Total Synthesis and Bioactivity Profile of (+)-Ieodomycins A and B and their Stereoisomers.

Herein, we report the first- and second-generation syntheses of (+)-ieodomycins A and B and their stereoisomers via the late-stage elaboration of their conjugated E-diene side chains. Key steps for successful synthesis included Keck asymmetric allylation to introduce a hydroxyl group at the C5 position, consecutive Wipf's carboalumination modification, iodination, Sharpless asymmetric dihydroxylation, one-carbon homologation via cyanation, Mukaiyama lactonization, and Stille cross-coupling to form the conjugated E-diene moiety. Further, the preliminary in vitro bioactivity profile against various disease-related molecular targets and cell lines was investigated. Results indicated that compounds 30b and 30c, diastereoisomers of (+)-ieodomycin B (2), serve as α-glucosidase inhibitors, while compounds 30b and 30d inhibit the angiotensin-converting enzyme.

Chemogenetic activation ofarcuate nucleus NPY and NPY/AgRP neurons increases feeding behaviour in mice.

Neuropeptide Y (NPY) plays a crucial role in controlling energy homeostasis and feeding behaviour. The role of NPY neurons located in the arcuate nucleus of the hypothalamus (Arc) in responding to homeostatic signals has been the focus of much investigation, but most studies have used AgRP promoter-driven models, which do not fully encompass Arc NPY neurons. To directly investigate NPY-expressing versus AgRP-expressing Arc neurons function, we utilised chemogenetic techniques in NPY-Cre and AgRP-Cre animals to activate Arc NPY or AgRP neurons in the presence of food and food-related stimuli. Our findings suggest that chemogenetic activation of the broader population of Arc NPY neurons, including AgRP-positive and AgRP-negative NPY neurons, has equivalent effects on feeding behaviour as activation of Arc AgRP neurons. Our results demonstrate that these Arc NPY neurons respond specifically to caloric signals and do not respond to non-caloric signals, in line with what has been observed in AgRP neurons. Activating Arc NPY neurons significantly increases food consumption and influences macronutrient selection to prefer fat intake.

Hormone replacement therapy and myocardial infarction and stroke in postmenopausal Korean women.

OBJECTIVE: This study aimed to investigate the association of hormone replacement therapy (HRT) use, type, duration and age of commencement with myocardial infarction (MI) and stroke in postmenopausal Korean women. METHODS: This nested case-control study used data from the National Health Insurance Service database to analyze 2017 data from women aged ≥50 years and diagnosed with natural menopause between 2004 and 2007. Among 356,160 eligible women, 36,446 used HRT for ≥1 year and 319,714 did not (controls). These two groups were matched 1:1 for statistical analysis. Type and duration were categorized into three categories. RESULTS: Women who started estrogen-progestogen therapy (EPT) or estrogen therapy (ET) in their 50s, or EPT or tibolone in their ≥60s exhibited a lower stroke risk than controls. MI risk was lower among women who used tibolone - regardless of duration - or EPT or ET for 1-3 years than among controls. Stroke risk was lower with tibolone use for ≥5 years or with EPT or ET use for 1-3 years or ≥5 years than non-users. CONCLUSION: Our study may support the beneficial effect of HRT by showing that Korean postmenopausal women who used HRT at a relatively younger and healthier age had a relative benefit for MI and stroke.

Antiviral Potential of Fucoxanthin, an Edible Carotenoid Purified from Sargassum siliquastrum, against Zika Virus.

Considering the lack of antiviral drugs worldwide, we investigated the antiviral potential of fucoxanthin, an edible carotenoid purified from Sargassum siliquastrum, against zika virus (ZIKV) infection. The antiviral activity of fucoxanthin was assessed in ZIKV-infected Vero E6 cells, and the relevant structural characteristics were confirmed using molecular docking and molecular dynamics (MD) simulation. Fucoxanthin decreased the infectious viral particles and nonstructural protein (NS)1 mRNA expression levels at concentrations of 12.5, 25, and 50 µM in ZIKV-infected cells. Fucoxanthin also decreased the increased mRNA levels of interferon-induced proteins with tetratricopeptide repeat 1 and 2 in ZIKV-infected cells. Molecular docking simulations revealed that fucoxanthin binds to three main ZIKV proteins, including the envelope protein, NS3, and RNA-dependent RNA polymerase (RdRp), with binding energies of -151.449, -303.478, and -290.919 kcal/mol, respectively. The complex of fucoxanthin with RdRp was more stable than RdRp protein alone based on MD simulation. Further, fucoxanthin bonded to the three proteins via repeated formation and disappearance of hydrogen bonds. Overall, fucoxanthin exerts antiviral potential against ZIKV by affecting its three main proteins in a concentration-dependent manner. Thus, fucoxanthin isolated from S. siliquastrum is a potential candidate for treating zika virus infections.

