Functional properties and skin care effects of sodium trehalose sulfate.

BACKGROUND: It is known that heparinoid, a mucopolysaccharide polysulfate, is effective in improving rough skin and promoting blood circulation as medicines for diseased areas. However, heparinoid has a molecular weight of more than 5000 and cannot penetrate healthy stratum corneum. OBJECTIVE: We tested the efficacy of sulfated oligosaccharides with a molecular weight of less than 2000 on the human skin barrier function and moisturizing function. METHODS: We measured the transepidermal water loss (TEWL) of a three-dimensional human epidermis model cultured for 3 days after topical application of sulfated oligosaccharides, then observed the effects on TEWL suppression. The mRNA levels of proteins involved in intercellular lipid transport and storage in the stratum corneum, and moisture retention were measured using RT-qPCR. RESULTS: An increase in the mRNA levels of the ATP-binding cassette subfamily A member 12 (ABCA12), which transports lipids into stratum granulosum, was confirmed. Increases were also observed in the mRNA levels of filaggrin (FLG), which is involved in the generation of natural moisturizing factors, and of caspase-14, calpain-1 and bleomycin hydrolase, which are involved in the degradation of FLG. Antibody staining confirmed that the application of sodium trehalose sulfate to 3D model skin resulted in more ABCA12, ceramide, transglutaminase1, and FLG than those in controls. In a randomized, placebo-controlled, double-blind study, participants with low stratum corneum water content applied a lotion and emulsion containing sodium trehalose sulfate to their faces for 4 weeks. Sodium trehalose sulfate decreased the TEWL and increased the stratum corneum water content. CONCLUSION: These results suggest that cosmetics containing sodium trehalose sulfate act on the epidermis by increasing barrier factors and moisturizing factors, thereby ameliorating dry skin.

Reactive oxygen species impair Na+ transport and renal components of the renin-angiotensin-aldosterone system after paraquat poisoning.

Paraquat (1,1'-dimethyl-4,4'-bipyridyl dichloride) is an herbicide widely used worldwide and officially banned in Brazil in 2020. Kidney lesions frequently occur, leading to acute kidney injury (AKI) due to exacerbated reactive O2 species (ROS) production. However, the consequences of ROS exposure on ionic transport and the regulator local renin-angiotensin-aldosterone system (RAAS) still need to be elucidated at a molecular level. This study evaluated how ROS acutely influences Na+-transporting ATPases and the renal RAAS. Adult male Wistar rats received paraquat (20 mg/kg; ip). After 24 h, we observed body weight loss and elevation of urinary flow and serum creatinine. In the renal cortex, paraquat increased ROS levels, NADPH oxidase and (Na++K+)ATPase activities, angiotensin II-type 1 receptors, tumor necrosis factor-α (TNF-α), and interleukin-6. In the medulla, paraquat increased ROS levels and NADPH oxidase activity but inhibited (Na++K+)ATPase. Paraquat induced opposite effects on the ouabain-resistant Na+-ATPase in the cortex (decrease) and medulla (increase). These alterations, except for increased serum creatinine and renal levels of TNF-α and interleukin-6, were prevented by 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (tempol; 1 mmol/L in drinking water), a stable antioxidant. In summary, after paraquat poisoning, ROS production culminated with impaired medullary function, urinary fluid loss, and disruption of Na+-transporting ATPases and angiotensin II signaling.

Sulfur-Oxidizing Bacteria Alleviate Salt and Cadmium Stress in Halophyte Tripolium pannonicum (Jacq.) Dobrocz.

