Discovery of N-(3,5-bis(1-pyrrolidylmethyl)-4-hydroxybenzyl)-4-methoxybenzenesulfamide (sulcardine) as a novel anti-arrhythmic agent.

AIM: To investigate the anti-arrhythmic effects of sulfamide analogues of changrolin and to characterize the sulfate of compound 6f (sulcardine sulfate, Sul) as a novel anti-arrhythmic agent. METHODS: The anti-arrhythmic effects of compounds were studied against aconitine-induced arrhythmias in rats and ouabain-induced arrhythmias in guinea pigs. The effects of Sul on transmembrane action potentials were investigated in isolated rabbit sinoatrial nodes and guinea-pig papillary muscles using intracellular recording. With a whole-cell recording technique, the effects of Sul on sodium current, calcium current, and potassium currents were examined in isolated single guinea-pig ventricular myocytes. RESULTS: In aconitine-induced arrhythmias of rats, sulfamide analogues of changrolin (4, 5, and 6a-6p) exhibited various anti-arrhythmic activities. The sulfate of compound 6f (Sul) increased the amount of aconitine required to induce arrhythmias in each treated animal. The ED50 value of Sul in rats was 196 mg/kg. In ouabain-induced arrhythmias of guinea pigs, 25, 50, and 100 mg/kg doses of Sul increased the dose of ouabain required to induce VP, VT, and VF in a dose-dependent manner. In papillary preparations, Sul produced a concentration-dependent decrease in APA and V(max), prolonged APD(90) and ERP, whereas RP was unaffected. In the spontaneously beating sinus nodes, Sul reduced APA and V(max) in a concentration-dependent manner. The whole-cell recording studies revealed that Sul produced a reversible reduction in I(Na) (IC50=26.9 µmol/L) and I(Ca,L)(IC50=69.2 µmol/L), whereas the inward rectifier (I(K1)) and the delayed rectifier potassium currents (I(K)) were unaffected. CONCLUSION: As a multi-ion channel blocker, Sul may have potent efficacy in anti-atrial and ventricular arrhythmias.

Low-intensity transcranial ultrasound stimulation facilitates hand motor function and cortical excitability: A crossover, randomized, double blind study.

Objective: Transcranial ultrasound stimulation (TUS) is a new form of non-invasive brain stimulation. Low-intensity TUS is considered highly safe. We aimed to investigate the effect of low-intensity TUS on hand reaction responses and cortical excitability in healthy adults. Methods: This study used a crossover, randomized, and double-blind design. A total of 20 healthy participants were recruited for the study. All the participants received TUS and sham stimulation on separate days in random order. The finger tapping test (tapping score by using a tablet) and motor evoked potential (MEP) were assessed before and after stimulation, and discomfort levels were assessed using a visual analog scale (VAS) score. Results: No significant differences in tapping score or MEP amplitude between the two experimental conditions were registered before stimulation. After stimulation, tapping scores were increased regardless of the specific treatment, and the real stimulation condition receiving TUS (90.4 ± 11.0 points) outperformed the sham stimulation condition (86.1 ± 8.4 points) (p = 0.002). The MEP latency of real TUS (21.85 ± 1.33 ms) was shorter than that of sham TUS (22.42 ± 1.43 ms) (p < 0.001). MEP amplitude of real TUS (132.18 ± 23.28 µV) was higher than that of sham TUS (114.74 ± 25.5 µV, p = 0.005). There was no significant difference in the discomfort score between the two conditions (p = 0.163). Conclusion: Transcranial ultrasound stimulation (TUS) can decrease the hand reaction response time and latency of the MEP, enhance the excitability of the motor cortex, and improve hand motor function in healthy individuals without obvious discomfort.

Complete plastid genome of Gracilaria bailiniae (Rhodophyta) and phylogenetic analysis.

The complete Gracilaria bailiniae plastid genome was determined and analyzed in this work. It had a circular mapping molecular with the length of 185,129 bp and contained 231 genes including 193 protein-coding, 3 rRNA, 1 tmRNA, 29 tRNA genes, and 5 unidentified open reading frames. Phylogenetic analysis showed that G. bailiniae clustered together with Gracilaria chorda and Gracilariopsis lemaneiformis. The complete plastid genome provided in this work would be useful for elucidation of Gracilaria evolution.

Physicochemical characterization of Gracilaria chouae sulfated polysaccharides and their antioxidant potential.

