL rearrangement, and to evaluate the effect of those mutations on the AML patients. METHODS: 53 cases involving translocations of chromosome 11q23 were identified by chromosome banding analysis. MLL rearrangements were detected by fluorescence in situ hybridization and/or multiplex nested PCR. The samples were screened for mutations in the candidate genes FLT3-ITD, FLT3-TKD, TET2, N-RAS, ASXLI, EZH2, DNMT3, C-Kit, NPM1, WT1, CEBPA by using genomic DNA-PCR and deep-sequencing. RESULTS: 21/53 MLL-rearranged AML cases showed at least one additional chromosomal aberrations. The most common additional aberration was +8. Gene mutations were observed in 23 cases (43.4%) and most cases showed singal mutation. N-RAS mutation was more frequent (8 cases, 15.1%), followed by WT1 mutation in 4 cases (7.5%), FLT3-ITD mutation in 3 cases, ASXL1 mutation in 2 cases, DNMT3A mutation in 2 cases, EZH2 mutation in 1 case, c-Kit17 mutation in 1 case, FLT3-TKD mutation in 1 case, and FLT3-ITD and TKD mutation coexistent in 1 case. No mutation was detected in CEBPA, NPM1, C-KIT8, TET2. Median OS for gene mutated patients was 8.5 months and 13 months for no mutated patients. Median OS for patients who received hematopoietic stem cell transplantation (HSCT) was 22.5 months and 7.5 months for patients who olny received chemotherapy. CONCLUSION: A relatively high mutation frequency is observed in AML patients with 11q23/MLL rearrangements and most cases shows single mutation. The RAS signaling pathway alterations are most common. Gene mutation does not affect the OS of these patients, who show poor prognosis. A significantly higher Hb at initial diagnosis in FLT3 mutated patients is significantly higher than that in FLT3 wild-type cases. Patients who underwent HSCT show a better prognosis than those only received chemotherapy.

3.
Ann Surg ; 2020 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-32516232

RESUMO

OBJECTIVE: To define geographic variations in emergency general surgery (EGS) care, we sought to determine how much variability exists in the rates of EGS operations and subsequent mortality in the Northeastern and Southeastern United States (US). SUMMARY BACKGROUND DATA: While some geographic variations in healthcare are normal, unwarranted variations raise questions about the quality, appropriateness, and cost-effectiveness of care in different areas. METHODS: Patients ≥18 years who underwent 1 of 10 common EGS operations were identified using the State Inpatient Databases (2011-2012) for 6 states, representing Northeastern (New York) and Southeastern (Florida, Georgia, Kentucky, North Carolina, Mississippi) US. Geographic unit of analysis was the hospital service area (HSA). Age-standardized rates of operations and in-hospital mortality were calculated and mapped. Differences in rates across geographic areas were compared using the Kruskal-Wallis test, and variance quantified using linear random-effects models. Variation profiles were tabulated via standardized rates of utilization and mortality to compare geographically heterogenous areas. RESULTS: 227,109 EGS operations were geospatially analyzed across the 6 states. Age-standardized EGS operation rates varied significantly by region (Northeast rate of 22.7 EGS operations per 10,000 in population versus Southeast 21.9; P < 0.001), state (ranging from 9.9 to 29.1; P < 0.001), and HSA (1.9-56.7; P < 0.001). The geographic variability in age-standardized EGS mortality rates was also significant at the region level (Northeast mortality rate 7.2 per 1000 operations vs Southeast 7.4; P < 0.001), state-level (ranging from 5.9 to 9.0 deaths per 1000 EGS operations; P < 0.001), and HSA-level (0.0-77.3; P < 0.001). Maps and variation profiles visually exhibited widespread and substantial differences in EGS use and morality. CONCLUSIONS: Wide geographic variations exist across 6 Northeastern and Southeastern US states in the rates of EGS operations and subsequent mortality. More detailed geographic analyses are needed to determine the basis of these variations and how they can be minimized.

