Molecular cloning and biochemical characterization of a novel erythrose reductase from Candida magnoliae JH110

<p>Abstract</p> <p>Background</p> <p>Erythrose reductase (ER) catalyzes the final step of erythritol production, which is reducing erythrose to erythritol using NAD(P)H as a cofactor. ER has gained interest because of its importance in the production of erythritol, which has extremely low digestibility and approved safety for diabetics. Although ERs were purified and characterized from microbial sources, the entire primary structure and the corresponding DNA for ER still remain unknown in most of erythritol-producing yeasts. <it>Candida magnoliae </it>JH110 isolated from honeycombs produces a significant amount of erythritol, suggesting the presence of erythrose metabolizing enzymes. Here we provide the genetic sequence and functional characteristics of a novel NADPH-dependent ER from <it>C. magnoliae </it>JH110.</p> <p>Results</p> <p>The gene encoding a novel ER was isolated from an osmophilic yeast <it>C. magnoliae </it>JH110. The ER gene composed of 849 nucleotides encodes a polypeptide with a calculated molecular mass of 31.4 kDa. The deduced amino acid sequence of ER showed a high degree of similarity to other members of the aldo-keto reductase superfamily including three ER isozymes from <it>Trichosporonoides megachiliensis </it>SNG-42. The intact coding region of ER from <it>C. magnoliae </it>JH110 was cloned, functionally expressed in <it>Escherichia coli </it>using a combined approach of gene fusion and molecular chaperone co-expression, and subsequently purified to homogeneity. The enzyme displayed a temperature and pH optimum at 42°C and 5.5, respectively. Among various aldoses, the <it>C. magnoliae </it>JH110 ER showed high specific activity for reduction of erythrose to the corresponding alcohol, erythritol. To explore the molecular basis of the catalysis of erythrose reduction with NADPH, homology structural modeling was performed. The result suggested that NADPH binding partners are completely conserved in the <it>C. magnoliae </it>JH110 ER. Furthermore, NADPH interacts with the side chains Lys252, Thr255, and Arg258, which could account for the enzyme's absolute requirement of NADPH over NADH.</p> <p>Conclusions</p> <p>A novel ER enzyme and its corresponding gene were isolated from <it>C. magnoliae </it>JH110. The <it>C. magnoliae </it>JH110 ER with high activity and catalytic efficiency would be very useful for <it>in vitro </it>erythritol production and could be applied for the production of erythritol in other microorganisms, which do not produce erythritol.</p

A scoping review of music-based interventions for swallowing difficulties: implications for treating older adults with presbyphagia

ObjectivesPresbyphagia refers to age-related changes in the swallowing mechanism (e.g., reduced skeletal muscle strength that decreases bolus control). If left untreated, these changes can lead to dysphagia, which refers to impaired swallowing (e.g., coughing or choking when eating). Given that swallowing difficulties are common among older adults that they make up the fastest growing age group globally, the need for interventions to address presbyphagia is gaining urgency. To begin to address this need, we conducted a scoping review to analyze music therapy research aimed at enhancing swallowing function. The objective was to identify key intervention characteristics and propose clinical implications for treating presbyphagia using music therapy.MethodsThis review followed the methodological frameworks outlined by Arksey and O’Malley and Levac et al. and used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Scoping Reviews for analysis and reporting. Four electronic databases (i.e., ProQuest, PubMed, RISS, Web of Science) were searched for quantitative and qualitative studies in English or Korean that used music-based interventions to address swallowing function in older adults. Content analysis was conducted to identify and compare the main features of music interventions for swallowing difficulties among older adults.ResultsTen articles were identified and analyzed. It was found that three core components–respiration, vocalization, and singing–were employed to enhance swallowing function in populations with neurological impairments, dementia, or head and neck cancer. Notably, actions closely linked to swallowing function, such as laryngeal elevation and oral movements, were utilized therapeutically to speak or sing. Based on these characteristics, clinical implications are proposed to address presbyphagia.ConclusionSinging entails a systematic and focused incorporation of stepwise activities that can be used to address swallowing disorders. In this context, critical clinical implications that music therapists should consider when treating individuals with presbyphagia include warmup breathing, vocalizing targeting laryngeal control, and singing targeting oral motor control. This review can contribute to the expansion of music therapy with older adults and the advancement of music therapy techniques

Bloody nipple discharge in an infant

Although milky nipple discharge appears frequently in infants, bloody nipple discharge is a very rare finding. We experienced a 4-month-old, breast-fed infant who showed bilateral bloody nipple discharge with no signs of infection, engorgement, or hypertrophy. The infant's hormonal examination and coagulation tests were normal, and an ultrasound examination revealed mammary duct ectasia. The symptoms resolved spontaneously within 6 weeks without any specific treatment, except that we advised the mother to refrain from taking herbal medicine. Since no such case has been previously reported in Korea, we present this case with a brief review of the literature