Initial screening for dental abnormalities identified by labial and buccal photographs in dogs and cats.

OBJECTIVE: To evaluate the dental abnormalities by visually assessing the labial and buccal photographs in dogs and cats and analyze their prevalence based on age and breed. ANIMALS: 1,096 client-owned dogs and 775 client-owned cats. METHODS: Data were collected from patients who visited 26 private veterinary clinics from January to December 2022. Each animal was evaluated through dental photographs taken from the labial and buccal sides. Correlations between the prevalence of the identified dental abnormalities and age, craniofacial type, and breed, were analyzed. RESULTS: Calculus, discoloration, epulis, fractured teeth, gingival recession, gingivitis, malocclusion, missing teeth, and persistent deciduous teeth could be identified by analyzing the dental photographs in both dogs and cats. Enamel defects in dogs and tooth resorption in cats could be identified. Brachycephalic dogs had a significantly higher prevalence of malocclusion (OR, 1.93; 95% CI, 1.36 to 2.75) and missing teeth (OR, 3.63; 95% CI, 2.71 to 4.91) compared to nonbrachycephalic dogs. Brachycephalic cats had a significantly higher prevalence of fractured teeth (OR, 1.95; 95% CI, 1.24 to 3.04) and a lower prevalence of gingival recession (OR, 0.30; 95% CI, 0.15 to 0.55) compared to nonbrachycephalic cats. Calculus, persistent deciduous teeth, and possibly gingivitis could be identified in dogs and cats by analyzing labial and buccal photographs. The assessment of some dental abnormalities such as fractured teeth, missing teeth, and tooth resorption can be limited without a complete dental examination under anesthesia. CLINICAL RELEVANCE: Although the assessment of dental conditions may be underestimated, the data on the prevalence of the dental abnormalities evaluated through the photographs could be utilized for screening dental diseases.

A Comprehensive Analysis of HOXB13 Expression in Hepatocellular Carcinoma.

Background and objectives: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and is caused by multiple factors. To explore novel targets for HCC treatment, we comprehensively analyzed the expression of HomeoboxB13 (HOXB13) and its role in HCC. Materials and Methods: The clinical significance of HCC was investigated using open gene expression databases, such as TIMER, UALCAN, KM, OSlihc, and LinkedOmics, and immunohistochemistry analysis. We also analyzed cell invasion and migration in HCC cell lines transfected with HOXB13-siRNA and their association with MMP9, E2F1, and MEIS1. Results: HOXB13 expression was higher in fibrolamellar carcinoma than in other histological subtypes. Its expression was associated with lymph node metastasis, histological stage, and tumor grade. It was positively correlated with immune cell infiltration of B cells (R = 0.246), macrophages (R = 0.182), myeloid dendritic cells (R = 0.247), neutrophils (R = 0.117), and CD4+ T cells (R = 0.258) and negatively correlated with immune cell infiltration of CD8+ T cells (R = -0.107). A positive correlation was observed between HOXB13, MMP9 (R = 0.176), E2F1 (R = 0.241), and MEIS1 (R = 0.189) expression (p < 0.001). The expression level of HOXB13 was significantly downregulated in both HepG2 and PLC/PFR/5 cell lines transfected with HOXB13-siRNA compared to that in cells transfected with NC siRNA (p < 0.05). Additionally, HOXB13 significantly affected cell viability and wound healing. Conclusions: HOXB13 overexpression may lead to poor prognosis in patients with HCC. Additional in vivo studies are required to improve our understanding of the biological role and the exact mechanism of action of HOXB13 in HCC.

In vitro Fertilization Outcomes of Frozen-thawed Embryo Transfer with Hatched Blastocysts versus with Hatching Blastocysts.

