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1.
Genes (Basel) ; 11(5)2020 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-32357425

RESUMO

In rice there are few genetic studies reported for allelopathy traits, which signify the ability of plants to inhibit or stimulate growth of other plants in the environment, by exuding chemicals. QTL analysis for allelopathic traits were conducted with 98 F8 RILs developed from the cross between the high allelopathic parents of 'Sathi' and non-allelopathic parents of 'Nong-an'. The performance of allelopathic traits were evaluated with inhibition rate on root length, shoot length, total length, root weight, shoot weight, and total weight of lettuce as a receiver plant. With 785 polymorphic DNA markers, we constructed a linkage map showing a total of 2489.75 cM genetic length and 3.17 cM of average genetic distance between each adjacent marker. QTL analysis detected on QTL regions on chromosome 8 responsible for the inhibition of shoot length and inhibition of total length. The qISL-8 explained 20.38% of the phenotypic variation for the inhibition on the shoot length. The qITL-8 explained 14.93% of the phenotypic variation for the inhibition on total length. The physical distance of the detected QTL region was 194 Kbp where 31 genes are located.

2.
Nat Commun ; 11(1): 2358, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398649

RESUMO

Sphingosine kinase1 (SphK1) is an acetyl-CoA dependent acetyltransferase which acts on cyclooxygenase2 (COX2) in neurons in a model of Alzheimer's disease (AD). However, the mechanism underlying this activity was unexplored. Here we show that N-acetyl sphingosine (N-AS) is first generated by acetyl-CoA and sphingosine through SphK1. N-AS then acetylates serine 565 (S565) of COX2, and the N-AS-acetylated COX2 induces the production of specialized pro-resolving mediators (SPMs). In a mouse model of AD, microglia show a reduction in N-AS generation, leading to decreased acetyl-S565 COX2 and SPM production. Treatment with N-AS increases acetylated COX2 and N-AS-triggered SPMs in microglia of AD mice, leading to resolution of neuroinflammation, an increase in microglial phagocytosis, and improved memory. Taken together, these results identify a role of N-AS in the dysfunction of microglia in AD.

3.
Allergy ; 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32416622

RESUMO

BACKGROUND: Obesity associated with various complications has increased worldwide. Body weight gain alters lipid metabolites (especially sphingolipids) contributing to obesity-induced inflammation. However, the significance of the metabolites in the development of obese asthma is not yet clear. METHODS: The serum levels of sphingolipids were measured using liquid chromatography-tandem mass spectrometry in obese controls (n = 7) and patients with asthma: the obese group (BMI > 25 kg/m3 , n = 13) vs the non-obese (n = 28) group. To examine the relationship between metabolic changes in sphingolipids and macrophage polarization, public microarray data were analyzed. In addition, the alteration in sphingolipid metabolism was investigated in wild-type BALB/c mice fed a high-fat diet. RESULTS: The obese asthma had higher levels of serum C18:0 and C20:0 ceramides than the non-obese asthma group (P = .028 and P = .040, respectively). The value of the serum C18:0 ceramide (184.3 ng/mL) for discriminating the obese asthma from the non-obese asthma group showed 53.9% sensitivity and 85.7% specificity (AUC = 0.721, P = .024). The microarray data showed significantly increased ceramide synthesis and metabolic shift to ceramide accumulation during M1 macrophage polarization in humans. Increased airway hyperresponsiveness, M1 macrophage polarization, and C18:0 ceramide levels were noted in obese mice, but not in non-obese mice. Increased expression of ceramide synthase (CerS) 1 and CerS6 (not CerS2) was noted in lung tissues of obese mice. CONCLUSION: Alteration in sphingolipid metabolism favoring ceramide accumulation (especially long-chain ceramides) may contribute to developing obese asthma.

