Folic acid reverses nitric oxide synthase uncoupling and prevents cardiac dysfunction in insulin resistance: Role of Ca2+/calmodulin-activated protein kinase II

Nitric oxide synthase (NOS) may be uncoupled to produce superoxide rather than nitric oxide (NO) under pathological conditions such as diabetes mellitus and insulin resistance, leading to cardiac contractile anomalies. Nonetheless, the role of NOS uncoupling in insulin resistance-induced cardiac dysfunction remains elusive. Given that folic acid may produce beneficial effects for cardiac insufficiency partially through its NOS recoupling capacity, this study was designed to evaluate the effect of folic acid on insulin resistance-induced cardiac contractile dysfunction in a sucrose-induced insulin resistance model. Mice were fed a sucrose or starch diet for 8 weeks before administration of folic acid in drinking water for an additional 4 weeks. Cardiomyocyte contractile and Ca²⁺ transient properties were evaluated and myocardial function was assessed using echocardiography. Our results revealed whole body insulin resistance after sucrose feeding associated with diminished NO production, elevated peroxynitrite (ONOO⁻) levels, and impaired echocardiographic and cardiomyocyte function along with a leaky ryanodine receptor (RYR) and intracellular Ca²⁺ handling derangement. Western blot analysis showed that insulin resistance significantly promoted Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) phosphorylation, which might be responsible for the leaky RYR and cardiac mechanical dysfunction. NOS recoupling using folic acid reversed insulin resistance-induced changes in NO and ONOO⁻, CaMKII phosphorylation, and cardiac mechanical abnormalities. Taken together, these data demonstrated that treatment with folic acid may reverse cardiac contractile and intracellular Ca²⁺ anomalies through ablation of CaMKII phosphorylation and RYR Ca²⁺ leak.     

CircRNA has_circ_0006427 suppresses the progression of lung adenocarcinoma by regulating miR-6783–3p/DKK1 axis and inactivating Wnt/β-catenin signaling pathway

Recently, circular RNAs (circRNAs) are identified as a novel class of noncoding RNAs playing important roles in human malignant tumors. However, the regulatory function of circRNA in lung adenocarcinoma (LUAD) is still largely unknown. Present study aimed to explore the role of circ_0006427 in LUAD progression. Firstly, the downregulation of circ_0006427 in LUAD tissues and cell lines was revealed by microarray analysis and qRT-PCR analysis. And we also confirmed the circ_0006427 as a prognostic target in LUAD patients. Functionally, overexpression of circ_0006427 effectively suppressed cell proliferation, migration and invasion. Mechanistically, circ_0006427 was found to be predominantly located in the cytoplasm of LUCA cell, and was further revealed to positively regulate DKK1 in LUAD by sponging miR-6783–3p. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and western blot analysis revealed that circ_0006427 inactivated Wnt/β-catenin signaling pathway by upregulating DKK1. At last, rescue assays proved the function of circ_0006427/miR-6783–3p/DKK1 axis in LUAD progression. In conclusion, our study revealed that circ_0006427 suppressed lung adenocarcinoma progression through regulating miR-6783–3p/DKK1 axis.     

Mode of action of a surfactant–polymer formulation to support performance of the entomopathogenic nematode Steinernema carpocapsae for control of diamondback moth larvae (Plutella xylostella)