The aim of this study was to investigate how introducing halophilic sulfur-oxidizing bacteria (SOB) Halothiobacillus halophilus to the growth substrate affects the physiological and biochemical responses of the halophyte Tripolium pannonicum (also known as sea aster or seashore aster) under salt and cadmium stress conditions. This study assessed the plant's response to these stressors and bacterial inoculation by analyzing various factors including the accumulation of elements such as sodium (Na), chloride (Cl), cadmium (Cd) and sulfur (S); growth parameters; levels of photosynthetic pigments, proline and phenolic compounds; the formation of malondialdehyde (MDA); and the plant's potential to scavenge 2,2-Diphenyl-1-picrylhydrazyl (DPPH). The results revealed that bacterial inoculation was effective in mitigating the deleterious effect of cadmium stress on some growth criteria. For instance, stem length was 2-hold higher, the growth tolerance index was 3-fold higher and there was a 20% increase in the content of photosynthetic pigments compared to non-inoculated plants. Furthermore, the SOB contributed to enhancing cadmium tolerance in Tripolium pannonicum by increasing the availability of sulfur in the plant's leaves, which led to the maintenance of an appropriate, about 2-fold-higher level of phenolic compounds (phenylpropanoids and flavonols), as well as chloride ions. The level of MDA decreased after bacterial application in all experimental variants except when both salt and cadmium stress were present. These findings provide novel insights into how halophytes respond to abiotic stress following inoculation of the growth medium with sulfur-oxidizing bacteria. The data suggest that inoculating the substrate with SOB has a beneficial effect on T. pannonicum's tolerance to cadmium stress.

The Rectal Gland of the Shark: The Road to Understanding the Mechanism and Regulation of Transepithelial Chloride Transport.

Pictured, described, and speculated on, for close to 400 years, the function of the rectal gland of elasmobranchs remained unknown. In the late 1950s, Burger discovered that the rectal gland of Squalus acanthias secreted an almost pure solution of sodium chloride, isosmotic with blood, which could be stimulated by volume expansion of the fish. Twenty five years later, Stoff discovered that the secretion of the gland was mediated by adenyl cyclase. Studies since then have shown that vasoactive intestinal peptide (VIP) is the neurotransmitter responsible for activating adenyl cyclase; however, the amount of circulating VIP does not change in response to volume expansion. The humoral factor involved in activating the secretion of the gland is C-type natriuretic peptide, secreted from the heart in response to volume expansion. C-type natriuretic peptide circulates to the gland where it stimulates the release of VIP from nerves within the gland, but it also has a direct effect, independent of VIP. Sodium, potassium, and chloride are required for the gland to secrete, and the secretion of the gland is inhibited by ouabain or furosemide. The current model for the secretion of chloride was developed from this information. Basolateral NaKATPase maintains a low intracellular concentration of sodium, which establishes the large electrochemical gradient for sodium directed into the cell. Sodium moves from the blood into the cell (together with potassium and chloride) down this electrochemical gradient, through a coupled sodium, potassium, and two chloride cotransporter (NKCC1). On activation, chloride moves from the cell into the gland lumen, down its electrical gradient through apical cystic fibrosis transmembrane regulator. The fall in intracellular chloride leads to the phosphorylation and activation of NKCC1 that allows more chloride into the cell. Transepithelial sodium secretion into the lumen is driven by an electrical gradient through a paracellular pathway. The aim of this review was to examine the history of the origin of this model for the transport of chloride and suggest that it is applicable to many epithelia that transport chloride, both in resorptive and secretory directions.

The effect of nano silver fluoride, self-assembling peptide and sodium fluoride varnish on salivary cariogenic bacteria: a randomized controlled clinical trial.

