Hendriksenborch5083

In this work, three isoxazoline-thiazolidine-2,4-dione derivatives were synthesized and characterized by FT-IR, 1H-NMR, 13C-NMR and ESI-MS spectrometry. All compounds have been investigated for their α-amylase and α-glucosidase inhibitory activities. In vitro enzymatic evaluation revealed that all compounds were inhibitory potent against α-glucosidase with IC50 values varied from 40.67 ± 1.81 to 92.54 ± 0.43 µM, and α-amylase with IC50 in the range of 07.01 ± 0.02 to 75.10 ± 1.06 µM. One of the tested compounds were found to be more potent inhibitor compared to other compounds and standard drug Acarbose (IC50 glucosidase= 97.12 ± 0.35 µM and IC50 amylase= 2.97 ± 0.01 μM). All compounds were then evaluated for their acute toxicity in vivo and shown their safety at a high dose with LD > 2000mg/kg BW. A cell-based toxicity evaluation was performed to determine the safety of compounds on liver cells, using the MTT assay against HepG2 cells, and the results shown that all compounds have non-toxic impact against cell viability and proliferation compared to reference drug (Pioglitazone). Furthermore, the molecular homology analysis, SAR and the molecular binding properties of compound with the active site of α-amylase and α-glucosidase were confirmed through computational analysis. This study has identified the inhibitory potential of a new class of synthesized isoxazoline-thiazolidine-2,4-dione derivatives in controlling both hyperglycemia and type 2 diabetes mellitus without any hepatic toxicity.Communicated by Ramaswamy H. Sarma.Objectives Ceramide (Cer), known as apoptotic markers, increases with prenatal ethanol (EtOH) exposure, resulting in neuroapoptosis. Whether maternal nutrition can impact Cer concentrations in brain, via altering plasma and brain fatty acid compositions have not been examined. This study compared a standard chow with a formulated semi-purified energy dense (E-dense) diet on fatty acid composition, Cer concentrations, and apoptosis in plasma and brain regions (cortex, cerebellum, and hippocampus) of pups exposed to EtOH during gestation. Methods Pregnant Sprague-Dawley rats were randomized into four groups chow (n = 6), chow + EtOH (20% v/v) (n = 7), E-dense (n = 6), and E-dense + EtOH (n = 8). At postnatal day 7, representing the peak brain growth spurt in rats, lipids, and apoptosis were analyzed by gas chromatography and a fluorometric caspase-3 assay kit, respectively. Results Maternal E-dense diet increased total fatty acid concentrations (p  less then  0.0001), including docosahexaenoic acid (DHA) (p  less then  0.0001) in plasma, whereas DHA concentrations were decreased in the cerebellum (p  less then  0.03) of pups than those from chow-fed dams. EtOH-induced Cer elevations in the hippocampus of pups born to dams fed chow were reduced by an E-dense diet (p  less then  0.02). No significant effects of maternal diet quality and EtOH were observed on caspase-3 activity. No significant correlations existed between plasma/brain fatty acids and Cer concentrations. Discussions Maternal diet quality affected fatty acid compositions and Cer concentrations of pups with prenatal EtOH exposure, differently. Maternal nutrition has the potential to prevent or alleviate some of the adverse effects of prenatal EtOH exposure.

The aim of this study was to determine the biological function of Sprouty 1 (SPRY1) on acute myeloid leukemia (AML), and to investigate the potential mechanism.

The expression of SPRY1 and the prognostic values of SPRY1 were assessed through the analysis of the Cancer Genome Atlas. Meanwhile, the expression of SPRY1 in AML cells was determined by qRT-PCR and western blot. Then, the biological function of SPRY1 on the proliferation, cell cycle and apoptosis in K-562 and HL-60 cells were tested using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony-formation assay, 5-ethynyl-20-deoxyuridine assay and flow cytometry. Additionally, the protein expressions were measured by western blot.

We found that SPRY1 was markedly overexpressed in the cells of the patients with AML, and the patients with AML having a high SPRY1 expression has a bad prognosis. The proliferation and cell cycle progression in K-562 and HL-60 cells were notably promoted by SPRY1 overexpression, but inhibited by SPRY1 knockdown. Meanwhile, the apoptosis of K-562 and HL-60 cells was significantly repressed by SPRY1 overexpression and facilitated by SPRY1 knockdown. In addition, we found that SPRY1 overexpression significantly activated the Hedgehog pathway in AML cells. The function of SPRY1 on the proliferation, cell cycle and apoptosis was reversed by Gli1 in K-562 and HL-60 cells.

Identifying new biomarkers and exploring the pathogenesis of AML is urgent to improve the disease surveillance for patients with AML.

SPRY1 could facilitate cell proliferation and cell cycle progression, and suppress cell apoptosis via activating the Hedgehog pathway in AML.