The use of entomopathogenic nematodes on cabbage leaves against larvae of the diamondback moth (DBM) Plutella xylostella requires the addition of formulation adjuvants to achieve satisfying control. Without adjuvants nematodes settle in the tank mix of backpack sprayers causing uneven distribution. The polymers arabic and guar gum, alginate and xanthan were used in concentrations between 0.05 and 0.3% to retard sedimentation of Steinernema carpocapsae. Arabic gum had no effect, guar gum prevented sedimentation at 0.3% but the effect dropped significantly at lower concentration. At 0.05%, xanthan prevented nematode sedimentation better than alginate. Deposition of nematodes on the leaves was significantly increased by the addition of any of the polymers. Spraying nematodes on leaves with an inclination of 45° without the addition of any formulation resulted in 70% run-off. Adding 0.2% alginate or xanthan reduced the losses to <20%. The use of a surfactant–polymer formulation significantly reduced defoliation by DBM larvae. Visual examinations provided evidence that nematodes are not ingested by DBM larvae. Invasion of S. carpocapsae is an active process via the anus. The function of the formulation is not to prolong nematode survival, but to provide environmental conditions which enable rapid invasion of the nematodes. Nematode performance was improved by selection of the best surfactant in combination with xanthan and by optimisation of the concentrations of the surfactant Rimulgan® and the polymer xanthan. The best control results were achieved with Rimulgan® at 0.3% together with 0.3% xanthan, causing DBM mortality of >90% at 80% relative humidity and >70% at 60%. The formulation lowered the LC₅₀ from 12 to 1 nematode/larva. The viscosity of the surfactant–polymer formulations correlated well with nematode efficacy, prevention of sedimentation and adherence to the leave. This physical parameter can therefore be recommended for improvement of nematode formulations to be used for foliar application against DBM.     

Bayesian Quantile Regression for Longitudinal Studies with Nonignorable Missing Data

Summary .  We study quantile regression (QR) for longitudinal measurements with nonignorable intermittent missing data and dropout. Compared to conventional mean regression, quantile regression can characterize the entire conditional distribution of the outcome variable, and is more robust to outliers and misspecification of the error distribution. We account for the within-subject correlation by introducing a   ℓ₂   penalty in the usual QR check function to shrink the subject-specific intercepts and slopes toward the common population values. The informative missing data are assumed to be related to the longitudinal outcome process through the shared latent random effects. We assess the performance of the proposed method using simulation studies, and illustrate it with data from a pediatric AIDS clinical trial.     

Patterns of reproduction and development of selected resident teleosts of Florida salt marshes

A wide variety of teleost fishes occur in tidal marshes of Atlantic and Gulf coasts of Florida, few of which breed in these habitats or remain there for extended periods of time. A significant fraction of teleosts that do so are members of one of five families. Eleven representative species belonging to these families, whose reproduction and development are considered here, include: Adinia xenica, Fundulus confluentus, F. grandis and F. similis (Fundulidae); Cyprinodon variegatus, Floridichthys carpio and Jordanella floridae (Cyprinodontidae); Gambusia holbrooki and Poecilia latipinna (Poeciliidae); Mugil cephalus (Mugilidae); and Dormitator maculatus (Eleotridae). Spawning or birth locations, patterns of growth and development, times of use of the salt marsh as a nursery area, and development of salinity tolerances/osmotic regulatory capabilities were evaluated for each, considering these in the context of variability of environmental conditions, especially of salinity. Five different patterns of reproduction are shown by these 11 species, and only A. xenica appears to be limited to reproducing in the salt marsh environment. Some of these species are capable of reproducing throughout the year. Several of the species are annuals, most others live only 2 or 3 years. Eight species (those other than M. cephalus, A. xenica and G. holbrooki) were found to show no size relationship, large juvenile to adult sizes, in osmotic regulatory capabilities.     

Antagonistic and synergistic interactions between aluminum and manganese on growth of Vigna unguiculata at low ionic strength

Concentrations of soluble aluminum (Al) and manganese (Mn) frequently reach phytotoxic levels in acid soils. While dose response relationships for these metals are well documented, the effects of combined exposure have received less attention. We have examined the effect of combinations of Al and Mn on growth and metal accumulation in Vigna unguiculata (L.) Walp. grown in solution culture under conditions of low ionic strength (conductivities typically < 100 µS cm⁻¹). The nature of interaction between these metals varied with the specific physiological response, the part of the plant investigated, and the relative amount of stress imposed. Analysis of growth data provided evidence for amelioration of metal toxicity (antagonistic effects), although this effect was dose dependent. Analysis of metal content data provided evidence for antagonistic and synergistic (exacerbation of toxicity) effects, again depending on dose. Analysis of foliar symptoms also provided evidence for antagonisms and synergisms, with the nature of the response dependent on the specific physiological response and specific plant part investigated. In contrast with previous reports, evidence for antagonistic, synergistic, and multiplicative effects on growth, metal uptake, and expression of foliar symptoms have been obtained under physiologically and environmentally relevant conditions. These results suggest a more detailed analysis of the potential for interactions between metals in the environment is required.     