4.
Surg Endosc ; 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32468261

RESUMO

BACKGROUND: Endoscopic submucosal dissection (ESD) has a favorable outcome, compared to esophagectomy, for early esophageal neoplasia. Recent studies used general anesthesia for esophageal ESD to minimize complications due to insufficient sedation and patient movement. We aimed to evaluate the safety of general anesthesia in comparison with conscious sedation provided by anesthesiologists for esophageal ESD. METHODS: We retrospectively reviewed the electronic medical records of 158 patients who underwent esophageal ESD under general anesthesia or conscious sedation provided by anesthesiologists. We evaluated the incidence of procedure-related complications, including perforation, post-ESD bleeding, cardiopulmonary adverse events (arrhythmia, hypotension, and hypoxemia), procedure failure, stricture, and new lung consolidation after ESD. Cases of frank perforation, post-ESD bleeding requiring a vigorous diagnostic approach, and cardiopulmonary adverse events were regarded as acute complications of ESD. RESULTS: Acute complications occurred only in the conscious sedation group (8/83 [9.6%] vs. 0/75 [0.0%]; p value = 0.007). The numbers of patients with frank perforation, post-ESD bleeding, and cardiopulmonary adverse events were four, one, and three, respectively. Moreover, new lung consolidation after ESD developed only in the conscious sedation group (7/83 [8.4%] vs. 0/75 [0.0%]; p value = 0.014). ESD failed in four patients in the conscious sedation group. The incidences of stricture that required stent insertion and hospital stay after ESD were comparable between the two groups. CONCLUSION: General anesthesia is associated with a lower incidence of acute procedure-related complications in esophageal ESD compared to conscious sedation provided by anesthesiologists. Therefore, we recommend general anesthesia as a safer option for esophageal ESD.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32464239

RESUMO

BACKGROUND: Rumination is a well-known risk factor for depression. It is also associated with negative and positive symptoms and suicidality in patients suffering from psychosis. However, no studies have addressed the effect of antipsychotics on rumination. METHODS: Using the Brooding Scale (BS), we investigated the effect of antipsychotics on rumination at the 6-month follow up in patients with first-episode psychosis (n = 257). The relationship between rumination and other clinical variables was explored by conducting a correlation analysis and structural equation modeling (SEM). The clinical characteristics and short-term outcomes were compared between high and low ruminators at 6 months. RESULTS: Significant reductions in rumination and various clinical variables were observed at the 6-month follow-up. A significant correlation was observed between rumination and the score on the positive subscale of the Positive and Negative Syndrome Scale (PANSS). A direct path between the PANSS score and rumination was identified by SEM. High ruminators had more severe psychopathology, experienced more childhood traumas, and took less exercise than low ruminators. The recovery rate at 6 months was higher in low ruminators than in high ruminators. CONCLUSIONS: Our findings suggest that antipsychotics are beneficial for reducing rumination in patients with first-episode psychosis. The outcomes at the 6-month follow-up were better in low ruminators than high ruminators.

6.
Nat Prod Res ; : 1-8, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32441150

RESUMO

Two new, aramatosides A and B (1 and 2), together with seven known oleanane-type triterpene saponins (3-9) were isolated from the leaves of Aralia armata. Their structures were determined by combination of HR-ESI-MS, 1 D and 2 D NMR spectral data as well as comparison with the previous literature. Compounds 6-9 exhibited cytotoxic effects towards three human cancer cell lines (HT29, A2058, and A549) with IC50 values ranging from 2.01 ± 0.17 to 18.8 ± 1.17 µM. Especially, compound 7 (narcissiflorin) showed significant cytotoxic activity against HT29 and A549 cell lines with IC50 values of 2.02 ± 1.65 and 2.01 ± 0.17 µM, respectively, which are smaller than those of positive control irinotecan hydrochloride (IC50 values of 10.3 ± 1.32 and 9.89 ± 0.19 µM).

7.
Nutrients ; 12(4)2020 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-32235401

RESUMO

Despite the excellent antimicrobial activity of aminoglycoside antibiotics, permanent inner ear damage associated with the use of these drugs has resulted in the need to develop strategies to address the ototoxic risk given their widespread use. In a previous study, we showed that avocado oil protects ear hair cells from damage caused by neomycin. However, the detailed mechanism by which this protection occurs is still unclear. Here, we investigated the auditory cell-protective mechanism of enhanced functional avocado oil extract (DKB122). RNA sequencing followed by pathway analysis revealed that DKB122 has the potential to enhance the expression of detoxification and antioxidant genes associated with glutathione metabolism (Hmox4, Gsta4, Mgst1, and Abcc3) in HEI-OC1 cells. Additionally, DKB122 effectively decreased ROS levels, resulting in the inhibition of apoptosis in HEI-OC1 cells. The expression of the inflammatory genes that encode chemokines and interleukins was also downregulated by DKB122 treatment. Consistent with these results, DKB122 significantly inhibited p65 nuclear migration induced by TNF-α or LPS in HEI-OC1 cells and THP-1 cells and the expression of inflammatory chemokine and interleukin genes induced by TNF-α was significantly reduced. Moreover, DKB122 treatment increased LC3-II and decreased p62 in HEI-OC1 cells, suggesting that DKB122 increases autophagic flux. These results suggest that DKB122 has otoprotective effects attributable to its antioxidant activity, induction of antioxidant gene expression, anti-inflammatory activity, and autophagy activation.