4.
Eur Respir J ; 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32513782

RESUMO

Pathological mechanisms of pulmonary arterial hypertension (PAH) remain largely unexplored. Effective treatment of PAH remains a challenge. The aim of this study was to discover the underlying mechanism of PAH through functional metabolomics and to help develop new strategies for prevention and treatment of PAH.Metabolomic profiling of plasma in patients with idiopathic PAH was evaluated through HPLC-MS, with spermine identified to be the most significant and validated in another independent cohort. The roles of spermine and spermine synthase (SMS) were examined in pulmonary arterial smooth muscle cells (PASMCs) and rodent models of pulmonary hypertension.Using targeted metabolomics, plasma spermine levels were found to be higher in patients with idiopathic PAH compared to healthy controls. Spermine administration promoted proliferation and migration of PASMCs and exacerbated vascular remodelling in rodent models of pulmonary hypertension. The spermine-mediated deteriorative effect can be attributed to a corresponding upregulation of its synthase (SMS) in the pathological process. Inhibition of SMS in vitro suppressed platelet-derived growth factor-BB-mediated proliferation of PASMCs, and in vivo attenuated monocrotaline-mediated pulmonary hypertension in rats.Plasma spermine promotes pulmonary vascular remodelling. Inhibiting spermine synthesis could be a therapeutic strategy for PAH.

5.
JMIR Form Res ; 4(5): e17179, 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32463374

RESUMO

BACKGROUND: Many children aged younger than 5 years living in low- and middle-income countries are at risk for poor development. Early child development (ECD) programs are cost-effective strategies to reduce poverty, crime, school dropouts, and socioeconomic inequality. With the spread of low-cost mobile phones and internet access in low- and middle-income countries, new service delivery models such as mobile phone-aided interventions have a great potential to improve early childhood development. OBJECTIVE: This study aimed to identify the beliefs on importance of ECD, feasibility of a proposed intervention using mobile phones and factors that may affect the usability of the intervention among mothers of newborns in a poverty-stricken area in southwestern China. METHODS: We conducted an in-depth, semistructured interview study of 25 low-income mothers of newborns recruited from two county hospitals in Yunnan Province. We applied the health belief model and cultural competence theories to identify the facilitators, barriers, and preferences among the target population for parenting knowledge. RESULTS: The results showed that the participants had low health literacy and high perceived needs for learning ECD knowledge. At the same time, they experienced several barriers to learning parenting information and following evidence-based instructions including having limited time, limited financial resources, and different opinions on childcare among family members. Many participants preferred to receive personalized messages tailored to their specific needs and preferred videos or graphics to text only in the messages. Many favored a separate module to support postpartum mental health. CONCLUSIONS: The study assessed the acceptability of an early childhood intervention using mobile phones to meet the needs of the target population based on their beliefs, traits, and preferences and provided suggestions to refine the intervention to improve its usability.

6.
Obes Surg ; 30(8): 3258-3259, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32424793

RESUMO

In the original articles there are data errors in some of the Figure 2 tables. The corrected Figure 2 tables follow.

7.
Anal Chem ; 92(12): 8487-8496, 2020 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-32412732

RESUMO

The profile of cholesteryl esters (CEs) is increasingly used in metabolic disease monitoring due to the roles of CE in regulating the cholesterol level. While electrospray ionization-tandem mass spectrometry is routinely applied for the identification and quantitation of CE, it has a limitation of not being able to provide the location of carbon-carbon double bond (C═C) within unsaturated fatty acyls. In this study, we paired offline 2-acetylpyridine (2-AP) Paternò-Büchi (PB) reaction and reversed-phase liquid chromatography-tandem mass spectrometry to achieve highly sensitive and structural informative CE analysis from complex mixtures. The 2-AP PB reactions of CE standards provided 20-30% conversion but resulted in enhanced ion signal relative to that of intact CE detected as ammonium adduct ions. MS/MS of 2-AP derivatized CE via collision-induced dissociation produced two abundant diagnostic ions for each C═C in a fatty acyl, leading to both sensitive identification and quantitation of C═C location isomers. Twelve saturated and twenty-seven unsaturated CEs were profiled in pooled human plasma; of the latter group, relative quantitation of 6 groups of C═C location isomers was achieved. A dehydrocholesteryl ester, DHE 18:2 (Δ9,12), was confidently differentiated from coexisting compositional isomers: CE 18:3 (Δ9,12,15) and CE 18:3 (Δ6,9,12). The above results represented improved CE coverage at the C═C location level over those reported by gas chromatography MS or acetone PB-MS/MS methods.