A complete absence of the physicochemical characterization of Gracilaria chouae polysaccharides (GCP) and its corresponding bioactivities urged the need for this study. It was found that GCP is a heteropolysaccharide which exists in linear random coil conformation. It contained a sulfate content of 7.9% in addition to 52.63% total sugar content and 9.62% galacturonic acid. Galactose and 3,6-anhydrogalactose were found in a molar ratio of 1.0:0.6. Its setting and melting points were determined as 41.3 and 71.7 °C, respectively, which makes it a suitable candidate for industrial processing where further heating is required and/or where the end-product needs to have extended shelf life in hot climate. GCP demonstrated 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis and hydroxyl radical scavenging activity (36.86, 27.42 and 19.07% at 3 mg·ml-1). Moreover, the results also suggested its potential use as a prebiotic due to its perceived high fermentability.

The effects of dietary fatty acids on liver fatty acid composition and Delta(6)-desaturase expression differ with ambient salinities in Siganus canaliculatus.

Delta(6)-Desaturase (linoleoyl-CoA desaturase, EC 1.14.19.3) is the rate-limiting enzyme in the biosynthetic pathway of highly unsaturated fatty acid (HUFA). In this report, a Delta6 desaturase-like cDNA was cloned, and the relation of HUFA biosynthetic activity in liver with ambient salinity as well as dietary fatty acids was investigated in the euryhaline teleost Siganus canaliculatus. After the juveniles were fed four formulated diets (D1-D4) with different essential fatty acid composition (D1 with 23.49% HUFA, D2-D4 were HUFA-free, linoleic and alpha-linolenic acids account for 21.1% and 0.38%, 13.99% and 11.64%, 18.31% and 5.82% of the total fatty acids, respectively) for nine weeks, the growth performance showed no difference among groups in brackish water (10 ppt) or seawater (32 ppt) (P>0.05). Comparing liver fatty acids with fish fed D1, the content of arachidonic acid in fish fed D2 or D4 was significantly higher in 10 ppt (P<0.05), but showed no difference in 32 ppt; the contents of eicosapentaenoic (EPA), docosapentaenoic (DPA) and docosahexaenoic (DHA) acids in 10 ppt, as well as EPA in 32 ppt in fish fed D3 showed no difference, whereas those of DPA and DHA were significantly lower in 32 ppt (P<0.05). These data suggest that S. canaliculatus may convert linoleic and alpha-linolenic acids into HUFA and such a capacity was stronger in low salinity than that in high salinity. Consistent with this, the liver levels of Delta6 desaturase mRNA in fish fed D2-D4 were generally higher than in fish fed D1 in both salinities, and the total expression level in 10 ppt was about 1.56 times of that in 32 ppt, suggesting that transcriptional control of Delta6 desaturase is involved in such a HUFA biosynthesis. To our knowledge, this is the first report showing the relation of HUFA biosynthetic activity with ambient salinity in a euryhaline fish.

Complete sequence of mitochondrial DNA of Gracilaria tenuistipitata var. liui (Rhodophyta).

Here, the complete Gracilaria tenuistipitata var. liui mitogenome was determined and analyzed. The complete G. tenuistipitata var. liui mitogenome length was 25,879 bp and contained 50 genes including 24 protein-coding, 2 rRNA, and 23 tRNA genes and one unidentified open reading frame (ORF). Of the 24 protein-coding genes, 23 (95.83%) terminated with the stop codon TAA, and one (4.17%) with TAG (rps3 gene). All protein-coding genes in G. tenuistipitata var. liui started with ATG codon. Mitogenome phylogenetic analysis revealed that G. tenuistipitata var. liui firstly clustered together with Gracilaria tenuistipitata. The complete mitogenome sequence would help in understanding Gracilaria evolution.

[Physiological responses of Gracilaria lemaneiformis to copper stress].

Gracilaria lemaneiformis was exposed to 0, 25, 50, 100, 250 and 500 microg x L(-1) of Cu2+ to study its physiological responses to Cu2+ stress. When the Cu2+ concentration was > or = 50 microg x L(-1), the relative growth rate (RGR) of G. lemaneiformis decreased significantly, and the optimal quantum yield (Fv/Fm), the maximum relative electron transfer rate (rETRmax), and the relative electron transfer efficiency (alpha) exhibited the same variation trend, compared with the control. With the increase of Cu2+ concentration, the maximum net photosynthetic rate (Pmax) and light saturation point (LSP) decreased significantly, light compensation point (LCP) had a significant increase, while chlorophyll a, carotenoid, and phycobiliprotein contents decreased after an initial increase. When the Cu2+ concentration reached 500 microg x L(-1), the chlorophyll a, carotenoid, and phycobiliprotein contents decreased significantly. It was suggested that G. lemaneiformis could tolerate low concentration Cu2+ stress, but its physiological activities were inhibited markedly when exposed to > or =50 microg x L(-1) of Cu2+.