Potassium dehydroandrographolide succinate regulates the MyD88/CDH13 signaling pathway to enhance vascular injury-induced pathological vascular remodeling.

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.

Potassium Magnesium Citrate Is Superior to Potassium Chloride in Reversing Metabolic Side Effects of Chlorthalidone.

BACKGROUND: Thiazide diuretics (TD) are the first-line treatment of hypertension because of its consistent benefit in lowering blood pressure and cardiovascular risk. TD is also known to cause an excess risk of diabetes, which may limit long-term use. Although potassium (K) depletion was thought to be the main mechanism of TD-induced hyperglycemia, TD also triggers magnesium (Mg) depletion. However, the role of Mg supplementation in modulating metabolic side effects of TD has not been investigated. Therefore, we aim to determine the effect of potassium magnesium citrate (KMgCit) on fasting plasma glucose and liver fat by magnetic resonance imaging during TD therapy. METHODS: Accordingly, we conducted a double-blinded RCT in 60 nondiabetic hypertension patients to compare the effects of KCl versus KMgCit during chlorthalidone treatment. Each patient received chlorthalidone alone for 3 weeks before randomization. Primary end point was the change in fasting plasma glucose after 16 weeks of KCl or KMgCit supplementation from chlorthalidone alone. RESULTS: The mean age of subjects was 59±11 years (30% Black participants). Chlorthalidone alone induced a significant rise in fasting plasma glucose, and a significant fall in serum K, serum Mg, and 24-hour urinary citrate excretion (all P<0.05). KMgCit attenuated the rise in fasting plasma glucose by 7.9 mg/dL versus KCl (P<0.05), which was not observed with KCl. There were no significant differences in liver fat between the 2 groups. CONCLUSIONS: KMgCit is superior to KCl, the common form of K supplement used in clinical practice, in preventing TD-induced hyperglycemia. This action may improve tolerability and cardiovascular safety in patients with hypertension treated with this drug class.

Vitamins and Minerals for Blood Pressure Reduction in the General, Normotensive Population: A Systematic Review and Meta-Analysis of Six Supplements.

Hypertension is the leading preventable risk factor for cardiovascular disease and all-cause mortality worldwide. However, studies have shown increased risk of mortality from heart disease and stroke even within the normal blood pressure (BP) range, starting at BPs above 110-115/70-75 mm Hg. Nutraceuticals, such as vitamins and minerals, have been studied extensively for their efficacy in lowering BP and may be of benefit to the general, normotensive population in achieving optimal BP. Our study investigated the effects of six nutraceuticals (Vitamins: C, D, E; Minerals: Calcium, Magnesium, Potassium) on both systolic blood pressure (SBP) and diastolic blood pressure (DBP) in this population. We performed a systematic review and pairwise meta-analysis for all six supplements versus placebo. Calcium and magnesium achieved significant reductions in both SBP and DBP of -1.37/-1.63 mm Hg and -2.79/-1.56 mm Hg, respectively. Vitamin E and potassium only yielded significant reductions in SBP with values of -1.76 mm Hg and -2.10 mm Hg, respectively. Vitamins C and D were not found to significantly lower either SBP or DBP. Future studies should determine optimal dosage and treatment length for these supplements in the general, normotensive population.

Anti-inflammatory, anticholinesterase, antioxidant, and memory enhancement potential of Phyllanthus amarus in potassium-dichromate induced neurotoxicity of male Wistar rats.

