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1.
Methods Mol Biol ; 2057: 79-92, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31595472

RESUMO

Nitrate, ammonium, or a combination of both is the form of N available for nitrogen assimilation from soil by the plants. Nitrogen is an important and integral part of amino acids, nucleotides, and defense molecules. Hence it is very important to study the role of nitrate and ammonium nutrition in plant defense via hypersensitive response (HR). Shifting plants from ammonium nitrate Hoagland solution to nitrate Hoagland nutrition slightly enhances root length and leaf area. HR phenotype is different in nitrate and ammonium grown plants when challenged with avirulent Pseudomonas syringae DC3000 avrRpm1. HR is also associated with increased production of reactive oxygen species (ROS) and nitric oxide (NO). Hence to understand HR development it is essential to measure HR lesions, cell death, ROS, NO, and bacterial growth. Here we provide a stepwise protocol of various parameters to study HR in Arabidopsis in response to nitrate and ammonium nutrition.

2.
Medicine (Baltimore) ; 98(41): e17348, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593084

RESUMO

Immune checkpoint inhibitors (ICIs) like cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4) and programmed death cell protein 1 (anti-PD1) have revolutionized cancer treatment. As ICI use becomes widespread, more immune-related adverse events (irAE's) are being reported. Our aim was to investigate the frequency and nature of new irAE's as well as report the frequency of flare-ups of pre-existing autoimmune conditions occurring after ICI therapy.We performed a retrospective chart review of all patients treated for cancer with anti-PD1 or anti-CTLA4 or combination therapy at our tertiary care center from January 2014 to April 2016. Demographic data, cancer type and stage, irAE's (new immune disorders and disease flares of pre-existing autoimmune disorders on ICI therapy), and drug treatment information were extracted.We identified 220 patients treated with ICI therapy during the study period out of which 27% (60/220) developed irAE's. 11% in anti-CTLA4 group and 16% among anti-PD1 treated patients developed irAE's. IrAE's resulted in discontinuation of cancer therapy in 28% of those who developed irAE's. 21.4% had a flare of their autoimmune disease but only 1 required discontinuation of immunotherapy.IrAE's are an important emerging clinical disease entity for specialists to be aware of. Our study shows that ICI's can be safely used in patients with pre-existing autoimmune conditions with close monitoring. However, there is still a large unmet need to have a better understanding of how to systematically evaluate and manage patients with irAE's as well as for identifying the predictors of irAE's.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Doenças do Sistema Imunitário/induzido quimicamente , Imunoterapia/efeitos adversos , Melanoma/tratamento farmacológico , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Feminino , Humanos , Doenças do Sistema Imunitário/imunologia , Masculino , Melanoma/imunologia , Pessoa de Meia-Idade , Neoplasias/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Estudos Retrospectivos
3.
Indian J Med Res ; 149(6): 763-770, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31496529

RESUMO

Background & objectives: In acute pancreatitis (AP) gut barrier dysfunction is considered as an important predisposing factor leading to increased intestinal permeability (IP). In this study a pooled analysis of data published in our previous four studies on various aspects of gut permeability and endotoxaemia in patients with AP was attempted to find an association between increased IP and severity of disease and associated complications. Methods: This study was a pooled analysis of data of four previously published prospective studies on AP. Gut permeability, assessed by lactulose/mannitol excretion in urine and endotoxin core antibodies type IgG and IgM (EndoCab IgG and IgM) were measured on days zero and seven (D0 and D7) of admission. All patients received standard treatment of AP. We studied whether IgG and IgM anti-endotoxin titres and lactulose-mannitol ratio (LMR) at admission and D7 were associated with organ failure, infection and mortality. Results: The titres of anti-endotoxin IgG and IgM were lower in all patients of AP (n=204), both in mild AP (n=24) and severe AP (n=180) in the first week, compared to controls (n=15). There was no significant difference in serum IgG and IgM anti-endotoxin levels and LMR at baseline and at D7 among patients with organ failure, infection and mortality. Interpretation & conclusions: Our findings showed that serum IgG and IgM anti-endotoxin titres and LMR at admission and at day 7 were not associated with organ failure, infection, and death of patients with AP.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31373768