8.
Oncol Rep ; 43(5): 1365-1374, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32323827

RESUMO

There is extensive evidence suggesting that microRNAs (miRs) can modulate the activity of oncogenes and tumor suppressors, and are associated with the occurrence of cancer. In the present study, the function of miR­363­3p in the progression of retinoblastoma (RB) was investigated. miR­363­3p expression in RB was decreased, and miR­363­3p protein levels were found to be inversely correlated with phosphatidylinositol­4,5­bisphosphate 3­kinase catalytic subunit α (PIK3CA) levels. Overexpression of miR­363­3p in an in vitro model of RB revealed that miR­363­3p had anticancer effects on RB and regulated PIK3CA, pyruvate dehydrogenase kinase 1 (PDK1) and phosphorylated protein kinase B (p­AKT) protein expression. Downregulation of miR­363­3p promoted cell proliferation of RB cells through PIK3CA, PDK1 and p­AKT protein expression. Knockdown of PIK3CA increased the anticancer effects of miR­363­3p in RB cells. Treatment with OSU­03012, a PDK1 inhibitor, accelerated the anticancer effects of miR­363­3p in RB cells. Taken together, the results demonstrate that miR­363­3p functions as a tumor suppressor in RB by targeting PIK3CA.

9.
Eur J Haematol ; 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32282962

RESUMO

BACKGROUND: Currently, the prognostic stratification and therapeutic evaluation systems for multiple myeloma (MM) lack specific molecular indicators. OC-STAMP is a new gene and is also highly expressed in MM. METHODS: A total of 160 MM patients have been investigated with both quantitative reverse transcription PCR (RT-qPCR), flow cytometry (FCM) and cytogenetic FISH on the same mononuclear cells isolated from bone marrow specimens. RESULTS: We found that OC-STAMP mRNA levels were significantly higher in newly diagnosed cases of MM than in healthy donors (median, 0.52% vs. 0.02%, P < .001). Moreover, the changes in the OC-STAMP mRNA levels paralleled the disease stages and minimal residual disease, as detected by FCM. Furthermore, we found that patients with high OC-STAMP mRNA levels were more likely to develop ≥3 bone lesions, be diagnosed with Durie-Salmon stages III, and have the P53 (17p13) deletion. In addition, advanced stage patients with high OC-STAMP mRNA levels had a lower 4-year progression-free survival (5.6% vs. 22.9%, P = .0055) and a worse 4-year overall survival (25.8% vs. 48.8%, P = .0137) compared to patients with low mRNA levels of this indicator. CONCLUSIONS: OC-STAMP may be a promising molecular indicator to monitor treatment effects and participate in the prognostic stratification of MM.

10.
Ageing Res Rev ; 60: 101058, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32234545

RESUMO

Although efforts have been made to develop therapeutic approaches, the clinical management of AD maintains a major challenge. CircRNAs are highly abundant and evolutionarily conserved in neuronal tissues in mammals. Accumulating data suggest that circRNAs regulate biological and pathological processes by sponging miRNAs, binding to RBPs, modulating mRNA stability, and being translated into peptides in various diseases, serving as biomarkers and potential therapeutic targets. Growing evidence demonstrates that circRNAs have been implicated in the pathogenesis of AD. Here, we summarized current studies on circRNAs involved in AD pathology, providing a theoretical basis for the use of circRNAs in AD treatment and diagnosis.

11.
Br J Haematol ; 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32103499

RESUMO

About 25% of patients with newly diagnosed acute myeloid leukaemia (AML) have normal cytogenetics and no nucleophosmin 1 (NPM1) mutation or Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD). The prognosis and best therapy for these patients is controversial. We evaluated 158 newly diagnosed adults with this genotype who achieved histological complete remission within two cycles of induction therapy and were assigned to two post-remission strategies with and without an allotransplant. Targeted regional sequencing at diagnosis was performed and data were used to estimate their prognosis, including relapse and survival. In multivariable analyses, having wild-type or mono-allelic mutated CCAAT/enhancer-binding protein alpha (CEBPA) [hazard ratio (HR) 2·39, 95% confidence interval (CI) 1·08-5·30; P = 0·032), mutated NRAS (HR 2·67, 95% CI 1·36-5·25; P = 0·004), mutated colony-stimulating factor 3 receptor (CSF3R) (HR 2·85, 95% CI 1·12-7·27; P = 0·028) and a positive measurable residual disease (MRD)-test after the second consolidation cycle (HR 2·88, 95% CI 1·32-6·30; P = 0·008) were independently correlated with higher cumulative incidence of relapse (CIR). These variables were also significantly associated with worse survival (HR 3·02, 95% CI 1·17-7·78, P = 0·022; HR 3·62, 95% CI 1·51-8·68, P = 0·004; HR 3·14, 95% CI 1·06-9·31, P = 0·039; HR 4·03, 95% CI 1·64-9·89, P = 0·002; respectively). Patients with ≥1 of these adverse-risk variables benefitted from a transplant, whereas the others did not. In conclusion, we identified variables associated with CIR and survival in patients with AML and normal cytogenetics without a NPM1 mutation or FLT3-ITD.