This study investigated the protective effect of aqueous Phyllanthus amarus leaf extract (APALE) in Potassium dichromate (PDc)-induced neurotoxicity. Seventy young adult male, Wistar rats with a weight of 130-150 g, were randomised into seven groups (n = 10): Group 1; distilled water; Group 2: 300 mg/kg APALE; Group 3: 17 mg/kg PDc; Group 4: 5 mg/kg Donepezil (DPZ); Group 5: 17 mg/kg PDc + 400 mg/kg APALE; Group 6:17 mg/kg PDc + 200 mg/kg APALE; Group 7: 17 mg/kg PDc + 5 mg/kg DPZ. All administrations were given once daily via an orogastric cannula for 28 consecutive days. Cognitive assessment tests were employed to ascertain the treatments' effects on the rats' cognitive function. At the end of the experiment, the rats were sacrificed, morphometric analysis was done, and the brains were dissected for histology, enzyme, and other biochemical analysis. Findings from this study showed that APALE significantly improved locomotive activity, recognition memory sensitivity, protection against fear and anxiety, enhanced decision-making, and improved memory function in a dose-dependent manner comparably to DPZ. In addition, APALE significantly increased antioxidants level, reducing oxidative stress in PDc-induced neurotoxic rats and significantly reducing brain acetylcholinesterase (AchE) activity by regulating gamma amino butyric acid (GABA) levels in PDc-induced neurotoxic rats compared to DPZ. Furthermore, APALE alleviated neuroinflammatory responses via maintaining histoarchitecture and down-regulation of IBA1 and Tau in PDc-induced rats. In conclusion, APALE protected against PDc-induced neurotoxicity via a combination of anti-inflammatory, anticholinergic, and antioxidant effects on the prefrontal cortex of rats.

The effect of increased plasma potassium on myocardial function; a randomized POTCAST substudy.

Plasma potassium (p-K) in the high-normal range has been suggested to reduce risk of cardiovascular arrythmias and mortality through electrophysiological and mechanical effects on the myocardium. In this study, it was to investigated if increasing p-K to high-normal levels improves systolic- and diastolic myocardial function in patients with low-normal to moderately reduced left ventricular ejection fraction (LVEF). The study included 50 patients (mean age 58 years (SD 14), 81% men), with a mean p-K 3.95 mmol/l (SD 0.19), mean LVEF 48% (SD 7), and mean Global Longitudinal Strain (GLS) -14.6% (SD 3.1) patients with LVEF 35-55% from "Targeted potassium levels to decrease arrhythmia burden in high-risk patients with cardiovascular diseases trial" (POTCAST). Patients were given standard therapy and randomized (1:1) to an intervention that included guidance on potassium-rich diets, potassium supplements, and mineralocorticoid receptor antagonists targeting high-normal p-K levels (4.5-5.0 mmol/l). Echocardiography was done at baseline and after a mean follow-up of 44 days (SD 18) and the echocardiograms were analyzed for changes in GLS, mechanical dispersion, E/A, e', and E/e'. At follow-up, mean difference in changes in p-K was 0.52 mmol/l (95%CI 0.35;0.69), P<0.001 in the intervention group compared to controls. GLS was improved with a mean difference in changes of -1.0% (-2;-0.02), P<0.05 and e' and E/e' were improved with a mean difference in changes of 0.9 cm/s (0.02;1.7), P = 0.04 and ? 1.5 (-2.9;-0.14), P = 0.03, respectively. Thus, induced increase in p-K to the high-normal range improved indices of systolic and diastolic function in patients with low-normal to moderately reduced LVEF.

Sophoridine manifests as a leading compound for anti-arrhythmia with multiple ion-channel blocking effects.