8.
Clin Res Cardiol ; 2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32236716

RESUMO

BACKGROUND: The study sought to assess the prognostic impact of potassium levels (K) in patients with ventricular tachyarrhythmias. METHODS: A large retrospective registry was used including all consecutive patients presenting with ventricular tachyarrhythmias on admission from 2002 to 2016. Patients with hypokalemia (i.e., K < 3.3 mmol/L), normokalemia (i.e., K 3.3-4.5 mmol/L), and hyperkalemia (i.e., K > 4.5 mmol/L) were compared applying multi-variable Cox regression models and propensity-score matching for evaluation of the primary endpoint of all-cause mortality at 3 years. Secondary endpoints were early cardiac death at 24 h, in-hospital death, death at 30 days, as well as the composite endpoint of early cardiac death at 24 h, recurrences of ventricular tachyarrhythmias, and appropriate ICD therapies at 3 years. RESULTS: In 1990 consecutive patients with ventricular tachyarrhythmias, 63% of the patients presented with normokalemia, 30% with hyperkalemia, and 7% with hypokalemia. After propensity matching, both hypokalemic (HR = 1.545; 95% CI 0.970-2.459; p = 0.067) and hyperkalemic patients (HR = 1.371; 95% CI 1.094-1.718; p = 0.006) were associated with the primary endpoint of all-cause mortality at 3 years compared to normokalemic patients. Hyperkalemia was associated with even worse prognosis directly compared to hypokalemia (HR = 1.496; 95% CI 1.002-2.233; p = 0.049). In contrast, potassium measurements were not associated with the composite endpoint at 3 years. CONCLUSION: In patients presenting with ventricular tachyarrhythmias, normokalemia was associated with best short- and long-term survival, whereas hyperkalemia and hypokalemia were associated with increased mortality at 30 days and at 3 years.

9.
Artif Cells Nanomed Biotechnol ; 48(1): 777-788, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32308043

RESUMO

Probiotic Gluconacetobacter strains are intestinal microbes with beneficial effects on human health. Recently, researchers have used these strains to biosynthesize metal and non-metal nanoparticles for treating various chronic diseases. Despite their importance in nanotechnology, gold nanoparticles (AuNPs) biosynthesized by Gluconacetobacter species have not been clearly identified for treating inflammation and inflammation-associated diseases. While ginsenoside CK has strong pharmaceutical activity, it also has strong cytotoxicity and hydrophobicity which is hurdle to make formulation. Peptide-nanoparticle hybrids are gaining increasing attention for their potential biomedical applications, including human inflammatory diseases. Herein, we developed peptide CopA3 surface conjugated and ginsenoside compound K (CK) loaded gold nanoparticles (GNP-CK-CopA3), which intracellularly synthesised by the probiotic Gluconacetobacter liquefaciens kh-1, to target lipopolysaccharide (LPS)-activated RAW264.7 macrophages. The synthetic GNP-CK-CopA3 was characterised by various instrumental techniques. The results of our cellular uptake and MTT assays exhibited obvious drug intracellular delivery without significant cytotoxicity. In addition, pre-treatment with GNP-CK-CopA3 significantly ameliorated LPS-induced nitric oxide (NO) and reactive oxygen species (ROS) production and suppressed the mRNA and protein expression of pro-inflammatory cytokines in macrophages. Furthermore, GNP-CK-CopA3 efficiently inhibited the activation of the nuclear factor-κB (NF-κB) and mitogen-activating protein kinase (MAPK) signalling pathways. Taken together, our findings highlight the potential of using peptide-nanoparticle hybrids in the development of anti-inflammatory approaches and providing the experimental foundation for further application.