This study aimed to elucidate the effect of hatching status on in vitro fertilization (IVF) outcomes in frozen-thawed blastocyst transfer cycles. Frozen-thawed embryo transfer (FET) cycles performed at a single fertility center between 2016 and 2021 were retrospectively assessed. Analyses were restricted to 6,821 frozen-thawed blastocyst transfers in women aged 24-47 years. For optimal comparability, double embryo transfer (ET) cycles consisting of one hatching and one hatched blastocyst were excluded. The implantation and pregnancy rates were evaluated and compared between the hatching and hatched blastocyst transfer groups based on patients' age (<38 vs. ≥38 years), blastocyst grade (good vs. bad grade), and the number of transferred embryos (single ET vs. double ET). Hatched blastocyst transfer was associated with higher implantation and clinical pregnancy rates in the single ET group (15.7% and 15.6%, respectively; p<0.001). The transfer of two hatched blastocysts had higher implantation and clinical pregnancy rates compared to the transfer of two hatching blastocysts (19.5% and 20.4%, respectively; p<0.001) in the double ET group. In the hatched blastocyst transfer group, the clinical pregnancy and implantation rates were higher, regardless of each woman's age and embryo quality. The IVF treatment outcomes were improved when the blastocysts were hatched during FET cycles. Hence, hatched blastocyst transfer in FET cycles could be considered a superior method in IVF practice.

Unveiling the Potential of Ultrasonic-Assisted Ethanol Extract from Sargassum horneri in Inhibiting Tyrosinase Activity and Melanin Production in B16F10 Murine Melanocytes.

BACKGROUNDS: Melanogenesis, regulated by genetic, hormonal, and environmental factors, occurs in melanocytes in the basal layer of the epidermis. Dysregulation of this process can lead to various skin disorders, such as hyperpigmentation and hypopigmentation. Therefore, the present study investigated the effect of ultrasonic-assisted ethanol extract (SHUE) from Sargassum horneri (S. horneri), brown seaweed against melanogenesis in α-melanocyte-stimulating hormone (MSH)-stimulated B16F10 murine melanocytes. METHODS: Firstly, yield and proximate compositional analysis of the samples were conducted. The effect of SHUE on cell viability has been evaluated by using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. After that, the melanin content and cellular tyrosinase activity in α-MSH-stimulated B16F10 murine melanocytes were examined. Western blot analysis was carried out to investigate the protein expression levels of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP1), and tyrosinase-related protein-2 (TRP2). In addition, the effect of extracellular signal-regulated kinase (ERK) on the melanogenesis process was assessed via Western blotting. RESULTS: As per the analysis, SHUE contained the highest average yield on a dry basis at 28.70 ± 3.21%. The findings showed that SHUE reduced the melanin content and cellular tyrosinase activity in α-MSH-stimulated B16F10 murine melanocytes. Additionally, the expression levels of MITF, TRP1, and TRP2 protein were significantly downregulated by SHUE treatment in α-MSH-stimulated B16F10 murine melanocytes. Moreover, SHUE upregulated the phosphorylation of ERK and AKT in α-MSH-stimulated B16F10 murine melanocytes. In addition, experiments conducted using the ERK inhibitor (PD98059) revealed that the activity of SHUE depends on the ERK signaling cascade. CONCLUSION: These results suggest that SHUE has an anti-melanogenic effect and can be used as a material in the formulation of cosmetics related to whitening and lightening.

Cardioprotection via mitochondrial transplantation supports fatty acid metabolism in ischemia-reperfusion injured rat heart.

In addition to cellular damage, ischemia-reperfusion (IR) injury induces substantial damage to the mitochondria and endoplasmic reticulum. In this study, we sought to determine whether impaired mitochondrial function owing to IR could be restored by transplanting mitochondria into the heart under ex vivo IR states. Additionally, we aimed to provide preliminary results to inform therapeutic options for ischemic heart disease (IHD). Healthy mitochondria isolated from autologous gluteus maximus muscle were transplanted into the hearts of Sprague-Dawley rats damaged by IR using the Langendorff system, and the heart rate and oxygen consumption capacity of the mitochondria were measured to confirm whether heart function was restored. In addition, relative expression levels were measured to identify the genes related to IR injury. Mitochondrial oxygen consumption capacity was found to be lower in the IR group than in the group that underwent mitochondrial transplantation after IR injury (p < 0.05), and the control group showed a tendency toward increased oxygen consumption capacity compared with the IR group. Among the genes related to fatty acid metabolism, Cpt1b (p < 0.05) and Fads1 (p < 0.01) showed significant expression in the following order: IR group, IR + transplantation group, and control group. These results suggest that mitochondrial transplantation protects the heart from IR damage and may be feasible as a therapeutic option for IHD.