12.
Obes Surg ; 30(5): 1917-1928, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32048152

RESUMO

BACKGROUND: Obesity is a worldwide epidemic leading to non-alcoholic fatty liver disease. Alterations in the liver fat fraction (LFF) assessed by MRI following bariatric surgery is a promising feature; however, few studies have been fully elucidated. PURPOSE: To determine the alterations in the LFF features following surgery using MRI, to determine the correlation with the clinical non-alcoholic steatohepatitis score (C-NASH score), and to identify the predictive factors for postoperative score changes. METHODS: Patients (n = 69) underwent MRI to measure the LFF at baseline and 3 months postoperatively. Paired sample t tests were applied to investigate the alterations in the major parameters. Univariate analyses were performed to evaluate the factors predicting C-NASH score changes after surgery. RESULTS: Compared with the baseline levels, the LFF significantly decreased 3 months postoperatively (P < 0.001). Significant positive correlations were detected between the C-NASH score and LFF levels (P < 0.001). Among the ROC curves for C-NASH score change, the AUC for the ROC curve of LFF was 0.812 (95% CI 0.707, 0.916) and the cut-off value was 6.16%. Weight at baseline was a significant predictive factor for postoperative changes when the C-NASH score was ≥ 3 (P < 0.001). The AUC for the ROC curve of weight was 0.897 (95% CI 0.782, 1.000) and 117 kg was the cut-off value. CONCLUSIONS: LFF decreased following bariatric surgery, which predicted C-NASH score changes after surgery. For patients with a higher risk of NASH (score ≥ 3) at baseline and lower preoperative body weight, we noted significantly greater effects of surgery on score change value.

13.
J Mater Chem B ; 8(7): 1445-1455, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-31993613

RESUMO

The tumor microenvironment (TME), which is characterised by high H2O2 and glutathione (GSH) levels, low pH value and hypoxia, imposes crucial influences on tumor therapeutic outcomes. Rational design and preparation of nanomaterial systems that are responsive to the intrinsic properties of the TME open a promising avenue towards tumor-specific treatment. Herein, CoMn-layered double hydroxide (CoMn-LDH) nanosheets were synthesized via a bottom-up method followed by surface modification with a photosensitizer, chlorin e6 (Ce6), which exhibited TME-responsive imaging as well as photodynamic and chemodynamic synergistic therapy (PDT/CDT). Due to their ultralow bond energy and large adsorption energy, CoMn-LDH nanosheets show fast self-degradability in a GSH (10 mM) microenvironment, giving an excellent CDT activity in mildly acidic conditions (pH = 6.5), superior GSH removal ability (99.82%) and O2 production (35.37 µg L-1 s-1). Moreover, Ce6/CoMn-LDH nanosheets display satisfactory photoacoustic (PA) imaging and GSH-enhanced magnetic resonance imaging (MRI) with a 45.1-fold T1-enhancement. In addition, both in vitro and in vivo therapeutic tests based on Ce6/CoMn-LDH demonstrate a satisfactory anticancer activity with complete cancer cell apoptosis and dramatic tumor elimination. This work provides a new perspective for the design of multifunctional 2D nanosheets towards a fully promoted TME-responsive synergistic therapy, which holds great promise for future clinical diagnosis and treatment.