OBJECTIVES: To compare the antibacterial effect of Nanosilver Fluoride varnish (NSF) varnish, P11-4 and Sodium Fluoride (NaF) varnish against salivary Streptococcus mutans (S. mutans) and Lactobacilli. METHODS: 66 patients aged 10-24 years old were randomly assigned to receive single application of NSF, P11-4 or NaF varnish. Baseline unstimulated saliva samples were collected before the agents were applied and S.mutans and Lactobacilli colony forming units (CFU) were counted. After one, three and six months, microbiological samples were re-assessed. Groups were compared at each time point and changes across time were assessed. Multivariable linear regression compared the effect of P11-4 and NSF to NaF on salivary S. mutans and Lactobacilli log count at various follow up periods. RESULTS: There was a significant difference in salivary S. mutans log count after 1 month between P11-4 (B= -1.29, p = 0.049) and NaF but not at other time points nor between NSF and NaF at any time point. The significant reduction in bacterial counts lasted up to one month in all groups, to three months after using P11-4 and NaF and returned to baseline values after six months. CONCLUSION: In general, the antimicrobial effect of P11-4 and NSF on salivary S. mutans and Lactobacilli was not significantly different from NaF varnish. P11-4 induced greater reduction more quickly than the two other agents and NSF antibacterial effect was lost after one month. CLINICAL RELEVANCE: NSF varnish and P11-4 have antimicrobial activity that does not significantly differ from NaF by 3 months. P11-4 has the greatest antibacterial effect after one month with sustained effect till 3 months. The antibacterial effect of NSF lasts for one month. NaF remains effective till 3 months. TRIAL REGISTRATION: This trial was prospectively registered on the clinicaltrials.gov registry with ID: NCT04929509 on 18/6/2021.

Partial Replacement of NaCl with KCl in Cooked Meat Could Reduce the Liver Damage Through Renin-Angiotensin System in Mice.

SCOPE: Dietary salt (sodium chloride, NaCl) is necessary for processed meat products, but intake of a high-sodium diet carries serious health risks. Considerable studies indicate that the partial substitution of NaCl with potassium chloride (KCl) can produce sodium-reduced cooked meat. However, most studies of sodium-reduced cooked meat focus on the production process in vitro, and the effect of cooked meat on health has not been well clarified in vivo. METHODS AND RESULTS: This study finds that compared to the high-sodium group (HS), serum renin, angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and the levels of some indicators of dyslipidemia are decreased in the reduced salt by partial substitution of NaCl with KCl group (RS + K). Furthermore, RS + K increases the antioxidation abilities, inhibits the renin-angiotensin system (RAS) through ACE/Ang II/Ang II type 1 receptor axis pathway, reduces synthesis of triglyceride and cholesterol and protein expressions of inflammatory factors interleukin-17A and nuclear factor-kappa B in the liver. CONCLUSION: Partial substitution of NaCl with KCl in cooked meat can be a feasible approach for improving the health benefits and developing novel functional meat products for nutritional health interventions.

Effects of sodium dodecylbenzene sulfonate (SDBS) on zebrafish (Danio rerio) gills and blood.

Sodium dodecylbenzene sulfonate (SDBS) is an important surfactant used as a cleaning agent and industrial additive to remove unwanted chemicals which have been detected in the aquatic environment. The aim of this study was to examine the toxicological potential of SDBS on the gills of adult male zebrafish (Danio rerio) exposed to this chemical. For the 96 hr acute exposure, fish were divided into three groups: control, 0.25 mg/L, and 0.5 mg/L of SDBS. After the experiment, morphophysiological analyses (gill histopathology and histochemistry), oxidative stress (determination of gill activities of superoxide dismutase (SOD) and catalase (CAT)), and hematological analyses (leukocyte differentiation) were conducted. Data demonstrated that SDBS at both tested concentrations altered the histopathological index and initiated circulatory disturbances, as well as adverse, progressive, and immunological changes in the gills. In the 0.5 mg/L group, SOD activity decreased significantly, but CAT activity was not altered. Prominent blood changes observed in this group were neutrophilia and lymphocytosis. The number of mucous and chloride cells increased significantly in both groups. Taken together, our findings demonstrated that exposure of D. rerio to SDBS, even for 96 hr, produced adverse morphological and hematological effects associated with a reduction in SOD activity. Our findings indicate that exposure of aquatic species to the anionic surfactant SDBS may lead to adverse consequences associated with oxidative stress. Therefore, this study highlights the risks that this substance may pose to aquatic ecosystems and emphasizes the need for further investigations and strict regulations on its disposal.

Effect of Low-Frequency Renal Nerve Stimulation on Renal Glucose Release during Normoglycemia and a Hypoglycemic Clamp in Pigs.

