Although a wide range of physiological information on Universal Stress Proteins (USPs) is available from many organisms, their biochemical, and molecular functions remain unidentified. The ...biochemical function of AtUSP (At3g53990) from Arabidopsis thaliana was therefore investigated. Plants over-expressing AtUSP showed a strong resistance to heat shock and oxidative stress, compared with wild-type and Atusp knock-out plants, confirming the crucial role of AtUSP in stress tolerance. AtUSP was present in a variety of structures including monomers, dimers, trimers, and oligomeric complexes, and switched in response to external stresses from low molecular weight (LMW) species to high molecular weight (HMW) complexes. AtUSP exhibited a strong chaperone function under stress conditions in particular, and this activity was significantly increased by heat treatment. Chaperone activity of AtUSP was critically regulated by the redox status of cells and accompanied by structural changes to the protein. Over-expression of AtUSP conferred a strong tolerance to heat shock and oxidative stress upon Arabidopsis, primarily via its chaperone function.
Background
The role of intraoperative magnesium for the prevention of emergence agitation or delirium is unclear as there have been conflicting results reported by several randomized controlled ...trials.
Aims
The aim of this study was to investigate the effect of magnesium sulfate on emergence agitation or emergence delirium in pediatric patients.
Methods
Electronic databases, including PubMed, EMBASE, CENTRAL, CINAHL, Scopus, and Web of Science, were searched to identify studies which evaluated the effects of magnesium on postoperative emergence agitation or emergence delirium. The primary outcome was the incidence of emergence agitation or emergence delirium during the post‐anesthesia stay. The secondary outcome was the agitation or delirium score upon admission to the post‐anesthesia care unit. We estimated the odds ratio and standardized mean difference using a random‐effect model.
Results
A total of 712 pediatric patients from 10 randomized controlled trials were included in the final analysis. The incidence of emergence agitation or emergence delirium was 29.7% in the magnesium group and 50.5% in the control group. The pooled effect size revealed that the administration of magnesium sulfate significantly reduced the incidence of postoperative emergence agitation or emergence delirium in pediatric patients undergoing surgery with general anesthesia (Odds ratio, 0.31; 95% confidence interval, 0.15 to 0.64; p = .002). Additionally, children in the magnesium group reported significantly lower agitation or delirium scores than those in the control group (standardized mean difference, −0.70; 95% confidence interval, −1.15 to ‐0.24; p = .003).
Conclusion
The administration of magnesium sulfate reduced the incidence and severity of emergence agitation or emergence delirium in pediatric patients after the use of general anesthesia during surgery.
The objective of this study was to determine whether erector spinae plane block (ESPB) can provide an effective analgesia for managing pain after thoracic surgery and compare the efficacy of ESPB ...with that of other regional analgesic techniques.
Systematic review and meta-analysis of randomized controlled trials.
PubMed, EMBASE, CENTRAL, CINAHL, Scopus, and Web of Science were searched.
Patients undergoing thoracic surgeries.
Erector spinae plane block with local anesthetics for postoperative analgesia.
Seventeen studies, including 1,092 patients, were included in the final analysis. Erector spinae plane block reduced 24-hour postoperative opioid consumption (mean difference MD –17.49, 95% CI –26.87 to –8.12), pain score at rest (MD –0.82, 95% CI –1.31 to –0.33), and pain score at movement (MD –0.77, 95% CI –1.20 to –0.3) compared to no block. Compared with other regional blocks, various results have been observed. Although statistical results showed that ESPB is inferior to thoracic paravertebral block and intercostal nerve block and superior to serratus anterior plan block in postoperative analgesia, clinical differences remain unclear. The incidence of hematoma was lower in the ESPB group than in the other groups (odds ratio 0.19, 95% CI 0.05-0.73).
Erector spinae plane block may provide effective analgesia after thoracic surgery. Compared with other techniques, it is a safer method, without clinically important differences, for postoperative pain control. Therefore, ESPB may be considered as a valuable option for postoperative pain management after thoracic surgery.