Utility of end-tidal carbon dioxide monitoring in intramuscular ketamine sedation in the pediatric emergency department

Purpose Recently, the use of end-tidal carbon dioxide (ETCO2) monitoring has been suggested for early detection of hypoventilation over oxygen saturation (SPO2) monitoring. We aimed to determine the usefulness of capnography in monitoring patients sedated using intramuscular (IM) ketamine in the pediatric emergency department (ED). Methods This study retrospectively reviewed medical records of patients younger than 16 years who were sedated using IM ketamine and whose ETCO2 values were documented in the ED. Age, sex, American Society of Anesthesiologists physical status classification (ASA classification), and purpose of sedation were investigated. Vital signs were recorded at pre-sedation, 5 and 10 minutes after sedation, and after recovery. Hypoventilation was defined as S P O2 < 95%, ETCO2 ≥ 50 mmHg or ≤30 mmHg, or increase in ETCO2 ≥ 10 mmHg from the baseline without tachypnea. Results A total of 49 patients were investigated; 42 of them belonged to ASA classification I, and 7 to II. There was no patient with SPO2 < 95%, or ETCO2 ≥ 50 mmHg, or increase in ETCO2 ≥ 10 mmHg from the pre-sedation value. However, 5 patients had an ETCO2 ≤ 30 mmHg, and 4 of them (8.2%) had normal respiratory rate and were suitable for hypopneic hypoventilation. Ten patients showed abnormal range of ETCO2 (normal range, 35–45 mmHg), but did not meet the definition of hypoventilation. No one had clinically serious respiratory events. Conclusion During sedation using IM ketamine, 8.2% of the patients had hypopneic hypoventilation without hypoxemia, and they were all younger than 36 months. Capnography for patients sedated using IM ketamine in the ED is useful in detecting hypopneic hypoventilation, and has the potential for preventing clinically serious respiratory events in patients, especially toddlers

Piceatannol, Natural Polyphenolic Stilbene, Inhibits Adipogenesis via Modulation of Mitotic Clonal Expansion and Insulin Receptor-dependent Insulin Signaling in Early Phase of Differentiation

Piceatannol, a natural stilbene, is an analog and a metabolite of resveratrol. Despite a well documented health benefit of resveratrol in intervention of the development of obesity, the role of piceatannol in the development of adipose tissue and related diseases is unknown. Here, we sought to determine the function of piceatannol in adipogenesis and elucidate the underlying mechanism. We show that piceatannol inhibits adipogenesis of 3T3-L1 preadipocytes in a dose-dependent manner at noncytotoxic concentrations. This anti-adipogenic property of piceatannol was largely limited to the early event of adipogenesis. In the early phase of adipogenesis, piceatannol-treated preadipocytes displayed a delayed cell cycle entry into G2/M phase at 24 h after initiation of adipogenesis. Furthermore, the piceatannol-suppressed mitotic clonal expansion was accompanied by reduced activation of the insulin-signaling pathway. Piceatannol dose-dependently inhibited differentiation mixture-induced phosphorylation of insulin receptor (IR)/insulin receptor substrate-1 (IRS-1)/Akt pathway in the early phase of adipogenesis. Moreover, we showed that piceatannol is an inhibitor of IR kinase activity and phosphatidylinositol 3-kinase (PI3K). Our kinetics study of IR further identified a Km value for ATP of 57.8 μm and a Ki value for piceatannol of 28.9 μm. We also showed that piceatannol directly binds to IR and inhibits IR kinase activity in a mixed noncompetitive manner to ATP, through which piceatannol appears to inhibit adipogenesis. Taken together, our study reveals an anti-adipogenic function of piceatannol and highlights IR and its downstream insulin signaling as novel targets for piceatannol in the early phase of adipogenesis

Heterogeneous nuclear ribonucleoprotein (hnRNP) L promotes DNA damage-induced cell apoptosis by enhancing the translation of p53

The tumor suppressor p53 is an essential gene in the induction of cell cycle arrest, DNA repair, and apoptosis. p53 protein is induced under cellular stress, blocking cell cycle progression and inducing DNA repair. Under DNA damage conditions, it has been reported that post-transcriptional regulation of p53 mRNA contributes to the increase in p53 protein level. Here we demonstrate that heterogeneous nuclear ribonucleoprotein (hnRNP) L enhances p53 mRNA translation. We found that hnRNP L is increased and binds to the 5&apos; UTR of p53 mRNA in response to DNA damage. Increased hnRNP L caused enhancement of p53 mRNA translation. Conversely, p53 protein levels were decreased following hnRNP L knock-down, rendering them resistant to apoptosis and arrest in the G2/M phase after DNA damage. Thus, our findings suggest that hnRNP L functions as a positive regulator of p53 translation and promotes cell cycle arrest and apoptosis.11Ysciescopu