14.
Clin Chim Acta ; 502: 120-127, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31891671

RESUMO

BACKGROUND AND AIM: Recently, the role of albumin-bilirubin (ALBI) score in chronic hepatitis B (CHB) has not been well-understood. We aimed to investigate the association of ALBI score with natural history of chronic HBV infection and treatment response of CHB patients. METHODS: The ALBI score in a cohort of 849 individuals including 721 chronic HBV-infected patients naïve to anti-HBV treatment in different phases and 128 healthy controls were estimated. Additionally, the dynamic changes of ALBI score of 243 hepatitis B e antigen (HBeAg)-positive CHB patients treated with pegylated interferon-alpha (PEG-IFN-α) or nucleos(t)ide analogues (NAs) were tested for 72 weeks. RESULTS: ALBI score differed among phases, with the highest score in HBeAg-positive CHB patients, followed by HBeAg-negative CHB patients, HBeAg-positive chronic HBV infection, and HBeAg-negative chronic HBV infection. Besides, CHB patients harbouring high baseline ALBI score exhibited a relatively stronger therapeutic response to PEG-IFN-α or NAs. Moreover, the rate of HBeAg and HBsAg loss in patients with ALBI grade 2 was persistently higher than that in patients with ALBI grade 1 throughout the course of treatment. Furthermore, ALBI score was an independent predictor of sustained response achievement. The combined use of ALBI score, HBeAg and ALT could enhance the predictive value of treatment response. CONCLUSIONS: ALBI score differed significantly across the natural course of chronic HBV infection and was correlated with PEG-IFN-α and NAs treatment response in HBeAg-positive CHB patients, which suggested that ALBI score could be useful as an auxiliary clinical factor to determine the initiation of therapy and predict stronger antiviral treatment response.

15.
Diabetes ; 69(4): 760-770, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31974145

RESUMO

Long-term hyperglycemia in patients with diabetes leads to human serum albumin (HSA) glycation, which may impair HSA function as a transport protein and affect the therapeutic efficacy of anticoagulants in patients with diabetes. In this study, a novel mass spectrometry approach was developed to reveal the differences in the profiles of HSA glycation sites between patients with diabetes and healthy subjects. K199 was the glycation site most significantly changed in patients with diabetes, contributing to different interactions of glycated HSA and normal HSA with two types of anticoagulant drugs, heparin and warfarin. An in vitro experiment showed that the binding affinity to warfarin became stronger when HSA was glycated, while HSA binding to heparin was not significantly influenced by glycation. A pharmacokinetic study showed a decreased level of free warfarin in the plasma of diabetic rats. A preliminary retrospective clinical study also revealed that there was a statistically significant difference in the anticoagulant efficacy between patients with diabetes and patients without diabetes who had been treated with warfarin. Our work suggests that larger studies are needed to provide additional specific guidance for patients with diabetes when they are administered anticoagulant drugs or drugs for treating other chronic diseases.

16.
J Hazard Mater ; 384: 121359, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31635821

RESUMO

The bio-oxidative dissolution of arsenopyrite, the most severe arsenic contamination source, can be mediated by organic substances, but pertinent studies on this subject are scarce. In this study, the bio-oxidative dissolution of arsenopyrite by Sulfobacillus thermosulfidooxidans and arsenic immobilization were evaluated in the presence of humic acid (HA). The mineral dissolution was monitored through analyses of the parameters in solution, phase and element speciation transformations on the mineral surface, and arsenic immobilization on the surfaces of cells and jarosites-HA. The results show that the presence of HA enhances the dissolution of arsenopyrite, e.g., 7.1% of arsenopyrite was in the residue after 12 d of bio-oxidation compared to 19.3% in the absence of HA. Meanwhile, the presence of HA led to changes of the fates of As and Fe and no accumulation of elemental sulfur (S0) or ferric arsenate on the mineral surface. Moreover, a flocculent porous structure was formed on the surfaces of both microbial cells and jarosites, on which a large amount of arsenic was adsorbed. These results clearly indicate that HA can simultaneously promote the dissolution of arsenopyrite and arsenic immobilization, which may be significant for bioleaching of arsenopyrite-bearing contaminated sites.