BACKGROUND: Sophoridine (SR) has shown the potential to be an antiarrhythmic agent. However, SR's electrophysiological properties and druggability research are relatively inadequate, which limits the development of SR as an antiarrhythmic candidate. PURPOSE: To facilitate the development process of SR as an antiarrhythmic candidate, we performed integrated studies on the electrophysiological properties of SR in vitro and ex vivo to gain more comprehensive insights into the multi-ion channel blocking effects of SR, which provided the foundation for the further drugability studies in antiarrhythmic and safety studies. Firstly, SR's electrophysiological properties and antiarrhythmic potentials were recorded and assessed at the cell and tissue levels by comprehensively integrating the patch clamp with the Electrical and Optical Mapping systems. Subsequently, the antiarrhythmic effects of SR were validated by aconitine and ouabain-induced arrhythmia in vivo. Finally, the safety of SR as an antiarrhythmic candidate compound was evaluated based on the guidelines of the Comprehensive in Vitro Proarrhythmia Assay (CiPA). STUDY DESIGN: The antiarrhythmic effect of SR was evaluated at the in vitro, ex vivo, and in vivo levels. METHODS: Isolated primary cardiomyocytes and stable cell lines were prepared to explore the electrophysiologic properties of being a multiple ion-channel blocker in vitro by whole-cell patch clamp. Using electrical and optical mapping, the negative chronotropic effect of SR was determined in langendorff-perfused rat or guinea-pig hearts.The antiarrhythmic activity of SR was assessed by the ex vivo tachyarrhythmia models induced by left coronary artery ligation (LCAL) and isoproterenol (ISO). Canonical models of aconitine and ouabain-induced arrhythmia were used to verify the antiarrhythmic effects in vivo. Finally, the pro-arrhythmic risk of SR was detected in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes (hSCCMs) using a Microelectrode array (MEA). RESULTS: Single-cell patch assay validated the multiple ion-channel blockers of SR in transient outward current potassium currents (Ito), l-type calcium currents (ICa-l), and rapid activation delayed rectifier potassium currents (IKr). SR ex vivo depressed heart rates (HR) and ventricular conduction velocity (CV) and prolonged Q-T intervals in a concentration-dependent manner. Consistent with the changes in HRs, SR extended the active time of hearts and increased the action potential duration measured at 90% repolarization (APD90). SR could also significantly lengthen the onset time and curtail the duration of spontaneous ventricular tachycardia (VT) in the ex vivo arrhythmic model induced by LCAL. Meanwhile, SR could also significantly upregulate the programmed electrical stimulation (PES) frequency after the ISO challenge in forming electrical alternans and re-entrant excitation. Furthermore, SR exerted antiarrhythmic effects in the tachyarrhythmia models induced by aconitine and ouabain in vivo. Notably, the pro-arrhythmic risk of SR was shallow for a moderate inhibition of the human ether-à-go-go-related gene (hERG) channel. Moreover, SR prolonged field potential duration (FPDc) of hSCCMs in a concentration-dependent manner without early after depolarization (EAD) and arrhythmia occurrence. CONCLUSION: Our results indicated that SR manifested as a multiple ion-channel blocker in the electrophysiological properties and exerts antiarrhythmic effects ex vivo and in vivo. Meanwhile, due to the low pro-arrhythmic risk in the hERG inhibition assay and the induction of EAD, SR has great potential as a leading candidate in the treatment of ventricular tachyarrhythmia.

Effect of potassium supplementation on osmoregulatory and stress response of Pangasianodon hypophthalmus (Sauvage, 1878) with Spinacia oleracea L. in aquaponics.

This study evaluated the effect of different potassium supplementation dosages on the physiological responses of Pangasianodon hypophthalmus reared in an aquaponic system with Spinacia oleracea L. for 60 days. The system comprised of a rectangular fish tank of 168 l capacity (water volume = 100 l) with nutrient film technique (NFT)-based hydroponic component with fish to plant ratio of 2.8 kg m-3 : 28 plants m-2 in all the treatments. The osmoregulatory and stress parameters of P. hypophthalmus at four different potassium dosages of T1 (90 mg l-1 ), T2 (120 mg l-1 ), T3 (150 mg l-1 ) and T4 (180 mg l-1 ) were compared with C (control, 0 mg l-1 ) to examine the potassium level to be applied to aquaponics. The water quality parameters and fish production were found to have no adverse impact due to potassium supplementation. The spinach yield during two harvests, i.e., before and after potassium supplementation, revealed that the yield was significantly higher (P < 0.05) after supplementation with the highest yield in T3 and T4. The osmoregulatory parameters such as plasma osmolality, Na+ , K+ ATPase activity in gill and plasma ionic profile (Cl- , Ca2+ and Na+ ) showed an insignificant variation (P > 0.05) between control and treatments except for higher plasma potassium concentration (1.98 ± 0.19 mmol l-1 ) in T4. The stress and antioxidant enzyme analysis exhibited significantly higher plasma glucose and superoxide dismutase (SOD) activity in gill and liver in T4, whereas cortisol and catalase showed an insignificant difference (P > 0.05). The experimental findings demonstrated that the potassium dosage up to 150 mg l-1 could be suggested as optimum for P. hypophthalmus and spinach aquaponics without impairing the health and oxidative status of P. hypophthalmus.