The Influence of Changes in Magnetic Variations and Light–Dark Cycle on Life-History Traits of Daphnia magna

Day–night cycle is the main zeitgeber (time giver) for biological circadian rhythms. Recently, it was suggested that natural diurnal geomagnetic variation may also be utilized by organisms for the synchronization of these rhythms. In this study, life-history traits in Daphnia magna were evaluated after short-term and multigenerational exposure to 16 h day/8 h night cycle, 32 h day/16 h night cycle, diurnal geomagnetic variation of 24 h, simulated magnetic variation of 48 h, and combinations of these conditions. With short-term exposure, the lighting mode substantially influenced the brood to brood period and the lifespan in daphnids. The brood to brood period, brood size, and body length of crustaceans similarly depended on the lighting mode during the multigenerational exposure. At the same time, an interaction of lighting mode and magnetic variations affected to a lesser extent brood to brood period, brood size, and newborn's body length. The influence of simulated diurnal variation on life-history traits in daphnids appeared distinctly as effects of synchronization between periods of lighting mode and magnetic variations during the multigenerational exposure. Newborn's body length significantly depended on the lighting regime when the periods of both studied zeitgebers were unsynchronized, or on the interaction of light regime with magnetic variations when the periods were synchronized. These results confirm the hypothesis that diurnal geomagnetic variation is an additional zeitgeber for biological circadian rhythms. Possible mechanisms for these observed effects are discussed. Bioelectromagnetics. © 2020 Bioelectromagnetics Society     

Optimization of pancreatic lipase inhibition by Cudrania tricuspidata fruits using response surface methodology

The fruits of Cudrania tricuspidata (Carr.) Bur. (Moraceae) significantly inhibited pancreatic lipase, which plays a key role in fat absorption. Optimization of extraction conditions with minimum pancreatic lipase activity and maximum yield was determined using response surface methodology with three-level-three-factor Box–Behnken design (BBD). Regression analysis showed a good fit of the experimental data and the optimal condition was obtained as ethanol concentration, 74.5%; temperature 61.9 °C and extraction time, 13.5 h. The pancreatic lipase activity and extraction yield under optimal conditions were found to be 65.5% and 54.0%, respectively, which were well matched with the predicted value of 65.8% and 47.1%. Further fractionation of C. tricuspidata extract resulted in the isolation of compound 1, which was identified as 5,7,4′-trihydroxy-6,8-diprenylisoflavone. It inhibited pancreatic lipase activity with IC₅₀ value of 65.0 μM. HPLC analysis suggested positive correlation between pancreatic lipase inhibition and 5,7,4′-trihydroxy-6,8-diprenylisoflavone of C. tricuspidata fruits.     

Analysis of potassium iodate reduction in tissue homogenates using high performance liquid chromatography–inductively coupled plasma-mass spectrometry

Potassium iodate (KIO₃) and potassium iodide (KI) are the major salt iodization agents used worldwide. Unlike iodide (I⁻), iodate (IO₃⁻) should be reduced to I⁻ before it can be effectively used by the thyroid. In this study, we developed a new method for analyzing IO₃⁻ and I⁻ in tissue homogenates using high performance liquid chromatography coupled to inductively coupled plasma mass spectrometry (HPLC–ICP-MS). We further applied the method to demonstrate the KIO₃ reduction process by tissues in vitro. The effects of KIO₃ on the total antioxidative activity (TAA) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) were also investigated here. Finally, we found that IO₃⁻ can be reduced to I⁻ by tissue homogenates and IO₃⁻ irreversibly decreases the antioxidant capability of tissues. Our studies suggest that KIO₃ might have a big effect on the redox balance of tissue and would further result in oxidative stress of organisms.