Abstract
Objective
To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TU2670, a novel orally active, nonpeptide gonadotropin-releasing hormone (GnRH) antagonist ...administered to healthy female participants.
Methods
This was a first-in-human, multicenter, phase 1, randomized, double-blind, placebo-controlled, single-dose ascending trial that took place in multiple medical centers. A total of 16 healthy premenopausal women (23 to 45 years of age) were randomized and received 20, 40, 80, and 160 mg TU2670 (GnRH antagonist) or placebo 7 days (±1 day) after the onset of menstrual bleeding. We performed a noncompartmental analysis for pharmacokinetic parameters and calculated relative minimum concentration values (Cmin, % Baseline) of serum pharmacodynamic (PD) markers (luteinizing hormone LH, follicle-stimulating hormone FSH, and estradiol).
Results
There were no significant differences among treatments with respect to vital signs, electrocardiography, adverse events, ovulation test results, and ultrasonography. The median Tmax of TU2670 occurred 0.75 to 1.00 hours after dosing, and concentrations then declined, with a mean apparent half-life (t1/2) of 3.0 to 5.9 hours. AUClast (17.7-417.9 ng·h/mL) and Cmax (8.1-95.4 ng/mL) increased in a dose-dependent manner. The PD analysis after a single administration of TU2670 revealed dose-dependent suppression of LH, FSH, and estradiol. Maximal suppression of the pre-dose baseline (%) was 58% to 82% at 6 to 8 hours for LH, 28% to 39% at 6 to 12 hours for FSH, and 34% to 82% at 12 to 24 hours for estradiol.
Conclusion
The single administration of TU2670 in healthy premenopausal women was well tolerated and resulted in the dose-dependent suppression of LH, FSH, and estradiol, suggesting rapid and significant inhibition of pituitary and ovarian hormones.
To identify novel roles of SMALL RUBBER PARTICLE PROTEIN Homolog in the non-rubber-producing plant Arabidopsis (AtSRP1), we isolated a T-DNA-insertion knock-out mutant (FLAG_543A05) and investigated ...its functional characteristics. AtSRP1 is predominantly expressed in reproductive organs and is localized to lipid droplets and ER. Compared to wild-type (WT) Arabidopsis, atsrp1 plants contain small siliques with a reduced number of heterogeneously shaped seeds. The size of anther and pollen grains in atsrp1 is highly irregular, with a lower grain number than WT. Therefore, AtSRP1 plays a novel role related to pollen growth and development in a non-rubber-producing plant.
•AtSRP1 is localized to lipid droplets and ER in plant cells.•atsrp1 mutants exhibit reduced fertility and abnormal seed shape.•AtSRP1 functions in pollen growth and development.
Suppression of the hypothalamic–pituitary–gonadal axis has been widely utilized for the management of gonadal-hormone-dependent diseases such as endometriosis. Efforts to develop orally available ...gonadotropin-releasing hormone (GnRH) antagonists for the treatment of gonadal-hormone-dependent diseases led to the discovery of SKI2670, a novel non-peptide GnRH antagonist. The present study was undertaken to pharmacologically characterize SKI2670 in vitro and in vivo.
We measured binding affinity and antagonistic activity of SKI2670 for the GnRH receptors. Immediate suppression of gonadotropins by single dosing of SKI2670 was examined in castrated monkeys. Subsequently, influence on gonadal hormones by prolonged administration of SKI2670 was assessed in naive female monkeys. To investigate in vivo efficacy of SKI2670, regression of ectopic implants by repeated administration of SKI2670 was examined in a rat endometriosis model.