Previously, we demonstrated that renal denervation in pigs reduces renal glucose release during a hypoglycemic episode. In this study we set out to examine changes in side-dependent renal net glucose release (SGN) through unilateral low-frequency stimulation (LFS) of the renal plexus with a pulse generator (2-5 Hz) during normoglycemia (60 min) and insulin-induced hypoglycemia ≤3.5 mmol/L (75 min) in seven pigs. The jugular vein, carotid artery, renal artery and vein, and both ureters were catheterized for measurement purposes, blood pressure management, and drug and fluid infusions. Para-aminohippurate (PAH) and inulin infusions were used to determine side-dependent renal plasma flow (SRP) and glomerular filtration rate (GFR). In a linear mixed model, LFS caused no change in SRP but decreased sodium excretion (p < 0.0001), as well as decreasing GFR during hypoglycemia (p = 0.0176). In a linear mixed model, only hypoglycemic conditions exerted significant effects on SGN (p = 0.001), whereas LFS did not. In a Wilcoxon signed rank exact test, LFS significantly increased SGN (p = 0.03125) and decreased sodium excretion (p = 0.0017) and urinary flow rate (p = 0.0129) when only considering the first instance LFS followed a preceding period of non-stimulation during normoglycemia. To conclude, this study represents, to our knowledge, the first description of an induction of renal gluconeogenesis by LFS.

Synthesis and Insecticidal Evaluation of 3,5-Dicyanopyridines Against Cotton Aphids via Microwave-Assisted Multicomponent Reactions.

Certain 2-amino-6-alkoxy-4-arylpyridine-3,5-dicyanide 1a-e were prepared via a straightforward process using microwave technology rather than conventional methods. This involved reaction of arylidenemalononitrile thru propanedinitrile in the occurrence of sodium alkoxide under MW. While, their positional isomer 4-amino-6-alkoxy-2-arylpyridine-3,5-dicyanide 3a-j have been separated from the reaction of aryl aldehydes with 2-aminoprop-1-ene-1,1,3-tricarbonitrile 2 in the presence of sodium alkoxide using microwave technic. Furthermore, the insecticidal properties of all synthesized compounds were observed with respect to Cotton aphid nymphs and adults. Neonicotinoid pesticides are indicated as the most effective pesticides toward aphids and many other pests. Many insecticides are discovered as novelties. As a result, several pyridine compounds were chemical method synthesized to serve as equivalents of neonicotinoids, a broad class of insecticides. With LC50 value of 0.03 mg/L, components 3g exhibit the highest insecticidal bioactivity. This work discusses how to find new chemicals that could be used as insecticidal agents in the future.

Sodium dodecylbenzene sulphonate (SDBS) present in detergents: action on the gills, skin, and blood of D. rerio fish.

1. Sodium dodecylbenzene sulphonate (SDBS) is one of the surfactants used worldwide in detergents which, due to high residual discharges, has great potential to cause ecotoxicological impacts. Therefore, the sublethal effects of SDBS on the gills and skin of male Danio rerio fish were investigated.2. The fish were distributed into three groups: GC (control), GT1 (0.25 mg/L of SDBS), and GT2 (0.5 mg/L of SDBS) and exposed for 21 days. After the experiment, histopathological analyses of the gills, histochemical analyses (counting of mucous cells), and biochemical analyses (antioxidant defense enzyme analysis, SOD, and CAT) were conducted.3. A significant increase (p < 0.05) in the incidence of circulatory disorders, progressive, and regressive alterations occurred in the GT1 and GT2 groups. Due to these changes, the total histopathological index of the gills was higher in these groups. Mucous cells in the gills and skin increased. There was an increase in SOD activity and a reduction in CAT activity in these groups. Haematology revealed neutrophilia and lymphocytosis in the blood of GT1 and GT2.4. The results clearly demonstrate that a 21-day exposure to SDBS causes severe morphophysiological damage to the gills, skin, and blood of D. rerio fish.