RESUMO

OBJECTIVE: Autoimmune conditions are associated with an increased risk of adverse pregnancy complications and outcomes, suggesting that pregnancy complications may mediate the excess risk. We performed a causal mediation analysis to quantify the mediated effects of autoimmune conditions on adverse pregnancy outcomes. METHODS: We queried a California birth cohort created from linked birth certificates and hospital discharge summaries. From 2,963,888 births, we identified women with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis and inflammatory bowel disease (IBD). Pregnancy complications included preeclampsia/hypertension, gestational diabetes and infection in pregnancy. Adverse pregnancy outcomes were preterm birth, cesarean delivery and small for gestational age. We performed a mediation analysis to estimate the total effects of each autoimmune condition and adverse pregnancy outcome, and the indirect effects through pregnancy complications. RESULTS: All four autoimmune conditions were associated with preterm birth and cesarean delivery, and RA, SLE and IBD were associated with small for gestational age offspring. The strongest mediator of RA, SLE, and psoriasis was preeclampsia/hypertension, accounting for 20-33% of the excess risk of preterm births and 10-19% of excess cesarean deliveries. Gestational diabetes and infections generally mediated <10% of excess adverse pregnancy outcomes. Of the four autoimmune conditions, selected pregnancy complications mediated the least amount of adverse pregnancy outcomes among women with IBD. CONCLUSIONS: We found evidence that some excess risk of adverse pregnancy outcomes is mediated through pregnancy complications, particularly preeclampsia/hypertension. Quantifying excess risk and associated pathways provides insight into the underlying etiologies of adverse pregnancy outcomes and can inform intervention strategies. This article is protected by copyright. All rights reserved.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31421018

RESUMO

OBJECTIVE: To determine the performance of administrative-based algorithms for classifying interstitial lung disease (ILD) complicating rheumatoid arthritis (RA). METHODS: Participants in a large, multicenter RA registry were screened for ILD using International Classification of Diseases (ICD) codes. Medical record review confirmed ILD among participants screening positive and a random sample of those screening negative. ICD and procedure codes, provider specialty, and dates were extracted from Veterans Affairs administrative data to construct ILD algorithms. Performance of these algorithms against medical record review was assessed by sensitivity, specificity, positive predictive value (PPV), negative predictive value, and Kappa using inverse probability weighting to account for sampling methods. RESULTS: Medical records of 536 RA patients were reviewed, confirming 182 (stringent definition) and 203 (relaxed definition) ILD cases. Initially, we identified ≥2 ICD codes from inpatient or outpatient encounters as optimal discriminating factors (specificity 96.0%, PPV 65.5%, Kappa 0.70). Subsequently, we constructed a set of ICD-9/10 codes that improved algorithm specificity (specificity 96.8%, PPV 69.5%, Kappa 0.72). Algorithms that included a pulmonologist diagnosis or chest CT plus pulmonary function testing or lung biopsy had improved performance (specificity 98.0%, PPV 77.4%, Kappa 0.75). PPV increased with exclusion of other ILD causes (78.5%), in comparisons with the relaxed ILD definition (82.4%), and in sensitivity analyses (83.4-86.3%). Gains in specificity and PPV with greater algorithm requirements were accompanied by declines in sensitivity. CONCLUSION: Administrative algorithms with optimal combinations of ICD codes, provider specialty, diagnostic testing, and exclusion of other ILD causes accurately classify ILD in RA.

7.
Indian J Gastroenterol ; 38(3): 220-246, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31352652

RESUMO

INTRODUCTION: These Asian Working Group guidelines on diet in inflammatory bowel disease (IBD) present a multidisciplinary focus on clinical nutrition in IBD in Asian countries. METHODOLOGY: The guidelines are based on evidence from existing published literature; however, if objective data were lacking or inconclusive, expert opinion was considered. The conclusions and 38 recommendations have been subject to full peer review and a Delphi process in which uniformly positive responses (agree or strongly agree) were required. RESULTS: Diet has an important role in IBD pathogenesis, and an increase in the incidence of IBD in Asian countries has paralleled changes in the dietary patterns. The present consensus endeavors to address the following topics in relation to IBD: (i) role of diet in the pathogenesis; (ii) diet as a therapy; (iii) malnutrition and nutritional assessment of the patients; (iv) dietary recommendations; (v) nutritional rehabilitation; and (vi) nutrition in special situations like surgery, pregnancy, and lactation. CONCLUSIONS: Available objective data to guide nutritional support and primary nutritional therapy in IBD are presented as 38 recommendations.