SKI2670 is a potent functional antagonist for the human GnRH receptor, with subnanomolar binding affinity. In castrated monkeys, single administration of SKI2670 lowered serum luteinizing hormone (LH) levels stronger with longer duration when compared to elagolix at equivalent doses. Moreover, repeated dosing of SKI2670 suppressed serum levels of gonadotropins and gonadal hormones in intact female monkeys while elagolix suppressed serum LH levels only. Finally, it exhibited regressive effects on ectopic implants in a rat endometriosis model without bone loss.
Our findings demonstrate robust GnRH antagonistic efficacy of SKI2670 in animal models, suggesting that SKI2670-induced suppression of the hypothalamic–pituitary–gonadal axis may be beneficial for the treatment of gonadal-hormone-dependent diseases such as endometriosis in humans.
This study was performed to evaluate the effectiveness of ramosetron orally disintegrating tablets (ODTs) in preventing post-discharge nausea and/or vomiting (PDNV) in female patients following ...outpatient surgery under general anesthesia.
This multicenter randomized study included three South Korean tertiary hospitals. Before surgery, 138 patients were randomly allocated into two groups. In the ramosetron group, ramosetron ODT 0.1 mg was administered after discharge in the morning of postoperative days 1 and 2. Metoclopramide 10 mg was administered as a rescue antiemetic (capped at 30 mg per day). In the control group, patients were administered only metoclopramide 10 mg when nausea and/or vomiting occurred. The primary outcome was the incidence of nausea during 24 h after discharge.
We found significant differences in the incidence (13% vs. 33%, P = 0.008) and severity (P = 0.011) of nausea between the ramosetron and the control groups during 24 h after discharge. In addition, the rate of rescue antiemetic (metoclopramide) administration during 24 h after discharge was lower in the ramosetron group (6%) than in the control group (18%) (P = 0.033). Patient satisfaction score was higher in the ramosetron group than in the control group (P < 0.001).
Ramosetron ODT reduces the incidence and severity of postoperative nausea after discharge during the first 24 h and may be a valuable option for the prevention of PDNV in female patients after day surgery under general anesthesia.
ClinicalTrials.gov, NCT04297293 . Registered on 05 March 2020.
Based on the metabolic effect of exogenous ATPase inhibitory factor 1 (IF1) on glucose metabolism, we tested whether IF1 treatment is effective in ameliorating weight gain and whether its effects are ...sex specific.
HFD-fed C57BL/6 mice were treated with IF1 (5 mg/kg body weight, injected intraperitoneally). The underlying mechanisms of effect of IF1 on body weight were investigated in vitro and in vivo. Associations between genotypes of IF1 and obesity and relevant phenotype were further tested at the population level.
Chronic treatment with IF1 significantly decreased body weight gain by regulating food intake of HFD-fed male mice. IF1 activated the AKT/mTORC pathway and modulated the expression of appetite genes in the hypothalamus of HFD-fed male mice and its effect was confirmed in hypothalamic cell lines as well as hypothalamic primary cells. This required the interaction of IF1 with β-F1-ATPase on the plasma membrane of hypothalamic cells, which led to an increase in extracellular ATP production. In addition, IF1 treatment showed sympathetic nerve activation as measured by serum norepinephrine levels and UCP-1 expression in the subcutaneous fat of HFD-fed male mice. Notably, administration of recombinant IF1 to HFD-fed ovariectomized female mice showed remarkable reductions in food intake as well as body weight, which was not observed in wild-type 5-week female mice. Lastly, sex-specific genotype associations of IF1 with obesity prevalence and metabolic traits were demonstrated at the population level in humans. IF1 genetic variant (rs3767303) was significantly associated with lower prevalence of obesity and lower levels of body mass index, waist circumference, hemoglobin A1c, and glucose response area only in male participants.
IF1 is involved in weight regulation by controlling food intake and potentially sympathetic nerve activation in a sex-specific manner.
•IF1 prevents obesity by regulating food intake and sympathetic nerve activation.•The effect of IF1 on food intake is sex-specific in HFD induced obese mice.•Genetic effect of IF1 on obesity prevalence is sex-specific at the population level.
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