The present study sought to investigate the effect of micronized resveratrol supplementation on serum levels of asymmetric de-methyl-arginine (ADMA) and paraoxonase-1 (PON1) activity in patients with type 2 diabetes (T2D). selleckchem In this double-blinded randomized trial, 76 patients with T2D were recruited. Participants were randomly assigned to consume 1,000 mg resveratrol or placebo capsules (methylcellulose) per day, for 8 weeks. Serum levels of ADMA and PON1 enzyme activity were measured at the beginning and end of the intervention using the enzyme-linked immunosorbent assay method. In total, 71 participants completed the study. Our results showed that resveratrol significantly decreased serum levels of ADMA (-0.16 ± 0.11, p less then  .001) and improved PON1 enzyme activity (15.39 ± 13.99, p less then  .001) compared with placebo, after adjusting for confounding factors (age, sex, and baseline body mass index). Our findings suggest that 8-week resveratrol supplementation may produce beneficial effects on serum levels of ADMA and PON1 enzyme activity in patients with T2DM. However, further research is needed to confirm the veracity of these results. © 2020 John Wiley & Sons, Ltd.Music is known for reducing stress, anxiety and depression, improving cognitive performance, and enhancing estrogen levels. However, its effect on non-auditory mammalian cell system and the molecular events leading to higher estrogen levels is less explored. Therefore, the present study targeted to know the direct effects of peaceful Vedic music on 3D cultured buffalo granulosa cell spheroids. The spheroids were daily exposed to the Mahamrityunjaya mantra, a kind of Vedic chants, for 1.5 h for six days. After six days, the music effect was analysed by the expression analysis of steroidogenic (CYP19A1, STAR and HSD17β1) and proliferative marker (PCNA) genes. Interestingly, the CYP19A1 gene expression was significantly up-regulated by 3.464±0.15 folds in the music exposed spheroids than the non-exposed spheroids. However, the expression of other steroidogenic and proliferative genes were unaltered. These observations provided a transcriptional clue for higher estradiol levels by the music and a scope to use Vedic chants for increasing the CYP19A1 expression to help tackle some pathophysiologcial conditions. This article is protected by copyright. All rights reserved.RATIONALE Analytical methods for the detection and identification of half nitrogen mustards (halfNMs), i.e., partial hydrolyzed product of nitrogen mustards (pHpNMs), using silyl derivatives are often associated with low sensitivity and selectivity. In order to overcome these limitations, the derivatization of halfNMs was performed using perfluoroacylation. METHODS Two efficient derivatization techniques using trifluroacetyl (TFA) and heptaflurobutyryl (HFB) groups were developed for the unambiguous identification of halfNMs. A mass spectral database was generated by performing gas chromatography electron ionization mass spectrometry (GC/EI-MS) and gas chromatography positive chemical ionization mass spectrometry (GC/PCI-MS). The fragmentation pathways were studied by tandem mass spectrometry (MS/MS) in both EI and PCI modes. RESULTS The EI-MS spectra of the TFA and HFB derivatives of halfNMs contain intense molecular ions and fragment ions, thus making perfluoroacylation preferable to silylation. In addition, the background-free chromatogram obtained using these derivatives provides unambiguous identification of these compounds in blind samples. The structures of the fragment ions were postulated, and the sources of significant ions were traced by performing MS/MS precursor ion scans. In the PCI-MS spectra, along with the protonated molecule significant peaks due to neutral loss of HF, HCl, CH3 Cl and CF3 COOH were observed. CONCLUSION This is the first report of the elucidation of the fragmentation pathways of perfluroacyl derivatives of halfNMs. The complementary GC/PCI-MS and GC/PCI-MS/MS data will be helpful in the identification of unknown metabolites in a fast and reliable fashion. This article is protected by copyright. All rights reserved.Cu/Zn superoxide dismutase (SOD1) is a front-line antioxidant enzyme catalysing superoxide breakdown and is important for most forms of eukaryotic life. The evolution of aerobic respiration by mitochondria increased cellular production of superoxide, resulting in an increased reliance upon SOD1. Consistent with the importance of SOD1 for cellular health, many human diseases of the central nervous system involve perturbations in SOD1 biology, with the clearest demonstration provided by cases of amyotrophic lateral sclerosis associated with SOD1 gene mutations. But far from providing a simple demonstration of how disease arises from SOD1 loss-of-function, attempts to elucidate pathways by which atypical SOD1 biology leads to neurodegeneration have revealed unexpectedly complex molecular characteristics delineating healthy, functional SOD1 protein from that which likely contributes to central nervous system disease. This review summarises contemporary understanding of SOD1 biology from SOD1 genetics through to protein function and stability. Our cumulative knowledge of these processes is advancing efforts to identify and target pathways of neurotoxicity driven by atypical mutant and wild-type SOD1 in multiple incurable neurodegenerative conditions. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.OBJECTIVE To evaluate the effect of preoperative pelvic floor muscle training (PFMT) on pelvic floor contraction, symptoms and anatomical pelvic organ prolapse (POP) six months after surgery and to study overall changes in contraction, symptoms and anatomy after surgery. METHODS Randomized controlled trial. Women scheduled for POP surgery (n=159) were randomized to intervention including daily PFMT from inclusion to surgery (n= 81) or control (n=78). Participants were examined at inclusion, day of surgery and after six months. Pelvic floor muscle contraction was assessed with palpation using the Modified Oxford Scale (MOS) (0-5), vaginal manometry, surface-EMG, and transperineal ultrasound measuring proportional change in levator hiatal anteroposterior diameter from rest to contraction. POP distance from hymen in most dominant compartment and organ descent in anterior, central and posterior compartment on ultrasound were measured. Sensation of vaginal bulge was graded using a visual analogue scale (VAS) (0-10central compartment 0.0 vs -1.2, p less then  0.001; posterior compartment 0.9 vs 0.4, p= 0.001 and bulge sensation (VAS) 57.6 vs 6.7, p less then  0.001 were reduced. CONCLUSION We found no effect of preoperative PFMT on contraction, symptomatic or anatomical prolapse after surgery. Over all, contraction and symptoms improved over time, most likely explained by the anatomical correction of POP after surgery. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Post-polypectomy surveillance is essential to reduce the morbidity and mortality of colorectal cancers (CRCs). The guidelines of the US Multi-Society Task Force (MSTF) and the European Society of Gastrointestinal Endoscopy (ESGE) recommended post-polypectomy colonoscopy surveillance intervals concerning baseline findings of colorectal neoplasia. Despite the presence of simple recommendation from Japanese clinical practice guidelines for management of colorectal polyps, there is no firm consensus of post-polypectomy surveillance program in Japan. This article is protected by copyright. All rights reserved.Bovine mammary epithelial cells (BMECs) of high-producing dairy cows are subject to constant oxidative stress as a result of high metabolic rate and physiological adaptation to intensive farming. Moringa (Moringa oleifera) leaf has been proposed to have the antioxidant potential in scavenging free radicals due to the presence of flavonoids. In this study, we investigated the cytoprotective effects of moringa leaf flavonoids in alleviating oxidative stress in BMECs in vitro. Oxidative stress was established by exposing isolated BMECs to H2 O2 for 2 hr. Doses of moringa leaf flavonoids were evaluated by treating BMECs for 12 hr. The optimal concentrations of H2 O2 and moringa leaf flavonoids were 500 μmol/L and 1.0 mg/ml, respectively. The results showed that moringa leaf flavonoids increased the activities of superoxide dismutase, catalase, and glutathione peroxidase; and reduced malondialdehyde activity and intracellular accumulation of reactive oxygen species (ROS) in the H2 O2 -induced oxidative stress system. A Hoechst33258 staining assay revealed that moringa leaf flavonoids decreased the apoptosis rate in BMECs, while leaving membrane integrity and nucleolar morphology unchanged. We concluded that moringa leaf flavonoids have the antioxidant capacity to effectively reduce oxidative stress in BMECs. © 2020 Blackwell Verlag GmbH.The human Niemann-Pick C1 (NPC1) gene encoding a 1278 AMino acid protein is very heterogeneous. While some variants represent benign polymorphisms, NPC disease carriers and patients may possess rare variants, whose functional importance remains unknown. An NPC1 cDNA construct known as NPC1 wild-type variant (WT-V), distributed between laboratories and used as a WT control in several studies, also contains changes regarding specific amino acids compared to the NPC1 Genbank reference sequence. To improve the dissection of subtle functional differences, we generated human cells stably expressing NPC1 variants from the AAVS1 safe-harbor locus on an NPC1-null background engineered by CRISPR/Cas9 editing. We then employed high-content imaging with automated image analysis to quantitatively assess LDL-induced, time-dependent changes in lysosomal cholesterol content and lipid droplet formation. Our results indicate that the L472P change present in NPC1 WT-V compromises NPC1 functionality in lysosomal cholesterol export. All-atom molecular dynamics simulations suggest that the L472P change alters the relative position of the NPC1 middle and the C-terminal luminal domains, disrupting the recently characterized cholesterol efflux tunnel. These results reveal functional defects in NPC1 WT-V and highlight the strength of simulations and quantitative imaging upon stable protein expression in elucidating subtle differences in protein function. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.PURPOSE To implement, optimize, and characterize lipid-insensitive binomial off-resonant RF excitation (LIBRE) pulses for fat-suppressed fully self-gated free-running 5D cardiac MRI. METHODS Bloch equation simulations were used to optimize LIBRE parameter settings in non-interrupted bSSFP prior to in vitro validation. Thus, optimized LIBRE pulses were subsequently applied to free-running coronary MRA in 20 human adult subjects, where resulting images were quantitatively compared to those obtained with non-fat-suppressing excitation (SP), conventional 1-2-1 water excitation (WE), and a previously published interrupted free-running (IFR) sequence. SAR and scan times were recorded. Respiratory-and-cardiac-motion-resolved images were reconstructed with XD-GRASP, and contrast ratios, coronary artery detection rate, vessel length, and vessel sharpness were computed. RESULTS The numerically optimized LIBRE parameters were successfully validated in vitro. In vivo, LIBRE had the lowest SAR and a scan time that was similar to that of WE yet 18% shorter than that of IFR.