8.
Obes Surg ; 2019 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-31302845

RESUMO

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) patients are recommended to take multiple oral vitamin supplements daily. Transdermal multivitamin patches are being advertised as an alternative for use in bariatric patients with no data to support their efficacy. The purpose of this study was to evaluate response to daily transdermal use of multivitamin patch after LRYGB and to compare them with a control group of similar patients who used oral supplements. METHODS: A retrospective review was carried out on patients who had LRYGB at a community hospital from February 2015 to February 2019. Patients who had completed preoperative and annual postoperative bariatric laboratory tests were included. They were divided into patch and pill (control) group. RESULTS: Seventeen patients were included in the patch and 27 in the pill group. Patients in each group used either patch or pills for 12 months and they were 1 year post LRYGB. Fourteen patients (82.35%) in patch group and 11 patients (40.74%) in pill group had at least 1 deficiency at annual postoperative blood work (P = .0116). Vitamin D deficiency was seen in 81% patients in patch group vs 36% in the pill group (P = .0092). Statistically significant lower postoperative serum concentrations of vitamin D, B1, and B12 were seen in the patch group. CONCLUSIONS: Multivitamin patch users are more likely to have vitamin D deficiency and lower serum concentration of various vitamins and minerals. Future large studies are needed on the efficacy of multivitamin patches before they can be recommended to bariatric patient population.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31153706

RESUMO

OBJECTIVE: An important extra-articular manifestation of rheumatoid arthritis (RA) is interstitial lung disease (ILD). The relationship between the usual interstitial pneumonia (UIP) pattern and mortality in patients with RA is unclear. The purpose of this study was to complete a systematic literature review and meta-analysis on the association between RA-ILD pattern and mortality risk. METHODS: We performed a systematic literature review through December 12, 2018. Study characteristics, unadjusted and adjusted relative risks (RR) of mortality for ILD pattern were extracted from the identified studies and quality assessments were performed. RR for mortality (RA-UIP vs. other RA-ILD) was pooled using inverse variance weighting and random effects models. RESULTS: Ten retrospective cohort studies met our eligibility criteria. A total of 1256 RA-ILD patients were included with 484 total deaths. Meta-analysis yielded a pooled RR of 1.66 (95% confidence interval1.07 to 2.56) for death among those with UIP RA-ILD compared with other patterns. In sub-group analysis when pooling studies comparing UIP to NSIP pattern of RA-ILD, the RR was 2.39 (95% CI 0.86-6.68). CONCLUSION: Through a systematic literature review and meta-analysis, we found UIP pattern to be associated with a higher mortality risk in RA-ILD compared to other patterns of RA-ILD although more recent studies emphasize the importance of pulmonary physiology and the extent of lung involvement as significant predictors of mortality rather than the pattern of RA-ILD. Recognizing the small number of studies satisfying eligibility and inconsistent accounting for confounders, further study of mortality risk in RA-ILD is needed with standardized assessment of various RA, ILD, and patient-related factors.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31074584