Effects of potassium fulvic acid and potassium humate on microbial biodiversity in bulk soil and rhizosphere soil of Panax ginseng.

Potassium fulvic acid (BSFA) and potassium humate (KHM), as organic fertilizers, can improve soil structure, increase soil nutrient levels and prevent plant diseases. However, knowledge is limited regarding how BSFA and KHM influence soil microbial communities and the interrelationships between community members associated with Panax ginseng. Soil pH and nutrient content increased significantly as a result of the addition of BSFA and KHM. The pH, NH4+-N, NO3--N, AP and AK increased by 1.72 %-5.55 %, 70.09 %-108.39 %, 35.38 %-216.20 %, 1.21 %-14.19 % and 3.40 %-5.94 %, respectively, in the BSFA and KHM treatments. The soil nutrient increase may be related to Micrococcaceae and arbuscular mycorrhizal fungi (AMF). The structure of the microbial community also changed radically from that of the control group, and Chloroflexi (2.69 %-3.15 %), Actinobacteria (4.33 %-7.53 %) and Acidobacteria (9.44 %-11.62 %) were the dominant microorganisms at the phylum level in bacteria. In contrast, the dominant fungi at the phylum level were Ascomycota (77.39 %-78.08 %), Glomeromycota (0.36 %-2.68), Olpidiomycota (0.02 %-3.78 %) and Basidiomycota (0.80 %-1.17 %). Fusarium oxysporum and Ascomycota were biomarkers for BSFA and KHM, which may be related to pathogenic bacteria. Network analysis revealed that the association among members of the soil microbial community was more positive than negative following application of KHM, and more positive (62.5 %) than negative (37.5 %) correlations were observed between bacteria, whereas the fungal community exhibited more positive (97.3 %) than negative (2.7 %) correlations. PICRUST predicted the microbial function of adding KHM and BSFA to the soil, and these pathways mainly belong to the degradation and metabolism of organic matter, saprophytic organisms and plant pathogens. In summary, our study demonstrated that the addition of BSFA and KHM increased the nutrients in the ginseng soil and reshaped the microbial function in soils, providing a theoretical foundation for soil improvement and biological control of ginseng diseases. However, due to the limitations of greenhouse cultivation, additional long-term experiments on farmland with different climate changes are recommended.

Selenomethionine modulates insulin secretion in the MIN6-K8 mouse insulinoma cell line.

Selenium is an essential trace element of interest for its potential role in glucose homeostasis. The present study investigated the impact of selenium supplementation as selenomethionine (SeMet) on insulin secretion in MIN6-K8 cells, a pancreatic ß-cell model. We found that SeMet enhanced percent glucose-induced insulin secretion, while also increasing tolbutamide- and KCl-induced percent insulin secretion. RNA-sequencing showed that SeMet supplementation altered expression of several selenoproteins, including glutathione peroxidase 3 (Gpx3) and selenoprotein P (SelP). Targeted knockdown of Gpx3 increased both percent and total insulin release, while SelP knockdown increased insulin content and insulin release. Collectively, these studies support a putative role for selenium and selenoproteins in the regulation of insulin secretion, glucose homeostasis, and diabetes risk.