Prenatal treatment with corticosterone via maternal injection induces learning and memory impairments via delaying postsynaptic development in hippocampal CA1 neurons of rats.

Previously, we reported that prenatal exposure to high corticosterone induced attention-deficit hyperactivity disorder (ADHD)-like behaviors with cognitive deficits after weaning. In the present study, cellular mechanisms underlying cortisol-induced cognitive dysfunction were investigated using rat pups (Corti.Pups) born from rat mothers that were repetitively injected with corticosterone during pregnancy. In results, Corti.Pups exhibited the failure of behavioral memory formation in the Morris water maze (MWM) test and the incomplete long-term potentiation (LTP) of hippocampal CA1 neurons. Additionally, glutamatergic excitatory postsynaptic currents (EPSCs) were remarkably suppressed in Corti.Pups compared to normal rat pups. Incomplete LTP and weaker EPSCs in Corti.Pups were attributed to the delayed postsynaptic development of CA1 neurons, showing a higher expression of NR2B subunits and lower expression of PSD-95 and BDNF. These results indicated that the prenatal treatment with corticosterone to elevate cortisol level might potently downregulate the BDNF-mediated signaling critical for the synaptic development of hippocampal CA1 neurons during brain development, and subsequently, induce learning and memory impairment. Our findings suggest a possibility that the prenatal dysregulation of cortisol triggers the epigenetic pathogenesis of neurodevelopmental psychiatric disorders, such as ADHD and autism.

Associations of concentrations of eight urinary phthalate metabolites with the frequency of use of common adult consumer and personal-care products.

This study analyzed the relationship between urine concentrations of phthalate metabolites (UCOM) and personal care products (PCPs) used in adults and examined the change in UCOM according to the usage frequency of PCPs based on raw data from the 3rd Korean National Environmental Health Survey conducted between 2015 and 2017. The relationship between PCP use frequency and UCOM was analyzed using multiple regression analysis, adjusting for baseline factors. The regression model consisted of a Crude Model with log-transformed UCOM before and after adjustment for urine creatinine concentrations. Model 1 was additionally adjusted for age, sex, and obesity, while Model 2 was additionally adjusted for smoking, alcohol consumption, pregnancy history, average monthly income of the household, and PCP exposure within the past 2 days. PCP usage frequency was significantly associated with the UCOM without adjustment for urine creatinine and correlated with demographic characteristics, urine creatinine concentration, and PCP exposure within the past 2 days. This study on exposure to urinary phthalates will play a crucial role in Korean public health by aligning with the fundamentals of research priorities and providing representative data on phthalate exposure for conducting population-level studies.

Effects of alternative sweeteners with or without xanthan gum on the physicochemical properties of scone products.

The physicochemical properties of scones made with alternative sweeteners (stevia, sucralose, and allulose) at different ratios (30, 70, and 100%) with or without xanthan gum were investigated. Nineteen samples were evaluated for crust color, moisture content, specific volume, and texture properties. Scones with allulose had lower L values but higher a and b values due to the Maillard and caramelization reactions. The moisture content increased with xanthan gum addition, thereby decreasing the specific volume. The sample with 30% of stevia (ST30), 30% of sucralose (SC30), and 30% of allulose and xanthan gum (AL30G) had similar characteristics to the sample with sucrose (CON). In the consumer acceptance test, CON was the most preferred, but ST30 showed no significant difference. AL30G was less preferred because of its lack of sweetness. Overall, the physicochemical properties and consumer acceptance of ST30 were closest to those of CON, suggesting its potential use in scone products. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01416-9.

Managing a difficult airway due to supraglottic masses: successful videolaryngoscopic intubation after induction of general anesthesia.