RESUMO

OBJECTIVE: Although hyperuricemia and gout can complicate the course of rheumatoid arthritis (RA), the impact of these factors on outcomes in RA is unclear. We examined associations of coexistent hyperuricemia and gout with RA disease measures, RA treatments, and survival. METHODS: Participants from a longitudinal RA study were categorized by the presence of gout and serum urate (sUA) status. Groups were compared by baseline patient characteristics, RA disease activity, treatments, and comorbidities. Associations of baseline sUA levels with all-cause and cardiovascular disease (CVD)-related mortality were examined in multivariable survival analyses. RESULTS: Of 1,999 participants with RA, 341 (17%) had sUA concentrations >6.8 mg/dl and 121 (6.1%) were diagnosed with gout. There were no significant associations of enrollment sUA or gout with RA disease activity or treatment with the exception that those with gout were more likely to be receiving sulfasalazine and less likely to be receiving NSAIDs. After age- and sex-adjustment, moderate hyperuricemia (sUA >6.8-8 mg/dl) was associated with an increased risk of CVD-related mortality (HR 1.56; 95% CI 1.11-2.21). This association was attenuated and not significant following additional adjustment for comorbidities that more commonly accompanied hyperuricemia. Results corresponding with sUA >8.0 mg/dl were similar, although not reaching statistical significance in any model. There were no associations of baseline sUA with all-cause mortality. CONCLUSION: Our study reports the frequency of hyperuricemia and gout in patients with RA. These results demonstrate strong associations of hyperuricemia with CVD mortality in this population, a risk that appears to be driven by excess comorbidity. This article is protected by copyright. All rights reserved.

11.
J Biomol Struct Dyn ; : 1-16, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31096863

RESUMO

Alzheimer's disease (AD) is considered as one of widespread dementia with no approved diagnosis, cure or prevention. Currently, only symptomatic relief can be provided upon administration of anti-AD drugs generally belonging to a category of anticholinesterases and antagonists of N-methyl-D-aspartate (NMDA) receptors. In present investigation, a sensing platform has been designed for studying recently developed anti-AD drugs viz., PC-25 (N-(2-{4-[(4-bromophenyl)methyl]piperazin-1-yl}ethyl)-7-methoxy-1,2,3,4-tetrahydroacridin-9-amine trihydrochloride), PC-37 (7-methoxy-N-(2-{4-[(3-methylphenyl)methyl]piperazin-1-yl}ethyl)-1,2,3,4-tetrahydroacridin-9-amine trihydrochloride) and PC-48 (N-(2-{4-[(3-bromophenyl) methyl]piperazin-1-yl}ethyl)-7-methoxy-1,2,3,4-tetrahydroacridin-9-amine trihydrochloride) and two known standard tacrine (THA) and donepezil drugs for their estimation of in vitro potency towards AD using spectroscopic method. Anti-AD drugs have been accounted for individually with highly fluorescent nitrogen-doped graphene quantum dots (NGQDs). The designed anti-AD drugs exerted the efficacy related to cholinergic hypothesis of AD. While the enzyme action is sensed by interacted species of NGQDs and acetylcholine, the fluorescence of NGQDs is quenched by the hydrolyzing action of acetylcholinesterase (AChE) enzyme but the lost fluorescence is recovered upon addition of anti-AD drugs. These alterations in fluorescence of NGQDs are expected to have biological relevance akin to sensing. Moreover, these results advocate that out of all the drugs tested PC-37 displayed maximum inhibition efficiency. Our investigations suggest that synthesized drugs have the AD treating potential and can be entrusted in the near future for AD treatment. The validation parameters such as LOD, LOQ and recovery (%) were calculated in the range of 2.87 mM, 9.58 mM and 85-96%, respectively. Communicated by Ramaswamy H. Sarma.