10.
Cardiology ; : 294-304, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32289772

RESUMO

OBJECTIVE: This study evaluates the impact of left ventricular ejection fraction (LVEF) on recurrences of ventricular tachyarrhythmias in recipients of implantable cardioverter defibrillator (ICD). BACKGROUND: Data regarding recurrences of ventricular tachyarrhythmias in ICD recipients according to LVEF is limited. METHODS: A large retrospective registry was used, including all consecutive ICD recipients with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2016. Patients with LVEF <35% were compared to patients with LVEF ≥35%. The primary end point was first recurrences of ventricular tachyarrhythmias at 5 years. Secondary end points were ICD-related therapies, rehospitalization, and all-cause mortality at 5 years. Cox regression, Kaplan Meier, and propensity score matching analyses were applied. RESULTS: A total of 528 consecutive ICD recipients were included (51% with LVEF ≥35% and 49% with LVEF <35%). LVEF <35% was associated with reduced freedom from recurrent ventricular tachyarrhythmias (40 vs. 49%, log rank p = 0.014; hazard ratio [HR] = 1.381; 95% confidence interval [CI] 1.066-1.788; p = 0.034), mainly attributed to recurrent sustained VT in primary preventive ICD recipients. Accordingly, LVEF <35% was associated with reduced freedom from first appropriate ICD therapies (28 vs. 41%, log rank p = 0.001; HR = 1.810; 95% CI 1.185-2.766; p = 0.001). Finally, LVEF <35% was associated with a higher rate of rehospitalization (23 vs. 34%; p = 0.005) and all-cause mortality at 5 years (13 vs. 29%; p = 0.001). CONCLUSION: LVEF <35% was associated with reduced freedom from recurrent ventricular tachyarrhythmias, appropriate device therapies, rehospitalization and all-cause mortality secondary to index ventricular tachyarrhythmias.

11.
Korean J Ophthalmol ; 34(2): 121-125, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32233145

RESUMO

PURPOSE: To evaluate the clinical features and prognosis of a delayed-onset consecutive esotropia (ET) after surgical correction of intermittent exotropia. METHODS: Thirty-four patients who developed consecutive ET after primary bilateral lateral rectus recession for the surgical correction of intermittent exotropia were evaluated retrospectively and were divided into two groups: delayed-onset consecutive ET group and the continuous consecutive ET group. Patients who developed esodeviation after once recovering to orthotropia within 1 month after the operation were included in the delayed-onset consecutive ET group, and patients with continuous esodeviation after the operation were included in the continuous consecutive ET group. We evaluated preoperative and postoperative angle of deviation, suppression, stereopsis, and follow up periods between the two groups and compared re-operation and success following non-surgical treatment between the continuous consecutive ET group and the delayed-onset consecutive ET group. RESULTS: Among 34 patients with consecutive ET, 27 patients (79.4%) were included in the delayed-onset consecutive ET group, and seven patients (23.3%) were included in the continuous group. Success rate of non-surgical treatment was not statistically significant between two groups (p = 0.55), but it was higher in the delayed-onset group with 37.5%, and 25% of patients in continuous group were successfully recovered to straight alignment. Duration of orthotropia in delayed-onset group was 7.4 ± 6.0 months (range, 2-29 months). Age, sex, preoperative refractive error, preoperative exodeviation, suppression, and near steroacuity were not statistically significant between two groups (p > 0.05, all). In the delayed-onset group, three patients (11.1%) underwent re-operation, while three patients (42.9%) in continuous consecutive ET group underwent re-operation (p = 0.048). CONCLUSIONS: Re-operation rate of delayed-onset consecutive ET after surgical correction of intermittent exotropia was lower than that of continuous consecutive ET.

12.
Sci Rep ; 10(1): 5199, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32251314

RESUMO

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. However, no reliable biomarkers have been identified to represent the clinical status. This study aimed to investigate whether diffusion tensor imaging (DTI) findings are useful imaging biomarkers to indicate the clinical status of ALS patients. Ninety-six probable or definite ALS cases and 47 age- and sex-matched, normal controls were enrolled. Demographic and clinical data were collected at the time of DTI. DTI data were acquired using a 3-Tesla magnetic resonance imaging scanner and analysed by voxel-wise statistical analyses for fractional anisotropy, axial diffusivity, radial diffusivity, mean diffusivity, and mode of anisotropy. Compared with the healthy control group, the ALS group had significant differences in DTI scalars in the diffuse tracts of the brain, which was predominant in the corticospinal tract at the brainstem and cerebellar peduncle area. Furthermore, the DTI values correlated with the ALS functional rating scale-revised (ALSFRS-R) scores and the delta ALSFRS-R score representing the rate of disease progression. The subgroup analysis revealed a more severe and widespread brain degeneration was observed in rapidly progressive ALS. Therefore, our results suggest that DTI findings are useful as imaging biomarkers for evaluating the clinical severity and rate of disease progression in ALS.