Rice seed (IR64) priming with potassium humate for improvement of seed germination, seedling growth and antioxidant defense system under arsenic stress.

The intolerable levels of arsenic (As) in groundwater and its application in rice cultivation are continuously affecting the rice production in Ganga-Meghna-Brahmaputra (GMB) plain. The reduced germination and plant growth rates under excessive As stress ultimately lead to lower yield. To mitigate this concerning issue, the present study was carried out to evaluate the potential of K-humate priming on seed germination and plant growth under As stress. Seeds were primed with 100 mg/l K-humate for 12 h prior to germination. The germination percentages in unprimed seeds were 65 ±â€¯5.0% and 58.3 ±â€¯7.6% under stress level of 50 µM AsV and 50 µM AsIII, respectively. However, germination percentage in K-humate primed seeds were 75 ±â€¯5.0% and 68.3 ±â€¯2.9% under AsV and AsIII stress, respectively. The vigour index I (VG I) and vigour index II (VG II) recorded on 12 DAS (days after seeding) were also increased by 1.47 and 1.51 fold, respectively with K-humate supplementation under As stress. Detrimental effects of AsIII on seed germination, seedling growth and other physiological parameters were more suppressive than AsV. Application of K-humate not only improved seed germination, seedling growth and nutrient uptake but also decreased the oxidative stress markers and antioxidant activities by minimizing As uptake and translocation in the seedlings.

Expression of potential reference genes in response to macronutrient stress in rice and soybean.

Given the complexity of nutrient stress responses and the availability of a few validated reference genes, we aimed to identify robust and stable reference genes for macronutrient stress in rice and soybean. Ten potential reference genes were evaluated using geNorm, NormFinder, BestKeeper, Comparative ΔCt method, and RefFinder algorithms under low and completely starved conditions of nitrogen (N), phosphorus (P), potassium (K), and sulphur (S). Results revealed distinct sets of reference gene pairs, showing stable expression under different experimental conditions. The gene pairs TIP41/UBC(9/10/18) and F-box/UBC10 were most stable in rice and soybean, respectively under N stress. Under P stress, UBC9/UBC10 in rice and F-Box/UBC10 in soybean were most stable. Similarly, TIP41/UBC10 in rice and RING FINGER/UBC9 in soybean were the best gene pairs under K stress while F-Box/TIP41 in rice and UBC9/UBC10 in soybean were the most stable gene pairs under S stress. These reference gene pairs were validated by quantifying the expression levels of high-affinity transporters like NRT2.1/NRT2.5, PT1, AKT1, and SULTR1 for N, P, K, and S stress, respectively. This study reiterates the importance of choosing reference genes based on crop species and the experimental conditions, in order to obtain concrete answers to missing links of gene regulation in response to macronutrient deficiencies.

Influence of essential inorganic elements on flavour formation during yeast fermentation.

The relative concentration of available inorganic elements is critical for yeast growth and metabolism and has potential to be a tool leading to directed yeast flavour formation during fermentation. This study investigates the influence of essential inorganic elements during alcoholic fermentation of brewers wort, fermented using three independent yeast strains, Saccharomyces pastorianus W34/70, and Saccharomyces cerevisiae strains M2 and NCYC2592 under a range of conditions replicated for each yeast strain. 10 treatments were applied: 1 control and 9 inorganic supplementations: standard brewers wort, ammonia-nitrogen, inorganic phosphate, potassium, magnesium, copper, zinc, iron, manganese and a composite mixture, Twenty-five chemical markers were evaluated by HPLC (ethanol, glycerol), and GC-MS (aroma). There was a significant change in volatile aroma compounds during fermentation, which was more prominent when supplemented with ammonia nitrogen, inorganic phosphate, potassium or magnesium (P < 0.05). Heavy metal ions mostly had a negative effect on the flavour formation.

Potassium and Sodium Salt Stress Characterization in the Yeasts Saccharomyces cerevisiae, Kluyveromyces marxianus, and Rhodotorula toruloides.