Inhibition of Sodium-Glucose Cotransporter-2 during Serum Deprivation Increases Hepatic Gluconeogenesis via the AMPK/AKT/FOXO Signaling Pathway.

BACKGRUOUND: Sodium-dependent glucose cotransporter 2 (SGLT2) mediates glucose reabsorption in the renal proximal tubules, and SGLT2 inhibitors are used as therapeutic agents for treating type 2 diabetes mellitus. This study aimed to elucidate the effects and mechanisms of SGLT2 inhibition on hepatic glucose metabolism in both serum deprivation and serum supplementation states. METHODS: Huh7 cells were treated with the SGLT2 inhibitors empagliflozin and dapagliflozin to examine the effect of SGLT2 on hepatic glucose uptake. To examine the modulation of glucose metabolism by SGLT2 inhibition under serum deprivation and serum supplementation conditions, HepG2 cells were transfected with SGLT2 small interfering RNA (siRNA), cultured in serum-free Dulbecco's modified Eagle's medium for 16 hours, and then cultured in media supplemented with or without 10% fetal bovine serum for 8 hours. RESULTS: SGLT2 inhibitors dose-dependently decreased hepatic glucose uptake. Serum deprivation increased the expression levels of the gluconeogenesis genes peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), glucose 6-phosphatase (G6pase), and phosphoenolpyruvate carboxykinase (PEPCK), and their expression levels during serum deprivation were further increased in cells transfected with SGLT2 siRNA. SGLT2 inhibition by siRNA during serum deprivation induces nuclear localization of the transcription factor forkhead box class O 1 (FOXO1), decreases nuclear phosphorylated-AKT (p-AKT), and p-FOXO1 protein expression, and increases phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK) protein expression. However, treatment with the AMPK inhibitor, compound C, reversed the reduction in the protein expression levels of nuclear p- AKT and p-FOXO1 and decreased the protein expression levels of p-AMPK and PEPCK in cells transfected with SGLT2 siRNA during serum deprivation. CONCLUSION: These data show that SGLT2 mediates glucose uptake in hepatocytes and that SGLT2 inhibition during serum deprivation increases gluconeogenesis via the AMPK/AKT/FOXO1 signaling pathway.

Diet supplementation with sodium pyruvate increases sleep time and lifespan in Drosophila model.

Sodium pyruvate is a natural metabolite commonly used in biological fields, including cell culture. This study investigated the effects of sodium pyruvate on the lifespan and other physiological characters of Drosophila melanogaster, by measuring feeding, fecundity, and spontaneous activity. The results indicated that 0.2 mol/L of sodium pyruvate increased the median lifespan of female flies by 8.33%. Moreover, the group sleep duration of female flies significantly increased by 53.98% when exposed to the sodium pyruvate concentration. However, the intake of sodium pyruvate did not significantly affect the fecundity or food intake of female flies. Our results also show that the effect of extending lifespan and increasing sleep time was dose-dependent and sex-specific. Our data provides the role of sodium pyruvate as an insect culture additive by enhancing survival.

Abrupt Decline in Estimated Glomerular Filtration Rate after Initiating Sodium-Glucose Cotransporter 2 Inhibitors Predicts Clinical Outcomes: A Systematic Review and Meta-Analysis.