13.
Clin Lab ; 66(3)2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32162892

RESUMO

BACKGROUND: Only few data evaluating the prognostic impact of blood-derived potassium levels (K) on arrhythmic endpoints in patients with implantable cardioverter-defibrillators (ICD) is available. Therefore, this study evaluates the prognostic impact of potassium levels on recurrences of ventricular tachyarrhythmias in consecutive ICD recipients. METHODS: A large retrospective registry was used including all consecutive patients presenting with ventricular tachyarrhythmias on admission from 2002 to 2016 at one institution. Patients were divided into three subgroups: hypokalemia (i.e., K < 3.3 mmol/L), normokalemia (i.e., K 3.3 - 4.5 mmol/L), and hyperkalemia (i.e., K > 4.5 mmol/L). Kaplan-Meier and Cox regression analyses were applied for the evaluation of the primary endpoint of first recurrences of ventricular tachyarrhythmias at one year. Secondary endpoints comprised of first appropriate ICD therapy, first cardiac rehospitalization, and all-cause mortality at one year. RESULTS: Five hundred and thirty ICD recipients with a median potassium level of 4.23 mmol/L were included (67%: normokalemia, 27%: hyperkalemia, and 6%: hypokalemia). Whereas hyperkalemia was not associated with increasing risk of recurrent ventricular tachyarrhythmias, hypokalemia was associated with decreasing freedom from recurrent ventricular tachyarrhythmias (HR = 2.135; 95% CI 1.158 - 3.937; p = 0.015), even after mul-tivariable adjustment (HR = 2.577; 95% CI 1.236 - 5.372; p = 0.012). Higher risk of recurrences was especially attributed to higher rates of electrical storm in the presence of hypokalemia (15% vs. 3 - 4%). Negative impact of hypokalemia was mainly attributed to secondary preventive ICD (HR = 2.637; 95% CI 1.325 - 5.248; p = 0.006). Moreover, hypokalemia was associated with increasing risk of appropriate ICD therapies (HR = 1.920; 95% CI 0.912 - 4.042; statistical trend: p = 0.086), which was still demonstrated after multivariable adjustment. In contrast, risk of first cardiac rehospitalization and all-cause mortality were not affected by potassium levels. CONCLUSIONS: In consecutive ICD recipients with ventricular tachyarrhythmias at index, hypokalemia - but not hyperkalemia - was associated with increasing risk of recurrent ventricular tachyarrhythmias and appropriate ICD therapies.

14.
Nat Prod Res ; : 1-8, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32081022

RESUMO

Four new pregnane glycosides, gymlatifosides A - D (1 - 4) and one known pregnane glycoside, verticilloside J (5) were isolated from the leaves of Gymnema latifolium Wall. ex Wight. Their chemical structures were elucidated on the basis of extensive spectroscopic methods, including 1D, 2D NMR, HR-ESI-MS, and in comparison with the reported data. All these compounds were tested for α-glucosidase and α-amylase inhibitory activities. Compound 5 exhibited the most anti α-glucosidase activity with inhibitory percentage of 37.8 ± 1.5% at the concentration of 200 µM. Compounds 1-4 showed moderate anti α-glucosidase activity with inhibitory percentage ranging from 7.0 to 30.1%. In addition, all compounds 1-5 showed moderate/weak anti α-amylase activity in the investigated test.