12.
Arthritis Rheumatol ; 71(9): 1483-1493, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30933423

RESUMO

OBJECTIVE: To compare serum anti-malondialdehyde-acetaldehyde (anti-MAA) antibody levels and MAA expression in lung tissue from patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) to those found in controls. METHODS: Anti-MAA antibody (IgA, IgM, IgG) concentrations were measured in patients with RA-ILD and compared to those of RA patients with chronic obstructive pulmonary disease (COPD) and RA patients without lung disease. Associations between anti-MAA antibody with RA-ILD were assessed using multivariable logistic regression. Lung tissue from patients with RA-ILD, other ILD, or emphysema, and from controls (n = 3 per group) were stained for MAA, citrulline, macrophages (CD68), T cells (CD3), B cells (CD19/CD27), and extracellular matrix proteins (type II collagen, fibronectin, vimentin). Tissue expression and colocalization with MAA were quantified and compared. RESULTS: Among 1,823 RA patients, 90 had prevalent RA-ILD. Serum IgA and IgM anti-MAA antibody concentrations were higher in RA-ILD than in RA with COPD or RA alone (P = 0.005). After adjustment for covariates, the highest quartiles of IgA anti-MAA antibody concentration (odds ratio 2.09 [95% confidence interval 1.11-3.90]) and IgM (odds ratio 2.23 [95% confidence interval 1.19-4.15]) were significantly associated with the presence of RA-ILD. MAA expression in RA-ILD lung tissue was greater than in tissue from all other groups (P < 0.001), and it colocalized with citrulline (r = 0.79), CD19+ B cells (r = 0.78), and extracellular matrix proteins (type II collagen [r = 0.72] and vimentin [r = 0.77]) to the greatest degree in RA-ILD. CONCLUSION: Serum IgA and IgM anti-MAA antibody is associated with ILD among RA patients. MAA is highly expressed in RA-ILD lung tissue, where it colocalizes with other RA autoantigens, autoreactive B cells, and extracellular matrix proteins, highlighting its potential role in the pathogenesis of RA-ILD.

13.
Angew Chem Int Ed Engl ; 58(23): 7797-7801, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-30950157

RESUMO

In this study, we report a remarkably active CeVO4 nanozyme that functionally mimics cytochrome c oxidase (CcO), the terminal enzyme in the respiratory electron transport chain, by catalyzing a four-electron reduction of dioxygen to water. The nanozyme catalyzes the reaction by using cytochrome c (Cyt c), the biological electron donor for CcO, at physiologically relevant pH. The CcO activity of the CeVO4 nanozymes depends on the relative ratio of surface Ce3+ /Ce4+ ions, the presence of V5+ and the surface-Cyt c interactions. The complete reduction of oxygen to water takes place without release of any partially reduced oxygen species (PROS) such as superoxide, peroxide and hydroxyl radicals.

14.
Artigo em Inglês | MEDLINE | ID: mdl-30875456

RESUMO

OBJECTIVE: We performed a systematic review and meta-analysis to evaluate the comparative effects of tumor necrosis factor-α inhibitors (TNFi), non-TNFi biologic and conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) on cardiovascular risk in rheumatoid arthritis (RA). METHODS: Through a systematic search through May 8, 2018, we included 14 observational studies in adults with RA treated with TNFi, non-TNFi biologics, tofacitinib or csDMARDs, reporting the risk of major adverse cardiovascular events (MACE) or stroke. Only studies reporting active comparators were included. We performed random effects meta-analysis and estimated odds ratios (OR) and 95% confidence interval (CI). RESULTS: As compared to TNFi, tocilizumab was associated with a decreased risk of MACE (OR, 0.59 [0.34-1.00]), whereas csDMARDs were associated with increased risk of MACE (csDMARDs, including methotrexate: OR, 1.45 [1.09-1.93]; without methotrexate: OR, 2.57 [1.32-5.00]), without heterogeneity (I2 =0%); there was no difference in risk of MACE between abatacept and TNFi (OR, 0.89 [0.71-1.11]), or between tocilizumab and abatacept (OR, 0.81 [0.57-1.16]). Based on 11 cohorts (n=135,053 patients), as compared to TNFi, csDMARDs were associated with increased risk of stroke (OR, 1.17 [1.01-1.36]); there was no difference in risk of stroke between different biologics (tocilizumab vs. TNFi: OR, 0.98 [0.59-1.61]; abatacept vs. TNFi: OR, 1.08 [0.86-1.34]; tocilizumab vs. abatacept: OR, 0.73 [0.39-1.38]), without heterogeneity (I2 =0%). No comparative studies on cardiovascular risk with tofacitinib were identified. CONCLUSION: Based on meta-analysis, as compared to TNFi, tocilizumab may be associated with reduced risk of MACE, whereas csDMARDs may be associated with increased risk of MACE and stroke.