BACKGRUOUND: The initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) typically leads to a reversible initial dip in estimated glomerular filtration rate (eGFR). The implications of this phenomenon on clinical outcomes are not well-defined. METHODS: We searched MEDLINE, Embase, and Cochrane Library from inception to March 23, 2023 to identify randomized controlled trials and cohort studies comparing kidney and cardiovascular outcomes in patients with and without initial eGFR dip after initiating SGLT2i. Pooled estimates were calculated using random-effect meta-analysis. RESULTS: We included seven studies in our analysis, which revealed that an initial eGFR dip following the initiation of SGLT2i was associated with less annual eGFR decline (mean difference, 0.64; 95% confidence interval [CI], 0.437 to 0.843) regardless of baseline eGFR. The risk of major adverse kidney events was similar between the non-dipping and dipping groups but reduced in patients with a ≤10% eGFR dip (hazard ratio [HR], 0.915; 95% CI, 0.865 to 0.967). No significant differences were observed in the composite of hospitalized heart failure and cardiovascular death (HR, 0.824; 95% CI, 0.633 to 1.074), hospitalized heart failure (HR, 1.059; 95% CI, 0.574 to 1.952), or all-cause mortality (HR, 0.83; 95% CI, 0.589 to 1.170). The risk of serious adverse events (AEs), discontinuation of SGLT2i due to AEs, kidney-related AEs, and volume depletion were similar between the two groups. Patients with >10% eGFR dip had increased risk of hyperkalemia compared to the non-dipping group. CONCLUSION: Initial eGFR dip after initiating SGLT2i might be associated with less annual eGFR decline. There were no significant disparities in the risks of adverse cardiovascular outcomes between the dipping and non-dipping groups.

Color stability of bleached tooth enamel brushed with different stain-removing toothpastes.

OBJECTIVE: The effects of four toothpastes on the color stability of in-office bleached tooth specimens were determined. MATERIALS AND METHODS: We evaluated an experimental toothpaste (EXP) and three commercially available toothpastes: Colgate Optic White (OPW), Aquafresh White & Protect (AWP), and Crest 3D White (CDW). OPW, AWP, and CDW contained inorganic abrasives, whereas EXP and AWP contained sodium polyphosphate. Forty-eight randomly selected human-extracted maxillary central incisors were bleached and brushed twice daily over 30 days. We analyzed the final color difference (ΔE*ab, ΔE00 , ΔWID ), arithmetic average surface roughness (Ra) of the enamel measured on days 0 and 30, and scanning electron microscopy images of enamel surfaces and toothpastes. ΔE*ab, ΔE00 , ΔWID , and Ra were analyzed using one-way analysis of variance and Tukey's test (α = 0.05). RESULTS: ΔE*ab and ΔE00 values were significantly lower after toothbrushing with EXP, OPW, and CDW than with AWP. OPW induced the greatest positive ΔWID . Ra was significantly increased by OPW and CDW, but slightly increased by AWP, with cube-like particles, and EXP, with no particle-like structures. CONCLUSIONS: Only EXP stabilized the color of bleached teeth without increasing the enamel surface roughness. Sodium polyphosphate with approximately 10 phosphate groups was effective at removing stains. CLINICAL SIGNIFICANCE: The effect of toothpaste on the color stability of bleached teeth depends on the constituting abrasives and chemical components. Polyphosphoric acid has different stain-removal effects depending on its degree of polymerization. Additionally, although certain types of abrasives may be effective for color stability, they also increase the surface roughness of the enamel.

Safinamide alleviates hyperalgesia via inhibiting hyperexcitability of DRG neurons in a mouse model of Parkinson's disease.

Pain is a widespread non-motor symptom that presents significant treatment challenges in patients with Parkinson's disease (PD). Safinamide, a new drug recently introduced for PD treatment, has demonstrated analgesic effects on pain in PD patients, though the underlying mechanisms remain unclear. To investigate the analgesic and anti-PD effect of safinamide, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model was used, and rasagiline as positive control on motor symptoms. Notably, only safinamide alleviated hyperalgesia in MPTP mice. Whole-cell patch-clamp recordings of dorsal root ganglion (DRG) neurons revealed hyperexcitability in MPTP mice, which safinamide counteracted in a concentration-dependent manner. The voltage clamp further demonstrated that sodium current in DRG neurons of MPTP mice was enhanced and safinamide reduced sodium current density. RT-qPCR identified upregulated Nav1.7 and Nav1.8 transcripts (Scn9a and Scn10a) in DRG neurons of MPTP mice. Our results suggest that safinamide could relieve hyperalgesia by inhibiting DRG neuron hyperexcitability in MPTP mice.