BACKGROUND: While awake, flexible bronchoscopic intubation has long been considered the gold standard for managing anticipated difficult airways, the videolaryngoscope has emerged as a viable alternative. In addition, the decision to perform awake intubation or to proceed with airway management after induction of general anesthesia should be grounded in a comprehensive assessment of risks and benefits. CASE PRESENTATION: A 41-year old female patient was scheduled for excision of bilateral, mobile, and pedunculated masses on both aryepiglottic folds, which covered almost the entire upper part of the glottis. We conducted a comprehensive evaluation of the patient's signs and symptoms, which included neither stridor nor dyspnea in any position, along with the otolaryngologist's opinion and the findings from the laryngeal fiberscopic examination. Given the potential challenges and risks associated with awake flexible bronchoscopic intubation for this patient, we decided to proceed with gentle tracheal intubation using a videolaryngoscope under general anesthesia. In case of failed mask ventilation and tracheal intubation, we had preplanned strategies, including awakening the patient or performing an emergent tracheostomy, along with preparations to support these strategies. Ensuring that mask ventilation was maintained with ease, the patient was sequentially administered intravenous propofol, remifentanil, and rocuronium. Under sufficient depth of anesthesia, intubation using a videolaryngoscope was successfully performed without any complications. CONCLUSIONS: Videolaryngoscopic intubation after induction of general anesthesia can be a feasible alternative for managing difficult airways in patients with supraglottic masses. This approachshould be based on a comprehensive preoperative evaluation, adequate preparation, and preplanned strategies to address potential challenges, such as inadequate oxygenation and unsuccessful tracheal intubation.

Lateral Tarsoplasty Combined with a Full-Thickness Skin Graft for Managing Severe Lower Eyelid Ectropion Following the Subciliary Approach for Infra-Orbital Rim Fracture: A Retrospective Observational Study.

Subciliary incision is a common approach for facial fracture surgery; however, it has a higher incidence of lower lid ectropion, which can be particularly challenging for beginning surgeons to manage. This study reports the usage of lateral tarsoplasty combined with a full-thickness skin graft (FTSG) to correct severe ectropion following the subciliary approach for infra-orbital rim fractures. We retrospectively reviewed all facial fracture cases involving infra-orbital rim fractures through a subciliary approach treated in our department between March 2021 and May 2023. Electronic medical records and clinical digital photographs of patients who met the inclusion criteria were reviewed. After reviewing 196 cases that used the subciliary approach, we found 6 patients (3.06%; 4 males and 2 females; mean age, 68.5 ± 4.89 years) with postoperative severe ectropion managed using lateral tarsoplasty and FTSG. The mean ectropion development and correction times after facial fracture surgery were 0.78 ± 0.24 and 0.91 ± 0.37 months, respectively. At the 12-month follow-up, all patients showed favorable outcomes, and the position of their lower eyelids was well maintained without ectropion recurrence. Based on these successful outcomes, lateral tarsoplasty combined with FTSG is proposed to be an effective and straightforward method for managing lower eyelid ectropion caused by facial fracture surgery.

Reconstruction of cervical necrotizing fasciitis defect with the modified keystone flap technique: Two case reports.

BACKGROUND: Cervical necrotizing fasciitis (CNF) is a rare, aggressive form of deep neck space infection with significant morbidity and mortality rates. Serial surgical debridement acts as the cornerstone of CNF treatment; however, it often results in defects requiring complex reconstructions. CASE SUMMARY: We report two cases in which the keystone flap (KF) was used for CNF defect coverage: Case 1, an 85-year-old patient with CNF in the anterior neck, and Case 2, a 54-year-old patient with CNF in the posterior neck. Both patients received empirical intravenous antibiotic therapy and underwent serial debridement, enabling adequate wound preparation and stabilization. The final defect size measured 5.5 cm × 12 cm in Case 1 and 6 cm × 11 cm in Case 2. For defect coverage, we employed an 8 cm × 19 cm type II KF based on perforators from the superior thyroid artery in Case 1 and a 9 cm × 18 cm type II KF based on perforators from the transverse cervical artery in Case 2. Both flaps showed complete survival. No postoperative complications occurred in both cases, and favorable outcomes were observed at 7- and 6-month follow-ups in case 1 and 2, respectively. CONCLUSION: We effectively treated CNF-associated defects using the KF technique; KF is viable for covering CNF defects in carefully selected cases.

Pre-mixing of omega-3 fatty acid-containing liposomes enhances the drug release rate and therapeutic efficacy of anticancer drugs loaded in liposomes.