15.
J Clin Gastroenterol ; 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30789855

RESUMO

BACKGROUND: Antioxidants (AO) supplementation in chronic pancreatitis (CP) has been evaluated for pain. But it is not clear whether AO in CP have an effect on pancreatic functions and other clinical outcomes. We evaluated effect of AO on endocrine function in CP. MATERIALS AND METHODS: Double-blind placebo (PL)-controlled randomized pilot study on 107 patients with CP assigned to receive daily combined AO or PL for 6 months. Primary outcome was: improvement in endocrine function (Homeostasis Model Assessment-Insulin Resistance). Secondary outcome measures were: improvement in C-peptide, Qualitative Insulin Sensitivity Check Index, exocrine pancreatic function (fecal elastase), surrogate markers of fibrosis (platelet-derived growth factor BB, transforming growth factor-ß1, α-smooth muscle actin), quality of life (QOL), pain, nutritional status, markers of oxidative stress (OS), AO status, and inflammation. RESULTS: There was an increase in levels of serum selenium (107.2±26.9 to 109.7±26.9 vs. 104.1±28.6 to 124.0±33.6 µg/L, P=0.022) and serum vitamin E [0.58 (range, 0.27-3.22) to 0.66 (range, 0.34-1.98) vs. 0.63 (range, 0.28-1.73) to 1.09 (range, 0.25-2.91) mg/dL, P=0.001] in the AO than the PL group. However, no significant differences were observed between groups in any of the primary or secondary outcome measures. CONCLUSIONS: Supplementation with AO to patients with CP causes a sustained increase in blood levels of AO; however, it has no addition benefit over PL on endocrine and exocrine functions, markers of fibrosis, OS and inflammation, nutritional status, pain and QOL. Further larger studies with adequate sample size are required.

16.
Nanoscale ; 11(9): 3855-3863, 2019 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-30758009

RESUMO

Biocompatible nanoparticles with an intrinsic ability to mimic the cellular antioxidant enzymes are potential candidates for the development of new therapeutics for various oxidative stress related disorders. However, the understanding of the interaction and the mechanistic crosstalk between the nanoparticles and the cellular biomolecules is limited. Here we show that the multienzyme mimic manganese(ii,iii) oxide, Mn3O4, in nanoform (Mp) rescues the cells from oxidative damage induced by reactive oxygen species (ROS). The nanoparticles provide remarkable protection to biomolecules against the ROS-mediated protein oxidation, lipid peroxidation and DNA damage. Interestingly, the endogenous antioxidant machinery remains unaltered in the presence of these nanozymes, indicating the small molecule targeting of these nanoparticles in the cellular redox modulation. This study delineates the possible mechanism by which the nanoparticles provide protection to the cells against the adverse effects of oxidative stress. Based on our observation, we suggest that the multienzyme mimic Mn3O4 nanoparticles possess great potential in suppressing the oxidative stress-mediated pathophysiological conditions under which the antioxidant system is overwhelmed.


Assuntos
Antioxidantes/metabolismo , Compostos de Manganês/química , Nanopartículas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Óxidos/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Glutationa/metabolismo , Células HEK293 , Humanos , Nanopartículas/química , Carbonilação Proteica/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
17.
Chem Commun (Camb) ; 55(3): 322-325, 2019 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-30534727

RESUMO

We demonstrate a novel strategy to synthesize highly stable luminescent mercaptoimidazole-capped copper nanoclusters (CuNCs). Herein we depict that a simple modification of substituents on the mercaptoimidazole ligand dictates the self-assembly and photophysical properties of the clusters. These CuNCs showed aggregation induced emission (AIE) with a large Stokes shift (Δλ > 200 nm), and the formation of clusters corresponding to Cu4L3 was confirmed by MALDI-TOF mass spectrometric analyses. Interestingly, these nanoclusters effectively internalize into mammalian cells while retaining their fluorescent properties and exhibit negligible toxicity.