Extracellular sodium regulates fibroblast growth factor 23 (FGF23) formation.

The bone-derived hormone fibroblast growth factor-23 (FGF23) has recently received much attention due to its association with chronic kidney disease and cardiovascular disease progression. Extracellular sodium concentration ([Na+]) plays a significant role in bone metabolism. Hyponatremia (lower serum [Na+]) has recently been shown to be independently associated with FGF23 levels in patients with chronic systolic heart failure. However, nothing is known about the direct impact of [Na+] on FGF23 production. Here, we show that an elevated [Na+] (+20 mM) suppressed FGF23 formation, whereas low [Na+] (-20 mM) increased FGF23 synthesis in the osteoblast-like cell lines UMR-106 and MC3T3-E1. Similar bidirectional changes in FGF23 abundance were observed when osmolality was altered by mannitol but not by urea, suggesting a role of tonicity in FGF23 formation. Moreover, these changes in FGF23 were inversely proportional to the expression of NFAT5 (nuclear factor of activated T cells-5), a transcription factor responsible for tonicity-mediated cellular adaptations. Furthermore, arginine vasopressin, which is often responsible for hyponatremia, did not affect FGF23 production. Next, we performed a comprehensive and unbiased RNA-seq analysis of UMR-106 cells exposed to low versus high [Na+], which revealed several novel genes involved in cellular adaptation to altered tonicity. Additional analysis of cells with Crisp-Cas9-mediated NFAT5 deletion indicated that NFAT5 controls numerous genes associated with FGF23 synthesis, thereby confirming its role in [Na+]-mediated FGF23 regulation. In line with these in vitro observations, we found that hyponatremia patients have higher FGF23 levels. Our results suggest that [Na+] is a critical regulator of FGF23 synthesis.

Melatonin alters the excitability of mouse cerebellar granule neurons by inhibiting voltage-gated sodium, potassium, and calcium channels.

Besides its role in the circadian rhythm, the pineal gland hormone melatonin (MLT) also possesses antiepileptogenic, antineoplastic, and cardioprotective properties, among others. The dosages necessary to elicit beneficial effects in these diseases often far surpass physiological concentrations. Although even high doses of MLT are considered to be largely harmless to humans, the possible side effects of pharmacological concentrations are so far not well investigated. In the present study, we report that pharmacological doses of MLT (3 mM) strongly altered the electrophysiological characteristics of cultured primary mouse cerebellar granule cells (CGCs). Using whole-cell patch clamp and ratiometric Ca2+ imaging, we observed that pharmacological concentrations of MLT inhibited several types of voltage-gated Na+ , K+ , and Ca2+ channels in CGCs independently of known MLT-receptors, altering the character and pattern of elicited action potentials (APs) significantly, quickly and reversibly. Specifically, MLT reduced AP frequency, afterhyperpolarization, and rheobase, whereas AP amplitude and threshold potential remained unchanged. The altered biophysical profile of the cells could constitute a possible mechanism underlying the proposed beneficial effects of MLT in brain-related disorders, such as epilepsy. On the other hand, it suggests potential adverse effects of pharmacological MLT concentrations on neurons, which should be considered when using MLT as a pharmacological compound.

The effect of silver nanoparticles in addition to sodium fluoride on remineralization of artificial root dentin caries.

BACKGROUND: Silver nanoparticle was developed to overcome the drawback of silver diamine fluoride. However, evidence is limited, especially in root caries. The aim of this study was to evaluate the remineralization effect of silver nanoparticles on root caries. MATERIALS AND METHODS: Fifty-five root human dentin slices size 5 × 5 mm2 from patients aged over 60 years old were immersed in demineralized solution to create artificial caries. Specimens were allocated into five groups according to the remineralizing agents: silver diamine fluoride (SDF), silver nanoparticles solution (AgNPs), silver nanoparticle solution followed by sodium fluoride varnish (AgNPs+NaF), sodium fluoride varnish (NaF), and tap water. After 8 days of pH-cycling challenge, the microhardness test, lesion depth evaluation, dentin surface morphology, and elemental analysis were performed. Data was analysed using F-test One-way ANOVA followed by Tukey's post hoc test and paired T-test. RESULTS: All test groups demonstrated a significantly higher microhardness value and lower lesion depth compared with the control group. AgNPs+NaF and NaF-treated groups showed lower efficacy than SDF. Crystal precipitation was presented in all groups composed of silver. CONCLUSION: Addition of fluoride varnish did not benefit for silver nanoparticles in preventing further demineralization. SDF provides the highest effectiveness in elderly root carious dentin.