Biotechnology requires efficient microbial cell factories. The budding yeast Saccharomyces cerevisiae is a vital cell factory, but more diverse cell factories are essential for the sustainable use of natural resources. Here, we benchmarked nonconventional yeasts Kluyveromyces marxianus and Rhodotorula toruloides against S. cerevisiae strains CEN.PK and W303 for their responses to potassium and sodium salt stress. We found an inverse relationship between the maximum growth rate and the median cell volume that was responsive to salt stress. The supplementation of K+ to CEN.PK cultures reduced Na+ toxicity and increased the specific growth rate 4-fold. The higher K+ and Na+ concentrations impaired ethanol and acetate metabolism in CEN.PK and acetate metabolism in W303. In R. toruloides cultures, these salt supplementations induced a trade-off between glucose utilization and cellular aggregate formation. Their combined use increased the beta-carotene yield by 60% compared with that of the reference. Neural network-based image analysis of exponential-phase cultures showed that the vacuole-to-cell volume ratio increased with increased cell volume for W303 and K. marxianus but not for CEN.PK and R. toruloides in response to salt stress. Our results provide insights into common salt stress responses in yeasts and will help design efficient bioprocesses. IMPORTANCE Characterization of microbial cell factories under industrially relevant conditions is crucial for designing efficient bioprocesses. Salt stress, typical in industrial bioprocesses, impinges upon cell volume and affects productivity. This study presents an open-source neural network-based analysis method to evaluate volumetric changes using yeast optical microscopy images. It allows quantification of cell and vacuole volumes relevant to cellular physiology. On applying salt stress in yeasts, we found that the combined use of K+ and Na+ improves the cellular fitness of Saccharomyces cerevisiae strain CEN.PK and increases the beta-carotene productivity in Rhodotorula toruloides, a commercially important antioxidant and a valuable additive in foods.

Interactive effect of potassium and cadmium on growth, root morphology and chlorophyll a fluorescence in tomato plant.

A hydroponic experiment was conducted to evaluate the role of potassium (K) in tomato plant growth exposed to cadmium (Cd) stress. In this work, the effects of three potassium nutrition regimes (155, 232 and 310 ppm of K) combined with Cd at different levels (0, 12 and 25 µM of CdCl2) on chlorophyll content index, root and shoot dry weights, root morphology, chlorophyll a fluorescence and translocation factor were analyzed. The results showed a negative effect of cadmium, at different concentrations, on all these parameters. However, optimization of K nutrition has shown promising results by limiting the negative effect of Cd. A positive effect of the high concentration of K (310 ppm) was observed on leaf chlorophyll content and chlorophyll a fluorescence compared to 232 and 155 ppm under Cd stress. K supply improved the electron transport at PSI side indicated by the increase in the amplitude of the I-P phase of OJIP transient. Also, K at a concentration of 310 ppm significantly reduced Cd translocation from root to shoot and improved root and shoot growth parameters in the presence of Cd. K supplementation can reduce the negative effect of Cd by improving photosynthesis and promoting chlorophyll synthesis. The optimization of nutrients composition and concentration might be a good strategy to reduce the impact of Cd on plant growth and physiology.

Potassium Effects on NCC Are Attenuated during Inhibition of Cullin E3-Ubiquitin Ligases.