17.
Appl Microbiol Biotechnol ; 104(2): 661-673, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31822984

RESUMO

We have recently derived a ß-N-acetylhexosaminidase, BbhI, from Bifidobacterium bifidum JCM 1254, which could regioselectively synthesize GlcNAcß1-3Galß1-4Glc with a yield of 44.9%. Here, directed evolution of BbhI by domain-targeted mutagenesis was carried out. Firstly, the GH20 domain was selected for random mutagenesis using MEGAWHOP method and a small library of 1300 clones was created. A total of 734 colonies with reduced hydrolytic activity were isolated, and three mutants with elevated transglycosylation yields, GlcNAcß1-3Galß1-4Glc yields of 68.5%, 74.7%, and 81.1%, respectively, were obtained. Subsequently, nineteen independent mutants were constructed according to all the mutation sites in these three mutants. After transglycosylation analysis, Asp714 and Trp773 were identified as key residues for improvement in transglycosylation ability and were chosen for the second round of directed evolution by site-saturation mutagenesis. Two most efficient mutants D714T and W773R that acted as trans-ß-N-acetylhexosaminidase were finally achieved. D714T with the substitution at the putative nucleophile assistant residue Asp714 by threonine showed high yield of 84.7% with unobserved hydrolysis towards transglycosylation product. W773R with arginine substitution at Trp773 residue locating at the entrance of catalytic cavity led to the yield up to 81.8%. The kcat/Km values of D714T and W773R for hydrolysis of pNP-ß-GlcNAc displayed drastic decreases. NMR investigation of protein-substrate interaction revealed an invariable mode of the catalytic cavity of D714T, W773R, and WT BbhI. The collective motions of protein model showed the mutations Thr714 and Arg773 exerted little effect on the dynamics of the inside but a large effect on the dynamics of the outside of catalytic cavity.

18.
J Sep Sci ; 43(1): 31-55, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31573133

RESUMO

The formation of DNA adducts by genotoxic agents is an early event in cancer development, and it may lead to gene mutations, thereby initiating tumor development. The measurement of DNA adducts can provide critical information about the genotoxic potential of a chemical and its mechanism of carcinogenesis. In recent decades, liquid chromatography coupled with mass spectrometry has become the most important technique for analyzing DNA adducts. The improvements in resolution achievable with new chromatographic separation techniques coupled with the high specificity and sensitivity and wide dynamic range of new mass spectrometry systems have been used for both qualitative and quantitative analyses of DNA adducts. This review discusses the challenges in qualitative and quantitative analyses of DNA adducts by liquid chromatography coupled with mass spectrometry and highlights recent developments towards overcoming the limitations of liquid chromatography coupled with mass spectrometry methods. The key steps and new solutions, such as sample preparation, mass spectrometry fragmentation, and method validation, are summarized. In addition, the fundamental principles and latest advances in DNA adductomic approaches are reviewed.

19.
Biochimie ; 170: 1-9, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31794784

RESUMO

IFN-γ (Interferon-gamma) is a pleiotropic cytokine. It is often involved in a variety of physiological processes by binding to the cell surface transmembrane receptor (IFN-γR) to initiate a series of signalling pathways that transmit external signals from cell surface receptors to the cell nucleus. Heparan sulphate (HS), a highly sulphated linear polysaccharide, is ubiquitous on the mammalian cell surface and extracellular matrix. Electrostatic interactions can be generated between the highly sulphated HS region and specific basic amino acid residues in the IFN-γ structure, thereby detaining IFN-γ on the cell surface, and the concentration of IFN-γ on the cell surface is thus, changed. IFN-γ retained on the cell surface will optimize the binding of IFN-γ to the transmembrane receptor resulting in high efficiency signalling. Heparin is a glycosaminoglycan with a structure similar to HS. The structural similarity provides a basis for modelling exogenous heparin dependence for interference with IFN-γ function. This model can be summarized as follows: First, the competitive binding effect; heparin bound to cytokines by competing with membrane-associated HS, causes a decrease in cytokine concentration on the cell surface. Second, the principle of priority occupancy; heparin can occupy the receptor binding site on cytokines, partially preventing the IFN-γ-IFN-γR interaction. These two models interfere with IFN-γ signal transmission. To decipher the mechanism by which heparin influences IFN-γ activity, studies of the structure-activity relationship are in progress. This paper summarizes research progress on the IFN-γ signalling pathway, heparin interference with IFN-γ activity and the structure-activity relationship between heparin and IFN-γ.

20.
Mitochondrion ; 50: 145-148, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31756516

RESUMO

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is caused by defective oxidative phosphorylation in the cerebral parenchyma, cerebral blood vessels, and leptomeningeal tissue. Although increased blood and cerebrospinal fluid (CSF) lactate level has been used as a diagnostic biomarker in patients with MELAS, no biomarkers reflecting disease activity exist. Since we have developed a highly sensitive ATP assay system using luciferase luminous reaction, we examined CSF ATP in patients with MELAS and found that it negatively correlates with disease activity and that it reflects the efficacy of the treatment. CSF ATP might be a novel disease monitoring marker for MELAS.

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