Combining the Physical-Chemical Approach with Standard Base Excess to Understand the Compensation of Respiratory Acid-Base Derangements: An Individual Participant Meta-analysis Approach to Data from Multiple Canine and Human Experiments.

BACKGROUND: Several studies explored the interdependence between Paco2 and bicarbonate during respiratory acid-base derangements. The authors aimed to reframe the bicarbonate adaptation to respiratory disorders according to the physical-chemical approach, hypothesizing that (1) bicarbonate concentration during respiratory derangements is associated with strong ion difference; and (2) during acute respiratory disorders, strong ion difference changes are not associated with standard base excess. METHODS: This is an individual participant data meta-analysis from multiple canine and human experiments published up to April 29, 2021. Studies testing the effect of acute or chronic respiratory derangements and reporting the variations of Paco2, bicarbonate, and electrolytes were analyzed. Strong ion difference and standard base excess were calculated. RESULTS: Eleven studies were included. Paco2 ranged between 21 and 142 mmHg, while bicarbonate and strong ion difference ranged between 12.3 and 43.8 mM, and 32.6 and 60.0 mEq/l, respectively. Bicarbonate changes were linearly associated with the strong ion difference variation in acute and chronic respiratory derangement (ß-coefficient, 1.2; 95% CI, 1.2 to 1.3; P < 0.001). In the acute setting, sodium variations justified approximately 80% of strong ion difference change, while a similar percentage of chloride variation was responsible for chronic adaptations. In the acute setting, strong ion difference variation was not associated with standard base excess changes (ß-coefficient, -0.02; 95% CI, -0.11 to 0.07; P = 0.719), while a positive linear association was present in chronic studies (ß-coefficient, 1.04; 95% CI, 0.84 to 1.24; P < 0.001). CONCLUSIONS: The bicarbonate adaptation that follows primary respiratory alterations is associated with variations of strong ion difference. In the acute phase, the variation in strong ion difference is mainly due to sodium variations and is not paralleled by modifications of standard base excess. In the chronic setting, strong ion difference changes are due to chloride variations and are mirrored by standard base excess.

Salt restriction for treatment of hypertension - current state and future directions.

PURPOSE OF REVIEW: Given the adverse effects of excess dietary sodium chloride (also known as table salt) on blood pressure (BP) and cardiovascular disease (CVD), restriction of dietary sodium is recommended by numerous guidelines. The strictest of these recommend no more than 1.5 g/day of dietary sodium among hypertensive persons. However, average dietary sodium intake in the population is closer to 5 g/day and there is debate about whether too much sodium restriction may be associated with increased CVD risk. Herein, we aim to provide a balanced update on this topic. RECENT FINDINGS: In 2021, the Salt Substitute and Stroke Study (SSaSS) demonstrated a significant reduction in BP, CVD, and death among Chinese adults randomized to a low sodium salt-substitute supplemented with potassium. This trial largely puts to rest any remaining debate about the benefits of dietary sodium restriction among persons with excess baseline intake (dietary sodium intake fell from approximately 5 down to 4 g/day in the active arm of SSaSS). However, whether achieving and maintaining a dietary sodium of less than1.5 g/day is feasible in real-world settings and whether this low an intake is harmful remain open questions. SUMMARY: Aiming for sodium intakes of 2--3 g/day in the general population and as low as 2 g/day in persons with hypertension or CVD seems most reasonable, but there is some uncertainty around lower targets.