The thiazide-sensitive sodium chloride cotransporter (NCC) plays a vital role in maintaining sodium (Na+) and potassium (K+) homeostasis. NCC activity is modulated by with-no-lysine kinases 1 and 4 (WNK1 and WNK4), the abundance of which is controlled by the RING-type E3 ligase Cullin 3 (Cul3) and its substrate adapter Kelch-like protein 3. Dietary K+ intake has an inverse correlation with NCC activity, but the mechanism underlying this phenomenon remains to be fully elucidated. Here, we investigated the involvement of other members of the cullin family in mediating K+ effects on NCC phosphorylation (active form) and abundance. In kidneys from mice fed diets varying in K+ content, there were negative correlations between NCC (phosphorylated and total) and active (neddylated) forms of cullins (Cul1, 3, 4, and 5). High dietary K+ effects on phosphorylated NCC were attenuated in Cul3 mutant mice (CUL3-Het/Δ9). Short-term (30 min) and long-term (24 h) alterations in the extracellular K+ concentration did not affect cullin neddylation levels in ex vivo renal tubules. In the short term, the ability of high extracellular K+ to decrease NCC phosphorylation was preserved in the presence of MLN4924 (pan-cullin inhibitor), but the response to low extracellular K+ was absent. In the long term, MLN4924 attenuated the effects of high extracellular K+ on NCC phosphorylation, and responses to low extracellular K+ were absent. Our data suggest that in addition to Cul3, other cullins are involved in mediating the effects of K+ on NCC phosphorylation and abundance.

A G-quadruplex nanoswitch in the SGK1 promoter regulates isoform expression by K+/Na+ balance and resveratrol binding.

BACKGROUND: High sodium intake can up-regulate the level of renal serum- and glucocorticoid-inducible kinase-1 (SGK1), which plays a pivotal role in controlling blood pressure via activation of the epithelial sodium channel (ENaC), which can lead to salt-sensitive hypertension. Increased potassium intake, or a vegetarian diet, counteracts salt-sensitive hypertension, but the underlying mechanisms are not fully understood. METHODS: Bioinformatics and molecular modeling were used to identify G-quadruplex (G4) and their conformations in the SGK1 promoter. CD spectra and UV melting dynamics were measured to study the stability of G4 as influenced by potassium/sodium balance and resveratrol. RT-PCR and Western blot were employed to study the effects of potassium and resveratrol on the SGK1 isoform expression. RESULTS: The SGK1 gene encodes a G4 structure in the proximal upstream of promoter-2; the G4 structure is stabilized by potassium or resveratrol, but destabilized by sodium. Super-physiological levels of sodium stimulate the transcription of all SGK1 isoforms, whereas resveratrol or potassium supplementation inhibits the transcription of iso-2 and iso-3, but not iso-1. CONCLUSIONS: Stabilizing the G4 by potassium or resveratrol induces alternative promoter usage and/or pre-mRNA splicing in the transcription of SGK1. GENERAL SIGNIFICANCE: Potassium/sodium ion balance or resveratrol binding can act to regulate G4 molecular switches for controlling SGK1 gene expression, thereby presenting a new avenue for drug development.

Ammonium Accumulation Caused by Reduced Tonoplast V-ATPase Activity in Arabidopsis thaliana.

Plant vacuoles are unique compartments that play a critical role in plant growth and development. The vacuolar H+-ATPase (V-ATPase), together with the vacuolar H+-pyrophosphatase (V-PPase), generates the proton motive force that regulates multiple cell functions and impacts all aspects of plant life. We investigated the effect of V-ATPase activity in the vacuole on plant growth and development. We used an Arabidopsisthaliana (L.) Heynh. double mutant, vha-a2 vha-a3, which lacks two tonoplast-localized isoforms of the membrane-integral V-ATPase subunit VHA-a. The mutant is viable but exhibits impaired growth and leaf chlorosis. Nitrate assimilation led to excessive ammonium accumulation in the shoot and lower nitrogen uptake, which exacerbated growth retardation of vha-a2 vha-a3. Ion homeostasis was disturbed in plants with missing VHA-a2 and VHA-a3 genes, which might be related to limited growth. The reduced growth and excessive ammonium accumulation of the double mutant was alleviated by potassium supplementation. Our results demonstrate that plants lacking the two tonoplast-localized subunits of V-ATPase can be viable, although with defective growth caused by multiple factors, which can be alleviated by adding potassium. This study provided a new insight into the relationship between V-ATPase, growth, and ammonium accumulation, and revealed the role of potassium in mitigating ammonium toxicity.