The therapeutic efficacy of anticancer drugs loaded in liposomes composed of rigid phosphatidylcholine (PC) is hindered by the limited release of these drugs at the tumor site, which in turn hampers delivery of the drug to its intracellular target. In an attempt to improve the therapeutic efficacy of liposomal anticancer drugs, we here explored the use of empty liposomes as "trigger" vehicles to induce drug release from drug-loaded liposomes through liposome-liposome interactions. Empty liposomes containing PC in which omega-3 fatty acids comprised both fatty acid strands (Omega-L) showed a triggering effect on drug release from doxorubicin (DOX)-loaded liposomes (Caelyx). The effectiveness of this triggered-release effect was dependent on the Omega-L composition as well as the mixing ratio of Omega-L to Caelyx. Cryo-TEM and differential calorimetry studies revealed that the Omega-L effect was associated with liposome-liposome interactions that led to loosened membrane packing and increased fluidity of Caelyx. In cultured cells, the intracellular/intranuclear DOX uptake and anticancer efficacy of Caelyx was greatly improved by Omega-L pre-mixing. Intravenous injection of rats with Caelyx, premixed with Omega-L, decreased the area under the plasma concentration-time curve from time zero to time infinity and increased clearance without significantly changing the mean residence time or terminal half-life of DOX compared with Caelyx alone. Ex vivo bioimaging showed that DOX fluorescence in tumors, but not in other organs, was significantly increased by Omega-L premixing. In the mouse xenograft model, premixing of Omega-L with Caelyx suppressed tumor growth 2.5-fold compared with Caelyx. Collectively, the data provide preliminary evidence that the Omega-L-triggered drug release that occurs before and after dosing, particularly at tumor site, improved the therapeutic efficacy of Caelyx. The simple approach described here could enhance the therapeutic value of Caelyx and other anticancer drug-loaded liposomes.

Relationship between menopausal hormone therapy and incidence of fractures in postmenopausal women.

OBJECTIVE: Long-term protective effects of menopausal hormone therapy (MHT) at fractures with different doses and components are controversial. We analyzed the effect of MHT on the incidence of spine and femur fractures according to MHT type, age at commencement, duration and dose of hormones in Korean women. METHOD: This retrospective study evaluated propensity score-matched patients with MHT from the Korean National Health Insurance Service database. Among women aged ≥50 years with menopause between 2004 and 2007, spine and femur fracture incidence until 2017 was analyzed in 36,446 women who had received MHT for >1 year. Estrogen-progesterone therapy (EPT), estrogen-only therapy (ET) or tibolone therapy was conducted. RESULTS: EPT significantly lowered the incidence of spine and femur fractures with a conventional dose, but not with a low dose. Tibolone significantly decreased the incidence of spine fractures in women aged 50-59 years when used for >5 years, and the incidence of femur fractures in women older than 60 years when used for >3 years. ET significantly lowered the risk of femur fractures when estradiol was used for >5 years. CONCLUSION: In menopausal women, all MHT including conventional-dose EPT, ET and tibolone tended to lower the incidence of fractures. The effects, however, varied with the type of fracture and type of MHT.