15.
Exp Mol Med ; 52(2): 253-265, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32009132

RESUMO

Patients with late-onset asthma (LOA) have poor clinical outcomes. Osteopontin (OPN) is associated with airway inflammation and remodeling. To investigate the role of OPN in LOA compared to early-onset asthma (EOA), serum OPN levels were compared between 131 adult asthma patients (48 LOA and 83 EOA patients) and 226 healthy controls (HCs). BALB/c mice were sensitized with ovalbumin with/without polyinosinic-polycytidylic acid (poly(I:C)) from week 6 (A6 mice) or week 12 (A12 mice) after birth. Airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid (BALF), cell counts, histology, and Spp1 expression were assessed. The levels of OPN, transforming growth factor ß1 (TGF-ß1), chitinase 3-like 1 (CH3L1), and interleukin (IL) 5 were measured by ELISA. The expression of Smad3 phosphorylation and tissue transglutaminase 2 (TGM2) was evaluated by Western blot. The serum OPN levels were significantly higher in asthma patients than in HCs and in LOA patients than in those with EOA (P < 0.05) and were positively correlated with serum TGF-ß1 and CH3L1 (r = 0.174, r = 0.264; P < 0.05). A12 mice showed elevated AHR with increased levels of OPN/TGF-ß1/IL-5 in BALF and Spp1 compared to A6 mice. Poly(I:C) induced remarkable TGF-ß1, CH3L1, Th2 cytokine, and OPN levels in BALF and the expression of phosphorylated Smad3, TGM2, and Spp1 in the lungs. OPN triggered TGF-ß1/Smad3 signaling in the lungs, which was suppressed by dexamethasone and anti-IL5 antibody. In conclusion, aging and exposure to viral infections may induce OPN release and consequently modulate inflammation and TGF-ß1/Smad3-related remodeling, contributing to the development of LOA.

16.
Allergy ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32072647

RESUMO

BACKGROUND: Asthma is associated with inflammatory dysregulation, but the underlying metabolic signatures are unclear. This study aimed to classify asthma inflammatory phenotypes based on cellular and metabolic features. METHODS: To determine cellular and metabolic profiles, we assessed inflammatory cell markers using flow cytometry, sphingolipid (SL) metabolites using LC-MS/MS, and serum cytokines using ELISA. Targeted gene polymorphisms were determined to identify genetic predispositions related to the asthma inflammatory phenotype. RESULTS: In total, 137 patients with asthma and 20 healthy controls (HCs) were enrolled. Distinct cellular and metabolic profiles were found between them; patients with asthma showed increased expressions of inflammatory cell markers and higher levels of SL metabolites compared to HCs (P < .05 for all). Cellular markers (CD66+ neutrophils, platelet-adherent eosinophils) and SL metabolic markers (C16:0 and C24:0 ceramides) for uncontrolled asthma were also identified; higher levels were observed in uncontrolled asthma compared to controlled asthma (P < .05 for all). Asthmatics patients with higher levels of CD66+ neutrophils had lower FEV1(%), higher ACQ (but lower AQLO) scores, and higher sphingosine and C16:0 ceramide levels compared to those with low levels of CD66+ neutrophils. Asthmatics patients with higher levels of platelet-adherent eosinophils had higher S1P levels compared to those with lower levels of platelet-adherent eosinophils. Patients carrying TT genotype of ORMDL3 had more CD66+ neutrophils; those with AG/ GG genotypes of SGMS1 exhibited higher platelet-adherent eosinophils. CONCLUSION: Patients with uncontrolled asthma possess distinct inflammatory phenotypes including increased CD66+ neutrophils and platelet-adherent eosinophils, with an imbalanced ceramide/S1P rheostat, potentially involving ORMDL3 and SGMS1 gene polymorphisms. Ceramide/S1P synthesis could be targeted to control airway inflammation.

17.
Neurology ; 94(15): e1657-e1663, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32071166

RESUMO

OBJECTIVE: To establish whether amyotrophic lateral sclerosis (ALS) is a multistep process in South Korean and Japanese populations when compared to Australian cohorts. METHODS: We generated incident data by age and sex for Japanese (collected between April 2009 and March 2010) and South Korean patients with ALS (collected between January 2011 and December 2015). Mortality rates were provided for Australian patients with ALS (collected between 2007 and 2016). We regressed the log of age-specific incidence against the log of age with least squares regression for each ALS population. RESULTS: We identified 11,834 cases of ALS from the 3 populations, including 6,524 Australian, 2,264 Japanese, and 3,049 South Korean ALS cases. We established a linear relation between the log incidence and log age in the 3 populations: Australia r 2 = 0.99, Japan r 2 = 0.99, South Korea r 2 = 0.99. The estimate slopes were similar across the 3 populations, being 5.4 (95% confidence interval [CI], 4.8-5.5) in Japanese, 5.4 (95% CI, 5.2-5.7) in Australian, and 4.4 (95% CI, 4.2-4.8) in South Korean patients. CONCLUSIONS: The linear relationship between log age and log incidence is consistent with a multistage model of disease, with slope estimated suggesting that 6 steps were required in Japanese and Australian patients with ALS while 5 steps were needed in South Korean patients. Identification of these steps could identify novel therapeutic strategies.