Optimal fertigation for high yield and fruit quality of greenhouse strawberry.

Nitrogen (N), phosphorus (P), potassium (K), and water are four crucial factors that have significant effects on strawberry yield and fruit quality. We used a 11 that involved 36 treatments with five levels of each of the four variables (N, P, and K fertilizers and water) to optimize fertilization and water combination for high yield and quality. Moreover, we used the SSC/TA ratio (the ratio of soluble solid content to titratable acid) as index of quality. Results showed that N fertilizer was the most important factor, followed by water and P fertilizer, and the N fertilizer had significant effect on yield and SSC/TA ratio. By contrast, the K fertilizer had significant effect only on yield. N×K fertilizer interacted significantly on yield, whereas the other interactions among the four factors had no significant effects on yield or SSC/TA ratio. The effects of the four factors on yield and SSC/TA ratio were ranked as N fertilizer > water > K fertilizer > P fertilizer and N fertilizer > P fertilizer > water > K fertilizer, respectively. The yield and SSC/TA ratio increased when NPK fertilizer and water increased, but then decreased when excessive NPK fertilizer and water were applied. The optimal fertilizer and water combination were 22.28-24.61 g plant-1 Ca (NO3)2·4H2O, 1.75-2.03 g plant-1 NaH2PO4, 12.41-13.91 g plant-1 K2SO4, and 12.00-13.05 L water plant-1 for yields of more than 110 g plant-1 and optimal SSC/TA ratio of 8.5-14.

Sphagnum growth under N saturation: interactive effects of water level and P or K fertilization.

Sphagnum biomass is a promising material that could be used as a substitute for peat in growing media and can be sustainably produced by converting existing drainage-based peatland agriculture into wet, climate-friendly agriculture (paludiculture). Our study focuses on yield maximization of Sphagnum as a crop. We tested the effects of three water level regimes and of phosphorus or potassium fertilization on the growth of four Sphagnum species (S. papillosum, S. palustre, S. fimbriatum, S. fallax). To simulate field conditions in Central and Western Europe we carried out a glasshouse experiment under nitrogen-saturated conditions. A constant high water table (remaining at 2 cm below capitulum during growth) led to highest productivity for all tested species. Water table fluctuations between 2 and 9 cm below capitulum during growth and a water level 2 cm below capitulum at the start but falling relatively during plant growth led to significantly lower productivity. Fertilization had no effect on Sphagnum growth under conditions with high atmospheric deposition such as in NW Germany (38 kg N, 0.3 kg P, 7.6 kg K·ha-1 ·year-1 ). Large-scale maximization of Sphagnum yields requires precise water management, with water tables just below the capitula and rising with Sphagnum growth. The nutrient load in large areas of Central and Western Europe from atmospheric deposition and irrigation water is high but, with an optimal water supply, does not hamper Sphagnum growth, at least not of regional provenances of Sphagnum.

Nutraceuticals and blood pressure control: a European Society of Hypertension position document.

: High-normal blood pressure (BP) is associated with an increased risk of cardiovascular disease, however the cost-benefit ratio of the use of antihypertensive treatment in these patients is not yet clear. Some dietary components and natural products seems to be able to significantly lower BP without significant side effects. The aim of this position document is to highlight which of these products have the most clinically significant antihypertensive action and wheter they could be suggested to patients with high-normal BP. Among foods, beetroot juice has the most covincing evidence of antihypertensive effect. Antioxidant-rich beverages (teas, coffee) could be considered. Among nutrients, magnesium, potassium and vitamin C supplements could improve BP. Among nonnutrient-nutraceuticals, soy isoflavones could be suggested in perimenopausal women, resveratrol in insulin-resistant patients, melatonin in study participants with night hypertension. In any case, the nutracutical approach has never to substitute the drug treatment, when needed.