Leaves and pseudostems extract of Curcuma longa attenuates immunoglobulin E/bovine serum albumin-stimulated bone marrow-derived cultured mast cell activation and passive cutaneous anaphylaxis in BALB/c mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Curcuma longa, known as turmeric, is an herbaceous perennial plant belonging to the genus Curcuma. It is dispersed throughout tropical and subtropical regions worldwide. Since ancient times, turmeric has been used as an ethnomedicinal plant in the Ayurvedic system, particularly in Asian countries. Rhizomes of turmeric possess several pharmacological properties that give high value as a medicinal remedy for treating a range of conditions, including inflammation, pain, allergies, and digestive issues. Moreover, turmeric leaves and pseudostems also contain a variety of health-enhancing secondary metabolites, such as curcumin, flavonoids, and other phenolic compounds, which exhibit anti-inflammatory, antitumor, antibacterial, and antioxidant properties. AIM OF THE STUDY: Allergic diseases are a group of immune-mediated disorders mainly caused by an immunoglobulin E (IgE)-dependent immunological response to an innocuous allergen. Therefore, this study aimed to investigate the effect of leaves and pseudostems extract of turmeric (TLSWE-8510) on IgE/bovine serum albumin (BSA)-stimulated allergic responses in mouse bone marrow-derived cultured mast cells (BMCMCs) and passive cutaneous anaphylaxis (PCA) in BALB/c mice. MATERIALS AND METHODS: The effect of TLSWE-8510 on mast cell degranulation has been evaluated by investigating the release of ß-hexosaminidase and histamine in IgE/BSA-stimulated BMCMCs. Additionally, anti-allergic properties of TLSWE-8510 on IgE/BSA-stimulated BMCMCs were investigated using suppression of nuclear factor-kappa B (NF-κB), and spleen tyrosine kinase (Syk)-linker for T-cell activation (LAT)-extracellular-signal-regulated kinase (ERK)-GRB2 associated binding protein 2 (Gab2) signaling pathway and downregulation of allergy-related cytokines and chemokines expression. Furthermore, in vivo, studies were conducted using IgE-mediated PCA in BALB/c mice. RESULTS: TLSWE-8510 treatment significantly inhibited the degranulation of IgE/BSA-stimulated BMCMCs by inhibiting the release of ß-hexosaminidase and histamine dose-dependently. Additionally, TLSWE-8510 reduced the expression of high-affinity IgE receptors (Fc epsilon receptor I-FcεRI) on the surface of BMCMCs and the binding of IgE to FcεRI. Besides, the expression of cytokines and chemokines is triggered by IgE/BSA stimulation via activating the allergy-related signaling pathways. TLSWE-8510 dose-dependently downregulated the mRNA expression and the production of allergy-related cytokines (interleukin (IL)-1ß, IL-3, IL-4, IL-5, IL-6, IL-13, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ), and chemokines (thymus and activation-regulated chemokine (TARC), and regulated upon activation, normal T cell expressed and secreted (RANTES)) by regulating the phosphorylation of downstream signaling molecules, NF-κB, and Syk, LAT, ERK and Gab2 in IgE/BSA-stimulated BMCMCs. Moreover, PCA reaction in IgE/BSA-stimulated BALB/c mice ears was effectively decreased by TLSWE-8510 treatment in a dose-dependent manner. CONCLUSIONS: These results collectively demonstrated that TLSWE-8510 suppressed mast cell degranulation by inhibiting the release of chemical mediators related to allergies. TLSWE-8510 downregulated the allergy-related cytokines and chemokines expression and phosphorylation of downstream signaling molecules in IgE/BSA-stimulated BMCMCs. Furthermore, in vivo studies with IgE-mediated PCA reaction in the BALB/c mice ears were attenuated by TLSWE-8510 treatment. These findings revealed that TLSWE-8510 has the potential as a therapeutic agent for the treatment of allergic diseases.

Nursing practice readiness improvement program tailored for newly graduated registered nurses: A quasi-experimental study.

BACKGROUND: Helping newly graduated registered nurses successfully adapt to clinical practice, evaluating work capabilities, identifying deficiencies, and continuously providing educational support to improve deficiencies are reported to be of paramount importance. OBJECTIVES: To develop a tailored nursing practice preparation improvement program for newly graduated registered nurses and assess its impact on the successful adaptation of nurses. DESIGN: A quasi-experimental study. SETTINGS: The study was performed at a tertiary general hospital in South Korea. PARTICIPANT: A total of 53 newly graduated registered nurses (experimental group = 28; comparison group = 25) participated. METHODS: The newly graduated registered nurses were recruited using purposive sampling to one of two groups. The study was conducted between February and May 2022. The experimental group underwent a 4-week education program that integrated various methods, whereas the control group underwent preceptor training in their department. Data were collected through a questionnaire survey and analyzed using the chi-square test, independent t-test, and analysis of covariance with the SPSS 26.0 program. RESULTS: The nursing practice readiness improvement program tailored for newly graduated registered nurses was effective in reducing the transition shock (F = 9.18, p = 0.004) of newly graduated registered nurses and improving nursing practice readiness (F = 19.90, p < 0.001), job satisfaction (F = 4.09, p = 0.049), and retention intention (F = 6.20, p = 0.016). CONCLUSIONS: This study presented an evidence based approach on the use of a nursing practice readiness improvement program for the successful adaptation of newly graduated registered nurses and the establishment of a nurse education system.