18.
Phytochemistry ; 172: 112255, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31935608

RESUMO

Six undescribed sesquiterpene glucosides, fissispallins A-F, and one known sesquiterpene glucoside, fissispallin, were discovered in the leaves of Fissistigma pallens (Finet & Gagnep.) Merr. The structures were determined using spectroscopic methods, including 1D, 2D NMR, and MS. All compounds were evaluated for cytotoxic activity against three human cancer cell lines, HT-29, A-2058, and A-549. Fissispallin A showed potent activity with the IC50 values less than 1.5 µM against all tested human cancer cell lines. Fissispallin also showed potent activity with IC50 value of 0.4 ± 0.3 on the A-2058 cancer cell lines. Fissispallins B-D showed significant cytotoxic activity against all the tested cancer cell lines with IC50 values ranging from 3.8 to 7.2 µM.


Assuntos
Annonaceae , Sesquiterpenos , Glucosídeos , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Folhas de Planta
19.
Nat Prod Res ; : 1-9, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31965859

RESUMO

Ten triterpenoid glycosides including two undescribed compounds (1 and 2) were isolated from the methanol extract of Allium ascalonicum rhizomes. These compounds were structurally elucidated to be 3ß-O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl-19α-hydroxyolean-12-ene-28-oic acid 28-O-[α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranosyl] ester (1), 3-O-ß-D-glucopyranosyl-(1→3)-[α-L-rhamnopyranosyl-(1→2)]-α-L-arabinopyranosyl-3ß,19α-dihydroxyoleanane-12-en-28-oic acid (2), lactifoloside C (3), lactifoloside H (4), randiasaponin IV (5), kudinoside G (6), ilexkudinoside W (7), lactifoloside G (8), kudinoside D (9), and ilexkudinoside T (10) by analyzing their HR-ESI-MS, NMR spectral data and by comparison with those reported in the literature. Compounds 1-10 were evaluated for anoctamin-1 (ANO1) inhibitory activity using yellow fluorescent protein reduction assays. At the concentration of 30 µM, compounds 2 and 9 displayed moderate ANO1 inhibitory percentages of 28.9 ± 0.85% and 26.2 ± 0.65%, respectively.

20.
J Pediatr Ophthalmol Strabismus ; 57(1): 21-26, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31972036

RESUMO

PURPOSE: To investigate recovery from suppression when the target motor alignment is achieved following surgery for intermittent exotropia. METHODS: The medical records of 237 patients who underwent surgery for exotropia were retrospectively reviewed. The age at surgery, sex, preoperative angle of deviation, suppression status, and near stereopsis were investigated. Suppression status was classified as no, alternate, or constant suppression. Target motor alignment was defined as 10 prism diopters (PD) or less of exodeviation or 2 PD of esodeviation at the final visit. RESULTS: The mean age at surgery was 8.2 ± 3.2 years and 115 (48.5%) patients were male. The preoperative angle of deviation was 26.3 ± 5.9 PD and the follow-up postoperative period was 21.6 ± 7.6 months. The preoperative suppression status included 23 (9.7%), 55 (23.2%), and 159 (67.1%) patients who showed no, alternate, or constant suppression, respectively. Two hundred fifteen (90.7%) patients obtained the target motor alignment by the final visit. Of the 144 patients who demonstrated constant suppression preoperatively but achieved the target motor alignment postoperatively, 12 (8.3%) patients demonstrated residual suppression. All 12 of these patients had a preoperative angle of exotropia of greater than 20 PD. CONCLUSIONS: Most patients undergoing surgery for intermittent exotropia obtained both successful motor alignment and fusion postoperatively. However, successful motor alignment did not guarantee recovery of suppression when the preoperative angle of exotropia was greater than 20 PD. The preoperative factors and functional implications underlying this finding are unclear and merit further study. [J Pediatr Ophthalmol Strabismus. 2020;57(1):21-26.].

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