SPRY1 could facilitate cell proliferation and cell cycle progression, and suppress cell apoptosis via activating the Hedgehog pathway in AML.Objectives and Methods Erdheim-Chester disease (ECD) is a rare histiocytic neoplasm with a heterogeneous clinical course, ranging from localized and asymptomatic bone lesions to a multisystem disease, causing significant morbidity and mortality. There are few cohorts published, mainly from North America and Europe. We retrospectively collected clinical data on sixteen biopsy-proven ECD patients diagnosed and treated at two Brazilian reference centres for histiocytic disorders from January 2006 to February 2020.Results Median time from onset of symptoms to diagnosis was 13 months (0.1-142). DT-061 cell line The main organ involved in ECD was bone (75%) and also 75% of the patients presented involvement of more than one organ, characterizing a multi-organic form. BRAF status was available in 81.2% of patients and BRAF V600E mutation was detected by Sanger sequencing in only 18.8%, which can be explained by the low sensitivity of this technique. All patients were treated due to symptomatic disease and a median of two lines (range 1-7) of therapy were needed. The most common first-line therapy used was α-interferon (75%). The median progression-free survival was 7.5 months, and the median OS was not reached.Discussion and Conclusion In the largest Latin American cohort of patients with ECD reported to date, we observed findings which resemble demographic characteristics, sites of involvement and treatment choices reported by other groups. The outcomes may be better with target therapies such as BRAF and MEK inhibitors in patients with mutation and with the adoption of recently published consensus recommendations for the management of ECD patients.Introduction Compared with the 3 + 7 regimen, the addition of gemtuzumab ozogamicin (GO) has improved survival in patients with acute myeloid leukemia (AML). We conducted a systematic review and meta-analysis to examine the overall efficacy and safety of GO in combination with conventional chemotherapy regimens in patients with AML.Methods We searched several databases (MEDLINE, Embase, Web of Science and Cochrane Library). Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for overall survival (OS) and relapse-free survival (RFS); odds ratios (ORs) with 95% CIs were calculated for the other outcomes.Results Ten records involving 11 randomized controlled trials (RCTs) met the inclusion criteria. GO plus induction chemotherapy significantly increased RFS (HR 0.84, 95% CI 0.73-0.98), decreased the incidence of relapse (OR 0.78, 95% CI 0.68-0.91) and resistant disease (OR 0.72, 95% CI 0.61-0.84), and had no significant effect on the rate of complete remission (CR) with or without incomplete platelet recovery (OR 1.21, 95% CI 0.94-1.55), 30-day mortality (OR 1.25, 95% CI 0.99-1.57). Subgroup analysis showed significant OS benefits for patients with favorable cytogenetic (HR 0.50, 95% CI 0.28-0.89) or given GO at induction stage (HR 0.91, 95% CI 0.84-1.00). Compared with other dosing schedule groups, 3 mg/m2 fractionated schedule had a greater RFS benefit (HR 0.52, 95% CI 0.36-0.76) and lower relapse risk (OR 0.48, 95% CI 0.28-0.84).Conclusions Adding low-dose GO to induction or both induction and post-remission chemotherapy has considerable efficacy and unequivocal safety for newly diagnosed adult AML.

The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial showed reduced renal and cardiovascular (CV) events in patients with type 2 diabetes (T2D) and diabetic kidney disease (DKD) treated with canagliflozin 100 mg added to Standard of Care (SoC) versus SoC alone. This led to an extension of the canagliflozin 100 mg European marketing authorisation, making canagliflozin the first pharmacological therapy to receive authorisation for the treatment of DKD since the RENAAL and IDNT trials more than 20years ago. Given the importance of cost-effectiveness analyses in health care, this study aimed to leverage the CREDENCE trial outcomes to estimate the cost-effectiveness of canagliflozin 100 mg from the perspective of the Belgian healthcare system.

A microsimulation model (CREDENCE Economic Model of DKD), developed using patient-level CREDENCE trial data, was leveraged to model the progression of DKD and CV outcomes, associated costs, and life quality. Unit costs and quality-adjusted life years (QALYs) were sourced from the literature. The time horizon was 10years and sensitivity analyses were performed.

Canagliflozin was associated with sizable gains in life-years and QALYs over 10years, and the incremental cost-effectiveness ratio cost offsets associated with reductions in CV and renal complications resulted in overall net cost savings from the perspective of the Belgian healthcare system.

Model-based results suggest that adding canagliflozin 100 mg to SoC can improve outcomes for patients with DKD while reducing overall net costs for the Belgian healthcare system.

Model-based results suggest that adding canagliflozin 100 mg to SoC can improve outcomes for patients with DKD while reducing overall net costs for the Belgian healthcare system.

There are minimal data on the relationship between DII and MCI in an elderly Chinese population and no research has assessed the potential effect of LTL.

We investigated the association between DII and MCI while taking into account the potential effect of LTL.

This cross-sectional study included 3,386 participants aged ≥ 60 years of age from the Tianjin Elderly Nutrition and Cognition Cohort study. DII score was constructed based on a validated self-administered food frequency questionnaire was calculated based on the method developed by Shivappa et al. LTL was measured by quantitative real-time polymerase chain reaction. Multivariable logistic regression analysis was used to analyze the association between DII, LTL and MCI. Moreover, mediation analysis was employed to test the mediation effect of LTL on the total effect of DII on MCI.

Compared with the participants in the lowest tertiles of LTL and DII score, the odds ratios (ORs) of MCI in the highest tertiles were 0.386(95% CI 0.281-0.529) and 1.650 (95% CI 1.