18.
Ann Bot ; 123(4): 691-705, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30535180

RESUMO

BACKGROUND AND AIMS: Nitrogen (N) levels vary between ecosystems, while the form of available N has a substantial impact on growth, development and perception of stress. Plants have the capacity to assimilate N in the form of either nitrate (NO3-) or ammonium (NH4+). Recent studies revealed that NO3- nutrition increases nitric oxide (NO) levels under hypoxia. When oxygen availability changes, plants need to generate energy to protect themselves against hypoxia-induced damage. As the effects of NO3- or NH4+ nutrition on energy production remain unresolved, this study was conducted to investigate the role of N source on group VII transcription factors, fermentative genes, energy metabolism and respiration under normoxic and hypoxic conditions. METHODS: We used Arabidopsis plants grown on Hoagland medium with either NO3- or NH4+ as a source of N and exposed to 0.8 % oxygen environment. In both roots and seedlings, we investigated the phytoglobin-nitric oxide cycle and the pathways of fermentation and respiration; furthermore, NO levels were tested using a combination of techniques including diaminofluorescein fluorescence, the gas phase Griess reagent assay, respiration by using an oxygen sensor and gene expression analysis by real-time quantitative reverse transcription-PCR methods. KEY RESULTS: Under NO3- nutrition, hypoxic stress leads to increases in nitrate reductase activity, NO production, class 1 phytoglobin transcript abundance and metphytoglobin reductase activity. In contrast, none of these processes responded to hypoxia under NH4+ nutrition. Under NO3- nutrition, a decreased total respiratory rate and increased alternative oxidase capacity and expression were observed during hypoxia. Data correlated with decreased reactive oxygen species and lipid peroxidation levels. Moreover, increased fermentation and NAD+ recycling as well as increased ATP production concomitant with the increased expression of transcription factor genes HRE1, HRE2, RAP2.2 and RAP2.12 were observed during hypoxia under NO3- nutrition. CONCLUSIONS: The results of this study collectively indicate that nitrate nutrition influences multiple factors in order to increase energy efficiency under hypoxia.

19.
Indian J Gastroenterol ; 37(5): 392-401, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30367395

RESUMO

Gluten-free diet (GFD) is the only definitive treatment for patients with celiac disease (CeD). Strict adherence to GFD improves the symptoms, nutritional deficiencies, and the overall well-being of the patients. The management of CeD is truly different and unique from the treatment of other medical or surgical diseases. While prescribing a GFD is easy, the key to the success lies in the dietary counseling by a nutrition specialist/physician and maintenance of adherence to the prescribed diet by the patient. When restricting gluten from all possible sources, it is pertinent to recommend a diet that is healthy and balanced for patients with celiac disease. Those following GFD must be counseled properly on the ways of balancing their diets and of avoiding cross contamination. They should be taught how to read food labels properly and given tips for dining out or during traveling. Regular follow up with patients is required for assessing the compliance and monitoring growth and the status of recovery. In this review article, we have compiled, for the physicians and gastroenterologists, the relevant information about GFD including counseling, adherence, nutritional adequacy, and many other related issues.

20.
Biochemistry ; 57(35): 5183-5187, 2018 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-29771508

RESUMO

The involvement of α-synuclein (α-Syn) amyloid formation in Parkinson's disease (PD) pathogenesis is supported by the discovery of α-Syn gene (SNCA) mutations linked with familial PD, which are known to modulate the oligomerization and aggregation of α-Syn. Recently, the A53V mutation has been discovered, which leads to late-onset PD. In this study, we characterized for the first time the biophysical properties of A53V, including the aggregation propensities, toxicity of aggregated species, and membrane binding capability, along with those of all familial mutations at the A53 position. Our data suggest that the A53V mutation accelerates fibrillation of α-Syn without affecting the overall morphology or cytotoxicity of fibrils compared to those of the wild-type (WT) protein. The aggregation propensity for A53 mutants is found to decrease in the following order: A53T > A53V > WT > A53E. In addition, a time course aggregation study reveals that the A53V mutant promotes early oligomerization similar to the case for the A53T mutation. It promotes the largest amount of oligomer formation immediately after dissolution, which is cytotoxic. Although in the presence of membrane-mimicking environments, the A53V mutation showed an extent of helix induction capacity similar to that of the WT protein, it exhibited less binding to lipid vesicles. The nuclear magnetic resonance study revealed unique chemical shift perturbations caused by the A53V mutation compared to those caused by other mutations at the A53 site. This study might help to establish the disease-causing mechanism of A53V in PD pathology.

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