Effect of Pertussis Toxin and Herbimycin A on Proteinase-Activated Receptor 2-Mediated Cyclooxygenase 2 Expression in Helicobacter pylori-Infected Gastric Epithelial AGS Cells

Helicobacter pylori (H. pylori) is an important risk factor for chronic gastritis, peptic ulcer, and gastric cancer. Proteinase-activated receptor 2 (PAR2), subgroup of G-protein coupled receptor family, is highly expressed in gastric cancer, and chronic expression of cyclooxygenase-2 (COX-2) plays an important role in H. pylori-associated gastric carcinogenesis and inflammation. We previously demonstrated that H. pylori induced the expression of PAR2 and COX-2 in gastric epithelial cells. Present study aims to investigate whether COX-2 expression induced by H. pylori in Korean isolates is mediated by PAR2 via activation of Gi protein and Src kinase in gastric epithelial AGS cells. Results showed that H. pylori-induced COX-2 expression was inhibited in the cells transfected with antisense oligonucleotide for PAR2 or treated with Gi protein blocker pertussis toxin, Src kinase inhibitor herbimycin A and soybean trypsin inbitor, indicating that COX-2 expression is mediated by PAR2 through activation of Gi protein and Src kinase in gastric epithelial cells infected with H. pylori in Korean isolates. Thus, targeting the activation of PAR2 may be beneficial for prevention or treatment of gastric inflammation and carcinogenesis associated with H. pylori infection

Health-related quality of life with KDQOL-36 and its association with self-efficacy and treatment satisfaction in Korean dialysis patients

BACKGROUND AND OBJECTIVES: This study was conducted to measure the level of health-related quality of life (HRQOL) and to reveal the association of self-efficacy and treatment satisfaction with it in Korean dialysis patients. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: The study subjects were 237 patients receiving either hemodialysis (HD) or peritoneal dialysis (PD) from two university hospitals, from February to June in 2010. We investigated HRQOL using the Korean version of Kidney Disease Quality of Life Short Form 36 (KDQOL-36), and self-efficacy and treatment satisfaction by self-administrative questionnaire and their dialysis-related variables by reviewing clinical records. The associations of self-efficacy and treatment satisfaction with HRQOL were assessed using multiple linear regression analysis. RESULTS: The mean HRQOL results were as follows: Physical component score (PCS) was 39.1 ± 8.5, Mental component score (MCS) 44.6 ± 6.8, symptom/problem list was 67.6 ± 17.1, effects of disease score was 58.5 ± 19.6, and burden of disease score was 41.1 ± 28.4. Between PD and HD patients, we could find significant difference only in the symptom/problem list. After removing confounder’s effects by multivariate analysis, respectively, treatment goal self-efficacy and treatment management self-efficacy were significantly related with all 5 domains, except PCS. Treatment satisfaction was significantly related with PCS, MCS, and effects of kidney disease. CONCLUSIONS: Patients’ self-efficacy and treatment satisfaction could influence their HRQOL. Regular and systematic monitoring using KDQOL-36 and interventions to increase self-efficacy and treatment satisfaction should be considered in dialysis care in Korea

The Clinical Frailty Scale as a Risk Assessment Tool for Dysphagia in Older Inpatients: A Cross-Sectional Study

Background Dysphagia is a common problem with potentially serious consequences including malnutrition, dehydration, pneumonia, and death. However, there are challenges in screening for dysphagia in older adults. We assessed the feasibility of using the Clinical Frailty Scale (CFS) as a risk assessment tool for dysphagia. Methods This cross-sectional study was conducted at a tertiary teaching hospital from November 2021 to May 2022 and included 131 older patients (age ≥65 years) admitted to acute wards. We used the Eating Assessment Tool-10 (EAT-10), which is a simple measure for identifying individuals at risk of dysphagia, to assess the relationship between EAT-10 score and frailty status as measured using the CFS. Results The mean age of the participants was 74.3±6.7 years, and 44.3% were male. Twenty-nine (22.1%) participants had an EAT-10 score ≥3. The CFS was significantly associated with an EAT-10 score ≥3 after adjusting for age and sex (odds ratio=1.48; 95% confidence interval [CI], 1.09–2.02). The CFS was able to classify the presence of an EAT-10 score ≥3 (area under the receiver operating characteristic [ROC] curve=0.650; 95% CI, 0. 544–0.756). The cutoff point for predicting an EAT-10 score ≥3 was a CFS of 5 according to the highest Youden index, with a sensitivity of 82.8% and a specificity of 46.1%. The positive and negative predictive values were 30.4% and 90.4%, respectively. Conclusion The CFS can be used as a tool to screen for the risk of swallowing difficulty in older inpatients to determine clinical management encompassing drug administration routes, nutritional support, prevention of dehydration, and further evaluation of dysphagia